US20120072124A1 - Genes associated with progression and response in chronic myeloid leukemia and uses thereof - Google Patents

Genes associated with progression and response in chronic myeloid leukemia and uses thereof Download PDF

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US20120072124A1
US20120072124A1 US13/207,282 US201113207282A US2012072124A1 US 20120072124 A1 US20120072124 A1 US 20120072124A1 US 201113207282 A US201113207282 A US 201113207282A US 2012072124 A1 US2012072124 A1 US 2012072124A1
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Jerald P. Radich
Hongyue Dai
Mao Mao
Janell M. Schelter
Peter S. Linsley
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Rosetta Inpharmatics LLC
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    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
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    • C12Q2600/00—Oligonucleotides characterized by their use
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Abstract

The invention provides molecular markers that are associated with the progression of chronic myeloid leukemia (CML), and methods and computer systems for monitoring the progression of CML in a patient based on measurements of these molecular markers. The present invention also provides CML target genes, and methods and compositions for treating CML patients by modulating the expression or activity of these CML target genes and/or their encoded proteins. The invention also provides genes that are associated with resistance to imatinib mesylate (Gleevec™) treatment in CML patients, and methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate treatment based on measurements of these genes and/or their encoded proteins. The invention also provides methods and compositions for enhancing the effect of Gleevec™ by modulating the expression or activity of these genes and/or their encoded proteins.

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • This application is a divisional of U.S. patent application Ser. No. 11/640,517 filed Dec. 14, 2006 which claims the benefit, under 35 U.S.C. §19(e), of U.S. Provisional Patent Application No. 60/751,455, filed on Dec. 15, 2005. Each of which is incorporated herein by reference in its entirety.
  • This invention was made with U.S. Government support under Contract Nos. CA-18029 and CA-85053 awarded by the National Institutes of Health of the United States Department of Health and Human Services. The U.S. Government has certain rights in the invention.
  • This application includes the Sequence Listing submitted in the parent application, entitled “Genes Associated with Progression and Response in Chronic Myeloid Leukemia and Uses Thereof” Ser. No. 11/640,517, filed Dec. 14, 2006, which is hereby incorporated by reference herein in its entirety.
    • TECHNICAL FIELD
  • The invention relates to molecular markers that are associated with the progression of chronic myeloid leukemia (CML). The invention also relates to methods and computer systems for evaluating the progression of CML based on these molecular markers. The present invention also relates to methods and compositions for treating CML patients by modulating the expression or activity of certain genes involved in CML progression and/or their encoded proteins. The invention further relates to methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate (Gleevec™)
    • BACKGROUND
  • Chronic myeloid leukemia (CML) is a hematopoetic stem cell disease with distinct biological and clinical features. In humans, a majority of CML (about 95%) has been found to be associated with a chromosomal abnormality that involves a t(9;22)(q34;q11) translocation, which results in the expression of the BCR/ABL fusion gene (Philadelphia Chromosome or Ph). The rest is associated with either a cryptic translocation that is invisible on G-banded chromosome preparations or a variant translocation involving another chromosome or chromosomes as well as chromosomes 9 and 22. CML usually presents in the so-called chronic phase, in which the clonal expansion of mature myeloid cells leads to an elevated white blood cell (WBC) count. Without curative intervention chronic phase CML will invariably transform through a phase of “acceleration,” often heralded by the appearance of increased immature myeloid cells in the bone marrow and peripheral blood, as well as new cytogenetic changes in addition to the Ph chromosome. Progression then proceeds quickly to blast crisis, with immature blast cells overwhelming the production of normal hematopoetic elements. Blast crisis is highly resistant to treatment, with death generally occurring from infection and bleeding complications secondary to the absence of normal granulocytes and platelets. The median time from diagnosis of chronic phase CML to progression blast crisis is approximately 3-4 years but the range of timing is quite broad, encompassing from 0.5-15 years (Faderl et al., 1999, Ann Intern Med 131:207).
  • There is a broad range of treatment options for CML. All treatments work far better on chronic phase disease than on accelerated or blast phase. The only known curative therapy for CML is stem cell transplantation, a complex and potentially toxic modality that carries a high potential for morbidity and mortality (Radich et al., 2003, Blood 102:31). Non-transplant therapy includes alpha interferon, which can produce a major reduction in the proportion of Ph positive cells and extend the natural history of the disease in approximately 10-20% of cases (Kantarjian et al., 1999, J Clin Oncol 17:284). The tyrosine kinase inhibitor, imatinib mesylate, suppresses the Ph to the point where it is undetectable by cytogenetic evaluation (“complete cytogenetic remission”) in >70% of newly diagnosed chronic phase CML cases (Druker et al., 2001, N Engl J Med 344:1031). The duration of such responses is unknown, as is potential for cure with imatinib. Resistance to imatinib occurs (especially in advanced phase disease) often accompanied by point mutations in the active area of imatinib binding in the abl gene (Shah et al., 2002, Cancer Cell 2:117). The natural history of such relapses is unknown, though some appear to have a speedy entry into advanced disease (Branford et al., 2003, Blood 102:276).
  • U.S. Patent Application Publication No. 2003/0104426 A1 discloses genetic markers whose expression correlates with progression of CML. Specifically, the patent application discloses sets of markers whose expression patterns can be used to differentiate chronic phase individuals from those in blast crisis, and methods of using these markers to distinguish these conditions. The patent application also discloses kits containing ready-to-use microarrays and computer data analysis software for carrying out the disclosed methods.
  • PRAME (Preferentially Expressed Antigen of Melanoma) was identified as a tumor antigen recognized by cytotoxic T-cells against a melanoma surface antigen (Matsushita et al., 2001, Br J Haematol 112:916, 2001; van Baren et al., 1998, Br J Haematol 102:1376). PRAME has been found to be overexpressed in over 25% of leukemia, and has been found to be induced by Bcr-Abl in CML cell lines (Watari et al., 2000, FEBS Lett 466:367). PRAME over-expression has been described as one of the few features that characterize the transient myeloproliferative syndrome of Down's syndrome from the progressive acute megakaryoblastic leukemia found in that disorder (McElwaine et al., 2004, Br J Haematol 125:729).
  • The genetic events that cause the progression of chronic phase to blast crisis CML are unknown (Calabretta et al., 2004, Blood 103:4010; Shet et al., 2002, Leukemia 16:1402). Numerous genetic abnormalities have been demonstrated, including chromosomal changes including a multiplication of the Ph, the disruption of TP53, the deletion of the p15/p16 tumor suppressor genes (the latter only in lymphoid blast crisis). However, none of these changes are particularly common. Genetic instability is apparent in the additional chromosomal changes that occur with progression, though standard assays of instability, such as alterations in minisatellite repeats, is relatively uncommon (Wada et al., 1994, Blood 83:3449; Mori et al., 1997, Leukemia 11:151). Unfortunately, clinical and molecular tests cannot predict where on the “clock” of progression an individual lies at the time of the initial diagnosis, and this makes it impossible to tailor therapy to the degree of risk that faces an individual CML patient. It is also not possible to identify the subset of patients who will benefit most from the variety of therapy options, such as interferon, imatinib, or transplantation. Thus, presently tailoring therapy to individual risk is difficult. There is therefore a need to identify genes whose levels of expression change during the evolution of the chronic phase to blast crisis. There is a need for methods that utilize measured expression levels of such genes to determine the phase and/or progression of CML in a patient. There is also a need for methods of treating CML by targeting such genes.
  • Discussion or citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention.
    • SUMMARY
  • The invention provides a method for determining the progression of chronic myeloid leukemia (CML) in a patient, comprising (a) classifying a marker profile comprising measurements of a plurality of gene products in a cell sample taken from said patient as a chronic phase (CP-CML) profile or as an advanced phase (ADV-CML) profile, wherein said gene products are respectively products of at least 5 of the genes listed in Table 1a and/or Table 1b or respective functional equivalents thereof, wherein at least one of said 5 genes is from Table 1a; and (b) determining said patient as in a chronic phase if said marker profile is classified as a CP-CML profile, or determining said patient as in an advanced phase if said marker profile is classified as an ADV-CML profile. In one embodiment, said plurality of gene products are of at least 5, 10, 20, 50, 70 or 100 of the genes listed in Table 1a. In one embodiment, said cell sample is a bone marrow sample or a peripheral blood sample.
  • In one embodiment, the method further comprises obtaining said marker profile by a method comprising measuring said plurality of gene products in a cell sample taken from said patient.
  • In preferred embodiments, said gene products are products of at least 10, at least 20, at least 40, at least 70, at least 100, or at least 500 of the genes, respectively, listed in Table 1a and/or 1b.
  • In another preferred embodiment, said gene products are products of at least 10, at least 20, at least 40, at least 70, at least 100, or at least 200 of the genes, respectively, listed in Table 2a.
  • In still another preferred embodiment, said gene products are products of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or all of the genes, respectively, corresponding to the markers listed in Table 3. In one embodiment, said gene products are products of at least 5, 6, 7, 8, 9 or all of the genes, respectively, corresponding to the up-regulated markers listed in Table 3, or are products of at least 5, 6, 7, 8, 9 or all of the genes, respectively, corresponding to the down-regulated markers listed in Table 3.
  • In one embodiment, each of said gene products is a gene transcript.
  • In one embodiment, measurement of each said gene transcript is obtained by a method comprising contacting a positionally-addressable microarray with nucleic acids from said cell sample or nucleic acids derived therefrom under hybridization conditions, and detecting the amount of hybridization that occurs, said microarray comprising one or more polynucleotide probes complementary to a hybridizable sequence of each said gene transcript.
  • In another embodiment, measurement of each said gene transcript is obtained by quantitative reverse transcriptase PCR (qRT-PCR).
  • In another embodiment, each of said plurality of gene products is a protein.
  • In a preferred embodiment, said classifying is carried out using a progression classifier, which receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is a CP-CML profile or an ADV-CML profile.
  • In one embodiment, said progression classifier is trained with training data from a plurality of training CML patients, wherein said training data comprise for each of said plurality of training CML patients (i) a training maker profile comprising measurements of said plurality of gene products in a cell sample taken from said training patient; and (ii) data indicating whether said training patient is in CP-CML or ADV-CML.
  • In a preferred embodiment, said progression classifier comprises a CP-CML template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients having CP-CML and/or an ADV-CML template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients having ADV-CML, and said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template and/or said ADV-CML template; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a high similarity to said CP-CML template and/or has a low similarity to said ADV-CML template, or classifying said marker profile as a ADV-CML profile if said marker profile has a high similarity to said ADV-CML template and/or has a low similarity to said CP-CML template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.
  • In a specific embodiment, said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template or said ADV-CML template; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a high similarity to said CP-CML template or has a low similarity to said ADV-CML template, or classifying said marker profile as a ADV-CML profile if said marker profile has a high similarity to said ADV-CML template or has a low similarity to said CP-CML template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.
  • In another specific embodiment, said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template and said ADV-CML template; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a higher similarity to said CP-CML template than to said ADV-CML template, or classifying said marker profile as a ADV-CML profile if said marker profile has a higher similarity to said ADV-CML template than to said CP-CML template.
  • In one embodiment, said similarity to said CP-CML template is represented by a correlation coefficient between said marker profile and said CP-CML template, wherein said similarity to said ADV-CML template is represented by a correlation coefficient between said marker profile and said ADV-CML template. In one embodiment, said correlation coefficients between said marker profile and said CP-CML template and said ADV-CML template are respectively calculated according to the equation

  • P i=({right arrow over (z)} i ·{right arrow over (y)})/(∥{right arrow over (z)} i ∥·∥{right arrow over (y)}∥)
  • where i=1 and 2, wherein {right arrow over (y)} represents said marker profile, {right arrow over (z)}1 represents said CP-CML template, and {right arrow over (z)}2 represents said ADV-CML template, P1 represents said correlation coefficient between said marker profile and said CP-CML template, and P2 represents said correlation coefficient between said marker profile and said ADV-CML template.
  • In one embodiment, the measurement of each gene product in said CP-CML template or said ADV-CML template is an average of the measurements of said gene product in a plurality of CP-CML patients or in a plurality of ADV-CML patients, respectively.
  • In one embodiment, said measurement of each gene product in said marker profile is a relative level of said gene product in said cell sample taken from the patient versus level of said gene product in a reference pool, represented as a log ratio; the respective measurement of each gene product in said CP-CML template is a relative level of said gene product representative of level of said gene product in a plurality of CP-CML patients versus level of said gene product in a reference pool, represented as a log ratio; and the respective measurement of each gene product in said ADV-CML template is a relative level of said gene product representative of level of said gene product in a plurality of ADV-CML patients versus level of said gene product in a reference pool, represented as a log ratio.
  • In one embodiment, the respective log ratio for each gene product in said CP-CML template or said ADV-CML template is an average of the log ratios for said gene product in a plurality of CP-CML patients or in a plurality of ADV-CML patients, respectively.
  • In another preferred embodiment, said progression classifier is an artificial neural network (ANN) or a support vector machine (SVM).
  • The invention also provides a method for assigning a therapeutic regimen for a CML patient, comprising (a) determining the progression of said patient using any of the above described methods; and (b) assigning said patient a therapeutic regimen according to the status of progression determined in step (a). In one embodiment, said patient is determined to be in ADV-CML, and said therapeutic regimen assigned to said patient comprises bone marrow transplant.
  • The invention also provides a method for enrolling CML patients for a clinical trial of an agent for treating CML, comprising (a) determining the progression of said patient using any of the above described methods; and (b) assigning each patient having a CP-CML to one patient group and each patient having an ADV-CML to another patient group, at least one of said patient group being enrolled in said clinical trial.
  • The invention also provides a method for determining the responsiveness of a chronic myeloid leukemia (CML) patient to imatinib mesylate (IM), comprising (a) determining the progression of said patient using any of the above described methods; and (b) determining said patient as responsive to IM treatment if said marker profile is classified as a CP-CML profile, or determining said patient as resistant to IM treatment if said marker profile is classified as an ADV-CML profile.
  • In another aspect, the invention provides a method for determining the responsiveness of a chronic myeloid leukemia (CML) patient to imatinib mesylate (IM), comprising (a) classifying a marker profile comprising measurements of a plurality of gene products in a cell sample taken from said patient as an IM-sensitive profile or an IM-resistant profile, wherein said gene products are respectively products of at least 5 of the genes listed in Table 4 or respective functional equivalents thereof; and (b) determining said patient as responsive to IM treatment if said marker profile is classified as an IM-sensitive profile, or determining said patient as resistant to IM treatment if said marker profile is classified as an IM-resistant profile. In one embodiment, said plurality of gene products are of at least 5 of the genes listed in Table 4. In one embodiment, said cell sample is a bone marrow sample or a peripheral blood sample.
  • In one embodiment, the method further comprises obtaining said marker profile by a method comprising measuring said plurality of gene products in a cell sample taken from said patient.
  • In preferred embodiments, said gene products are products of at least 10, at least 20, at least 40, at least 70, at least 100, or at least 200 of the genes, respectively, listed in Table 4.
  • In one embodiment, each of said gene products is a gene transcript.
  • In one embodiment, measurement of each said gene transcript is obtained by a method comprising contacting a positionally-addressable microarray with nucleic acids from said cell sample or nucleic acids derived therefrom under hybridization conditions, and detecting the amount of hybridization that occurs, said microarray comprising one or more polynucleotide probes complementary to a hybridizable sequence of each said gene transcript.
  • In another embodiment, each of said plurality of gene products is a protein.
  • In a preferred embodiment, said classifying is carried out by a method comprising using a progression classifier, wherein said progression classifier receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is an IM-sensitive profile or an IM-resistant profile.
  • In one embodiment, said progression classifier is trained with training data from a plurality of tranining CML patients, wherein said training data comprise for each of said plurality of training CML patients (i) a training maker profile comprising measurements of said plurality of gene products in a cell sample taken from said training patient; and (ii) data indicating whether said training patient is sensitive or resistant to imatinib mesylate.
  • In one embodiment, said progression classifier comprises an IM-sensitive template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients responsive to IM treatment and/or an IM-resistant template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients resistant to IM treatment, and said step of classifying is carried out by a method comprising (a1) comparing said marker profile with said IM-sensitive template and/or said IM-resistant template; and (a2) classifying said marker profile as a IM-sensitive profile if said marker profile has a high similarity to said IM-sensitive template and/or has a low similarity to said IM-resistant template, or classifying said marker profile as a IM-resistant profile if said marker profile has a high similarity to said IM-resistant template and/or has a low similarity to said IM-sensitive template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.
  • In a specific embodiment, said step of classifying is carried out by a method comprising (a1) comparing said marker profile with said IM-sensitive template or said IM-resistant template; and (a2) classifying said marker profile as an IM-sensitive profile if said marker profile has a high similarity to said IM-sensitive template or has a low similarity to said IM-resistant template, or classifying said marker profile as a IM-resistant profile if said marker profile has a high similarity to said IM-resistant template or has a low similarity to said IM-sensitive template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.
  • In another specific embodiment, said step of classifying is carried out by a method comprising (a1) comparing said marker profile with said IM-sensitive template and said IM-resistant template; and (a2) classifying said marker profile as an IM-sensitive profile if said marker profile has a higher similarity to said IM-sensitive template than to said IM-resistant template, or classifying said marker profile as a IM-resistant profile if said marker profile has a higher similarity to said IM-resistant template than to said IM-sensitive template.
  • In one embodiment, said similarity to said IM-sensitive template is represented by a correlation coefficient between said marker profile and said IM-sensitive template, and said similarity to said IM-resistant template is represented by a correlation coefficient between said marker profile and said IM-resistant template.
  • In one embodiment, said correlation coefficients between said marker profile and said IM-sensitive template and said IM-sensitive template are respectively calculated according to the equation

  • P i=({right arrow over (z)} i ·{right arrow over (y)})/(∥{right arrow over (z)} i ∥·∥{right arrow over (y)}∥)
  • where i=1 and 2, wherein {right arrow over (y)} represents said marker profile, {right arrow over (z)}1 represents said IM-sensitive template, and {right arrow over (z)}2 represents said IM-resistant template, P1 represents said correlation coefficient between said marker profile and said IM-sensitive template, and P2 represents said correlation coefficient between said marker profile and said IM-resistant template.
  • In one embodiment, the measurement of each gene product in said IM-sensitive template or said IM-resistant template is an average of the measurements of said gene product in a plurality of patients responsive to IM treatment or in a plurality of patients resistant to IM treatment, respectively.
  • In one embodiment, said measurement of each gene product in said marker profile is a relative level of said gene product in said cell sample taken from the patient versus level of said gene product in a reference pool, represented as a log ratio; the respective measurement of each gene product in said IM-sensitive template is a relative level of said gene product representative of level of said gene product in a plurality of patients responsive to IM treatment versus level of said gene product in a reference pool, represented as a log ratio; and the respective measurement of each gene product in said IM-resistant template is a relative level of said gene product representative of level of said gene product in a plurality of patients resistant to IM treatment versus level of said gene product in a reference pool, represented as a log ratio.
  • In one embodiment, the respective log ratio for each gene product in said IM-sensitive template or said IM-resistant template is an average of the log ratios for said gene product in a plurality of patients responsive to IM treatment or in a plurality of ADV-CML patients, respectively.
  • In another preferred embodiment, said progression classifier is an artificial neural network (ANN) or a support vector machine (SVM).
  • The invention also provides a method for assigning a treatment regimen for a CML patient, comprising (i) determining whether said patient is responsive or resistant to imatinib mesylate using a method as described above; and (ii) assigning said patient a treatment regimen comprising bone marrow transplant if said patient is determined to be resistant to imatinib mesylate.
  • The invention also provides a method for enrolling CML patients for a clinical trial of a treatment modality for treating CML, comprising (i) determining whether said patient is responsive or resistant to imatinib mesylate using a method as described above; and (ii) assigning each patient who is predicted to be resistant to imatinib mesylate to one patient group and each patient who is predicted to be responsive to imatinib mesylate to another patient group, at least one of said patient group being enrolled in said clinical trial.
  • In still another aspect, the invention provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a treatment regimen, said treatment regimen comprising one or more agents that modulate the expression and/or activity of one or more different genes listed in one or more of Tables 2a, 2b, 5a and 5b and/or their encoded proteins, wherein said patient exhibits aberrant regulation of said one or more genes.
  • In one embodiment, said one or more different genes are selected from the different genes listed in one or more of Tables 2a and 5a.
  • In another embodiment, said one or more different genes are selected from the genes listed in both Tables 2a and 5a, i.e., genes common in Tables 2a and 5a.
  • In still another embodiment, said one or more different genes are selected from the genes listed in Table 3.
  • In one embodiment, said one or more different genes are selected from the up-regulated genes listed in Table 3, and said treatment regimen comprises a substance selected from the group consisting of siRNA, antisense nucleic acid, ribozyme, and triple helix forming nucleic acid, each reducing the expression of one or more of said one or more different genes in said patient.
  • In another embodiment, said one or more different genes are selected from the up-regulated genes listed in Table 3, and said treatment regimen comprises a substance selected from the group consisting of antibody, peptide, and small molecule, each reducing the activity of one or more of proteins encoded by said one or more different genes in said patient.
  • In a preferred embodiment, said treatment regimen comprises an siRNA targeting said one or more different genes.
  • In preferred embodiment, said one or more different genes consisting of 2, 3, 4, 5, 6, or 10 different genes.
  • In another embodiment, said one or more different genes are selected from the down-regulated genes listed in Table 3, and said treatment regimen comprises subjecting said patient to gene therapy, said gene therapy enhancing the expression of said one or more different genes in said patient.
  • In one embodiment, the methods of the invention further comprises determining a transcript level of each of said one or more different genes, and said patient is determined to exhibit aberrant regulation of said different gene if said transcript level deviated from a predetermined threshold level. In some embodiments, said transcript level deviates from said predetermined threshold level by at least 1.5-fold, 2-fold or 3-fold.
  • In one embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said different gene using one or more polynucleotide probes, each of said one or more polynucleotide probes comprising a nucleotide sequence complementary to a hybridizable sequence in said transcript of said different gene. In one embodiment, said one or more polynucleotide probes are polynucleotide probes on a microarray.
  • In another embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said different gene using quantitative reverse transcriptase PCT (qRT-PCR).
  • In still another aspect, the invention provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a treatment regimen, said treatment regimen comprising (i) an effective amount of imatinib mesylate (IM), and (ii) an agent other than IM, wherein said agent modulates the expression and/or activity of 1, 2, 3, 4, 5, 10 or more of the genes listed in Table 4 and/or their encoded proteins, and wherein said patient exhibits aberrant regulation of said one or more genes.
  • In one embodiment, said one or more genes are selected from the group consisting of the up-regulated genes listed in Table 4, and said agent comprises a substance selected from the group consisting of siRNA, antisense nucleic acid, ribozyme, and triple helix forming nucleic acid, each reducing the expression of one or more of said one or more genes in said patient.
  • In another embodiment, said one or more genes are selected from the group consisting of the up-regulated genes listed in Table 4, and said agent comprises a substance selected from the group consisting of antibody, peptide, and small molecule, each reducing the activity of one or more of proteins encoded by said one or more genes in said patient.
  • In one embodiment, said treatment regimen comprises an siRNA targeting said one or more target genes.
  • In some embodiments, said one or more genes consists of at least 2, 3, 4, 5, 6, or target genes.
  • In one embodiment, said one or more genes are selected from the group consisting of the down-regulated genes listed in Table 4, and said agent comprises subject said patient to gene therapy, said gene therapy enhancing the expression of said one or more genes in said patient.
  • The methods can further comprises determining a transcript level of each said gene, and said patient is determined to exhibit aberrant regulation of said gene if said transcript level deviated from a predetermined threshold level. In some embodiment, said transcript level deviates from said predetermined threshold level by at least 1.5-fold, 2-fold or 3-fold.
  • In one embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said gene using one or more polynucleotide probes, each of said one or more polynucleotide probes comprising a nucleotide sequence complementary to a hybridizable sequence in said transcript of said different gene.
  • In one embodiment, said one or more polynucleotide probes are polynucleotide probes on a microarray.
  • In another embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said CML target gene using quantitative reverse transcriptase PCT (qRT-PCR).
  • In still another aspect, the invention provides a method for diagnosing whether a patient has advanced phase chronic myeloid leukemia (CML), comprising (a) contacting cells a cell sample from said patient with an antibody conjugate, said antibody conjugate comprising an antibody that binds a PRAME protein, said antibody being conjugated with a label; and (b) detecting said label on said cells, wherein detection of said label above a predetermined threshold indicates that said patient has advanced phase CML. The cell sample can be a bone marrow sample or a peripheral blood sample.
  • In one embodiment, said antibody is a monoclonal antibody.
  • In another embodiment, said label is fluorescence label, and said detecting is carried out using a fluorescence activated cell sorter.
  • In still another aspect, the invention provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a therapeutically sufficient amount of an antibody, wherein said antibody binds a PRAME protein, and wherein said patient expresses PRAME protein on hematopoetic stem cells and/or immature myeloid cells. The invention also provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a therapeutically sufficient amount of an antibody conjugate comprising an antibody that binds a PRAME protein, said antibody being conjugated with a therapeutic molecule, wherein said patient expresses PRAME protein on hematopoetic stem cells and/or immature myeloid cells.
  • In one embodiment, said antibody is a monoclonal antibody.
  • The invention also provides a method for ex vivo depletion of advanced phase hematopoetic stem cells and/or immature myeloid cells from a bone marrow or peripheral blood sample of a patient, comprising (a) incubating said bone marrow or peripheral blood sample with an antibody that binds a PRAME protein; and (b) removing cells having said antibody attached. The invention also provides a method for treating a patient having chronic myeloid leukemia (CML), comprising (i) depleting advanced phase hematopoetic stem cells and/or immature myeloid cells from a bone marrow or peripheral blood sample of said patient using the method described above; and (ii) transplanting the sample obtained in step (i) to said patient.
  • In still another aspect, the invention provides a method for identifying a set of genes that are associated with progression of chronic myeloid leukemia (CML), comprising: (a) subtracting from each of a plurality of CML expression profiles a CD34+ expression profile to obtain a plurality of CD34+(−) CML expression profiles, each said CML expression profile comprising levels of expression of a plurality of genes in cells of one of a plurality of chronic myeloid leukemia (CML) patients, said CD34+ expression profile comprising levels of expression of said plurality of genes in non cancerous immature CD34+ cells, said plurality of CML patients comprising patients of different phases of CML; (b) comparing said plurality of CD34+(−) CML expression profiles; and (c) identifying one or more genes that exhibit significant differences in levels of expression between different phases of CML across said plurality of CD34+(−) CML expression profiles.
  • In one embodiment, said comparing is carried out by ANOVA and said identifying is carried out by identifying one or more genes one or more genes whose p-value corresponds to a predetermined significance level. In one embodiment, said predetermined significance level is p<10−8.
  • The method can further comprise: (d) comparing levels of expression of said identified genes between cells of CML blast crisis and normal immature CD34+ cells; and (e) selecting those genes that exhibit significant differences in expression.
  • In another embodiment, said comparing is carried out by ANOVA and said selecting is carried out by selecting one or more genes whose p-value corresponds to a predetermined significance level. In one embodiment, said predetermined significance level is p-value <0.01%.
  • The invention also provides a computer system comprising a processor, and a memory coupled to said processor and encoding one or more programs, wherein said one or more programs cause the processor to carry out any one of the methods of the invention.
  • The invention also provides a computer program product for use in conjunction with a computer having a processor and a memory connected to the processor, said computer program product comprising a computer readable storage medium having a computer program mechanism encoded thereon, wherein said computer program mechanism may be loaded into the memory of said computer and cause said computer to carry out any one of the methods of the invention.
  • In still another aspect, the invention provides a microarray comprising for each of a plurality of genes, said genes being at least 5 of the genes selected from the group consisting of the genes as identified respectively by SEQ ID NOS: 1-3968, wherein at least one of said 5 genes is not a gene selected from the group consisting of genes as identified respectively by SEQ ID NOS: 56, 65, 70, 177, 190, 199, 1758, 1773, 1774, 1776, 1786, 1815, 1823, 3925, 3933, 3947, 3956, and 3961, one or more polynucleotide probes complementary and hybridizable to a sequence in said gene, wherein polynucleotide probes complementary and hybridizable to said genes constitute at least 50%, 70%, 80%, 90% or 98% of the probes on said microarray.
  • In one embodiment, said plurality of genes is at least 10, 20, 40, 70, 100, or 200 genes.
  • In another embodiment, said plurality of genes is selected from the group consisting of the genes listed in Tables 1a and/or 1b.
  • In still another embodiment, said plurality of genes is selected from the group consisting of the genes listed in Tables 2a and/or 2b.
  • In still another embodiment, said plurality of genes is at least 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or all 20 of the genes listed in Table 3.
  • In still another embodiment, said plurality of genes are selected from the group consisting of the genes listed in Table 4.
  • In still another embodiment, said plurality of genes is selected from the group consisting of the genes listed in Tables 5a and/or 5b.
    • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1. Genes associated with CML progression. Samples of CML cases in chronic phase, accelerated by cytogenetic criteria only, accelerated phase, blast crisis, and blast crisis “in remission” were compared to a pool of chronic phase RNA. Approximately 3,000 genes were significantly associated with progressive disease at a significance level of p<10−11. Each row represents one sample, and each column represents one gene. A darker color indicates over-expression relative to the control pool, and a lighter color indicates low-expression.
  • FIG. 2. 2 a: Genes differentially expressed in blast crisis CML compared to normal CD34+ stem cells. CML blast crisis samples with >70% blasts were compared to normal CD34+ bone marrow stem cells. 2 b: Approximately 400 genes were significantly differentially expressed between CML blasts and their immature CD34+ normal counterparts (ANOVA P<0.1%). 2 c: Phase genes corrected for normal CD34+ gene expression (ANOVA P<1×10−8). The gene expression of normal CD34+ cells was subtracted from each disease sample. The resulting pattern reflects genes associated with progression independent of normal blast biology.
  • FIG. 3. Genes expression signature of genes associated with specific promoter sequences. Genes with specific promoter sequences were tested for their differential enrichment across different phases of CML (see Methods). FIG. 3 a shows genes bearing a MZF promoter; FIG. 3 b shows expression of genes under putative control of delta EF1.
  • FIG. 4. Gene expression in Imatinib failure cases. 4 a: All CML cases including cases of imatinib failure; gene expression is based on the previously obtained ˜3,000 phase reporter set. 4 b: Cases are ranked and sorted by the correlation of summed gene expression, with cases representing the most “cp-like” and most “bc-like” forming the boundaries of gene expression patterns. Cases of imatinib failures are shown. 4 c: Genes differentially expressed in imatinib resistant cases that are not associated with progression gene set. The boxed areas represent genes differentially expressed in the imatinib resistant cases compared to blast crisis cases.
  • FIG. 5. Comparison of gene expression in accelerated phase versus blast phase CML. The graph shows the scatter plot of log(ratio) of all 25K genes in blast crisis and accelerated phase cases. Each blue dot represents a gene. Thus, genes in the upper left hand box are up in accelerated phase, but down in blast crisis. Genes in the upper right box are up both in accelerated and blast crisis. The gene expression levels are very highly correlated between accelerated and blast crisis (r=0.81).
  • FIG. 6. Phase reporter genes after removal of normal CD34+ signature. The gene expression signature of normal CD34+ cells was subtracted from the data of CML cases. The genes shown are the genes differentially expressed across disease phases after genome wide removal of CD34+ signatures (p-value of <10−4).
  • FIG. 7. Comparison of gene expression between bone marrow and peripheral blood. In three cases of blast crisis samples were simultaneously drawn from marrow and blood. The figures show a high correlation of gene expression for these three cases.
  • FIG. 8 illustrates an exemplary embodiment of a computer system for implementing the methods of this invention.
    •  DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
  • The invention provides molecular markers, i.e., genes, the expression levels of which can be used for evaluating the progression of chronic myeloid leukemia (CML) from chronic phase to advanced phase. The identities of these markers and the measurements of their respective gene products, e.g., measurements of levels (abundances) of their encoded mRNAs or proteins, can be used by application of a pattern recognition algorithm to develop a progression classifier that discriminates between different phases of CML based on measurements of such gene products in a sample from a patient. As used herein, the term “gene product” includes mRNA transcribed from the gene and protein encoded by the gene.
  • Chronic myelogenous leukemia (CML) is characterized by high peripheral white blood cell (WBC) counts with granulocyte predominance and extramedullary hematopoiesis. CML typically evolves through 3 clinically distinct stages or phases: chronic phase (CP-CML or CP), accelerated phase (AP-CML or AP), and blast phase (BP-CML or BP), which is also called acute phase or blast crisis (BC-CML or BC). The chronic phase lasts several years and is characterized by accumulation of myeloid precursors and mature cells in bone marrow, peripheral blood, and extramedullary sites. During the chronic phase, patients typically have fewer than 10% blasts (or 20% blasts and promyelocytes combined) in blood or bone marrow samples. These patients usually have relatively mild symptoms and usually respond to standard treatments. The chronic phase progresses into the accelerated phase, which lasts about 4 to 6 months. During the accelerated phase, patients typically have more than 10% blasts (or 20% blasts and promyelocytes combined) but less than 30% blasts and promyelocytes in their bone marrow or blood samples. These patients often have fever, poor appetite, and weight loss. Symptoms and blood counts of an AP-CML patient are not as responsive to treatments as they are during the chronic phase. The leukemia cells often have developed new chromosomal changes, in addition to the Philadelphia chromosome. The accelerated phase progresses to the blast phase, which lasts for a few months. During the blast phase, patients typically have more than 30% blasts and promyelocytes in their bone marrow and/or blood samples. The blast cells often spread to tissues and organs beyond the bone marrow. The accelerated phase and the blast phase are often grouped together into an advanced phase of CML (ADV-CML or ADV). The molecular markers of the invention are particular useful for evaluating the progression of a CML patient from the chronic phase to the advanced phase.
  • The invention provides a list of genes that are differentially expressed across different phases of CML (Tables 1a and 1b, infra). This set of genes is called the phase reporter geneset. Measurements of gene products of these molecular markers, as well as of their functional equivalents, can be used for staging a CML patient. A functional equivalent with respect to a gene, designated as gene A, refers to a gene that encodes a protein or mRNA that at least partially overlaps in physiological function in the cell to that of the protein or mRNA encoded by gene A. In particular, CML staging in a patient is carried out by a method comprising determining whether the patient is in a chronic phase or an advanced phase (accelerated phase or blast phase) based on a profile of measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200, 500 or all of the genes in Tables 1a and/or 1b; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 1a and/or 1b, or functional equivalents of such genes, in an appropriate cell sample from the patient, e.g., a bone marrow or blood sample obtained from the patient, wherein at least 1, 2, 3, 5, or 10 genes as appropriate are from Table 1a. Such a profile of measurements is also referred to herein as an “expression profile” or a “marker profile.” In a specific embodiment, the evaluation of CML progression in a patient is carried out using measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200, 500 or all of the genes in Tables 1a; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 1a, or functional equivalents of such genes. In another specific embodiment, the evaluation of CML progression in a patient is carried out using measurements of gene products of less than 30, 40, 50, 70, 100, 200, 300, 400, or 500 total genes, in which all or at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes are from Tables 1a and/or 1b or their functional equivalents, or at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 of the genes are from Tables 1a and/or 1b or their functional equivalents. In one embodiment, if the patient expression profile is classified as a CP-CML profile, the patient is determined as in chronic phase, whereas if the patient expression profile is classified as a ADV-CML profile, the patient is determined as in an advanced phase (accelerated phase or blast crisis).
  • The invention also provides a list of genes that are associated with CML progression (Tables 2a and 2b, infra). These genes are also termed “progression genes” in the application. This set of genes is called the progression geneset. Measurements of gene products of these molecular markers, as well as of their functional equivalents, can be used for staging a CML patient. Since these genes are associated with CML progression, they are also targets for therapeutic intervention of CML. For example, a CML patient exhibiting aberrant regulation of such genes can be treated by therapies targeting such genes. Thus, measurements of gene products of these molecular markers, as well as of their functional equivalents, can also be used for determining an appropriated treatment regimen for a CML patient.
  • Different subcombination of CML progression genes can also be used. Thus, in various embodiments, the markers that are the genes listed in Tables 2a-2b or 3 are used. Measurements of gene products of these molecular markers and/or their functional equivalents can be used for evaluating the progression of CML in a patient. The evaluation of CML progression in a patient is carried out by a method comprising determining whether the patient is in a chronic phase or an advanced phase (accelerated phase or blast phase) based on a profile of measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200 or all of the genes in Tables 2a and/or 2b, or at least 5, 10, 15 or all of the genes in Table 3; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 2a and/or 2b or in Table 3, or functional equivalents of such genes, in an appropriate cell sample from the patient, e.g., a bone marrow or peripheral blood sample obtained from the patient, wherein at least 1, 2, 3, 5, or 10 genes as appropriate are from Table 2a. In a specific embodiment, the evaluation of CML progression in a patient is carried out using measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200, 300 or all of the genes in Tables 2a; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 2a, or functional equivalents of such genes. In one embodiment, if the patient expression profile is classified as a CP-CML profile, the patient is determined as in chronic phase, whereas if the patient expression profile is classified as a ADV-CML profile, the patient is determined as in an advanced phase (accelerated phase or blast crisis).
  • The invention also provides a list of genes that are associated with resistance to imatinib mesylate (Table 4, infra). These genes are also termed “imatinib resistance genes” in the application. This set of genes is called the imatinib resistance geneset. Measurements of gene products of these molecular markers, as well as of their functional equivalents, can be used for evaluating the responsiveness of a CML patient to imatinib treatment. The evaluation of responsiveness of a patient to imatinib is carried out by a method comprising determining whether the patient is likely to be responsive to imatinib treatment based on a profile of measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200 or all of the genes in Table 4; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Table 4, or functional equivalents of such genes, in an appropriate cell sample from the patient, e.g., a bone marrow or peripheral blood sample obtained from the patient. In one embodiment, if the patient expression profile is classified as a IM-resistance profile, the patient is determined as likely to be resistant to imatinib treatment, whereas if the patient expression profile is classified as a IM-sensitive profile, the patient is determined as likely to be responsive to imatinib treatment. In a specific embodiment, a CML patient in the chronic phase is evaluated for responsiveness to imatinib treatment based on an expression profile of such imatinib resistance genes. If the patient's expression profile indicates that the patient is likely to be resistant to imatinib treatment, bone marrow transplantation and/or other investigative treatment regimens may be assigned to the patient.
  • In another embodiment, the responsiveness of a CML patient to imatinib treatment can also be evaluated based on expression of phase reporters or progression genes. In this embodiment, the patient expression profile comprising measurements of phase reporter genes (Table 1a and/or 1b) or progression genes (Table 2a and/or 2b) is evaluated using a method described above. If the patient expression profile is classified as a ADV-CML profile, the patient is determined as likely to be resistant to imatinib treatment.
  • The measurements in the profiles of the gene products that are used can be any suitable measured values representative of the expression levels of the respective genes. The measurement of the expression level of a gene can be direct or indirect, e.g., directly of abundance levels of RNAs or proteins or indirectly, by measuring abundance levels of cDNAs, amplified RNAs or DNAs, proteins, or activity levels of RNAs or proteins, or other molecules (e.g., a metabolite) that are indicative of the foregoing. In one embodiment, the profile comprises measurements of abundances of the transcripts of the marker genes. The measurement of abundance can be a measurement of the absolute abundance of a gene product. The measurement of abundance can also be a value representative of the absolute abundance, e.g., a normalized abundance value (e.g., an abundance normalized against the abundance of a reference gene product) or an averaged abundance value (e.g., average of abundances obtained at different time points or from different tumor cell samples from the patients, or average of abundances obtained using different probes, etc.), or a combination of both. As an example, the measurement of abundance of a gene transcript can be a value obtained using an Affymetrix® GeneChip® to measure hybridization to the transcript.
  • In another embodiment, the expression profile is a differential expression profile comprising differential measurements of a plurality of transcripts in a sample derived from the patient versus measurements of the plurality of transcripts in a reference sample, e.g., a cell sample of normal cells. Each differential measurement in the profile can be but is not limited to an arithmetic difference, a ratio, or a log(ratio). As an example, the measurement of abundance of a gene transcript can be a value for the transcript obtained using an ink-jet array or a cDNA array in a two-color measurement. In a preferred embodiment, the reference sample comprise target polynucleotide molecules from normal cell samples (i.e., cell sample, e.g., bone marrow or peripheral blood, from those not afflicted with CML). In another preferred embodiment, the reference sample comprise target polynucleotide molecules from cell samples, e.g., bone marrow or peripheral blood, from chronic phase CML patients.
  • The invention also provides methods and computer systems for evaluating the progression of CML in a patient based on a measured marker profile comprising measurements of the markers of the present invention, e.g., an expression profile comprising measurements of transcripts of at least some of the genes listed in Tables 1a and/or 1b, e.g., at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 in Tables 1a and/or 1b or functional equivalents of such genes, wherein at least 1, 2, 3, 5 or 10 genes are from Table 1a. The methods and systems of the invention use a progression classifier for evaluating the progression of CML. The progression classifier can be based on any appropriate pattern recognition method (such as those described in Section 5.2) that receives an input comprising a marker profile and provides an output comprising data indicating which phase the patient belongs, i.e., chronic phase or advanced phase. The progression classifier can be constructed with training data from a plurality of CML patients for whom marker profiles and progression status are known. The plurality of patients used for training the progression classifier is also referred to herein as the training population. The training data comprise for each patient in the training population (a) a marker profile comprising measurements of gene products of a plurality of genes, respectively, in an appropriate cell sample, e.g., a bone marrow or peripheral blood sample, taken from the patient; and (b) progression status information (e.g., the CML phase of the patient). Various progression classifiers that can be used in conjunction with the present invention are described in Section 5.2., infra. In some embodiments, additional patients having known marker profiles and progression status can be used to test the accuracy of the progression classifier obtained using the training population. Such additional patients are also called “the testing population.”
  • The markers in the marker sets are selected based on their ability to discriminate patients having different CML phases in a plurality of CML patients for whom the progression status are known. Various methods can be used to evaluate the correlation between marker levels and CML progression. For example, genes whose expression levels are significantly different across patients in different CML phases can be identified using an appropriate statistical method, e.g., ANOVA.
  • The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., enhancing or reducing, the expression and/or activities of one or more CML progression genes and/or target genes and/or their gene products. The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., enhancing or reducing, certain CML pathways that involve in CML progression and response. The CML progression genes include those genes listed in Tables 2a and 2b. The CML target genes include those genes listed in Tables 5a and 5b. The CML pathways include FLT3; Rras2; beta-catenin; and SOCS2. The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., enhancing or reducing, certain proteosomes and chaperone proteins. The invention also provides methods and compositions for treating a patient having CML by modulating genes controlled by a promoter selected from the group consisting of the following MZF, delta EF1, SPI-B, Yin Yang, and Ahr-ARNT. The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., reducing, the expression and/or activity of CD47. The invention also provides methods and compositions for treating a patient having CML by targeting PRAME. The invention is based, at least in part, on the identification of aberrant regulation of these genes and pathways in CML.
  • Thus, the invention provides methods and compositions for treating CML by modulating the expression and/or activity of CML progression genes and/or CML target genes and/or their gene products, and/or by modulating interactions of the CML progression genes and/or target genes and/or their gene products with other proteins or molecules, e.g., substrates. The methods and compositions can be used for treating CML patient who exhibit aberrant regulation in such CML progression/target genes. Thus, such methods and compositions can be used in conjunction with imatinib mesylate. In one embodiment, the expression of one or more of the CML progression/target genes is modulated, e.g., reduced or enhanced, to treat a CML patient exhibiting aberrant regulation of these CML progression/target genes. Such modulation can be achieved by, e.g., using siRNA, antisense nucleic acid, ribozyme, and/or triple helix forming nucleic acid that target the CML progression/target genes. In another embodiment, the activity of one or more CML progression/target proteins is modulated, e.g., reduced or enhanced, to enhance the effects of chemotherapy agents. Such modulation can be achieved by, e.g., using antibodies, peptide molecules, and/or small molecules that target a CML progression/target protein.
  • The invention also provides methods and compositions for treating CML by modulating the expression and/or activity of imatinib mesylate resistance genes and/or their gene products, and/or by modulating interactions of the IM-resistance genes and/or their gene products with other proteins or molecules, e.g., substrates, in combination of imatinib mesylate. In one embodiment, the expression of one or more of the IM-resistance genes is modulated, e.g., reduced or enhanced, to treat a CML patient undergoing imatinib mesylate treatment. Such modulation can be achieved by, e.g., using siRNA, antisense nucleic acid, ribozyme, and/or triple helix forming nucleic acid that target the imatinib mesylate genes. In another embodiment, the activity of one or more imatinib mesylate proteins is modulated, e.g., reduced or enhanced, to enhance the effects of chemotherapy agents. Such modulation can be achieved by, e.g., using antibodies, peptide molecules, and/or small molecules that target imatinib mesylate proteins.
  • The invention also provides methods and compositions for utilizing CML progression/target genes or IM-resistance genes, and/or their products for screening for agents that modulate their expression and/or activity and/or modulating their interactions with other proteins or molecules. Agents that modulate expression and/or activity of CML progression/target genes can be used for treating CML patient exhibiting aberrant regulation of one or more CML progression/target genes. Agents that modulate expression and/or activity of IM-resistance genes can be used in combination with IM for treating CML patient exhibiting resistance to IM treatment. Thus, the invention provides methods and compositions for utilizing CML progression/target genes and gene products for screening for agents that are useful in modulating expression and/or activity of CML progression/target genes or IM resistance genes and/or their products and/or modulating their interactions with other proteins or molecules in a CML patient exhibiting aberrant regulation of one or more CML progression/target genes or IM resistance genes. The compositions of the invention include but not limited to siRNA, antisense nucleic acid, ribozyme, triple helix forming nucleic acid, antibody, peptide or polypeptide molecules, and small organic or inorganic molecules.
  • The present invention also provides methods and compositions for identifying other extra- or intra-cellular molecules, e.g., genes and proteins, which interacts with the CML progression/target genes or IM resistance genes, and/or their gene products, and/or CML progression pathways. The present invention also provides methods and compositions for treating CML by modulating such cellular constituents and/or pathways.
  • As used herein, a patient is an animal having CML. The patient can be but is not limited to a human, or, in a veterinary context, from non-human animals such as ruminants, horses, swine or sheep, or from domestic companion animals such as felines and canines. In a preferred embodiment, the patient is a human patient. Suitable samples that can be used in conjunction with the present invention include but are not limited to bone marrow samples and peripheral blood samples.
    • 5.1. Genes Associated with CML Progression and Response
  • The invention provides molecular marker sets (of genes) that can be used for evaluating progression and/or imatinib resistance in a CML patient based on a profile of the markers in the marker set (containing measurements of marker gene products).
  • Tables 1a and 1b list genes that are differentially expressed across different phases of CML. This set of genes is called the phase reporter geneset. The phase reporter genes are identified by their SEQ ID NOs in Tables 1a and 1b. Tables 1a and 1b also listed for each gene the log ratio of expression level of the gene in samples from patients of a particular phase (e.g., CP, AP, or BC) versus expression level of the gene in a pool of CML bone marrow samples from chronic phase patients. Each log ratio column thus contains expression levels of markers for a particular phase. Information for these genes is presented in Table 8. In Table 8, the following information is presented for each gene: gene identifier (column 1), gene name (column 2), the SEQ ID NO of the sequence of the gene (column 3), and the SEQ ID NO of the probe sequence used in the present application (column 4). The first column of Table 8 shows the identifiers of genes disclosed in the application. The term “SUBS” is shorthand for substance identifier. For those genes listed in Table 8 that have a GenBank® accession number, the GenBank® accession number is listed. For those genes in Table 8 that do not have a GenBank® Accession No, the Contig ID numbers of the transcript sequences in the Phil Green assembly (Nat Genet. 2000 June; 25(2):232-4) is listed. Phil Green's group at the University of Washington assembled ESTs from the Washington University-Merck Human EST Project and CGAP archives. Analysis of expressed sequence tags indicates 35,000 human genes (Nat Genet. 2000 June; 25(2):232-4). This assembly, dated Mar. 17, 2000, resulted in 62,064 contigs representing 795,000 ESTs. These contigs have the word “contig” included in their identifiers. Table 1a lists phase reporters that were not disclosed in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Table 1b lists phase reporters that were also identified in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003.
  • TABLE 1a
    phase reporter genes
    SEQ ID NO log(ratio) CP log(ratio) AP log(ratio) BC
    1 −0.00406 0.196563 0.331631
    2 −0.013036 0.331191 0.13619
    3 −0.01517 −0.1969 −0.51997
    4 −0.01226 0.234703 0.506317
    5 −0.01055 −0.11513 −0.25239
    6 0.02333 0.2234 0.385294
    7 0.001109 −0.04225 −0.38922
    8 0.022178 0.320491 0.362686
    9 −0.01332 −0.22505 −0.26552
    10 0.002491 0.107514 0.40248
    11 −0.03342 −0.12983 −0.34856
    12 −0.02396 −0.1739 −0.56037
    13 0.004316 −0.16534 −0.15954
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    1520 0.024372 0.086503 0.336729
    1521 −0.00251 −0.32015 −0.61272
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    1528 −0.03814 −0.28518 −0.64558
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    1560 0.005559 −0.19059 −0.29348
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    1567 0.027937 0.392011 0.694665
    1568 0.003947 0.306649 0.252871
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    1570 −0.01613 0.291768 0.433549
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    1573 0.008427 −0.19856 −0.17834
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    1575 −0.04733 −0.23751 −0.34215
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    1577 −0.04503 −0.32515 −1.47513
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    1579 0.039573 0.455784 0.593108
    1580 0.01488 0.167381 0.337448
    1581 0.01578 0.966015 0.747213
    1582 0.021767 −0.06571 −0.22201
    1583 −0.03377 0.957743 0.952139
    1584 0.000102 0.375168 0.427444
    1585 0.012221 0.364757 0.498008
    1586 −0.05968 0.131214 0.231979
    1587 −0.00129 0.256818 0.354398
    1588 −0.02064 0.251769 0.448226
    1589 −0.00735 −0.29792 −0.46534
    1590 0.000483 −0.24237 −0.56028
    1592 0.005932 1.051292 1.07381
    1593 0.023196 −0.1622 −0.44821
    1594 −0.00259 −0.26185 −0.42202
    1595 0.016322 0.245038 0.401239
    1596 −0.012267 0.315077 0.462982
    1597 0.013869 0.626753 0.569707
    1598 0.01648 0.44301 0.702287
    1599 −0.00148 −0.17565 −0.30065
    1600 0.021685 0.273528 0.471675
    1601 0.011557 0.134017 0.300655
    1602 −0.03634 −0.1835 −0.37405
    1603 −0.05299 −0.10304 −0.76
    1604 0.027767 0.464555 0.635743
    1605 −0.01022 −0.11629 −0.70459
    1606 0.016358 0.157395 0.275139
    1607 0.025792 0.397509 0.672154
    1609 −0.01086 −0.0143 0.380983
    1610 −0.03769 −0.15816 −1.14581
    1611 0.026536 0.611073 0.637773
    1612 0.009768 −0.17633 −0.20219
    1613 0.018672 0.639835 0.686131
    1614 −0.00595 −0.17151 −0.41225
    1615 −0.03355 −0.29946 −0.40616
    1616 −0.00505 0.107402 0.15699
    1617 −0.04052 −0.29872 −0.68389
    1618 −0.00668 1.111867 1.053921
    1619 0.015573 −0.03576 −0.21323
    1620 0.020609 0.286474 0.393224
    1621 −0.0087 0.323935 0.339016
    1622 0.022252 0.265231 0.499298
    1623 0.0309 0.498198 0.657198
    1624 −0.003494 −0.128858 −0.416283
    1625 −0.05632 −0.39999 −0.43886
    1626 −0.0135 0.314884 0.649048
    1627 0.028772 0.488679 0.759761
    1628 0.00467 0.427485 0.588063
    1629 0.002155 0.764925 0.732094
    1630 0.025418 0.22508 0.31406
    1631 −0.01046 0.209115 0.386983
    1632 −0.01049 0.878023 0.775566
    1633 0.025532 0.342507 0.502738
    1634 0.015481 0.560252 0.538429
    1635 −0.04353 0.259742 0.659249
    1636 0.020275 0.093339 0.361063
    1637 0.007208 0.157407 0.25487
    1638 −0.04262 −0.28323 −0.87579
    1639 0.051421 0.491945 0.653117
    1640 −0.01018 0.347268 0.588021
    1641 −0.04504 −0.35082 −0.89888
    1642 −0.02474 −0.25739 −0.47619
    1644 −0.01609 −0.09535 −0.5932
    1645 −0.03235 −0.16356 −0.39665
    1646 0.028968 0.32258 0.520166
    1647 0.032173 0.590062 0.811258
    1648 −0.02776 −0.13951 −0.5018
    1649 −0.00272 0.163307 0.253524
    1650 0.019266 0.438798 0.499089
    1651 0.005638 −0.13247 −0.31381
    1653 −0.00021 0.090548 0.295377
    1654 −0.005 −0.24979 −0.53688
    1655 −0.07359 0.053071 −0.91511
    1656 0.007697 0.469061 0.570563
    1658 0.0295 0.19296 0.359484
    1659 0.010231 0.902353 0.804032
    1660 −0.00649 −0.15261 −0.1773
    1661 0.012219 0.613912 0.549935
    1662 −0.06415 −0.43774 −0.43472
    1663 −0.0078 −0.18865 −0.16956
    1664 0.016452 0.122548 0.318295
    1665 −0.09894 −0.44748 −1.18835
    1666 0.007163 0.450631 0.65784
    1667 0.020618 −0.152906 −0.073514
    1668 −0.01219 −0.23803 −0.24918
    1669 0.029924 0.452512 0.78049
    1670 0.008377 −0.24035 −0.39003
    1672 −0.02109 −0.04326 −0.9614
    1673 −0.0073 −0.28445 −0.2691
    1674 0.001052 0.230389 0.365551
    1675 −0.00228 0.235454 0.555381
    1676 −0.03523 0.279516 0.556005
    1677 0.014496 0.700022 0.772568
    1678 −0.00423 −0.26803 −0.59474
    1679 −0.01749 0.064239 0.393283
    1680 0.014303 −0.15699 −0.52949
    1681 0.003697 0.131817 0.317734
    1682 −0.00306 −0.17935 −0.30964
    1683 −0.0044 0.152742 0.356869
    1684 −0.07893 −0.43101 −0.57506
    1685 −0.026 −0.35847 −0.50814
    1686 0.016683 −0.18902 −0.1842
    1687 −0.01704 −0.2493 −0.23759
    1688 0.008536 −0.19671 −0.16612
    1690 0.034281 0.168494 0.297968
    1691 −0.04203 −0.24984 −0.58657
    1692 0.040546 0.2054 0.409934
    1693 −0.00929 0.113601 0.330141
    1694 0.022539 0.351281 0.470963
    1695 0.029892 0.267705 0.486644
    1696 −0.00019 −0.22543 −0.49238
    1697 −0.01354 −0.06666 −0.54425
    1698 0.005153 −0.16834 −0.24091
    1699 0.01957 0.216329 0.399487
    1700 −0.03822 0.049127 −0.79641
    1701 −0.02074 0.357989 0.53794
    1702 −0.01378 0.190993 0.424559
    1703 −0.05184 −0.19677 −0.78632
    1704 0.025577 0.210863 0.323976
    1705 0.02774 0.305447 0.724292
    1706 0.017741 0.35252 0.640083
    1707 −0.10203 −0.508005 −0.433948
    1709 0.003448 0.250131 0.265264
    1710 −0.02108 0.135059 0.6295
    1713 −0.000033 0.227119 0.293211
    1714 −0.00418 0.263371 0.406272
    1715 0.02106 0.336823 0.533121
    1716 0.000778 −0.28099 −0.34591
    1717 0.067455 0.340627 0.53487
    1718 −0.00514 −0.18407 −0.44943
    1719 0.025175 0.199487 0.343829
    1720 0.010343 0.282449 0.476896
    1721 −0.06784 −0.30027 −0.86635
    1722 −0.02954 0.372542 0.464872
    1723 0.014127 0.37886 0.600633
    1725 −0.03063 −0.15378 −0.66852
    1726 0.005904 −0.22601 −0.39312
    1727 0.016504 0.319758 0.47473
    1729 −0.03897 0.806008 1.067372
    1730 −0.0123 −0.28524 −0.2969
    1732 0.018434 −0.15661 −0.14247
    1733 −0.02347 −0.17755 −0.57093
    1734 0.018422 0.189645 0.382171
    1735 0.023911 0.165244 0.391311
    1736 −0.01529 −0.19416 −0.4205
    1737 0.009313 −0.12753 −0.23184
    1738 −0.05497 −0.17588 −0.45726
    1739 −0.00577 −0.13309 −0.61854
    1740 0.000129 0.082648 0.202706
    1741 0.003693 0.225827 0.345689
    1742 0.031605 0.089372 0.312142
    1743 0.010364 0.348908 0.367908
    1744 −0.02434 −0.09144 0.156156
    1745 −0.02231 −0.20802 −0.22645
    1746 −0.04199 −0.25892 −1.00436
    1747 −0.01659 −0.1995 −0.30164
    1748 −0.03118 −0.26385 −0.39963
    1749 0.001133 −0.16781 −0.22877
    1750 −0.0074 −0.24548 −0.5296
    1751 0.030846 0.50771 0.564782
    1752 −0.0023 0.557287 0.447554
    1753 0.044274 −0.18457 −0.17418
    1754 0.005458 0.258669 0.438507
    1755 0.026709 0.265936 0.433134
    1756 −0.07289 −0.28387 −0.87405
    1759 0.017564 0.231565 0.588896
    1760 −0.00904 −0.20562 −0.2297
    1761 0.034479 0.143745 0.281478
    1763 0.002059 0.422689 0.661307
    1764 0.015931 0.381083 0.601851
    1765 −0.069608 0.229406 −0.942888
    1766 −0.01109 0.23371 0.474147
    1768 0.04507 0.229723 0.345461
    1769 −0.07627 0.156128 0.250496
    1770 0.01144 0.346982 0.490984
    1771 −0.02162 −0.28795 −0.27807
    1772 0.019225 0.236177 0.441341
    1775 0.022918 0.183774 0.301866
    1777 0.010911 0.118611 0.209198
    1778 −0.05232 −0.2939 −1.18191
    1779 0.011474 0.267102 0.353548
    1780 0.032706 0.233902 0.480801
    1782 −0.00163 −0.14093 −0.26973
    1783 0.030167 0.180356 0.299337
    1784 0.015401 0.594929 0.862064
    1785 −0.00264 0.291894 0.36507
    1787 −0.01282 −0.21492 −0.34306
    1788 0.009731 −0.13302 −0.11645
    1789 −0.00598 −0.0331 −0.28125
    1790 0.008607 −0.16296 −0.20062
    1791 0.002438 0.388732 0.329922
    1792 0.001959 0.023872 0.208334
    1793 0.010073 0.404828 0.426744
    1794 −0.03895 −0.21887 −0.5835
    1795 −0.0592 −0.09279 −0.44737
    1796 −0.0262 −0.25466 −0.21655
    1797 −0.12257 −0.31528 −1.5223
    1798 0.006863 0.125618 0.179833
    1801 0.002794 −0.12806 −0.33744
    1802 −0.006187 −0.271892 −0.547214
    1803 −0.02679 −0.23885 −0.46079
    1804 0.007217 −0.21745 −0.20809
    1805 −0.11509 −0.38375 −0.60223
    1806 −0.02318 −0.33783 −1.07263
    1807 −0.00505 −0.2652 −0.35813
    1808 0.004754 0.169766 0.345844
    1809 −0.01864 −0.17631 −0.30283
    1810 −0.01537 −0.11929 −0.49832
    1811 −0.02414 −0.22298 −0.56307
    1812 −0.05789 −0.46577 −0.67116
    1813 0.004929 0.074195 −0.38902
    1814 −0.12994 −0.5422 −0.67394
    1816 0.000462 −0.29172 −0.78629
    1817 −0.05267 −0.08425 −0.56209
    1818 0.021928 0.103957 0.612197
    1819 −0.04001 −0.08007 −0.62152
    1821 0.012366 0.608222 0.811802
    1822 0.008709 0.058535 0.172787
    1824 0.055901 1.019295 1.14166
    1825 −0.01941 −0.32585 −0.35338
    1826 0.024815 0.359143 0.586203
    1827 −0.01719 −0.20544 −0.21855
    1829 −0.0351 0.382362 0.463074
    1830 0.012246 −0.22063 −0.17454
    1831 −0.01595 −0.15761 −0.40073
    1832 0.018962 0.22087 0.566994
    1833 0.029653 0.034092 0.253365
    1834 −0.01445 −0.24365 −0.30384
    1835 −0.02682 −0.22033 −0.32568
    1836 −0.09901 −0.30331 −1.47414
    1837 0.030238 0.239652 0.470628
    1838 0.002423 −0.19623 −0.5761
    1841 −0.03342 −0.13149 −0.66763
    1842 0.029358 0.337117 0.459639
    1843 0.001903 −0.21172 −0.37406
    1844 −0.03995 −0.30379 −0.41743
    1845 −0.00479 −0.13037 −0.30756
    1846 −0.00041 −0.34946 −0.65983
    1847 −0.00414 −0.14024 −0.31772
    1848 −0.01386 −0.22644 −0.32931
    1850 0.01079 0.211982 0.326417
    1851 −0.02231 −0.2043 −1.19046
    1852 0.015181 0.111086 0.251967
    1853 −0.01527 −0.28004 −0.47715
    1854 0.000932 −0.24516 −0.28454
    1855 0.033597 0.184815 0.265554
    1856 −0.03302 −0.34634 −0.76554
    1857 0.005193 −0.22844 −0.62729
    1858 −0.05483 −0.30502 −0.82935
    1859 0.001499 −0.10385 −0.32329
    1860 0.013105 0.210462 0.248993
    1861 0.008675 0.496561 0.927091
    1862 0.010826 −0.21583 −0.30859
    1863 −0.02181 −0.43456 −0.94264
    1864 −0.01059 −0.24026 −0.50607
    1865 −0.01382 0.374521 0.555237
    1866 −0.12558 −0.46355 −1.21848
    1867 0.016134 −0.25351 −0.57052
    1868 0.001577 0.372509 0.34609
    1869 −0.14247 −0.50568 −1.11469
    1871 −0.03321 −0.44414 −1.2074
    1872 0.022755 0.237358 0.526712
    1874 0.015851 0.398675 0.461731
    1875 0.028164 0.290971 0.40534
    1876 −0.00363 0.330491 0.472481
    1877 −0.01271 −0.28482 −0.41247
    1878 −0.05324 −0.21202 −0.97494
    1879 −0.01231 0.272185 0.50145
    1880 0.009419 −0.16361 −0.28568
    1881 0.024008 0.385428 0.510505
    1882 −0.01343 −0.30202 −0.25117
    1883 0.019995 0.230682 0.273889
    1884 −0.0234 0.35963 0.444844
    1885 0.026138 0.213097 0.383805
    1886 −0.00891 0.004522 −0.56889
    1887 −0.00744 −0.28972 −0.55691
    1888 0.016743 0.303348 0.429235
    1889 0.001491 0.145451 0.360623
    1890 −0.00739 −0.14358 −0.51551
    1891 −0.01196 −0.17613 −0.29865
    1892 −0.04341 −0.18291 −1.32937
    1894 0.036374 0.308875 0.347083
    1895 −0.01486 −0.35427 −0.75272
    1896 0.020399 −0.17097 −0.28996
    1897 0.00121 −0.17923 −0.19633
    1899 −0.02719 −0.20241 −0.70406
    1900 −0.00544 −0.1899 −0.31452
    1901 −0.02757 −0.18302 −1.14281
    1902 0.002335 −0.21384 −0.30124
    1903 0.022039 0.236533 0.451828
    1904 −0.02356 −0.35422 −0.59893
    1905 0.012193 0.149476 0.324708
    1906 −0.018987 −0.066969 −0.26783
    1907 0.006033 0.110037 0.284895
    1908 0.001763 −0.19256 −0.24906
    1909 −0.03746 −0.27994 −0.98912
    1910 −0.014553 −0.104128 −0.202699
    1911 −0.00195 −0.19606 −0.26083
    1912 −0.00425 −0.25347 −0.32548
    1913 −0.09292 −0.0302 −0.94519
    1914 −0.01006 −0.17543 −0.72417
    1915 0.016217 −0.11786 −0.33524
    1916 −0.23712 −0.79448 −1.17987
    1917 0.020851 −0.31695 −0.30797
    1918 −0.00017 −0.20379 −0.42295
    1919 0.003761 0.079721 0.31422
    1920 −0.01211 −0.21388 −0.23505
    1921 −0.23852 −0.78111 −1.15703
    1922 −0.01943 −0.36905 −0.84702
    1923 −0.11396 −0.29114 −1.28313
    1924 −0.02134 −0.19369 −0.87972
    1925 0.019202 −0.23042 −0.31619
    1927 0.016189 0.022638 −0.210103
    1928 −0.11288 −0.43825 −1.01888
    1929 −0.15456 −0.55089 −1.75387
    1930 −0.04421 −0.41059 −1.08044
    1931 −0.02591 −0.15838 −0.64711
    1932 −0.03919 −0.38915 −1.40276
    1933 0.017422 0.39976 0.60926
    1934 −0.09323 −0.42485 −1.39982
    1935 −0.00778 −0.23173 −0.65059
    1936 −0.04034 −0.37519 −0.84927
    1937 −0.00128 0.221931 0.260665
    1938 −0.02216 −0.35136 −0.76624
    1939 −0.04121 −0.30657 −0.73842
    1940 −0.00255 −0.03829 −0.60883
    1941 0.001721 −0.28062 −0.72685
    1942 −0.0357 −0.30908 −0.99946
    1943 0.001724 0.258581 0.240667
    1945 −0.02465 −0.27186 −0.86081
    1946 −0.08093 −0.47696 −1.43226
    1947 −0.03385 −0.32059 −0.3286
    1950 0.002196 −0.17359 −0.19672
    1951 0.006991 −0.20072 −0.25329
    1952 −0.00608 −0.40942 −0.73578
    1953 0.005028 −0.15884 −0.16945
    1954 −0.01496 −0.38759 −0.80625
    1955 −0.00401 −0.23755 −0.2686
    1956 −0.0131 −0.35273 −0.47846
    1957 −0.33149 −0.64113 −1.67356
    1958 0.011706 0.158574 0.307924
    1960 0.001843 0.620171 0.791092
    1961 0.007272 0.209398 0.407065
    1962 −0.03168 −0.28618 −0.39373
    1963 −0.03105 −0.33984 −1.10317
    1964 −0.02235 −0.19517 −0.60335
    1966 −0.01351 −0.15096 −0.50109
    1967 −0.0447 −0.30407 −0.77666
    1968 0.018818 0.632814 1.006789
    1969 −0.02596 −0.08579 −0.5593
    1970 −0.00539 −0.12713 −0.51489
    1971 −0.00231 −0.27674 −0.53183
    1972 0.011694 −0.16092 −0.17151
    1973 0.025222 0.269645 −0.254999
    1974 0.005887 −0.23322 −0.3102
    1975 0.010273 0.158669 0.375971
    1976 0.01164 0.069451 0.30272
    1977 0.003153 0.020107 0.291161
    1978 0.010275 0.035343 0.290966
    1979 −0.00726 0.290123 0.41272
    1980 0.027274 0.114447 0.317692
    1981 −0.00299 −0.18464 −0.18655
    1982 0.003371 −0.20588 −0.27555
    1983 −0.02234 −0.24084 −0.25563
    1984 −0.01421 −0.27928 −0.47362
    1985 −0.01976 −0.32802 −0.50237
    1986 0.007511 0.140653 0.381245
    1987 −0.07456 −0.17753 −1.53576
    1988 −0.11518 −0.48269 −0.6296
    1989 −0.02835 −0.34393 −0.51483
    1992 0.025232 0.10373 0.212754
    1993 −0.01001 0.495077 0.431265
    1994 0.011564 0.199355 0.29528
    1995 −0.08513 −0.34241 −0.75858
    1996 0.009808 −0.08644 −0.66723
    1997 −0.00362 −0.24336 −0.58573
    1998 −0.027543 −0.140155 −0.699914
    1999 0.010602 0.381886 0.466869
    2000 0.005232 0.090412 0.303792
    2001 −0.04158 −0.10036 −0.75716
    2002 0.00709 −0.25448 −0.42862
    2003 0.020328 0.349002 0.540023
    2004 −0.10392 −0.26626 −1.14552
    2005 −0.00395 −0.14092 −0.81253
    2006 0.018924 0.16205 0.301643
    2008 0.017035 −0.18494 −0.32494
    2009 −0.0108 −0.2725 −0.60257
    2010 0.062715 0.858399 1.070711
    2011 −0.00319 −0.23151 −0.40707
    2013 0.016426 0.585105 0.735072
    2014 0.015113 −0.07451 −0.25615
    2015 0.015706 0.227053 0.434043
    2016 −0.01066 −0.06296 −0.26564
    2017 0.029794 0.296055 0.351559
    2018 0.029692 0.437282 0.898887
    2019 0.021497 0.043623 0.287068
    2020 0.012762 −0.00058 0.249706
    2021 0.019174 0.298194 0.539625
    2022 −0.00953 0.15747 0.378583
    2024 0.002746 0.021635 0.240366
    2025 −0.01867 0.148242 0.393055
    2026 0.012409 0.29772 0.537753
    2027 −0.10141 −0.42795 −0.96011
    2028 −0.04498 −0.43649 −1.45709
    2029 −0.00698 0.084208 0.226775
    2030 −0.01906 −0.07943 −0.3736
    2031 0.037343 0.135145 0.345018
    2034 0.016288 0.26475 0.36449
    2035 0.006041 −0.39239 −0.2779
    2036 0.005805 −0.16315 −0.18766
    2037 0.008439 −0.20905 −0.20892
    2038 −0.04899 −0.25655 −0.65559
    2039 0.008925 −0.17251 −0.16471
    2041 0.025259 0.472669 0.602447
    2042 0.003359 −0.068862 −0.130822
    2043 −0.02582 −0.14361 −0.66288
    2044 0.009058 0.271975 0.401515
    2045 0.003375 0.481213 0.58199
    2046 0.030247 0.202417 0.360615
    2047 −0.01954 −0.24101 −0.52265
    2048 0.02079 0.122979 0.287027
    2049 0.01841 0.128683 0.297137
    2050 −0.07838 −0.3133 −0.81839
    2051 0.035655 0.12048 0.325558
    2052 0.019567 0.208663 0.305192
    2053 0.006616 −0.14349 −0.25109
    2054 0.01283 0.763707 1.304963
    2055 0.011199 0.145867 0.391723
    2056 0.017212 −0.089889 −0.160576
    2057 0.020607 −0.18267 −0.20839
    2058 −0.01011 0.234598 0.4539
    2059 0.028485 0.975327 1.038984
    2060 −0.00122 −0.11435 −0.26342
    2061 0.007696 −0.15684 −0.41357
    2062 −0.10026 −0.36029 −1.4428
    2063 −0.0135 −0.27765 −0.73306
    2065 0.013947 0.089198 0.20872
    2066 −0.00563 −0.28159 −0.25268
    2067 −0.034481 −0.314757 −0.571005
    2068 0.014892 0.234483 0.341533
    2069 0.013673 −0.24452 −0.31746
    2070 −0.03035 −0.24676 −0.33611
    2071 0.016716 0.069954 0.274927
    2072 −0.00023 −0.14279 −0.18875
    2074 0.020103 0.397908 0.358054
    2075 0.000883 −0.16172 −0.27555
    2076 0.004859 0.17127 0.332493
    2077 0.01037 −0.21565 −0.18888
    2078 −0.01703 −0.29207 −0.3353
    2079 0.004482 −0.13823 −0.1988
    2080 −0.00423 0.264912 0.538955
    2083 −0.01884 −0.22222 −0.54983
    2084 0.002429 0.191739 0.286946
    2086 −0.11171 −0.3468 −1.66202
    2089 −0.00222 −0.2653 −0.22905
    2090 −0.00873 −0.25551 −0.39288
    2091 0.017863 0.3995 0.563314
    2092 −0.02737 −0.29124 −0.54792
    2093 0.001438 0.393312 0.645013
    2094 −0.00161 0.329179 0.599467
    2095 −0.04662 −0.4555 −1.39345
    2096 0.00868 −0.14575 −0.16084
    2097 −0.01069 0.438307 0.530558
    2098 0.005224 −0.1524 −0.57137
    2099 −0.00512 −0.23121 −0.20581
    2100 0.01594 −0.11251 −0.15343
    2102 −0.03821 −0.13991 −0.37379
    2103 −0.0791 −0.56806 −0.76943
    2105 −0.0032 0.184921 0.613022
    2107 0.028212 0.476891 0.557632
    2108 0.016664 −0.18764 −0.19983
    2109 0.024344 0.270797 0.434368
    2110 0.016946 0.26032 0.406567
    2111 −0.03403 −0.18774 −0.47693
    2112 −0.03586 −0.18075 −0.81904
    2113 −0.03026 −0.30742 −0.71977
    2114 0.047553 1.260344 1.156552
    2115 −0.01266 −0.26929 −0.3155
    2116 −0.09454 −0.21809 −1.42535
    2117 −0.12163 −0.41838 −1.70565
    2118 −0.03225 −0.24102 −0.4328
    2119 −0.0277 −0.23099 −0.76403
    2120 0.00625 −0.06197 −0.47991
    2121 −0.01834 −0.27363 −0.90414
    2122 0.011765 0.253516 0.398825
    2123 0.00067 −0.1136 −0.48147
    2124 0.017464 −0.20661 −0.22346
    2125 −0.0182 −0.13711 −0.28222
    2127 −0.042666 0.689794 0.248637
    2128 0.002977 −0.20398 −0.24483
    2129 −0.05143 0.803666 0.887101
    2130 0.00574 −0.21235 −0.29382
    2131 −0.00303 −0.18488 −0.88168
    2132 −0.001535 0.140887 0.196882
    2133 −0.00393 −0.06911 −0.36393
    2134 −0.03722 0.513288 0.815222
    2135 −0.01418 −0.07171 −0.47154
    2136 −0.016679 0.5014 0.158751
    2137 −0.03413 −0.34893 −1.14123
    2138 0.021545 0.163729 0.280431
    2139 0.001657 −0.20288 −0.32099
    2140 −0.04362 −0.26001 −0.88714
    2141 −0.0604 −0.3014 −1.2413
    2142 0.014533 −0.1873 −0.2803
    2143 −0.1554 −0.1203 −1.28143
    2144 −0.06871 −0.3596 −1.3171
    2146 −0.03532 0.861553 0.9609
    2147 −0.08402 −0.07325 −1.17694
    2148 0.007504 −0.089503 −0.424451
    2149 −0.0109 0.3989 0.462382
    2150 0.017122 0.249082 0.421175
    2152 0.000207 −0.21526 −0.62205
    2153 −0.0968 −0.31175 −1.50181
    2154 0.027642 0.21952 0.323357
    2155 −0.12683 −0.4516 −1.8255
    2156 0.010058 −0.11429 −0.24262
    2157 0.00001 −0.29205 −0.35927
    2158 0.02961 −0.09941 −0.51043
    2159 −0.00806 0.652361 0.831233
    2160 0.001866 −0.1929 −0.58327
    2162 −0.018781 −0.151041 −0.25681
    2163 0.006228 0.064327 0.297762
    2164 −0.05889 −0.38329 −1.43636
    2165 0.016516 0.619334 0.805191
    2166 −0.04869 −0.23011 −0.83923
    2167 0.003504 −0.18951 −0.192
    2168 −0.02315 −0.07567 −0.8944
    2169 −0.03608 −0.27598 −1.16409
    2170 −0.02692 −0.43046 −1.39025
    2171 0.002668 −0.37727 −0.52856
    2173 0.012166 0.238158 0.457493
    2175 −0.01559 −0.12915 −0.2724
    2176 0.025237 −0.09022 −0.19988
    2177 −0.03027 −0.22427 −1.29209
    2179 −0.000017 0.118178 −0.51895
    2180 0.016951 0.103897 0.333014
    2182 −0.01191 −0.17284 −0.30344
    2184 −0.03966 −0.14011 −0.49395
    2185 −0.01437 −0.17107 −0.62149
    2186 0.01792 0.058324 0.385451
    2187 0.014317 0.571045 0.979284
    2188 0.010466 −0.25055 −0.42237
    2190 0.018541 0.327989 0.417322
    2191 −0.0577 −0.35017 −0.72494
    2192 −0.0357 −0.26097 −0.34259
    2193 0.006228 −0.2797 −0.73328
    2194 0.015071 0.359311 0.477458
    2195 0.005636 −0.20457 −0.22518
    2196 0.001252 −0.045446 −0.145241
    2197 0.019099 0.161504 0.47798
    2198 0.013844 −0.2143 −0.37091
    2201 −0.02295 −0.15527 −0.34364
    2202 −0.05247 −0.1837 −1.02532
    2203 0.013674 0.140593 0.249899
    2204 −0.0042 −0.15621 −0.88249
    2205 −0.03294 −0.48168 −1.48088
    2208 −0.0036 −0.14616 −0.24644
    2209 0.007125 0.199427 0.311049
    2210 0.002471 0.203327 0.374323
    2211 −0.02716 −0.35947 −0.74654
    2213 0.022013 0.236032 0.427654
    2214 −0.0196 −0.21397 −0.72637
    2215 −0.00274 −0.14692 −0.25459
    2216 −0.00131 −0.17937 −0.19394
    2217 −0.02213 −0.13748 −0.35095
    2218 −0.001994 0.132273 0.102983
    2219 −0.01994 −0.35781 −0.39975
    2220 0.000037 −0.30384 −0.35871
    2221 −0.05789 −0.22934 −0.50878
    2222 0.008979 0.538623 0.735942
    2223 −0.01819 −0.49118 −0.4376
    2225 0.003237 −0.23548 −0.30838
    2226 −0.0949 −0.38963 −1.44171
    2227 −0.00725 0.248686 0.395542
    2229 0.009271 0.114522 0.376512
    2230 0.00848 0.206059 0.401043
    2231 0.003439 −0.20575 −0.19678
    2232 −0.02501 −0.18181 −0.55661
    2233 0.000061 −0.20966 −0.25777
    2234 0.012291 −0.1024 −0.19623
    2235 0.012667 −0.11775 −0.14831
    2236 −0.04859 −0.21001 −0.44239
    2237 −0.01381 −0.12472 −0.48142
    2238 0.03163 0.593249 0.946711
    2239 0.012068 0.31605 0.517375
    2240 −0.00959 −0.37927 −0.9435
    2241 −0.00071 −0.20447 −0.16281
    2242 0.021262 0.323219 0.630179
    2243 −0.0233 −0.27218 −0.27146
    2245 −0.02948 0.435608 0.648983
    2246 −0.01451 −0.11772 −0.40097
    2247 −0.01953 −0.32074 −0.89551
    2248 −0.012664 0.324801 0.485921
    2249 −0.11577 −0.70415 −1.88167
    2250 0.012475 −0.08448 −0.52598
    2251 0.019459 0.082497 0.306636
    2254 −0.01464 0.4015 0.607716
    2255 0.008703 −0.03485 −0.2459
    2256 −0.00734 −0.24854 −0.35887
    2257 −0.1667 −0.29214 −1.57416
    2258 0.025576 0.284406 0.328053
    2259 −0.04541 −0.3858 −1.56258
    2260 0.001392 0.250803 0.374406
    2261 0.009299 −0.21002 −0.19307
    2262 0.018302 0.251187 0.347344
    2263 −0.02879 −0.29245 −0.45105
    2264 −0.01469 0.142428 0.400088
    2265 −0.05956 −0.10194 −1.14857
    2267 0.018365 0.286151 0.448262
    2268 0.018301 0.088642 0.351184
    2270 0.016318 0.184584 0.437909
    2271 0.00117 −0.17535 −0.18357
    2272 −0.0067 0.145926 0.465509
    2273 0.028317 0.260572 0.407932
    2274 0.003924 0.100185 0.394108
    2275 0.001144 −0.01617 0.237965
    2276 −0.00554 −0.27487 −0.4612
    2277 −0.05148 −0.1106 −1.37907
    2278 0.000259 0.217995 0.369969
    2279 −0.00916 −0.136 −0.27663
    2280 0.006631 0.197481 0.573742
    2281 0.025366 0.076441 −0.41989
    2282 0.003573 −0.28411 −0.296893
    2283 0.011297 0.42849 0.742061
    2284 −0.01898 −0.2316 −0.65533
    2286 −0.00426 −0.361198 −0.342302
    2287 0.004729 0.137132 0.328942
    2288 0.018171 0.241546 0.359732
    2290 −0.01784 −0.18518 −0.20255
    2291 −0.01003 −0.11266 −0.29419
    2293 0.010189 −0.1935 −0.72632
    2294 −0.03967 −0.08272 −0.37749
    2295 −0.01802 −0.14871 −0.63321
    2296 −0.01662 −0.15705 −0.53086
    2297 0.028114 0.118132 0.19296
    2298 −0.0099 −0.20647 −0.37635
    2299 −0.06665 −0.49226 −0.76252
    2300 0.003024 0.185532 0.329792
    2301 0.003459 −0.09165 −0.17224
    2302 0.008627 −0.135924 −0.184813
    2303 0.001354 −0.20444 −0.38761
    2305 −0.02601 −0.27937 −0.93622
    2306 −0.032 −0.17657 −0.40731
    2307 −0.02362 −0.24769 −0.48945
    2308 −0.01428 −0.1252 −0.56253
    2309 0.004879 −0.01626 0.177099
    2310 −0.001488 −0.154965 −0.151611
    2311 −0.0355 −0.06494 −0.81527
    2314 0.000047 0.173299 0.33084
    2315 0.014775 −0.21485 −0.26234
    2316 −0.0855 −0.4418 −1.05437
    2317 −0.1403 −0.11166 −1.30303
    2318 0.019665 0.322236 0.461469
    2319 0.00727 −0.17689 −0.17482
    2321 0.029903 −0.18599 −0.1737
    2322 −0.01996 −0.20753 −0.47119
    2323 0.019525 0.499532 0.706726
    2324 −0.00226 −0.09615 −0.26922
    2325 0.002831 −0.12896 −0.40715
    2326 −0.03027 −0.29217 −0.52745
    2327 −0.03554 −0.15001 −0.44243
    2328 0.027305 0.107061 0.404793
    2330 0.002761 0.078152 0.232141
    2331 0.014591 −0.20659 −0.24591
    2332 −0.01237 −0.3604 −0.96262
    2333 0.003339 −0.13529 −0.30058
    2334 0.020232 0.178617 0.405091
    2335 0.010095 0.152031 0.299269
    2336 0.018881 0.098289 0.233411
    2337 0.01485 0.109005 0.284366
    2338 0.014368 0.188275 0.327004
    2339 0.015409 0.134288 0.185346
    2340 0.00381 0.083288 0.228486
    2341 −0.00868 0.174526 0.205402
    2342 0.002769 0.167636 0.260991
    2343 0.023292 0.082431 0.207825
    2344 0.009922 0.174544 0.389325
    2345 0.028308 0.299421 0.363884
    2346 −0.05802 −0.49477 −0.53976
    2347 0.006781 −0.16619 −0.50252
    2348 −0.00471 −0.24265 −0.40632
    2349 −0.00289 −0.26804 −0.24449
    2350 −0.00163 −0.26011 −0.6722
    2351 −0.01717 −0.49896 −0.45749
    2352 −0.03309 −0.1127 −0.78667
    2353 −0.01112 −0.18403 −0.67658
    2355 −0.05419 −0.28594 −1.00055
    2357 −0.00326 −0.2309 −0.30353
    2358 0.001835 −0.08573 −0.21332
    2359 −0.01645 −0.1167 −0.28613
    2360 −0.01825 −0.20883 −0.34224
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    2364 −0.00207 −0.18193 −0.15526
    2365 −0.0054 −0.20264 −0.3212
    2366 −0.00365 0.345983 0.585183
    2367 0.00371 0.348181 0.574241
    2368 −0.00047 −0.39854 −0.27045
    2369 0.004161 −0.11105 −0.25499
    2370 0.009182 −0.2079 −0.21171
    2371 0.005776 −0.16574 −0.17686
    2373 −0.07101 −0.19618 −1.27507
    2374 −0.05482 −0.24994 −1.2083
    2375 −0.08589 −0.36391 −1.39884
    2376 0.012739 0.206079 0.359452
    2377 0.011456 −0.12574 −0.42451
    2378 0.011457 0.252312 0.495695
    2379 −0.00327 −0.2122 −0.37955
    2380 −0.01316 −0.25034 −0.60606
    2381 −0.01115 −0.19235 −0.40341
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    2383 −0.06705 −0.47182 −1.61495
    2384 0.006198 0.205257 0.192964
    2385 −0.01366 −0.28913 −0.30197
    2386 0.003211 −0.20733 −0.22757
    2388 −0.057599 0.240909 0.4755
    2389 −0.01387 −0.23521 −0.40967
    2390 −0.00202 −0.24353 −0.61697
    2391 0.00954 0.313285 0.540015
    2392 −0.00821 −0.28209 −0.34509
    2393 −0.01174 −0.24409 −0.30122
    2394 −0.0009 −0.23828 −0.28305
    2395 −0.00185 −0.15898 −0.18266
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    2397 −0.01208 −0.20406 −0.25478
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    2400 −0.0331 −0.10996 −0.63571
    2401 −0.06494 0.342079 0.465985
    2402 −0.04543 −0.21281 −0.34911
    2403 0.01053 0.149484 0.288128
    2404 0.008288 −0.20655 −0.46411
    2405 −0.00489 0.133801 0.312915
    2407 −0.02636 −0.26027 −0.34624
    2408 0.019185 0.130116 0.27178
    2409 0.020264 0.01922 0.337092
    2410 0.031527 0.419581 0.586724
    2411 0.014796 0.186449 0.312028
    2412 0.014163 0.110452 0.254911
    2413 0.020538 0.201187 0.42546
    2414 0.01084 0.14581 0.272706
    2415 −0.01583 0.331777 0.392434
    2416 −0.026 −0.20967 −0.78121
    2417 0.009603 0.134698 0.344874
    2418 0.001308 −0.26017 −0.41484
    2419 0.013034 0.147238 0.234368
    2420 −0.00937 −0.22861 −0.37108
    2421 0.027995 0.500671 0.712713
    2422 −0.00456 0.06091 0.306779
    2423 −0.01058 −0.10054 −0.31111
    2424 0.019249 −0.14345 −0.14736
    2425 −0.00553 −0.21816 −0.23095
    2426 0.018803 −0.12179 −0.16992
    2428 0.029088 0.15182 0.39338
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    2431 0.000421 −0.20582 −0.26891
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    2438 0.02318 0.143816 0.482143
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    2445 −0.08669 −0.23792 −1.06465
    2446 0.005175 0.027188 0.217852
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    2448 −0.03247 −0.26674 −0.66752
    2450 −0.0089 −0.1816 −0.41721
    2451 −0.009 −0.18197 −0.25772
    2452 0.011127 0.14173 0.594525
    2453 0.010407 0.147058 0.493581
    2455 −0.03877 −0.35242 −0.72069
    2456 0.016955 0.224789 0.295622
    2457 0.014259 0.230541 0.457636
    2458 −0.01036 0.97751 0.84787
    2459 −0.00972 −0.22179 −0.27712
    2460 −0.01003 0.282259 0.249375
    2461 −0.00813 −0.26674 −0.38386
    2462 −0.04743 −0.42331 −1.04892
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    2464 −0.01496 0.25609 0.530373
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    3888 0.014393 0.484554 0.495931
    3889 0.001776 0.262078 0.383028
    3890 0.011023 −0.01062 −0.44164
    3892 0.004332 −0.00059 −0.38242
    3893 0.001464 −0.14286 −0.18126
    3894 −0.01231 −0.2316 −0.32005
    3895 0.018186 0.089257 0.210466
    3896 0.0075 −0.17357 −0.27499
    3897 −0.00568 −0.14148 −0.37829
    3898 0.002511 −0.14907 −0.15297
    3899 −0.0092 −0.1654 −0.41466
    3900 0.01744 0.108167 0.303529
    3902 −0.21525 −0.62727 −0.88264
    3903 0.012294 0.101754 0.422339
    3904 0.007328 −0.12993 −0.17647
    3906 0.032547 0.2237 0.374842
    3907 0.020824 0.455249 0.666732
    3908 0.001958 −0.08941 −0.20901
    3909 −0.03403 −0.28041 −0.66761
    3910 0.005124 0.373303 0.456396
    3911 0.007527 0.436713 0.635286
    3912 −0.01004 −0.18805 −0.1945
    3913 −0.13841 0.130768 −0.78612
    3914 0.005593 −0.24982 −0.45921
    3916 0.007871 0.294561 0.472056
    3917 0.000456 0.350453 0.512085
    3918 −0.00721 −0.20685 −0.30782
    3919 0.00249 0.4553 0.467418
    3920 0.003433 0.234106 0.347743
    3921 0.02159 0.267666 0.272491
    3922 −0.01034 −0.23596 −0.40316
    3923 −0.0218 −0.17331 −0.31503
    3924 −0.01052 −0.2608 −0.45258
    3926 0.005481 −0.19415 −0.38862
    3927 −0.00198 −0.15223 −0.26378
    3928 −0.00481 −0.19212 −0.60011
    3929 −0.02907 −0.31237 −0.67115
    3930 0.018932 0.502499 0.630779
    3931 0.007823 0.330178 0.374828
    3932 −0.00625 −0.19177 −0.36188
    3934 −0.01138 −0.16719 −0.62327
    3936 0.013418 −0.12059 −0.21994
    3937 −0.00602 −0.17249 −0.19886
    3938 −0.00093 −0.18338 −0.21621
    3940 −0.0063 0.32237 0.447277
    3941 −0.03123 0.753525 1.028617
    3942 −0.03893 −0.15886 −1.03693
    3943 0.016177 0.318878 0.500708
    3944 0.029472 −0.14649 −0.37317
    3945 −0.15185 −0.49868 −0.607
    3946 −0.09644 −0.46037 −0.57596
    3948 0.010157 0.279247 0.48872
    3949 0.002141 −0.34666 −0.2661
    3950 −0.03206 −0.28804 −0.36911
    3951 0.006273 0.122116 0.414685
    3952 −0.04024 0.176953 0.383377
    3953 0.0072 −0.23691 −0.34253
    3954 0.012744 −0.16741 −0.24655
    3955 −0.019735 −0.159647 −0.33003
    3957 −0.00172 0.066009 0.290683
    3958 0.000007 0.258618 0.366426
    3959 −0.07307 −0.35372 −0.42584
    3960 −0.005 −0.29445 −0.89736
    3962 −0.00971 −0.14007 −0.77128
    3963 −0.0012 −0.19036 −0.18134
    3964 −0.00871 −0.31654 −0.73351
    3965 0.007545 −0.19764 −0.31117
    3967 −0.09077 −0.42429 −0.50192
    3968 0.002684 −0.24249 −0.27393
  • TABLE 1b
    phase reporter genes
    SEQ ID NO log(ratio) CP log(ratio) AP log(ratio) BC
    56 −0.01844 −0.2843 −0.52572
    65 −0.043 −0.27935 −0.61442
    70 −0.02677 0.321263 0.479287
    177 −0.02343 −0.25951 −0.53988
    190 −0.04631 −0.22027 −0.61104
    199 −0.19435 −0.66091 −1.74771
    1758 −0.0427 −0.06237 −0.68566
    1773 0.032164 0.295407 0.487261
    1774 0.02296 0.304684 0.561645
    1786 0.014041 0.225619 0.584752
    1815 0.035253 0.254518 0.53063
    1823 0.014591 0.300107 0.456781
    3925 −0.04398 −0.3128 −0.99975
    3933 −0.0347 −0.12523 −0.74375
    3947 −0.04231 −0.53589 −1.45253
    3956 −0.00856 −0.16684 −0.95119
  • Tables 2a and 2b list a set of 386 progression genes identified by searching for phase reporter genes after removing CD34 content (p<10−8) (the “progression geneset”). The CD34 content is removed by subtracting the expression level of each gene in a sample of CD34+ cells from the expression level of the gene in a tumor sample from a CML patient. The progression genes are identified by their SEQ ID NOs in Tables 2a and 2b. Information for these genes is presented in Table 8. Table 2a lists progression genes that were not disclosed in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Table 2b lists progression genes that were also identified in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Tables 2a and 2b also listed for each gene the log ratio of CD34+(−) expression level of the gene (i.e., the expression level of the gene in a tumor sample from a CML patient minus the expression level of the gene in a sample of CD34+ cells) in samples from patients of a particular phase (e.g., CP, AP, or BC) versus CD34+(−) expression level of the gene in a pool of CML bone marrow samples from chronic phase patients. Each log ratio column thus contains expression levels of markers for a particular phase.
  • TABLE 2a
    progression genes
    SEQ ID NO log(ratio) CP log(ratio) AP log(ratio) BC
    2 −0.013036 0.331191 0.13619
    22 −0.027625 0.25124 0.297168
    44 −0.008283 −0.175784 −0.35176
    74 −0.018621 0.110352 −0.541362
    75 0.012898 −0.15485 −0.081578
    98 −0.0065 0.226199 0.384576
    118 0.0235 0.413795 0.572899
    120 −0.068801 −0.238346 −0.788486
    123 −0.014776 0.153884 0.315337
    127 0.014361 0.2732 0.196317
    146 −0.062898 −0.026859 −0.467529
    166 −0.008117 −0.02223 −0.588809
    192 −0.03375 −0.376045 −0.824014
    201 −0.046038 0.745451 0.938831
    252 −0.011159 −0.181168 −0.338022
    260 −0.014983 0.169381 0.378207
    261 0.002136 −0.013939 0.252784
    277 −0.059071 0.153895 −0.707755
    282 −0.011292 0.246831 0.217263
    300 −0.015553 0.264616 0.213715
    312 −0.006268 −0.169392 −0.415121
    321 0.017293 0.264073 0.351815
    329 0.015519 −0.110525 −0.132442
    348 0.003377 0.292866 0.385025
    359 0.011735 −0.238758 −0.159133
    361 0.0199 −0.29195 −0.308127
    369 0.015105 −0.30705 −0.467622
    379 0.011972 0.153175 0.287232
    382 −0.034613 0.539856 0.385649
    392 −0.018091 0.211741 0.151359
    397 0.001911 −0.204817 −0.142157
    398 −0.055256 0.454774 0.463563
    401 0.010902 −0.0223 −0.435077
    407 0.022957 −0.146156 −0.144178
    408 0.000587 0.042633 0.171636
    413 −0.004104 −0.021944 −0.541188
    432 −0.021105 0.318234 0.36938
    453 0.000187 −0.016503 −0.233794
    462 0.015733 −0.049378 −0.203749
    464 −0.007901 −0.242419 −0.192786
    468 −0.069818 0.055712 −0.792861
    483 0.022087 0.013675 −0.264371
    487 −0.044506 −0.226859 −0.730255
    490 0.032225 0.697253 0.473438
    493 0.005365 0.117615 0.279824
    506 0.002222 0.244418 0.413136
    508 −0.001048 0.149848 0.252886
    513 −0.025942 0.105185 −0.589267
    532 0.013898 −0.091144 −0.105794
    535 −0.02973 0.31094 −0.640132
    549 −0.024057 −0.192808 −0.507538
    562 −0.007465 −0.085295 −0.451408
    564 0.010706 0.16159 0.377863
    565 −0.013377 0.189935 0.358398
    596 −0.027369 −0.300983 −0.676728
    602 −0.02947 0.152602 0.288592
    607 −0.03208 0.163679 0.433561
    629 −0.017135 0.164754 0.393246
    631 −0.005919 0.029702 0.182895
    638 0.005995 0.158171 0.295784
    641 −0.002351 0.141381 −0.371398
    644 0.011035 −0.188829 −0.236191
    648 −0.000305 0.09399 0.156447
    671 −0.052686 0.224817 −0.778464
    678 −0.011662 −0.03032 −0.483853
    686 −0.044146 0.393448 0.352519
    687 0.004128 0.014188 0.147004
    688 −0.007112 0.135577 −0.384238
    692 0.01078 −0.193913 −0.339249
    694 0.026903 0.238728 0.198984
    699 0.002836 −0.136336 −0.204499
    700 −0.003573 0.186663 0.111998
    702 −0.004795 0.43693 0.231795
    704 0.008652 0.448527 0.623811
    708 0.035423 −0.072534 −0.243577
    710 0.00051 −0.260385 −0.325256
    715 −0.031368 −0.034762 −0.28179
    725 0.018721 −0.110491 −0.07631
    727 0.011701 0.352484 0.599663
    730 0.007214 −0.100867 −0.390067
    739 −0.021549 0.313399 0.230556
    758 0.006066 0.197232 0.154028
    774 −0.011428 0.297906 0.460758
    781 0.049464 0.661373 0.621414
    789 −0.011135 0.073025 0.220549
    794 0.00587 −0.124811 −0.092198
    852 −0.009777 0.061913 0.217413
    862 0.012512 0.101103 0.346959
    878 −0.007159 0.624676 0.342539
    879 0.015292 0.310113 −0.619546
    902 0.01057 0.108517 0.282889
    906 0.009153 0.106628 0.432846
    912 −0.03355 −0.086456 −0.556116
    913 −0.002153 −0.162393 −0.176945
    934 −0.001515 0.49437 0.349162
    949 −0.009006 −0.003959 −0.260665
    969 0.009521 −0.194416 −0.088755
    983 −0.009189 −0.179037 −0.279808
    984 0.003783 0.428077 −0.304577
    995 0.018194 0.115536 0.453015
    1005 −0.004206 0.264613 0.406912
    1006 0.013715 0.253173 −0.48171
    1014 −0.027032 0.218431 0.369874
    1027 −0.097802 0.14838 −0.409138
    1030 0.012193 −0.156904 −0.129918
    1036 0.018457 0.150121 0.282032
    1042 0.016406 0.12399 0.254155
    1047 −0.010956 0.160388 0.293704
    1053 −0.003597 0.168234 0.188554
    1065 0.041337 0.356808 0.457428
    1086 0.012167 0.126556 0.308808
    1089 −0.056921 0.265345 0.488138
    1092 0.031164 0.741399 0.650443
    1093 −0.019458 0.265262 0.281598
    1100 −0.026376 −0.107488 0.120579
    1105 0.000402 0.241675 0.374547
    1106 0.013275 0.053145 0.284804
    1111 0.006695 0.390109 0.467033
    1113 0.00931 −0.151037 −0.094238
    1145 −0.003373 −0.121256 −0.288823
    1161 −0.036419 −0.112814 −0.289979
    1169 0.004364 −0.149179 −0.137703
    1180 −0.003015 0.149485 0.243152
    1181 −0.006552 0.354743 0.273738
    1182 −0.063925 0.133911 −0.796733
    1201 −0.024631 0.061529 −0.462534
    1211 −0.0131 0.42541 0.389219
    1227 0.003709 −0.172158 −0.119982
    1228 −0.001968 −0.182794 −0.15988
    1234 0.003295 −0.168464 −0.233929
    1264 0.007382 −0.120962 −0.228059
    1288 −0.025178 0.393585 0.566352
    1294 0.004545 0.126708 0.283647
    1308 −0.051939 −0.225136 −1.142094
    1324 0.000802 0.195216 0.368476
    1327 0.0232 0.29162 0.330751
    1328 0.016117 −0.125314 −0.193334
    1333 −0.001615 0.157104 0.160918
    1334 −0.003194 0.078374 −0.585411
    1352 −0.013243 −0.259131 −0.724495
    1364 0.020286 −0.059623 −0.36669
    1394 −0.038031 0.569499 0.281012
    1400 −0.034692 −0.392913 −0.855372
    1408 0.012613 0.202286 −0.410509
    1421 0.015803 0.301704 −0.280571
    1434 0.023441 0.24849 0.404885
    1465 0.011301 1.119758 0.380817
    1475 0.002495 −0.174538 −0.144746
    1489 −0.005825 0.171399 0.198891
    1503 −0.010846 0.33961 0.344346
    1538 0.008774 0.250497 0.380736
    1544 −0.001566 −0.118486 −0.225612
    1565 0.003841 −0.24087 −0.188087
    1586 −0.05968 0.131214 0.231979
    1596 −0.012267 0.315077 0.462982
    1598 −0.040336 0.405119 0.295977
    1600 0.016473 0.171937 0.480309
    1613 0.018672 0.639835 0.686131
    1615 0.003796 −0.155045 −0.123787
    1621 0.000743 0.182262 0.22026
    1622 −0.01422 0.108504 0.441113
    1624 −0.003494 −0.128858 −0.416283
    1631 −0.066238 0.08156 0.35517
    1644 0.012751 0.004567 −0.256495
    1653 −0.051037 0.575903 0.659891
    1666 −0.005018 0.304418 0.391773
    1667 0.020618 −0.152906 −0.073514
    1674 0.001052 0.230389 0.365551
    1707 −0.10203 −0.508005 −0.433948
    1713 −0.000033 0.227119 0.293211
    1723 −0.008555 −0.013157 0.311742
    1726 0.01878 −0.134004 −0.114544
    1729 0.017853 0.122885 0.403719
    1740 0.000129 0.082648 0.202706
    1744 −0.008165 0.028902 0.157605
    1754 −0.03329 0.24969 0.276391
    1756 −0.006572 −0.090777 −0.187299
    1764 −0.023292 0.061919 0.439367
    1765 −0.069608 0.229406 −0.942888
    1769 0.004735 0.111816 0.380203
    1772 −0.053231 0.914364 0.703125
    1784 0.011665 0.266176 0.262102
    1798 0.006863 0.125618 0.179833
    1802 −0.006187 −0.271892 −0.547214
    1813 0.004929 0.074195 −0.38902
    1822 0.008709 0.058535 0.172787
    1851 −0.038706 0.176417 −0.585557
    1854 0.011347 −0.148867 −0.08759
    1856 0.023502 −0.039695 −0.260378
    1857 0.001175 −0.00306 −0.260983
    1864 −0.023131 −0.110894 −0.595764
    1902 0.011275 −0.14224 −0.083923
    1906 −0.018987 −0.066969 −0.26783
    1910 −0.014553 −0.104128 −0.202699
    1927 0.016189 0.022638 −0.210103
    1936 −0.008747 −0.190402 −0.17087
    1966 0.009815 −0.207021 −0.109949
    1973 0.025222 0.269645 −0.254999
    1997 0.000408 −0.206852 −0.093692
    1998 −0.027543 −0.140155 −0.699914
    2024 0.002746 0.021635 0.240366
    2041 −0.006546 0.162101 0.390622
    2042 0.003359 −0.068862 −0.130822
    2054 0.003287 0.188219 0.311283
    2056 0.017212 −0.089889 −0.160576
    2059 −0.020181 1.117376 0.593213
    2067 −0.034481 −0.314757 −0.571005
    2069 0.020052 −0.126164 −0.092528
    2084 −0.030024 0.35537 0.651561
    2116 0.013573 −0.038963 −0.25063
    2121 −0.071015 0.041386 −0.850915
    2127 −0.042666 0.689794 0.248637
    2132 −0.001535 0.140887 0.196882
    2136 −0.016679 0.5014 0.158751
    2148 0.007504 −0.089503 −0.424451
    2162 −0.018781 −0.151041 −0.25681
    2196 0.001252 −0.045446 −0.145241
    2197 0.011939 0.082814 0.421803
    2211 0.016656 −0.118424 −0.17814
    2218 −0.001994 0.132273 0.102983
    2222 −0.080043 0.129091 0.187538
    2247 0.014934 −0.139989 −0.120912
    2248 −0.012664 0.324801 0.485921
    2259 0.009135 0.109045 −0.390417
    2276 0.010096 −0.162022 −0.120129
    2277 0.013334 0.571954 −0.227756
    2282 0.003573 −0.28411 −0.296893
    2286 −0.00426 −0.361198 −0.342302
    2298 −0.042053 −0.27671 −0.589169
    2302 0.008627 −0.135924 −0.184813
    2310 −0.001488 −0.154965 −0.151611
    2334 0.022782 0.118742 0.155021
    2344 −0.046131 −0.043556 0.354686
    2373 0.013698 0.020747 −0.300319
    2388 −0.057599 0.240909 0.4755
    2392 0.007643 −0.159192 −0.126831
    2398 −0.04217 0.124478 −0.490219
    2414 0.006247 0.039279 0.231344
    2458 −0.047592 −0.021181 0.62265
    2464 0.009492 0.497028 0.550105
    2465 −0.061732 0.844778 0.746645
    2474 −0.010535 0.317139 0.32638
    2479 0.009625 −0.032207 −0.206553
    2482 0.007713 0.134365 0.22816
    2486 0.008277 −0.165135 −0.505359
    2494 −0.008876 −0.013903 −0.345788
    2495 0.023159 −0.11675 −0.103801
    2501 0.024313 −0.133841 −0.10317
    2517 0.010041 −0.026346 −0.284518
    2541 0.001637 −0.123709 −0.165061
    2555 0.009862 −0.295888 −0.195271
    2561 0.003441 0.143297 0.393623
    2563 −0.001684 −0.157035 −0.180935
    2567 0.018774 0.481516 0.617251
    2580 0.001717 0.072093 0.449871
    2584 −0.108511 0.237285 0.358945
    2591 −0.014377 0.016583 0.170925
    2599 −0.004314 0.138559 −0.449886
    2603 0.011638 −0.148946 −0.141157
    2606 −0.008722 −0.002843 −0.263652
    2612 0.006823 −0.083968 −0.181774
    2627 0.033377 −0.002066 −0.307558
    2631 −0.091338 −0.170022 −1.015137
    2637 0.000709 −0.02223 −0.36686
    2654 −0.018035 −0.080645 −0.380195
    2659 0.022976 0.537017 0.816212
    2664 −0.002476 −0.035144 −0.354387
    2696 0.061699 0.295673 0.624181
    2698 −0.008783 −0.162188 −0.319096
    2699 0.021373 −0.029099 −0.143444
    2700 0.004112 0.278744 0.204271
    2707 0.014731 −0.005959 −0.192094
    2750 0.007282 −0.224306 −0.335665
    2769 −0.085357 0.275787 −0.772084
    2772 0.017216 −0.120145 −0.343286
    2775 −0.011673 0.769212 0.451896
    2810 0.004075 −0.190069 −0.240619
    2811 0.009903 −0.176453 −0.085968
    2813 0.003336 0.202659 0.191714
    2815 0.006303 0.092394 0.150836
    2824 0.00192 −0.131874 −0.166371
    2835 0.020297 −0.126422 −0.206971
    2856 0.006157 −0.130875 −0.287515
    2864 −0.012584 0.112957 0.202569
    2865 0.002638 −0.150304 −0.265439
    2868 −0.002354 0.025594 0.276877
    2873 −0.003375 −0.040933 −0.559433
    2891 0.012968 0.26685 0.212612
    2897 −0.004267 0.32308 0.463093
    2905 −0.045096 −0.397135 −0.859917
    2926 −0.005235 0.098392 0.200836
    2931 0.024967 0.193228 0.410268
    2936 0.024484 −0.182182 −0.112346
    2938 0.01805 −0.289863 −0.273244
    2946 0.005996 −0.125692 −0.084214
    2964 0.019559 −0.127505 −0.385534
    2965 0.007544 −0.131222 −0.15763
    2972 −0.062089 0.082359 0.199472
    2973 0.003145 0.146062 0.413226
    2976 0.007741 0.072786 −0.299474
    2981 −0.018057 −0.15181 −0.335472
    2995 0.012536 −0.169059 −0.090252
    3004 −0.004586 0.054952 0.213188
    3014 0.005466 −0.153481 −0.203641
    3022 0.015475 −0.112142 −0.208532
    3059 −0.014859 0.269937 0.241767
    3079 −0.011007 −0.20423 −0.516356
    3085 −0.007467 −0.154645 −0.263535
    3094 0.009534 −0.137767 −0.14642
    3105 0.023282 0.325101 0.254346
    3120 0.0307 0.350781 −0.241198
    3130 0.009997 −0.13136 −0.143976
    3132 0.011847 −0.085343 −0.251605
    3161 0.008344 −0.156984 −0.187369
    3185 −0.011662 0.324166 0.476811
    3194 0.002083 0.14088 0.284904
    3211 0.004157 0.206272 0.386628
    3214 0.025459 0.102741 0.240957
    3215 0.00353 −0.064073 −0.167793
    3228 0.017223 −0.161965 −0.0726
    3237 0.002668 −0.009235 0.21907
    3245 −0.039738 −0.344767 −0.512409
    3269 −0.033522 −0.404287 −0.588228
    3279 −0.059744 0.264262 0.389371
    3288 −0.001709 −0.176379 −0.380142
    3328 −0.001545 0.072595 0.2077
    3337 0.01359 0.244776 0.208125
    3338 −0.020347 −0.138845 −0.506552
    3341 −0.049209 −0.011969 −0.419139
    3356 0.023516 −0.13485 −0.110476
    3357 0.000456 −0.135074 −0.091856
    3380 −0.012204 −0.399725 −0.454969
    3387 0.008267 0.330665 0.191095
    3390 −0.002049 0.248303 0.32703
    3395 −0.006382 −0.249059 −0.201365
    3402 −0.084896 0.054938 0.463716
    3416 −0.039529 −0.201668 −0.578439
    3420 −0.000395 −0.09677 −0.20635
    3423 0.012558 0.087882 0.242394
    3426 0.01107 0.146821 −0.432986
    3443 −0.015748 −0.058532 −0.400899
    3444 −0.017838 0.112361 0.21707
    3470 0.01235 0.202663 0.425686
    3473 0.007791 0.222727 0.486992
    3477 −0.007804 −0.012007 0.180183
    3496 −0.078914 0.88838 0.619244
    3516 −0.03045 −0.252169 −0.485051
    3522 0.014247 0.255693 0.387975
    3549 0.012122 1.072368 0.652041
    3560 0.010452 0.067171 0.167825
    3569 0.008055 0.236448 0.463364
    3571 0.012994 −0.148049 −0.087744
    3579 0.004924 −0.17069 −0.122234
    3585 −0.001411 0.203954 0.124424
    3594 0.022686 −0.159764 −0.113605
    3595 0.00889 0.778268 0.724542
    3627 −0.018961 −0.122255 −0.455286
    3649 −0.00753 −0.075377 −0.245985
    3655 −0.009543 −0.030372 0.280245
    3658 0.010488 −0.100563 −0.316822
    3662 −0.021261 −0.177479 −0.164925
    3678 −0.018901 −0.069804 −0.40405
    3689 0.008179 0.111666 0.212243
    3715 0.000597 0.19448 0.237315
    3720 0.006975 0.316981 −0.554667
    3724 −0.006756 0.02331 −0.392742
    3727 −0.023638 −0.142935 −0.651747
    3749 0.01003 0.043979 0.215776
    3751 0.029168 −0.073576 −0.140182
    3754 0.001496 0.107186 0.165913
    3755 −0.021919 0.195442 0.379175
    3774 0.008601 0.081842 0.189429
    3781 −0.027603 −0.124679 −0.389211
    3795 −0.009508 −0.235417 −0.340756
    3848 0.008156 −0.137025 −0.091425
    3853 0.00189 −0.145487 −0.229147
    3854 −0.009932 −0.323309 −0.627916
    3865 −0.006782 0.081835 0.099887
    3869 0.026028 −0.164373 −0.08952
    3874 0.002977 0.004837 −0.354182
    3878 −0.00536 −0.135863 −0.293698
    3908 0.01371 −0.080601 −0.140019
    3938 0.005563 −0.114606 −0.098469
    3941 0.018012 0.177639 0.090444
    3955 −0.019735 −0.159647 −0.33003
  • TABLE 2b
    progression genes
    SEQ ID NO log(ratio) CP log(ratio) AP log(ratio) BC
    3925 0.003797 −0.153433 −0.114664
  • Table 3 lists the “top ten” genes that are associated with progression and response, independent of normal CD34+ expression, based on log 10 ratio of expression compared to the chronic phase pool. These genes are identified by their SEQ ID NOs in Table 3. Information for these genes is presented in Table 8.
  • TABLE 3
    “top ten” genes
    SEQ
    ID NO log(ratio) CP log(ratio) AP log(ratio) BC REGULATION
    902 0 0 0.599663 up
    984 0 0 −0.77846 down
    1334 0 0 −0.94289 down
    1756 0 0 −0.78849 down
    1813 0 0 −0.85091 down
    1973 0 0 −0.79673 down
    2056 0 0 −1.01514 down
    2211 0 0 −0.82401 down
    2561 0 0 0.686131 up
    2810 0 0 −0.85992 down
    2813 0 0 0.652041 up
    2815 0 0 0.816212 up
    2824 0 0 −1.14209 down
    2864 0 0 0.651561 up
    2973 0 0 0.746645 up
    3085 0 0 −0.85537 down
    3211 0 0 0.617251 up
    3477 0 0 0.619244 up
    3749 0 0 0.703125 up
    3941 0 0 0.659891 up
  • Table 4 lists a set of 228 genes associated with imatinib resistance (the “imatinib resistance genes”). The imatinib resistance genes are identified by their SEQ ID NOs in Table 4. Information for these genes is presented in Table 8. Table 4 also listed for each gene the log ratio of expression level of the gene in samples from patients of a particular phase (e.g., CP, AP, or BC) or IM resistance (IM) versus expression level of the gene in a pool of CML bone marrow samples from chronic phase patients. Each log ratio column thus contains expression levels of markers for a particular phase or IM resistance.
  • TABLE 4
    genes associated with imatinib resistance
    SEQ ID NO log(ratio) CP log(ratio) AP log(ratio) BC log(ratio) IM
    20 0 0 −0.38709 0.263887
    28 0 0 −0.01912 0.265124
    50 0 0 0.04967 0.383703
    72 0 0 −0.03184 0.248668
    77 0 0 −0.1097 0.230979
    91 0 0 −0.21363 0.302135
    93 0 0 0.012872 0.248989
    97 0 0 0.084015 0.441542
    124 0 0 0.230888 0.535462
    134 0 0 −0.03703 0.179006
    150 0 0 −0.0693 0.172068
    155 0 0 −0.13679 0.157108
    171 0 0 0.196959 0.633551
    195 0 0 0.02123 0.207227
    243 0 0 0.11112 0.695707
    254 0 0 −0.08112 0.269401
    269 0 0 −0.03573 0.298949
    275 0 0 −0.15251 0.212305
    283 0 0 −0.03596 0.21647
    292 0 0 0.20614 0.549719
    342 0 0 0.208194 0.677793
    371 0 0 −0.06027 0.449786
    372 0 0 −0.02106 0.351234
    377 0 0 −0.16901 0.161438
    386 0 0 −0.07531 0.180776
    406 0 0 −0.06767 0.371699
    426 0 0 −0.05036 0.281576
    442 0 0 −0.14473 0.198718
    456 0 0 −0.05428 0.215394
    459 0 0 −0.03202 0.345771
    469 0 0 −0.18903 0.227286
    480 0 0 0.038217 0.684655
    531 0 0 −0.17195 0.414879
    568 0 0 −0.06414 0.098452
    622 0 0 −0.40798 0.833497
    662 0 0 −0.00884 0.217496
    663 0 0 −0.09438 0.107198
    670 0 0 −0.17245 0.1338
    709 0 0 0.187456 0.553818
    722 0 0 −0.11073 0.162124
    768 0 0 −0.10115 0.42413
    785 0 0 0.219511 0.690758
    796 0 0 −0.12656 0.145981
    856 0 0 −0.01924 0.400575
    880 0 0 −0.10236 0.278475
    894 0 0 −0.02732 0.206984
    917 0 0 −0.25561 0.212912
    924 0 0 0.224269 0.708077
    973 0 0 −0.01275 0.730765
    977 0 0 −0.10317 0.400818
    980 0 0 −0.1785 0.286644
    1008 0 0 −0.10928 0.108172
    1014 0 0 0.148244 0.865065
    1023 0 0 0.098335 0.878985
    1037 0 0 −0.33476 0.837053
    1038 0 0 −0.20627 0.621468
    1052 0 0 −0.2069 0.236861
    1059 0 0 0.148036 0.402311
    1074 0 0 −0.33264 0.239842
    1089 0 0 0.174284 0.985452
    1095 0 0 0.304656 0.927005
    1124 0 0 −0.07093 0.616113
    1143 0 0 −0.18175 0.201291
    1157 0 0 −0.18174 0.21747
    1170 0 0 −0.08377 0.431166
    1173 0 0 −0.09515 0.560044
    1182 0 0 −0.45446 0.142546
    1190 0 0 0.041007 0.359776
    1215 0 0 −0.06781 0.83596
    1219 0 0 −0.07224 0.165806
    1224 0 0 −0.05776 0.205308
    1247 0 0 −0.08694 0.185421
    1249 0 0 0.263515 0.605748
    1267 0 0 0.263464 1.063745
    1323 0 0 −0.2206 0.10102
    1329 0 0 −0.00537 0.436924
    1331 0 0 −0.01409 0.755256
    1336 0 0 −0.15667 0.34331
    1367 0 0 −0.3207 0.489696
    1379 0 0 −0.17026 0.205201
    1389 0 0 0.079937 0.359209
    1435 0 0 0.092179 0.722108
    1449 0 0 −0.467 0.171956
    1451 0 0 0.425181 0.859676
    1478 0 0 −0.152 0.122073
    1482 0 0 0.111952 0.395553
    1494 0 0 −0.16752 0.177726
    1526 0 0 −0.15569 0.166092
    1534 0 0 0.10057 0.802351
    1549 0 0 −0.01958 0.262207
    1566 0 0 −0.07228 0.314048
    1591 0 0 0.253125 0.761339
    1657 0 0 −0.02703 0.334287
    1671 0 0 −0.13532 0.128801
    1708 0 0 −0.03956 0.206351
    1709 0 0 0.265264 0.510844
    1731 0 0 −0.16089 0.119466
    1789 0 0 −0.28125 0.246382
    1820 0 0 −0.42872 0.604742
    1839 0 0 −0.01985 0.652489
    1840 0 0 0.057241 0.774482
    1898 0 0 −0.39467 0.378527
    1948 0 0 0.082745 0.793455
    1949 0 0 −0.18208 0.868135
    1959 0 0 −0.22455 0.344545
    1965 0 0 −0.26522 0.569866
    2012 0 0 −0.35247 0.31479
    2033 0 0 0.040006 0.345342
    2073 0 0 0.039277 0.877752
    2081 0 0 −0.05539 0.149592
    2087 0 0 −0.29516 0.404949
    2088 0 0 −0.02581 0.326797
    2106 0 0 −0.23592 0.332507
    2126 0 0 −0.02439 0.515267
    2145 0 0 −0.2559 0.725553
    2151 0 0 −0.01135 0.414351
    2172 0 0 −0.08199 0.39351
    2178 0 0 −0.26619 0.102312
    2181 0 0 −0.06055 0.158135
    2183 0 0 0.223605 0.977949
    2189 0 0 0.216936 1.068883
    2199 0 0 −0.27714 0.840265
    2207 0 0 −0.29681 0.440807
    2228 0 0 −0.05689 0.930733
    2244 0 0 −0.37335 0.576383
    2269 0 0 −0.17482 0.171115
    2285 0 0 −0.05323 0.923962
    2286 0 0 −0.11188 0.142335
    2289 0 0 −0.31747 0.354229
    2292 0 0 0.437319 0.959855
    2354 0 0 −0.06186 0.222863
    2387 0 0 −0.60522 0.324344
    2388 0 0 −0.11786 0.725499
    2408 0 0 0.27178 0.449011
    2427 0 0 −0.0812 0.174195
    2437 0 0 0.027895 1.082811
    2449 0 0 0.012028 0.297163
    2479 0 0 −0.22582 0.179989
    2492 0 0 −0.25009 0.349156
    2531 0 0 0.07276 0.662312
    2545 0 0 0.021603 0.945236
    2553 0 0 −0.01276 0.395767
    2564 0 0 −0.28345 0.250146
    2568 0 0 −0.10977 0.19616
    2582 0 0 0.253015 0.634172
    2615 0 0 0.128864 1.013705
    2618 0 0 −0.2905 0.559533
    2629 0 0 −0.06243 0.410775
    2633 0 0 −0.41692 0.392893
    2652 0 0 0.205031 0.647252
    2653 0 0 −0.00396 0.377357
    2660 0 0 −0.53433 0.393617
    2665 0 0 0.062554 0.686441
    2666 0 0 0.017231 0.276612
    2686 0 0 0.074055 0.352962
    2697 0 0 0.142879 0.722647
    2756 0 0 0.033883 0.281303
    2780 0 0 −0.43199 0.457222
    2802 0 0 0.032077 0.248953
    2807 0 0 0.088818 0.865409
    2828 0 0 0.375805 0.936957
    2844 0 0 −0.10182 0.193285
    2879 0 0 −0.11063 0.376181
    2896 0 0 −0.12602 0.433851
    2942 0 0 0.038329 0.261638
    2955 0 0 0.337985 0.616413
    2977 0 0 0.006318 0.640784
    2980 0 0 −0.06256 0.752042
    2984 0 0 −0.0839 0.535325
    2989 0 0 −0.04767 0.23291
    2994 0 0 −0.12413 0.24541
    3004 0 0 −0.22221 0.402371
    3015 0 0 −0.38468 0.767185
    3040 0 0 −0.15874 0.553807
    3051 0 0 −0.16014 0.258388
    3095 0 0 −0.23449 0.453399
    3145 0 0 0.046709 0.349592
    3149 0 0 −0.07479 0.13184
    3172 0 0 −0.09216 0.235379
    3178 0 0 −0.16051 0.189495
    3181 0 0 −0.18123 0.657828
    3183 0 0 −0.08563 0.644291
    3234 0 0 −0.09319 0.622993
    3239 0 0 −0.15225 0.543178
    3263 0 0 −0.09885 0.51508
    3267 0 0 −0.0802 0.247087
    3272 0 0 −0.06519 0.20193
    3284 0 0 −0.39928 0.564677
    3317 0 0 0.042257 0.663222
    3324 0 0 −0.0387 0.202691
    3334 0 0 −0.14218 0.402162
    3342 0 0 0.094368 0.377785
    3360 0 0 −0.18153 0.352019
    3370 0 0 −0.07291 0.154629
    3373 0 0 0.266208 1.01143
    3378 0 0 0.154822 0.471737
    3389 0 0 0.096215 0.292396
    3402 0 0 0.166222 0.929501
    3433 0 0 −0.08958 0.164089
    3476 0 0 −0.02612 0.185903
    3479 0 0 −0.23806 0.307206
    3482 0 0 0.017378 0.267581
    3546 0 0 0.071637 0.321201
    3554 0 0 −0.10865 0.21563
    3620 0 0 −0.18183 0.230787
    3632 0 0 0.04804 0.247622
    3677 0 0 −0.14473 0.201314
    3683 0 0 0.00301 0.2633
    3686 0 0 −0.03852 0.375431
    3692 0 0 −0.59334 0.407906
    3711 0 0 −0.07697 0.1336
    3725 0 0 −0.1157 0.688963
    3746 0 0 −0.09686 0.406243
    3765 0 0 −0.38459 0.568063
    3785 0 0 −0.02761 0.586677
    3793 0 0 −0.01682 0.432956
    3800 0 0 0.093978 0.693084
    3804 0 0 0.149344 0.963817
    3812 0 0 0.078875 0.719019
    3836 0 0 0.245725 0.62927
    3876 0 0 −0.10377 0.245747
    3891 0 0 0.056743 0.30804
    3905 0 0 −0.18947 0.77305
    3935 0 0 −0.1837 0.688495
    3939 0 0 −0.13203 0.177443
    3946 0 0 −0.57596 0.119957
    3966 0 0 −0.14854 0.290791
  • Tables 5a and 5b list 386 target genes, which are differentially expressed between CML blast crisis and normal immature CD34+ cells (p<0.1%) (the “target geneset”). The target genes are identified by their SEQ ID NOs in Tables 5a and 5b. Information for these genes is presented in Table 8. Table 5a lists target genes that that were not disclosed in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Table 5b lists target genes that were also identified in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003.
  • TABLE 5a
    CML target genes
    SEQ ID NO
    2
    8
    51
    74
    88
    99
    105
    109
    116
    142
    146
    158
    174
    184
    185
    191
    204
    246
    252
    261
    267
    298
    309
    312
    321
    337
    343
    359
    365
    370
    379
    390
    393
    432
    444
    483
    490
    493
    494
    495
    503
    506
    522
    562
    564
    565
    571
    576
    596
    600
    602
    605
    607
    615
    628
    629
    631
    638
    644
    659
    664
    665
    675
    676
    688
    700
    701
    727
    728
    730
    741
    745
    759
    766
    781
    788
    790
    809
    813
    843
    840
    841
    845
    847
    873
    878
    884
    900
    902
    906
    908
    915
    934
    960
    962
    983
    1000
    1012
    1014
    1020
    1027
    1036
    1051
    1054
    1067
    1089
    1093
    1106
    1112
    1132
    1138
    1140
    1145
    1158
    1160
    1161
    1164
    1165
    1183
    1188
    1197
    1202
    1223
    1245
    1254
    1288
    1300
    1306
    1308
    1311
    1325
    1331
    1334
    1346
    1352
    1380
    1400
    1409
    1410
    1411
    1415
    1416
    1440
    1441
    1446
    1452
    1456
    1464
    1472
    1489
    1495
    1500
    1502
    1503
    1522
    1527
    1532
    1534
    1575
    1596
    1608
    1614
    1643
    1652
    1674
    1689
    1711
    1712
    1713
    1724
    1728
    1756
    1757
    1762
    1767
    1772
    1781
    1785
    1798
    1799
    1800
    1802
    1803
    1813
    1828
    1849
    1870
    1873
    1893
    1910
    1926
    1927
    1944
    1990
    1991
    1998
    2007
    2011
    2023
    2032
    2040
    2042
    2056
    2064
    2082
    2085
    2101
    2104
    2136
    2161
    2162
    2174
    2188
    2200
    2206
    2211
    2212
    2213
    2218
    2224
    2248
    2252
    2253
    2266
    2279
    2304
    2310
    2312
    2313
    2320
    2329
    2356
    2372
    2388
    2406
    2442
    2454
    2462
    2469
    2479
    2505
    2525
    2534
    2554
    2561
    2563
    2565
    2567
    2591
    2600
    2631
    2632
    2649
    2654
    2658
    2664
    2665
    2670
    2676
    2696
    2699
    2721
    2726
    2734
    2739
    2766
    2775
    2777
    2788
    2810
    2824
    2825
    2830
    2842
    2862
    2863
    2864
    2892
    2894
    2900
    2903
    2921
    2928
    2938
    2953
    2964
    2967
    2981
    3003
    3019
    3020
    3027
    3029
    3047
    3048
    3067
    3075
    3085
    3093
    3094
    3097
    3103
    3136
    3185
    3191
    3194
    3196
    3215
    3222
    3238
    3240
    3241
    3245
    3248
    3254
    3279
    3312
    3329
    3339
    3348
    3361
    3364
    3373
    3380
    3395
    3396
    3398
    3400
    3402
    3428
    3456
    3462
    3470
    3500
    3514
    3533
    3538
    3555
    3569
    3582
    3583
    3611
    3628
    3640
    3642
    3646
    3650
    3655
    3658
    3685
    3689
    3696
    3718
    3755
    3763
    3792
    3844
    3845
    3849
    3857
    3880
    3901
    3915
    3937
    3940
    3955
  • TABLE 5b
    CML target genes
    SEQ ID NO log(ratio) BC
    1776 0
    3961 0
  • Genes that are not listed in Table 1a or 1b but which are functional equivalents of any gene listed in Table 1a or 1b can also be used with or in place of the gene listed in the table. A functional equivalent of a gene A refers to a gene that encodes a protein or mRNA that at least partially overlaps in physiological function in the cell to that of the protein or mRNA of gene A.
  • In various specific embodiments, different numbers and subcombinations of the genes listed in Tables 1a and/or 1b are selected as the marker set, whose profile is used in the methods of the invention, as described in Section 5.2., infra. In various embodiments, all or a subset of those genes listed in each of Tables 2a and/or 2b or Table 3, supra, or their respective functional equivalents are used.
  • In one embodiment, one or more genes that cluster together with one or more genes listed in a table can be selected to represent the cluster such that the marker set contains genes representing a plurality of different clusters.
  • In a specific embodiment, measurements of gene products of the genes, respectively, shown in Tables 2a and/or 2b, or their respective functional equivalents, are used for CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100 or 200 of the genes listed in Tables 2a and/or 2b are used.
  • In another embodiment, measurements of the gene products of the set of 20 genes shown in Table 3 (which is a subset of the genes listed in Table 2a and Table 5a) or their respective functional equivalents are used CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 10, 15 or 20 of the genes listed in Table 3 are used.
  • In another embodiment, measurements of the gene products of the set of 10 up-regulated genes shown in Table 3 or their respective functional equivalents are used CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 6, 7, 8, 9 or all 10 of the up-regulated genes listed in Table 3 are used.
  • In another embodiment, measurements of the gene products of the set of 10 down-regulated genes shown in Table 3 or their respective functional equivalents are used CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 6, 7, 8, 9 or all 10 of the down-regulated genes listed in Table 3 are used.
  • In still another embodiment, measurements of the genes, respectively, shown in Table 4 or their respective functional equivalents are used for determining imatinib resistance in a patient. In a particular embodiment, measurements of gene products of all or at least 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100 or 200 of the genes listed in Table 4 are used. In a specific embodiment, imatinib resistance is determined according to the measurements of gene products of all or at least 5, 6, 7, or 8 of the genes selected from the group consisting of serine threonine kinases CTRL, MAP21K14, CLK3, MAP kinase MKNK2, the tyrosine kinase oncogene FYN, TCF7 (a putatively T cell specific transcription factor), guanine nucleotide binding proteins GNAZ and GNG11, and the MAF.
  • The invention also provides sets of promoter controlled genes, measurements of which can be used for evaluating the progression of CML in a patient. In one embodiment, measurements of the gene products of genes that are controlled by one or more of the promoters shown in Table 6 or their respective functional equivalents are used for evaluating CML progression. In a particular embodiment, measurements of gene products controlled by a promoter selected from the group consisting of set of promoters shown in Table 6 or their respective functional equivalents are used.
  • TABLE 6
    Promoters associated with CML progression
    EXPEC-
    PROMOTER P-VALUE TATION SOURCE SPECIES
    MZF_1-4 0 0 Genes with common Homo
    promoter sites sapiens
    S8 1.22E−12 7.69E−11 Genes with common Homo
    promoter sites sapiens
    deltaEF1 5.87E−11 3.70E−09 Genes with common Homo
    promoter sites sapiens
    SPI-B 1.48E−10 9.35E−09 Genes with common Homo
    promoter sites sapiens
    Yin-Yang 1.48E−09 9.30E−08 Genes with common Homo
    promoter sites sapiens
    Ahr-ARNT 1.60E−09 1.01E−07 Genes with common Homo
    promoter sites sapiens
    MZF_5-13 1.26E−06 7.96E−05 Genes with common Homo
    promoter sites sapiens
    c-MYB_1 5.10E−06 0.000321 Genes with common Homo
    promoter sites sapiens
  • The invention provides methods for identifying a set of genes for evaluating stage/progression of CML. The methods make use of measured expression profiles of a plurality of genes (e.g., measurements of abundance levels of the corresponding gene products) in bone marrow or blood samples from a plurality of patients whose CML stage/progression status are known. As used herein, a patient is animal inflicted with CML. The patient can be but is not limited to a human, or, in a veterinary context, from non-human animals such as ruminants, horses, swine or sheep, or from domestic companion animals such as felines and canines. In one embodiment, for each of the plurality of genes a metric of correlation between expression level of the gene and survival outcome in the plurality of CML patients is determined. One or more genes are then selected based on their metrics of correlation.
  • Progression markers can be obtained by identifying genes whose expression levels are significantly different across CML patients of different phases of CML. In preferred embodiments, genes whose expression levels exhibit differences across different phrase groups to at least a predetermined level are selected as the genes whose expression levels correlate with CML phases. In one embodiment, the expression level differences among patients of different CML phases are evaluated using ANOVA. In one embodiment, a gene is selected if the p-value of the gene corresponds to a predetermined significance level, e.g., a p-value less than 10−11.
  • The invention also provides a computer system comprising a processor, and a memory coupled to said processor and encoding one or more programs, wherein said one or more programs cause the processor to carry out a method described above.
  • The invention also provides a computer program product for use in conjunction with a computer having a processor and a memory connected to the processor, said computer program product comprising a computer readable storage medium having a computer program mechanism encoded thereon, wherein said computer program mechanism may be loaded into the memory of said computer and cause said computer to carry out a method described above.
    • 5.2. Methods of Evaluating CML Progression and Responses
  • The invention provides methods for determining the stage or progression status in a CML patient using a measured marker profile comprising measurements of the gene products of genes, e.g., the sets of genes described in Section 5.1., supra.
    • 5.2.1. Methods for Evaluating Progression Based on Expression Profiles
  • In preferred embodiments, the methods of the invention use a progression classifier, also called a classifier, for predicting CML progression and/or responsiveness to imatinib mesylate in a patient. The progression classifier can be based on any appropriate pattern recognition method that receives an input comprising a marker profile and provides an output comprising data indicating which phase the patient belongs. The progression classifier can be trained with training data from a training population of CML patients. Typically, the training data comprise for each of the CML patients in the training population a training marker profile comprising measurements of respective gene products of a plurality of genes in a suitable sample taken from the patient and CML progression information. In a preferred embodiment, the training population comprises patients from each of the different stages of CML, i.e., CP-CML, ADV-CML, or AP-CML and BC-CML. In another preferred embodiment, the training population comprises patients from each of the different IM response groups, i.e., IM resistant and IM responsive.
  • In preferred embodiments, the progression classifier can be based on a classification (pattern recognition) method described below, e.g., profile similarity (Section 5.2.1.1., infra); artificial neural network (Section 5.2.1.2., infra); support vector machine (SVM, Section 5.2.1.3., infra); logic regression (Section 5.2.1.4., infra), linear or quadratic discriminant analysis (Section 5.2.1.5., infra), decision trees (Section 5.2.1.6., infra), clustering (Section 5.2.1.7., infra), principal component analysis (Section 5.2.1.8., infra), nearest neighbor classifier analysis (Section 5.2.1.9., infra). Such progression classifiers can be trained with the training population using methods described in the relevant sections, infra.
  • The marker profile can be obtained by measuring the plurality of gene products in a CML cell sample from the patient using a method known in the art, e.g., a method described in Section 5.2.4-5.2.5., infra.
  • Various known statistical pattern recognition methods can be used in conjunction with the present invention. A progression classifier based on any of such methods can be constructed using the marker profiles and progression data of training patients. Such a progression classifier can then be used to evaluate the progression status of a CML patient based on the patient's marker profile. The methods can also be used to identify markers that discriminate between different progression status and/or imatinib resistance using a marker profile and progression and/or imatinib resistance data of training patients. For simplicity, the methods are often discussed with respect to evaluation of the progression status. It will be understood by a person skilled in the art that the methods are equally applicable to evaluation of IM responsiveness.
    • 5.2.1.1. Profile Matching
  • A patient's CML stage or progression status can be evaluated by comparing a marker profile obtained in a suitable sample from the patient with a marker profile that is representative of a particular CML phase. Such a marker profile is also termed a “template profile” or a “template.” The degree of similarity to such a template profile provides an evaluation of the patient's CML stage or progression status. If the degree of similarity of the patient marker profile and a template profile is above a predetermined threshold, the patient is assigned a CML phase or progression status represented by the template. For example, a patient's CML stage or progression status can be evaluated by comparing a marker profile of the patient to a predetermined template profile corresponding to a certain CML stage or progression status, e.g., an ADV-CML template comprising measurements of the plurality of markers which are representative of levels of the markers in a plurality of advanced phase patients or a CP-CML template comprising measurements of the plurality of markers which are representative of levels of the markers in a plurality of chronic phase patients.
  • In one embodiment, the similarity is represented by a correlation coefficient between the patient's profile and the template. In one embodiment, a correlation coefficient above a correlation threshold indicates a high similarity, whereas a correlation coefficient below the threshold indicates a low similarity.
  • In a specific embodiment, Pi measures the similarity between the patient's profile {right arrow over (y)} and a template profile, e.g., a template profile comprising measurements of marker gene products representative of measurements of marker gene products of a level of progression of CML, e.g., the CP-CML template {right arrow over (z)}CP or the ADV-CML template {right arrow over (z)}ADV. Such a coefficient, Pi, can be calculated using the following equation:

  • P i=({right arrow over (z)} i ·{right arrow over (y)})/(∥{right arrow over (z)} i ∥·∥{right arrow over (y)}∥)
  • where i designates the ith template. For example, i is CP for CP-CML template. Thus, in one embodiment, {right arrow over (y)} is classified as a CP-CML profile if PCP is greater than a selected correlation threshold. In another embodiment, {right arrow over (y)} is classified as an ADV-CML profile if PADV is greater than a selected correlation threshold. In preferred embodiments, the correlation threshold is set as 0.3, 0.4, 0.5 or 0.6. In another embodiment, {right arrow over (y)} is classified as a CP-CML profile if PCP is greater than PADV, whereas {right arrow over (y)} is classified as a ADV-CML profile if PCP is less than PADV.
  • In another embodiment, the correlation coefficient is a weighted dot product of the patient's profile {right arrow over (y)} and a template profile, in which measurements of each different marker is assigned a weight.
  • In another embodiment, similarity between a patient's profile and a template is represented by a distance between the patient's profile and the template. In one embodiment, a distance below a given value indicates high similarity, whereas a distance equal to or greater than the given value indicates low similarity.
  • In one embodiment, the Euclidian distance according to the formula

  • D i =∥{right arrow over (y)}−{right arrow over (z)} i∥
  • is used, where Di measures the distance between the patient's profile {right arrow over (y)} and a template profile comprising measurements of marker gene products representative of measurements of marker gene products of a level of progression of CML, e.g., the CP-CML template {right arrow over (z)}CP, the ADV-CML template {right arrow over (z)}ADV or the AP-CML template {right arrow over (z)}AP or BC-CML template {right arrow over (z)}Bc. In other embodiments, the Euclidian distance is squared to place progressively greater weight on cellular constituents that are further apart. In alternative embodiments, the distance measure Di is the Manhattan distance provide by
  • D i = ∑ n y ( n ) - z i ( n )
  • where y(n) and zi(n) are respectively measurements of the nth marker gene product in the patient's profile {right arrow over (y)} and a template profile.
  • In another embodiment, the distance is defined as Di=1−Pi where Pi is the correlation coefficient or normalized dot product as described above.
  • In still other embodiments, the distance measure may be the Chebychev distance, the power distance, and percent disagreement, all of which are well known in the art.
  • A distance based similarity measure is particularly useful for classifying advanced phase CML patients as either AP-CML or BC-CML since the marker profiles of AP-CML and BC-CML differ from each other in a quantitative rather than qualitative manner. Thus, in one embodiment, the invention provides a method for classifying an advanced phase CML patient as either AP-CML or BC-CML by comparing the distances between a marker profile of the patient with an AP-CML template and a BC-CML template, and classifying the patient as either AP-CML or BC-CML if the distance to the corresponding template is smaller.
  • A person skilled in the art would understand that the above described methods can be applied to expression profiles of IM resistance genes for evaluation of IM responsiveness. For example, the methods can be used to compare a patient expression profile to IM resistance template and IM responsive template by calculating a Pi measuring the similarity between the patient's profile {right arrow over (y)} and the IM resistance template comprising measurements of marker gene products representative of measurements of marker gene products in IM resistant patients, {right arrow over (z)}resist, and/or IM responsive template comprising measurements of marker gene products representative of measurements of marker gene products in IM responsive patients, {right arrow over (z)}resp. Such a coefficient, Pi, can be calculated using the equation described above.
    • 5.2.1.2. Artificial Neural Network
  • In some embodiments, a neural network is used to classify a patient marker profile. The neural network takes the patient marker profile as an input and generates an output comprising the progression status and/or IM responsiveness. A neural network can be constructed for a selected set of molecular markers of the invention. A neural network is a two-stage regression or classification model. A neural network has a layered structure that includes a layer of input units (and the bias) connected by a layer of weights to a layer of output units. For regression, the layer of output units typically includes just one output unit. However, neural networks can handle multiple quantitative responses in a seamless fashion.
  • In multilayer neural networks, there are input units (input layer), hidden units (hidden layer), and output units (output layer). There is, furthermore, a single bias unit that is connected to each unit other than the input units. Neural networks are described in Duda et al., 2001, Pattern Classification, Second Edition, John Wiley & Sons, Inc., New York; and Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York.
  • The basic approach to the use of neural networks is to start with an untrained network, present a training pattern, e.g., marker profiles from training patients, to the input layer, and to pass signals through the net and determine the output, e.g., the status of progression and/or the status of imatinib resistance in the training patients, at the output layer. These outputs are then compared to the target values; any difference corresponds to an error. This error or criterion function is some scalar function of the weights and is minimized when the network outputs match the desired outputs. Thus, the weights are adjusted to reduce this measure of error. For regression, this error can be sum-of-squared errors. For classification, this error can be either squared error or cross-entropy (deviation). See, e.g., Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York.
  • Three commonly used training protocols are stochastic, batch, and on-line. In stochastic training, patterns are chosen randomly from the training set and the network weights are updated for each pattern presentation. Multilayer nonlinear networks trained by gradient descent methods such as stochastic back-propagation perform a maximum-likelihood estimation of the weight values in the model defined by the network topology. In batch training, all patterns are presented to the network before learning takes place. Typically, in batch training, several passes are made through the training data. In online training, each pattern is presented once and only once to the net.
  • In some embodiments, consideration is given to starting values for weights. If the weights are near zero, then the operative part of the sigmoid commonly used in the hidden layer of a neural network (see, e.g., Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York) is roughly linear, and hence the neural network collapses into an approximately linear model. In some embodiments, starting values for weights are chosen to be random values near zero. Hence the model starts out nearly linear, and becomes nonlinear as the weights increase. Individual units localize to directions and introduce nonlinearities where needed. Use of exact zero weights leads to zero derivatives and perfect symmetry, and the algorithm never moves. Alternatively, starting with large weights often leads to poor solutions.
  • Since the scaling of inputs determines the effective scaling of weights in the bottom layer, it can have a large effect on the quality of the final solution. Thus, in some embodiments, at the outset all expression values are standardized to have mean zero and a standard deviation of one. This ensures all inputs are treated equally in the regularization process, and allows one to choose a meaningful range for the random starting weights. With standardization inputs, it is typical to take random uniform weights over the range [−0.7, +0.7].
  • A recurrent problem in the use of networks having a hidden layer is the optimal number of hidden units to use in the network. The number of inputs and outputs of a network are determined by the problem to be solved. In the present invention, the number of inputs for a given neural network can be the number of molecular markers in the selected set of molecular markers of the invention. The number of output for the neural network will typically be just one. However, in some embodiment more than one output is used so that more than just two states can be defined by the network. If too many hidden units are used in a neural network, the network will have too many degrees of freedom and is trained too long, there is a danger that the network will overfit the data. If there are too few hidden units, the training set cannot be learned. Generally speaking, however, it is better to have too many hidden units than too few. With too few hidden units, the model might not have enough flexibility to capture the nonlinearities in the data; with too many hidden units, the extra weight can be shrunk towards zero if appropriate regularization or pruning, as described below, is used. In typical embodiments, the number of hidden units is somewhere in the range of 5 to 100, with the number increasing with the number of inputs and number of training cases.
  • One general approach to determining the number of hidden units to use is to apply a regularization approach. In the regularization approach, a new criterion function is constructed that depends not only on the classical training error, but also on classifier complexity. Specifically, the new criterion function penalizes highly complex models; searching for the minimum in this criterion is to balance error on the training set with error on the training set plus a regularization term, which expresses constraints or desirable properties of solutions:

  • J=J pat +λJ reg.
  • The parameter λ is adjusted to impose the regularization more or less strongly. In other words, larger values for λ will tend to shrink weights towards zero: typically cross-validation with a validation set is used to estimate λ. This validation set can be obtained by setting aside a random subset of the training population. Other forms of penalty can also be used, for example the weight elimination penalty (see, e.g., Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York).
  • Another approach to determine the number of hidden units to use is to eliminate—prune—weights that are least needed. In one approach, the weights with the smallest magnitude are eliminated (set to zero). Such magnitude-based pruning can work, but is nonoptimal; sometimes weights with small magnitudes are important for learning and training data. In some embodiments, rather than using a magnitude-based pruning approach, Wald statistics are computed. The fundamental idea in Wald Statistics is that they can be used to estimate the importance of a hidden unit (weight) in a model. Then, hidden units having the least importance are eliminated (by setting their input and output weights to zero). Two algorithms in this regard are the Optimal Brain Damage (OBD) and the Optimal Brain Surgeon (OBS) algorithms that use second-order approximation to predict how the training error depends upon a weight, and eliminate the weight that leads to the smallest increase in training error.
  • Optimal Brain Damage and Optimal Brain Surgeon share the same basic approach of training a network to local minimum error at weight w, and then pruning a weight that leads to the smallest increase in the training error. The predicted functional increase in the error for a change in full weight vector δw is:
  • δ J = ( ∂ J ∂ w ) t · δ w + 1 2 δ w t · ∂ 2 J ∂ w 2 · δ w + O ( δ w 3 )
  • where
  • ∂ 2 J ∂ w 2
  • is the Hessian matrix. The first term vanishes because we are at a local minimum in error; third and higher order terms are ignored. The general solution for minimizing this function given the constraint of deleting one weight is:
  • δ w = - w q [ H - 1 ] qq H - 1 · u q and L q = 1 2 - w q 2 [ H - 1 ] qq
  • Here, uq is the unit vector along the qth direction in weight space and Lq is approximation to the saliency of the weight q—the increase in training error if weight q is pruned and the other weights updated δw. These equations require the inverse of H. One method to calculate this inverse matrix is to start with a small value, H0 −1=α−1I, where α is a small parameter—effectively a weight constant. Next the matrix is updated with each pattern according to
  • H m + 1 - 1 = H m - 1 - H m - 1 X m + 1 X m + 1 T H m - 1 n a m + X m + 1 T H m - 1 x m + 1
  • where the subscripts correspond to the pattern being presented and am decreases with m. After the full training set has been presented, the inverse Hessian matrix is given by H−1=Hn −1. In algorithmic form, the Optimal Brain Surgeon method is:
  •
      begin initialize nH, w, θ
     train a reasonably large network to minimum error
     do compute H−1 by Eqn. 1
       q * ← arg min q w q 2 / ( 2 [ H - 1 ] qq ) ( saliency L q )
       w ← w - w q * [ H - 1 ] q * q * H - 1 e q * ( saliency L q )
      until J(w) > θ
     return w
    end
  • The Optimal Brain Damage method is computationally simpler because the calculation of the inverse Hessian matrix in line 3 is particularly simple for a diagonal matrix. The above algorithm terminates when the error is greater than a criterion initialized to be θ. Another approach is to change line 6 to terminate when the change in J(w) due to elimination of a weight is greater than some criterion value.
  • In some embodiments, a back-propagation neural network (see, for example Abdi, 1994, “A neural network primer”, J. Biol System. 2, 247-283) containing a single hidden layer of ten neurons (ten hidden units) found in EasyNN-Plus version 4.0 g software package (Neural Planner Software Inc.) is used. In a specific example, parameter values within the EasyNN-Plus program are set as follows: a learning rate of 0.05, and a momentum of 0.2. In some embodiments in which the EasyNN-Plus version 4.0 g software package is used, “outlier” samples are identified by performing twenty independently-seeded trials involving 20,000 learning cycles each.
    • 5.2.1.3. Support Vector Machine
  • In some embodiments of the present invention, support vector machines (SVMs) are used to classify subjects using expression profiles of marker genes described in the present invention. The SVM takes the patient marker profile as an input and generates an output comprising the progression status and/or IM responsiveness. General description of SVM can be found in, for example, Cristianini and Shawe-Taylor, 2000, An Introduction to Support Vector Machines, Cambridge University Press, Cambridge, Boser et al., 1992, “A training algorithm for optimal margin classifiers, in Proceedings of the 5th Annual ACM Workshop on Computational Learning Theory, ACM Press, Pittsburgh, Pa., pp. 142-152; Vapnik, 1998, Statistical Learning Theory, Wiley, New York; Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc.; Hastie, 2001, The Elements of Statistical Learning, Springer, N.Y.; and Furey et al., 2000, Bioinformatics 16, 906-914. Applications of SVM in biological applications are described in Jaakkola et al., Proceedings of the 7th International Conference on Intelligent Systems for Molecular Biology, AAAI Press, Menlo Park, Calif. (1999); Brown et al., Proc. Natl. Acad. Sci. 97(1):262-67 (2000); Zien et al., Bioinformatics, 16(9):799-807 (2000); Furey et al., Bioinformatics, 16(10):906-914 (2000)
  • In one approach, when a SVM is used, the gene expression data is standardized to have mean zero and unit variance and the members of a training population are randomly divided into a training set and a test set. For example, in one embodiment, two thirds of the members of the training population are placed in the training set and one third of the members of the training population are placed in the test set. The expression values for a selected set of genes of the present invention is used to train the SVM. Then the ability for the trained SVM to correctly classify members in the test set is determined. In some embodiments, this computation is performed several times for a given selected set of molecular markers. In each iteration of the computation, the members of the training population are randomly assigned to the training set and the test set. Then, the quality of the combination of molecular markers is taken as the average of each such iteration of the SVM computation.
  • Support vector machines map a given set of binary labeled training data to a high-dimensional feature space and separate the two classes of data with a maximum margin hyperplane. In general, this hyperplane corresponds to a nonlinear decision boundary in the input space. Let XεR0 ⊂
    Figure US20120072124A1-20120322-P00001
    n be the input vectors, yε{−1,+1} be the labels, and φ: R0→F be the mapping from input space to feature space. Then the SVM learning algorithm finds a hyperplane (w,b) such that the quantity
  • γ = min i y i { 〈 w , φ ( X i ) 〉 - b }
  • is maximized, where the vector w has the same dimensionality as F, b is a real number, and γ is called the margin. The corresponding decision function is then

  • ƒ(X)=sign(
    Figure US20120072124A1-20120322-P00002
    w,φ(X)
    Figure US20120072124A1-20120322-P00003
    −b)
  • This minimum occurs when
  • w = ∑ i α i y i φ ( X i )
  • where {αi} are positive real numbers that maximize
  • ∑ i α i - ∑ ij α i α j y i y j 〈 φ ( X i ) , φ ( X j ) 〉
  • subject to
  • ∑ i α i y i = 0 , α i > 0
  • The decision function can equivalently be expressed as
  • f ( X ) = sign ( ∑ i α i y i 〈 φ ( X i , φ ( X ) 〉 - b )
  • From this equation it can be seen that the αi associated with the training point Xi expresses the strength with which that point is embedded in the final decision function. A remarkable property of this alternative representation is that only a subset of the points will be associated with a non-zero αi. These points are called support vectors and are the points that lie closest to the separating hyperplane. The sparseness of the α vector has several computational and learning theoretic consequences. It is important to note that neither the learning algorithm nor the decision function needs to represent explicitly the image of points in the feature space, φ(Xi), since both use only the dot products between such images,
    Figure US20120072124A1-20120322-P00002
    φ(Xi),φ(Xj)
    Figure US20120072124A1-20120322-P00003
    . Hence, if one were given a function K(X,Y)=
    Figure US20120072124A1-20120322-P00002
    φ(X),φ(X)
    Figure US20120072124A1-20120322-P00003
    , one could learn and use the maximum margin hyperplane in the feature space without ever explicitly performing the mapping. For each continuous positive definite function K(X,Y) there exists a mapping φ such that K(X,Y)=
    Figure US20120072124A1-20120322-P00002
    φ(X),φ(X)
    Figure US20120072124A1-20120322-P00003
    for all X, YεR0 (Mercer's Theorem). The function K(X,Y) is called the kernel function. The use of a kernel function allows the support vector machine to operate efficiently in a nonlinear high-dimensional feature spaces without being adversely affected by the dimensionality of that space. Indeed, it is possible to work with feature spaces of infinite dimension. Moreover, Mercer's theorem makes it possible to learn in the feature space without even knowing φ and F. The matrix Kij=
    Figure US20120072124A1-20120322-P00002
    φ(Xi),φ(Xj)
    Figure US20120072124A1-20120322-P00003
    is called the kernel matrix. Finally, note that the learning algorithm is a quadratic optimization problem that has only a global optimum. The absence of local minima is a significant difference from standard pattern recognition techniques such as neural networks. For moderate sample sizes, the optimization problem can be solved with simple gradient descent techniques. In the presence of noise, the standard maximum margin algorithm described above can be subject to overfitting, and more sophisticated techniques should be used. This problem arises because the maximum margin algorithm always finds a perfectly consistent hypothesis and does not tolerate training error. Sometimes, however, it is necessary to trade some training accuracy for better predictive power. The need for tolerating training error has led to the development the soft-margin and the margin-distribution classifiers. One of these techniques replaces the kernel matrix in the training phase as follows:

  • K←K+λI
  • while still using the standard kernel function in the decision phase. By tuning λ, one can control the training error, and it is possible to prove that the risk of misclassifying unseen points can be decreased with a suitable choice of λ.
  • If instead of controlling the overall training error one wants to control the trade-off between false positives and false negatives, it is possible to modify K as follows:

  • K←K+λD
  • where D is a diagonal matrix whose entries are either d+ or d−, in locations corresponding to positive and negative examples. It is possible to prove that this technique is equivalent to controlling the size of the αi in a way that depends on the size of the class, introducing a bias for larger αi in the class with smaller d. This in turn corresponds to an asymmetric margin; i.e., the class with smaller d will be kept further away from the decision boundary. In some cases, the extreme imbalance of the two classes, along with the presence of noise, creates a situation in which points from the minority class can be easily mistaken for mislabelled points. Enforcing a strong bias against training errors in the minority class provides protection against such errors and forces the SVM to make the positive examples support vectors. Thus, choosing
  • d + = 1 n + and d - = 1 n -
  • provides a heuristic way to automatically adjust the relative importance of the two classes, based on their respective cardinalities. This technique effectively controls the trade-off between sensitivity and specificity.
  • In the present invention, a linear kernel can be used. The similarity between two marker profiles X and Y can be the dot product X·Y. In one embodiment, the kernel is

  • K(X,Y)=X·Y+1
  • In another embodiment, a kernel of degree d is used

  • K(X,Y)=(X·Y+1)d, where d can be either 2, 3, . . .
  • In still another embodiment, a Gaussian kernel is used
  • K ( X , Y ) = exp ( - X - Y 2 2 σ 2 )
  • where σ is the width of the Gaussian.
    • 5.2.1.4. Logistic Regression
  • In some embodiments, the progression classifier is based on a regression model, preferably a logistic regression model. Such a regression model includes a coefficient for each of the molecular markers in a selected set of molecular markers of the invention. In such embodiments, the coefficients for the regression model are computed using, for example, a maximum likelihood approach. In particular embodiments, molecular marker data from two different clinical groups, e.g., chronic phase and advanced phase or imatinib resistant and imatinib sensitive, is used and the dependent variable is the clinical status of the patient for which molecular marker characteristic data are from.
  • Some embodiments of the present invention provide generalizations of the logistic regression model that handle multicategory (polychotomous) responses. Such embodiments can be used to discriminate an organism into one or three or more clinical groups, e.g., chronic phase, accelerated phase, and blast phase. Such regression models use multicategory logit models that simultaneously refer to all pairs of categories, and describe the odds of response in one category instead of another. Once the model specifies logits for a certain (J-1) pairs of categories, the rest are redundant. See, for example, Agresti, An Introduction to Categorical Data Analysis, John Wiley & Sons, Inc., 1996, New York, Chapter 8, which is hereby incorporated by reference.
    • 5.2.1.5. Discriminant Analysis
  • Linear discriminant analysis (LDA) attempts to classify a subject into one of two categories based on certain object properties. In other words, LDA tests whether object attributes measured in an experiment predict categorization of the objects. LDA typically requires continuous independent variables and a dichotomous categorical dependent variable. In the present invention, the expression values for the selected set of molecular markers of the invention across a subset of the training population serve as the requisite continuous independent variables. The clinical group classification of each of the members of the training population serves as the dichotomous categorical dependent variable.
  • LDA seeks the linear combination of variables that maximizes the ratio of between-group variance and within-group variance by using the grouping information. Implicitly, the linear weights used by LDA depend on how the expression of a molecular marker across the training set separates in the two groups (e.g., a group that has CP-CML and a group that have ADV-CMP) and how this gene expression correlates with the expression of other genes. In some embodiments, LDA is applied to the data matrix of the N members in the training sample by K genes in a combination of genes described in the present invention. Then, the linear discriminant of each member of the training population is plotted. Ideally, those members of the training population representing a first subgroup (e.g. those subjects that have CP-CML) will cluster into one range of linear discriminant values (e.g., negative) and those member of the training population representing a second subgroup (e.g. those subjects that have ADV-CML) will cluster into a second range of linear discriminant values (e.g., positive). The LDA is considered more successful when the separation between the clusters of discriminant values is larger. For more information on linear discriminant analysis, see Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc; and Hastie, 2001, The Elements of Statistical Learning, Springer, N.Y.; Venables & Ripley, 1997, Modern Applied Statistics with s-plus, Springer, N.Y.
  • Quadratic discriminant analysis (QDA) takes the same input parameters and returns the same results as LDA. QDA uses quadratic equations, rather than linear equations, to produce results. LDA and QDA are interchangeable, and which to use is a matter of preference and/or availability of software to support the analysis. Logistic regression takes the same input parameters and returns the same results as LDA and QDA.
    • 5.2.1.6. Decision Trees
  • In some embodiments of the present invention, decision trees are used to classify patients using expression data for a selected set of molecular markers of the invention. Decision tree algorithms belong to the class of supervised learning algorithms. The aim of a decision tree is to induce a classifier (a tree) from real-world example data. This tree can be used to classify unseen examples which have not been used to derive the decision tree.
  • A decision tree is derived from training data. An example contains values for the different attributes and what class the example belongs. In one embodiment, the training data is expression data for a combination of genes described in the present invention across the training population.
  • The following algorithm describes a decision tree derivation:
  •
    Tree(Examples,Class,Attributes)
      Create a root node
      If all Examples have the same Class value, give the
      root this label
      Else if Attributes is empty label the root according to the
      most common value
      Else begin
        Calculate the information gain for each attribute
        Select the attribute A with highest information gain and
    make this the root attribute
        For each possible value, v, of this attribute
          Add a new branch below the root, corresponding to A = v
          Let Examples(v) be those examples with A = v
          If Examples(v) is empty, make the new branch a leaf node
          labeled with the most common value among Examples
          Else let the new branch be the tree created by
           Tree(Examples(v),Class,Attributes - {A})
      end

    A more detailed description of the calculation of information gain is shown in the following. If the possible classes vi of the examples have probabilities P(vi) then the information content I of the actual answer is given by:
  • I ( P ( v 1 ) , … , P ( v n ) ) = ∑ i = 1 n - P ( v i ) log 2 P ( v i )
  • The I-value shows how much information we need in order to be able to describe the outcome of a classification for the specific dataset used. Supposing that the dataset contains p positive (e.g. has ADV-CML) and n negative (e.g. has CP-CML) examples (e.g. individuals), the information contained in a correct answer is:
  • I ( p p + n , n p + n ) = - p p + n log 2 p p + n - n p + n log 2 n p + n
  • where log2 is the logarithm using base two. By testing single attributes the amount of information needed to make a correct classification can be reduced. The remainder for a specific attribute A (e.g. a gene) shows how much the information that is needed can be reduced.
  • Remainder ( A ) = ∑ i = 1 v p i + n i p + n I ( p i p i + n i , n i p i + n i )
  • “v” is the number of unique attribute values for attribute A in a certain dataset, “i” is a certain attribute value, “pi” is the number of examples for attribute A where the classification is positive (e.g. cancer), “ni” is the number of examples for attribute A where the classification is negative (e.g. healthy).
  • The information gain of a specific attribute A is calculated as the difference between the information content for the classes and the remainder of attribute A:
  • Gain ( A ) = I ( p p + n , n p + n ) - Remainder ( A )
  • The information gain is used to evaluate how important the different attributes are for the classification (how well they split up the examples), and the attribute with the highest information.
  • In general there are a number of different decision tree algorithms, many of which are described in Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc. Decision tree algorithms often require consideration of feature processing, impurity measure, stopping criterion, and pruning. Specific decision tree algorithms include, cut are not limited to classification and regression trees (CART), multivariate decision trees, ID3, and C4.5.
  • In one approach, when an exemplary embodiment of a decision tree is used, the gene expression data for a selected set of molecular markers of the invention across a training population is standardized to have mean zero and unit variance. The members of the training population are randomly divided into a training set and a test set. For example, in one embodiment, two thirds of the members of the training population are placed in the training set and one third of the members of the training population are placed in the test set. The expression values for a select combination of genes described in the present invention is used to construct the decision tree. Then, the ability for the decision tree to correctly classify members in the test set is determined. In some embodiments, this computation is performed several times for a given combination of molecular markers. In each iteration of the computation, the members of the training population are randomly assigned to the training set and the test set. Then, the quality of the combination of molecular markers is taken as the average of each such iteration of the decision tree computation.
    • 5.2.1.7. Clustering
  • In some embodiments, the expression values for a selected set of molecular markers of the invention are used to cluster a training set. For example, consider the case in which ten genes described in the present invention are used. Each member m of the training population will have expression values for each of the ten genes. Such values from a member m in the training population define the vector:
  •
    X1m X2m X3m X4m X5m X6m X7m X8m X9m X10m

    where Xim is the expression level of the ith gene in organism m. If there are m organisms in the training set, selection of i genes will define m vectors. Note that the methods of the present invention do not require that each the expression value of every single gene used in the vectors be represented in every single vector m. In other words, data from a subject in which one of the ith genes is not found can still be used for clustering. In such instances, the missing expression value is assigned either a “zero” or some other normalized value. In some embodiments, prior to clustering, the gene expression values are normalized to have a mean value of zero and unit variance.
  • Those members of the training population that exhibit similar expression patterns across the training group will tend to cluster together. A particular combination of genes of the present invention is considered to be a good classifier in this aspect of the invention when the vectors cluster into the trait groups found in the training population. For instance, if the training population includes patients with chronic phase and advanced phase CML, a clustering classifier will cluster the population into two groups, with each group uniquely representing either chronic phase or advanced phase.
  • Clustering is described on pages 211-256 of Duda and Hart, Pattern Classification and Scene Analysis, 1973, John Wiley & Sons, Inc., New York. As described in Section 6.7 of Duda, the clustering problem is described as one of finding natural groupings in a dataset. To identify natural groupings, two issues are addressed. First, a way to measure similarity (or dissimilarity) between two samples is determined. This metric (similarity measure) is used to ensure that the samples in one cluster are more like one another than they are to samples in other clusters. Second, a mechanism for partitioning the data into clusters using the similarity measure is determined.
  • Similarity measures are discussed in Section 6.7 of Duda, where it is stated that one way to begin a clustering investigation is to define a distance function and to compute the matrix of distances between all pairs of samples in a dataset. If distance is a good measure of similarity, then the distance between samples in the same cluster will be significantly less than the distance between samples in different clusters. However, as stated on page 215 of Duda, clustering does not require the use of a distance metric. For example, a nonmetric similarity function s(x, x′) can be used to compare two vectors x and x′. Conventionally, s(x, x′) is a symmetric function whose value is large when x and x′ are somehow “similar”. An example of a nonmetric similarity function s(x, x′) is provided on page 216 of Duda.
  • Once a method for measuring “similarity” or “dissimilarity” between points in a dataset has been selected, clustering requires a criterion function that measures the clustering quality of any partition of the data. Partitions of the data set that extremize the criterion function are used to cluster the data. See page 217 of Duda. Criterion functions are discussed in Section 6.8 of Duda.
  • More recently, Duda et al., Pattern Classification, 2nd edition, John Wiley & Sons, Inc. New York, has been published. Pages 537-563 describe clustering in detail. More information on clustering techniques can be found in Kaufman and Rousseeuw, 1990, Finding Groups in Data: An Introduction to Cluster Analysis, Wiley, New York, N.Y.; Everitt, 1993, Cluster analysis (3d ed.), Wiley, New York, N.Y.; and Backer, 1995, Computer-Assisted Reasoning in Cluster Analysis, Prentice Hall, Upper Saddle River, N.J. Particular exemplary clustering techniques that can be used in the present invention include, but are not limited to, hierarchical clustering (agglomerative clustering using nearest-neighbor algorithm, farthest-neighbor algorithm, the average linkage algorithm, the centroid algorithm, or the sum-of-squares algorithm), k-means clustering, fuzzy k-means clustering algorithm, and Jarvis-Patrick clustering.
    • 5.2.1.8. Principal Component Analysis
  • Principal component analysis (PCA) has been proposed to analyze gene expression data. Principal component analysis is a classical technique to reduce the dimensionality of a data set by transforming the data to a new set of variable (principal components) that summarize the features of the data. See, for example, Jolliffe, 1986, Principal Component Analysis, Springer, N.Y. Principal components (PCs) are uncorrelate and are ordered such that the kth PC has the kth largest variance among PCs. The kth PC can be interpreted as the direction that maximizes the variation of the projections of the data points such that it is orthogonal to the first k−1 PCs. The first few PCs capture most of the variation in the data set. In contrast, the last few PCs are often assumed to capture only the residual ‘noise’ in the data.
  • PCA can also be used to create a progression classifier in accordance with the present invention. In such an approach, vectors for a selected set of molecular markers of the invention can be constructed in the same manner described for clustering above. In fact, the set of vectors, where each vector represents the expression values for the select genes from a particular member of the training population, can be considered a matrix. In some embodiments, this matrix is represented in a Free-Wilson method of qualitative binary description of monomers (Kubinyi, 1990, 3D QSAR in drug design theory methods and applications, Pergamon Press, Oxford, pp 589-638), and distributed in a maximally compressed space using PCA so that the first principal component (PC) captures the largest amount of variance information possible, the second principal component (PC) captures the second largest amount of all variance information, and so forth until all variance information in the matrix has been accounted for.
  • Then, each of the vectors (where each vector represents a member of the training population) is plotted. Many different types of plots are possible. In some embodiments, a one-dimensional plot is made. In this one-dimensional plot, the value for the first principal component from each of the members of the training population is plotted. In this form of plot, the expectation is that members of a first group (e.g. chronic phase patients) will cluster in one range of first principal component values and members of a second group (e.g., advance phase patients) will cluster in a second range of first principal component values.
  • In one example, the training population comprises two groups: chronic phase patients and advanced phase patients or imatinib resistant and imatinib sensitive. The first principal component is computed using the molecular marker expression values for the select genes of the present invention across the entire training population data set. Then, each member of the training set is plotted as a function of the value for the first principal component. In this example, those members of the training population in which the first principal component is positive are the chronic phase (or imatinib sensitive) patients and those members of the training population in which the first principal component is negative are advanced phase (or imatinib resistant) patients.
  • In some embodiments, the members of the training population are plotted against more than one principal component. For example, in some embodiments, the members of the training population are plotted on a two-dimensional plot in which the first dimension is the first principal component and the second dimension is the second principal component. In such a two-dimensional plot, the expectation is that members of each subgroup represented in the training population will cluster into discrete groups. For example, a first cluster of members in the two-dimensional plot will represent subjects with CP-CML, a second cluster of members in the two-dimensional plot will represent subjects with ADV-CML, and so forth.
  • In some embodiments, the members of the training population are plotted against more than two principal components and a determination is made as to whether the members of the training population are clustering into groups that each uniquely represents a subgroup found in the training population. In some embodiments, principal component analysis is performed by using the R mva package (Anderson, 1973, Cluster Analysis for applications, Academic Press, New York 1973; Gordon, Classification, Second Edition, Chapman and Hall, CRC, 1999.). Principal component analysis is further described in Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc.
    • 5.2.1.9. Nearest Neighbor Classifier Analysis
  • Nearest neighbor classifiers are memory-based and require no model to be fit. Given a query point x0, the k training points x(r), r, . . . , k closest in distance to x0 are identified and then the point x0 is classified using the k nearest neighbors. Ties can be broken at random.
  • In some embodiments, Euclidean distance in feature space is used to determine distance as:

  • d (i) =∥x (i) −x 0∥.
  • Typically, when the nearest neighbor algorithm is used, the expression data used to compute the linear discriminant is standardized to have mean zero and variance 1. In the present invention, the members of the training population are randomly divided into a training set and a test set. For example, in one embodiment, two thirds of the members of the training population are placed in the training set and one third of the members of the training population are placed in the test set. Profiles of a selected set of molecular markers of the invention represents the feature space into which members of the test set are plotted. Next, the ability of the training set to correctly characterize the members of the test set is computed. In some embodiments, nearest neighbor computation is performed several times for a given combination of genes of the present invention. In each iteration of the computation, the members of the training population are randomly assigned to the training set and the test set. Then, the quality of the combination of genes is taken as the average of each such iteration of the nearest neighbor computation.
  • The nearest neighbor rule can be refined to deal with issues of unequal class priors, differential misclassification costs, and feature selection. Many of these refinements involve some form of weighted voting for the neighbors. For more information on nearest neighbor analysis, see Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc; and Hastie, 2001, The Elements of Statistical Learning, Springer, N.Y.
    • 5.2.1.10. Evolutionary Methods
  • Inspired by the process of biological evolution, evolutionary methods of classifier design employ a stochastic search for an optimal classifier. In broad overview, such methods create several classifiers—a population—from measurements of gene products of the present invention. Each classifier varies somewhat from the other. Next, the classifiers are scored on expression data across the training population. In keeping with the analogy with biological evolution, the resulting (scalar) score is sometimes called the fitness. The classifiers are ranked according to their score and the best classifiers are retained (some portion of the total population of classifiers). Again, in keeping with biological terminology, this is called survival of the fittest. The classifiers are stochastically altered in the next generation—the children or offspring. Some offspring classifiers will have higher scores than their parent in the previous generation, some will have lower scores. The overall process is then repeated for the subsequent generation: The classifiers are scored and the best ones are retained, randomly altered to give yet another generation, and so on. In part, because of the ranking, each generation has, on average, a slightly higher score than the previous one. The process is halted when the single best classifier in a generation has a score that exceeds a desired criterion value. More information on evolutionary methods is found in, for example, Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc.
    • 5.2.1.11. Bagging, Boosting and the Random Subspace Method
  • Bagging, boosting and the random subspace method are combining techniques that can be used to improve weak classifiers. These techniques are designed for, and usually applied to, decision trees. In addition, Skurichina and Duin provide evidence to suggest that such techniques can also be useful in linear discriminant analysis.
  • In bagging, one samples the training set, generating random independent bootstrap replicates, constructs the classifier on each of these, and aggregates them by a simple majority vote in the final decision rule. See, for example, Breiman, 1996, Machine Learning 24, 123-140; and Efron & Tibshirani, An Introduction to Bootstrap, Chapman & Hall, New York, 1993.
  • In boosting, classifiers are constructed on weighted versions of the training set, which are dependent on previous classification results. Initially, all objects have equal weights, and the first classifier is constructed on this data set. Then, weights are changed according to the performance of the classifier. Erroneously classified objects (molecular markers in the data set) get larger weights, and the next classifier is boosted on the reweighted training set. In this way, a sequence of training sets and classifiers is obtained, which is then combined by simple majority voting or by weighted majority voting in the final decision. See, for example, Freund & Schapire, “Experiments with a new boosting algorithm,” Proceedings 13th International Conference on Machine Learning, 1996, 148-156.
  • To illustrate boosting, consider the case where there are two phenotypic groups exhibited by the population under study, phenotype 1 (e.g., advanced phase patients), and phenotype 2 (e.g., chronic phase patients). Given a vector of molecular markers X, a classifier G(X) produces a prediction taking one of the type values in the two value set: {phenotype 1, phenotype 2}. The error rate on the training sample is
  • err _ = 1 N ∑ i = 1 N I ( y i ≠ G ( x i ) )
  • where N is the number of subjects in the training set (the sum total of the subjects that have either phenotype 1 or phenotype 2).
  • A weak classifier is one whose error rate is only slightly better than random guessing. In the boosting algorithm, the weak classification algorithm is repeatedly applied to modified versions of the data, thereby producing a sequence of weak classifiers Gm(x), m,=1, 2, . . . , M. The predictions from all of the classifiers in this sequence are then combined through a weighted majority vote to produce the final prediction:
  • G ( x ) = sign ( ∑ m = 1 M α m G m ( x ) )
  • Here α1, α2, . . . , αM are computed by the boosting algorithm and their purpose is to weigh the contribution of each respective Gm(x). Their effect is to give higher influence to the more accurate classifiers in the sequence.
  • The data modifications at each boosting step consist of applying weights w1, w2, . . . , wn to each of the training observations (xi, yi), i=1, 2, . . . , N. Initially all the weights are set to wi=1/N, so that the first step simply trains the classifier on the data in the usual manner. For each successive iteration m=2, 3, . . . , M the observation weights are individually modified and the classification algorithm is reapplied to the weighted observations. At stem m, those observations that were misclassified by the classifier Gm-1(x) induced at the previous step have their weights increased, whereas the weights are decreased for those that were classified correctly. Thus as iterations proceed, observations that are difficult to correctly classify receive ever-increasing influence. Each successive classifier is thereby forced to concentrate on those training observations that are missed by previous ones in the sequence.
  • The exemplary boosting algorithm is summarized as follows:
  •
     1. Initialize the observation weights wi = 1/N, i = 1, 2, . . . , N.
     2. For m = 1 to M:
      (a) Fit a classifier Gm(x) to the training set using weights wi.
      (b) Compute
        err m = ∑ i = 1 N w i I ( y i ≠ G m ( x i ) ) ∑ i = 1 N w i
     (c) Compute αm = log((l − errm)/errm).
     (d) Set wi ← wi · exp[αm · I(yi ≠ Gm(xi))], i = 1, 2, . . . , N.
    3. Output G ( x ) = sign ⌊ ∑ m = 1 M α m G m ( x ) ⌋

    In the algorithm, the current classifier Gm(x) is induced on the weighted observations at line 2a. The resulting weighted error rate is computed at line 2b. Line 2c calculates the weight αm given to Gm(x) in producing the final classifier G(x) (line 3). The individual weights of each of the observations are updated for the next iteration at line 2d. Observations misclassified by Gm(x) have their weights scaled by a factor exp(αm), increasing their relative influence for inducing the next classifier Gm+1/(x) in the sequence. In some embodiments, modifications of the Freund and Schapire, 1997, Journal of Computer and System Sciences 55, pp. 119-139, boosting method are used. See, for example, Hasti et al., The Elements of Statistical Learning, 2001, Springer, N.Y., Chapter 10. In some embodiments, boosting or adaptive boosting methods are used.
  • In some embodiments, modifications of Freund and Schapire, 1997, Journal of Computer and System Sciences 55, pp. 119-139, are used. For example, in some embodiments, feature preselection is performed using a technique such as the nonparametric scoring methods of Park et al., 2002, Pac. Symp. Biocomput. 6, 52-63. Feature preselection is a form of dimensionality reduction in which the genes that discriminate between classifications the best are selected for use in the classifier. Then, the LogitBoost procedure introduced by Friedman et al., 2000, Ann Stat 28, 337-407 is used rather than the boosting procedure of Freund and Schapire. In some embodiments, the boosting and other classification methods of Ben-Dor et al., 2000, Journal of Computational Biology 7, 559-583 are used in the present invention. In some embodiments, the boosting and other classification methods of Freund and Schapire, 1997, Journal of Computer and System Sciences 55, 119-139, are used.
  • In the random subspace method, classifiers are constructed in random subspaces of the data feature space. These classifiers are usually combined by simple majority voting in the final decision rule. See, for example, Ho, “The Random subspace method for constructing decision forests,” IEEE Trans Pattern Analysis and Machine Intelligence, 1998; 20(8): 832-844.
    • 5.2.1.12. Other Algorithms
  • The pattern classification and statistical techniques described above are merely examples of the types of models that can be used to construct a model for classification. Moreover, combinations of the techniques described above can be used. Some combinations, such as the use of the combination of decision trees and boosting, have been described. However, many other combinations are possible. In addition, in other techniques in the art such as Projection Pursuit and Weighted Voting can be used to construct a progression classifier.
    • 5.2.2. Methods of Determining Aberrant Regulation of CML Target Genes
  • The invention also provides methods and compositions for determining aberrant regulation in CML target genes and/or their encoded proteins. Such information can be used to determine a treatment regimen for a patient. For example, patients who have a defective regulation of a CML target gene can be identified. A treatment regimen including a therapy to regulate the gene can be prescribed to the patient. Thus, the invention provides methods and composition for assigning treatment regimen for a cancer patient. The invention also provides methods and composition for monitoring treatment progress for a CML patient based on the status of one or more of the CML target proteins.
  • A variety of methods can be employed for the diagnostic and prognostic evaluation of patients for their status of CML target genes or proteins. In one embodiment, measurements of expression level of one or more of the CML target genes listed in Tables 5a and 5b, and/or abundance or activity level the encoded proteins are used. One or more of these genes or proteins having a level of expression or activity deviated from a respective predetermined threshold indicate aberrant regulation of the genes or proteins.
  • In one embodiment, the method comprises determining an expression level of a CML target gene (a gene listed in Table 5a or 5b) in the sample of a patient, and determining whether the expression level is deviated (above or below) a predetermined threshold, and the expression level deviated from a predetermined threshold level indicates aberrant regulation of the gene in the patient. Preferably, the predetermined threshold level is at least 2-fold, 4-fold, 8-fold, or 10-fold of the normal expression level of an aberrantly up-regulated CML target gene or less than 50%, 25%, 10% or 1% of the normal level of an aberrantly down-regulated CML target gene. In another embodiment, the method comprises determining a level of abundance of a CML target protein, i.e., a protein encoded by a CML target gene, in a sample from a patient, and determining whether the level of abundance is deviated a predetermined threshold, and a level of abundance of the protein deviated from a predetermined threshold level indicates aberrant regulation of the protein in the patient. In still another embodiment, the method comprises determining a level of activity of a protein encoded by the CML target gene in a sample of a patient, and determining whether the level of activity is deviated a predetermined threshold, and an activity level deviated from a predetermined threshold level indicates aberrant regulation of the protein in the patient. A reduced activity may be a result of mutation of the CML target gene. Thus, the invention also provides a method for evaluating the status of CML target in a patient, comprising determining a mutation in a CML target gene or a protein encoded by the CML target gene in a sample from the patient, and the detection of a mutation causing the activity of the CML target protein to deviate from a predetermined threshold level indicates aberrant regulation of the protein in the patient. Preferably, the predetermined threshold level of abundance or activity is at least 2-fold, 4-fold, 8-fold, or 10-fold above the normal level of abundance or activity of an aberrantly up-regulated CML target protein or less than 50%, 25%, 10% or 1% of the normal level of an aberrantly down-regulated CML target protein. In the foregoing embodiments, and the embodiments described below, the sample can be an ex vivo cell sample, e.g., cells in a cell culture, or in vivo cells.
  • In a specific embodiment, the method comprises determining an expression level of a CML target gene selected from the group consisting of the up-regulated genes listed in Table 3 (which is a subset of the genes listed in Table 5a) in the sample of a patient, and determining whether the expression level is above a predetermined threshold, and an expression level above a predetermined threshold level indicates aberrant regulation of the gene in the patient. Preferably, the predetermined threshold level is at least 2-fold, 4-fold, 8-fold, or 10-fold of the normal expression level of the gene. In another embodiment, the method comprises determining a level of abundance of a protein encoded by a gene selected from the group consisting of the up-regulated genes listed in Table 3 in a sample from a patient, and determining whether the level is above a predetermined threshold, and a level of abundance of the protein above a predetermined threshold level indicates aberrant regulation of the protein in the patient.
  • In another specific embodiment, the method comprises determining an expression level of a CML target gene selected from the group consisting of the down-regulated genes listed in Table 3 in the sample of a patient, and determining whether the expression level is below a predetermined threshold, and an expression level below a predetermined threshold level indicates aberrant regulation of the gene in the patient. Preferably, the predetermined threshold level is a level less than 50%, 25%, 10% or 1% of the normal expression level of the gene. In another embodiment, the method comprises determining a level of abundance of a protein encoded by a gene selected from the group consisting of the down-regulated genes listed in Table 3 in a sample from a patient, and determining whether the level is below a predetermined threshold, and a level of abundance of the protein below a predetermined threshold level indicates aberrant regulation of the protein in the patient.
  • In one embodiment, the method comprises determining an expression level of an imatinib resistance gene (a gene listed in Table 4) in the sample of a patient, and determining whether the expression level is deviated (above or below) a predetermined threshold, and an expression level deviated from a predetermined threshold level indicates that the patient is resistant to imatinib treatment. Preferably, the predetermined threshold level is at least 2-fold, 4-fold, 8-fold, or 10-fold of the normal expression level of an aberrantly up-regulated imatinib resistance gene or less than 50%, 25%, 10% or 1% of the normal level of an aberrantly down-regulated imatinib resistance gene. In another embodiment, the method comprises determining a level of abundance of an imatinib resistance protein, i.e., a protein encoded by an imatinib resistance gene, in a sample from a patient, and determining whether the level is deviated (above or below) a predetermined threshold, and a level of abundance of the protein deviated from a predetermined threshold level indicates that the patient is resistant to imatinib treatment. In still another embodiment, the method comprises determining a level of activity of a protein encoded by an imatinib resistance gene in a sample of a patient, and determining whether the level is deviated (above or below) a predetermined threshold, and an activity level deviated from a predetermined threshold level indicates that the patient is resistant to imatinib treatment. Such reduce activity may be a result of mutation of the imatinib resistance gene. Thus, the invention also provides a method for evaluating imatinib resistance in a patient, comprising determining a mutation in an imatinib resistance gene or a protein encoded by the imatinib resistance gene in a sample from the patient, and the detection of a mutation causing the activity of the imatinib resistance protein to deviate from a predetermined threshold level indicates the patient is resistant to imatinib treatment. Preferably, the predetermined threshold level of abundance or activity is at least 2-fold, 4-fold, 8-fold, or 10-fold above the normal level of abundance or activity of an aberrantly up-regulated imatinib resistance protein or less than 50%, 25%, 10% or 1% of the normal level of an aberrantly down-regulated imatinib resistance protein.
  • In a specific embodiment, imatinib resistance is determined according to the expression levels of one or more genes selected from the group consisting of serine threonine kinases CTRL, MAP21K14, CLK3, MAP kinase MKNK2, the tyrosine kinase oncogene FYN, TCF7 (a putatively T cell specific transcription factor), guanine nucleotide binding proteins GNAZ and GNG11, and the MAF.
  • Such methods may, for example, utilize reagents such as nucleotide sequences and antibodies, e.g., the CML progression nucleotide sequences, and antibodies directed against CML progression proteins, including peptide fragments thereof. Specifically, such reagents may be used, for example, for: (1) the detection of the presence of mutations in a CML progression gene, or the detection of either over- or under-expression of a CML progression gene relative to the normal expression level; and (2) the detection of either an over- or an under-abundance of a CML progression protein relative to the normal CML progression protein level. These methods are also applicable to imatinib resistance genes and/or proteins.
  • The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising nucleic acid of at least one specific CML progression gene or an antibody that binds a CML progression/target protein or an IM resistance protein described herein, which may be conveniently used, e.g., in clinical settings, to diagnose patients exhibiting CML progression/target protein related disorder or abnormalities or exhibiting IM resistance.
  • For the detection of mutations in a CML progression/target gene or an IM resistance gene, any nucleated cell can be used as a starting source for genomic nucleic acid, e.g., bone marrow or peripheral blood. For the detection of expression of a CML progression/target gene or an IM resistance gene or CML progression/target gene or IM resistance gene products, any cell type or tissue in which the CML progression/target gene or the IM resistance gene is expressed may be utilized.
  • Nucleic acid-based detection techniques and peptide detection techniques are described in Section 5.3., infra. In one embodiment, the expression levels of one or more marker genes are measured using qRT-PCR.
    • 5.2.3. Methods of Detecting CML Cells
  • The invention also provides diagnostic methods for the detection of CML cells, e.g., advanced phase CML hematopoetic stem cells and/or immature myeloid cells, by detecting a cell surface expressed CML progression protein (e.g., PRAME or CD47) or conserved variants or peptide fragments thereof, using, for example, immunoassays wherein the CML progression protein or conserved variants or peptide fragments are detected by their interaction with an anti-CML progression protein antibody.
  • For example, antibodies, or fragments of antibodies, such as those described in the present invention may be used to quantitatively or qualitatively detect advanced phase CML hematopoetic stem cells and/or immature myeloid cells by the presence of a CML progression protein or conserved variants or peptide fragments thereof on their surfaces. This can be accomplished, for example, by immunofluorescence techniques employing a fluorescently labeled antibody (see below, this Section) coupled with light microscopic, flow cytometric, or fluorimetric detection.
  • The antibodies (or fragments thereof) useful in the present invention may, additionally, be employed histologically, as in immunofluorescence or immunoelectron microscopy, for in situ detection of a CML progression protein or conserved variants or peptide fragments thereof. In situ detection may be accomplished by removing a histological specimen from a patient, e.g., bone marrow, and applying thereto a labeled antibody of the present invention. The antibody (or fragment) is preferably applied by overlaying the labeled antibody (or fragment) onto a biological sample. Through the use of such a procedure, it is possible to determine not only the presence of the CML progression protein, or conserved variants or peptide fragments, but also its distribution in the examined tissue. Using the present invention, those of ordinary skill will readily perceive that any of a wide variety of histological methods (such as staining procedures) can be modified in order to achieve such in situ detection.
  • Immunoassays for a CML progression protein or conserved variants or peptide fragments thereof will typically comprise incubating a sample, such as a biological fluid, a tissue extract, freshly harvested cells, or lysates of cells which have been incubated in cell culture, in the presence of a detectably labeled antibody capable of identifying A CML progression protein or conserved variants or peptide fragments thereof, and detecting the bound antibody by any of a number of techniques well-known in the art.
  • The biological sample may be brought in contact with and immobilized onto a solid phase support or carrier such as nitrocellulose, or other solid support which is capable of immobilizing cells, cell particles or soluble proteins. The support may then be washed with suitable buffers followed by treatment with the detectably labeled antibody specific for a CML progression protein. The solid phase support may then be washed with the buffer a second time to remove unbound antibody. The amount of bound label on solid support may then be detected by conventional means.
  • By “solid phase support or carrier” is intended any support capable of binding an antigen or an antibody. Well-known supports or carriers include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylases, natural and modified celluloses, polyacrylamides, gabbros, and magnetite. The nature of the carrier can be either soluble to some extent or insoluble for the purposes of the present invention. The support material may have virtually any possible structural configuration so long as the coupled molecule is capable of binding to an antigen or antibody. Thus, the support configuration may be spherical, as in a bead, or cylindrical, as in the inside surface of a test tub, or the external surface of a rod. Alternatively, the surface may be flat such as a sheet, test strip, etc. Preferred supports include polystyrene beads. Those skilled in the art will know many other suitable carriers for binding antibody or antigen, or will be able to ascertain the same by use of routine experimentation.
  • The binding activity of a given lot of an antibody may be determined according to well-known methods. Those skilled in the art will be able to determine operative and optimal assay conditions for each determination by employing routine experimentation.
  • One of the ways in which the antibody specific to a CML progression protein can be detectably labeled is by linking the same to an enzyme and use in an enzyme immunoassay (EIA) (Voller, A., “The Enzyme Linked Immunosorbent Assay (ELISA)”, 1978, Diagnostic Horizons 2:1-7, Microbiological Associates Quarterly Publication, Walkersville, Md.); Voller, A. et al., 1978, J. Clin. Pathol. 31:507-520; Butler, J. E., 1981, Meth. Enzymol. 73:482-523; Maggio, E. (ed.), 1980, Enzyme Immunoassay, CRC Press, Boca Raton, Fla.,; Ishikawa, E. et al., (eds.), 1981, Enzyme Immunoassay, Kgaku Shoin, Tokyo). The enzyme which is bound to the antibody will react with an appropriate substrate, preferably a chromogenic substrate, in such a manner as to produce a chemical moiety which can be detected, for example, by spectrophotometric, fluorimetric or by visual means. Enzymes which can be used to detectably label the antibody include, but are not limited to, malate dehydrogenase, staphylococcal nuclease, delta-5-steroid isomerase, yeast alcohol dehydrogenase, alpha-glycerophosphate, dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-6-phosphate dehydrogenase, glucoamylase and acetylcholinesterase. The detection can be accomplished by colorimetric methods which employ a chromogenic substrate for the enzyme. Detection may also be accomplished by visual comparison of the extent of enzymatic reaction of a substrate in comparison with similarly prepared standards.
  • Detection may also be accomplished using any of a variety of other immunoassays. For example, by radioactively labeling the antibodies or antibody fragments, it is possible to detect a CML progression protein through the use of a radioimmunoassay (RIA) (see, for example, Weintraub, B., Principles of Radioimmunoassays, Seventh Training Course on Radioligand Assay Techniques, The Endocrine Society, March, 1986, which is incorporated by reference herein). The radioactive isotope can be detected by such means as the use of a gamma counter or a scintillation counter or by autoradiography.
  • It is also possible to label the antibody with a fluorescent compound. When the fluorescently labeled antibody is exposed to light of the proper wave length, its presence can then be detected due to fluorescence. Among the most commonly used fluorescent labeling compounds are fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde and fluorescamine.
  • The antibody can also be detectably labeled using fluorescence emitting metals such as 152Eu, or others of the lanthanide series. These metals can be attached to the antibody using such metal chelating groups as diethylenetriaminepentacetic acid (DTPA) or ethylenediaminetetraacetic acid (EDTA).
  • The antibody also can be detectably labeled by coupling it to a chemiluminescent compound. The presence of the chemiluminescent-tagged antibody is then determined by detecting the presence of luminescence that arises during the course of a chemical reaction. Examples of particularly useful chemiluminescent labeling compounds are luminol, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester.
  • Likewise, a bioluminescent compound may be used to label the antibody of the present invention. Bioluminescence is a type of chemiluminescence found in biological systems in, which a catalytic protein increases the efficiency of the chemiluminescent reaction. The presence of a bioluminescent protein is determined by detecting the presence of luminescence. Important bioluminescent compounds for purposes of labeling are luciferin, luciferase and aequorin.
  • An antibody that is specific to a CML progression protein conjugated to detectable substances can be utilized to sort advanced phase CML cells from normal cells by methods known to those of skill in the art. In one embodiment, the advanced phase CML cells are sorted using a fluorescence activated cell sorter (FACS). Fluorescence activated cell sorting (FACS) is a well-known method for separating particles, including cells, based on the fluorescent properties of the particles (Kamarch, 1987, Methods Enzymol, 151:150-165). Laser excitation of fluorescent moieties in the individual particles results in a small electrical charge allowing electromagnetic separation of positive and negative particles from a mixture.
  • In one embodiment, cells, e.g, cells in bone marrow or peripheral blood, obtained from a patient, e.g., a human, are incubated with fluorescently labeled antibody specific for the CML progression protein for a time sufficient to allow the labeled antibodies to bind to the cells. In an alternative embodiment, such cells are incubated with the antibody, the cells are washed, and the cells are incubated with a second labeled antibody that recognizes the CML progression protein-specific antibody. In accordance with these embodiments, the cells are washed and processed through the cell sorter, allowing separation of cells that bind both antibodies to be separated from hybrid cells that do not bind both antibodies. FACS sorted particles may be directly deposited into individual wells of 96-well or 384-well plates to facilitate separation and further characterization.
    • 5.2.4. Sample Collection
  • In the present invention, gene products, such as target polynucleotide molecules or proteins, are extracted from a sample taken from a CML patient. The sample may be collected in any clinically acceptable manner, but must be collected such that marker-derived polynucleotides (i.e., RNA) are preserved (if gene expression is to be measured) or proteins are preserved (if encoded proteins are to be measured). In one embodiment, bone marrow samples are used. In another embodiment, peripheral blood samples are used. In one embodiment, the pre-treatment bone marrow or peripheral blood sample from a patient is used. In another embodiment, the treatment bone marrow or peripheral blood sample from a patient after and/or during treatment is used. In one embodiment, the unsorted bone marrow or peripheral blood sample from a patient is used. In one embodiment, the unsorted bone marrow or peripheral blood sample from a clinical chronic phase patient is used. In another embodiment, the sorted bone marrow or peripheral blood sample from a patient after and/or during treatment is used. Other suitable samples may comprise any clinically relevant tissue sample, such as a tumor biopsy or fine needle aspirate, or a sample of body fluid, such as blood, plasma, serum, lymph, ascitic fluid, cystic fluid, or urine. The sample may be taken from a human, or, in a veterinary context, from non-human animals such as ruminants, horses, swine or sheep, or from domestic companion animals such as felines and canines.
  • In a specific embodiment, mRNA or nucleic acids derived therefrom (i.e., cDNA or amplified RNA or amplified DNA) are preferably labeled distinguishably from polynucleotide molecules of a reference sample, and both are simultaneously or independently hybridized to a microarray comprising some or all of the markers or marker sets or subsets described above. Alternatively, mRNA or nucleic acids derived therefrom may be labeled with the same label as the reference polynucleotide molecules, wherein the intensity of hybridization of each at a particular probe is compared.
  • Methods for preparing total and poly(A)+ RNA are well known and are described generally in Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989)) and Ausubel et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, vol. 2, Current Protocols Publishing, New York (1994)). Preferably, total RNA, or total mRNA (poly(A)+ RNA) is measured in the methods of the invention directly or indirectly (e.g., via measuring cDNA or cRNA).
  • RNA may be isolated from eukaryotic cells by procedures that involve lysis of the cells and denaturation of the proteins contained therein. Cells of interest include wild-type cells (i.e., non-cancerous), drug-exposed wild-type cells, tumor- or tumor-derived cells, modified cells, normal or tumor cell line cells, and drug-exposed modified cells. Preferably, the cells are breast cancer tumor cells.
  • Additional steps may be employed to remove DNA. Cell lysis may be accomplished with a nonionic detergent, followed by microcentrifugation to remove the nuclei and hence the bulk of the cellular DNA. In one embodiment, RNA is extracted from cells of the various types of interest using guanidinium thiocyanate lysis followed by CsCl centrifugation to separate the RNA from DNA (Chirgwin et al., Biochemistry 18:5294-5299 (1979)). Poly(A)+ RNA is selected by selection with oligo-dT cellulose (see Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989). Alternatively, separation of RNA from DNA can be accomplished by organic extraction, for example, with hot phenol or phenol/chloroform/isoamyl alcohol.
  • If desired, RNase inhibitors may be added to the lysis buffer. Likewise, for certain cell types, it may be desirable to add a protein denaturation/digestion step to the protocol.
  • For many applications, it is desirable to preferentially enrich mRNA with respect to other cellular RNAs, such as transfer RNA (tRNA) and ribosomal RNA (rRNA). Most mRNAs contain a poly(A) tail at their 3′ end. This allows them to be enriched by affinity chromatography, for example, using oligo(dT) or poly(U) coupled to a solid support, such as cellulose or Sephadex™ (see Ausubel et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, vol. 2, Current Protocols Publishing, New York (1994). Once bound, poly(A)+ mRNA is eluted from the affinity column using 2 mM EDTA/0.1% SDS.
  • In a specific embodiment, total RNA or total mRNA from cells is used in the methods of the invention. The source of the RNA can be cells of an animal, e.g., human, mammal, primate, non-human animal, dog, cat, mouse, rat, bird, etc. In specific embodiments, the method of the invention is used with a sample containing total mRNA or total RNA from 1×106 cells or less. In another embodiment, proteins can be isolated from the foregoing sources, by methods known in the art, for use in expression analysis at the protein level.
  • Probes to the homologs of the marker sequences disclosed herein can be employed preferably when non-human nucleic acid is being assayed.
    • 5.2.5. Determination of Abundance Levels of Gene Products
  • The abundance levels of the gene products of the genes in a sample may be determined by any means known in the art. The levels may be determined by isolating and determining the level (i.e., amount) of nucleic acid transcribed from each marker gene. Alternatively, or additionally, the level of specific proteins encoded by a marker gene may be determined
  • The levels of transcripts of specific marker genes can be accomplished by determining the amount of mRNA, or polynucleotides derived therefrom, present in a sample. Any method for determining RNA levels can be used. For example, RNA is isolated from a sample and separated on an agarose gel. The separated RNA is then transferred to a solid support, such as a filter. Nucleic acid probes representing one or more markers are then hybridized to the filter by northern hybridization, and the amount of marker-derived RNA is determined. Such determination can be visual, or machine-aided, for example, by use of a densitometer. Another method of determining RNA levels is by use of a dot-blot or a slot-blot. In this method, RNA, or nucleic acid derived therefrom, from a sample is labeled. The RNA or nucleic acid derived therefrom is then hybridized to a filter containing oligonucleotides derived from one or more marker genes, wherein the oligonucleotides are placed upon the filter at discrete, easily-identifiable locations. Hybridization, or lack thereof, of the labeled RNA to the filter-bound oligonucleotides is determined visually or by densitometer. Polynucleotides can be labeled using a radiolabel or a fluorescent (i.e., visible) label.
  • The levels of transcripts of particular marker genes may also be assessed by determining the level of the specific protein expressed from the marker genes. This can be accomplished, for example, by separation of proteins from a sample on a polyacrylamide gel, followed by identification of specific marker-derived proteins using antibodies in a western blot. Alternatively, proteins can be separated by two-dimensional gel electrophoresis systems. Two-dimensional gel electrophoresis is well-known in the art and typically involves isoelectric focusing along a first dimension followed by SDS-PAGE electrophoresis along a second dimension. See, e.g., Hames et al, 1990, GEL ELECTROPHORESIS OF PROTEINS: A PRACTICAL APPROACH, IRL Press, New York; Shevchenko et al., Proc. Nat'l Acad. Sci. USA 93:1440-1445 (1996); Sagliocco et al., Yeast 12:1519-1533 (1996); Lander, Science 274:536-539 (1996). The resulting electropherograms can be analyzed by numerous techniques, including mass spectrometric techniques, western blotting and immunoblot analysis using polyclonal and monoclonal antibodies.
  • Alternatively, marker-derived protein levels can be determined by constructing an antibody microarray in which binding sites comprise immobilized, preferably monoclonal, antibodies specific to a plurality of protein species encoded by the cell genome. Preferably, antibodies are present for a substantial fraction of the marker-derived proteins of interest. Methods for making monoclonal antibodies are well known (see, e.g., Harlow and Lane, 1988, ANTIBODIES: A LABORATORY MANUAL, Cold Spring Harbor, N.Y., which is incorporated in its entirety for all purposes). In one embodiment, monoclonal antibodies are raised against synthetic peptide fragments designed based on genomic sequence of the cell. With such an antibody array, proteins from the cell are contacted to the array, and their binding is assayed with assays known in the art. Generally, the expression, and the level of expression, of proteins of diagnostic or prognostic interest can be detected through immunohistochemical staining of tissue slices or sections.
  • Finally, levels of transcripts of marker genes in a number of tissue specimens may be characterized using a “tissue array” (Kononen et al., Nat. Med. 4(7):844-7 (1998)). In a tissue array, multiple tissue samples are assessed on the same microarray. The arrays allow in situ detection of RNA and protein levels; consecutive sections allow the analysis of multiple samples simultaneously.
    • 5.2.5.1. Microarrays
  • In preferred embodiments, polynucleotide microarrays are used to measure expression so that the expression status of each of the markers above is assessed simultaneously. Generally, microarrays according to the invention comprise a plurality of markers informative for clinical category determination, for a particular disease or condition.
  • The invention also provides a microarray comprising for each of a plurality of genes, said genes being all or at least 5, 10, 20, 30, 40, 50, 70, 100 or 200 of the genes listed in Tables 1a and/or 1b or any of Tables 2a-2b, 4 and 5a-5b, or all or at least 5, 10, or 15 of the genes listed in Table 3, one or more polynucleotide probes complementary and hybridizable to a sequence in said gene, wherein polynucleotide probes complementary and hybridizable to said genes constitute at least 50%, 60%, 70%, 80%, 90%, 95%, or 98% of the probes on said microarray. In a particular embodiment, the invention provides such a microarray wherein the plurality of genes comprises the 20 genes listed in Table 3 or the 228 genes listed in Table 4 or the 368 genes listed in Tables 5a and 5b. The microarray can be in a sealed container.
  • The microarrays preferably comprise at least 2, 3, 4, 5, 7, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 150, 200 or more of markers, or all of the markers, or any combination of markers, identified as informative for CML progression and/or imatinib resistance, e.g., within Tables 1a and 1b or any of Tables 2a-2b, 3, 4, and 5a-5b. The actual number of informative markers the microarray comprises will vary depending upon the particular condition of interest.
  • In other embodiments, the invention provides polynucleotide arrays in which the CML progression markers comprise at least 50%, 60%, 70%, 80%, 85%, 90%, 95% or 98% of the probes on the array. In another specific embodiment, the microarray comprises a plurality of probes, wherein said plurality of probes comprise probes complementary and hybridizable to at least 75% of the CML progression markers.
  • General methods pertaining to the construction of microarrays comprising the marker sets and/or subsets above are described in the following sections.
    • 5.2.5.2. Construction of Microarrays
  • Microarrays are prepared by selecting probes which comprise a polynucleotide sequence, and then immobilizing such probes to a solid support or surface. For example, the probes may comprise DNA sequences, RNA sequences, or copolymer sequences of DNA and RNA. The polynucleotide sequences of the probes may also comprise DNA and/or RNA analogues, or combinations thereof. For example, the polynucleotide sequences of the probes may be full or partial fragments of genomic DNA. The polynucleotide sequences of the probes may also be synthesized nucleotide sequences, such as synthetic oligonucleotide sequences. The probe sequences can be synthesized either enzymatically in vivo, enzymatically in vitro (e.g., by PCR), or non-enzymatically in vitro.
  • The probe or probes used in the methods of the invention are preferably immobilized to a solid support which may be either porous or non-porous. For example, the probes may be polynucleotide sequences which are attached to a nitrocellulose or nylon membrane or filter covalently at either the 3′ or the 5′ end of the polynucleotide. Such hybridization probes are well known in the art (see, e.g., Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989). Alternatively, the solid support or surface may be a glass or plastic surface. In a particularly preferred embodiment, hybridization levels are measured to microarrays of probes consisting of a solid phase on the surface of which are immobilized a population of polynucleotides, such as a population of DNA or DNA mimics, or, alternatively, a population of RNA or RNA mimics. The solid phase may be a nonporous or, optionally, a porous material such as a gel.
  • In preferred embodiments, a microarray comprises a support or surface with an ordered array of binding (e.g., hybridization) sites or “probes” each representing one of the markers described herein. Preferably the microarrays are addressable arrays, and more preferably positionally addressable arrays. More specifically, each probe of the array is preferably located at a known, predetermined position on the solid support such that the identity (i.e., the sequence) of each probe can be determined from its position in the array (i.e., on the support or surface). In preferred embodiments, each probe is covalently attached to the solid support at a single site.
  • Microarrays can be made in a number of ways, of which several are described below. However produced, microarrays share certain characteristics. The arrays are reproducible, allowing multiple copies of a given array to be produced and easily compared with each other. Preferably, microarrays are made from materials that are stable under binding (e.g., nucleic acid hybridization) conditions. The microarrays are preferably small, e.g., between 1 cm2 and 25 cm2, between 12 cm2 and 13 cm2, or 3 cm2. However, larger arrays are also contemplated and may be preferable, e.g., for use in screening arrays. Preferably, a given binding site or unique set of binding sites in the microarray will specifically bind (e.g., hybridize) to the product of a single gene in a cell (e.g., to a specific mRNA, or to a specific cDNA derived therefrom). However, in general, other related or similar sequences will cross hybridize to a given binding site.
  • The microarrays of the present invention include one or more test probes, each of which has a polynucleotide sequence that is complementary to a subsequence of RNA or DNA to be detected. Preferably, the position of each probe on the solid surface is known. Indeed, the microarrays are preferably positionally addressable arrays. Specifically, each probe of the array is preferably located at a known, predetermined position on the solid support such that the identity (i.e., the sequence) of each probe can be determined from its position on the array (i.e., on the support or surface).
  • According to the invention, the microarray is an array (i.e., a matrix) in which each position represents one of the markers described herein. For example, each position can contain a DNA or DNA analogue based on genomic DNA to which a particular RNA or cDNA transcribed from that genetic marker can specifically hybridize. The DNA or DNA analogue can be, e.g., a synthetic oligomer or a gene fragment. In one embodiment, probes representing each of the markers are present on the array. In a preferred embodiment, the array comprises probes for each of the markers listed in Tables 1a and/or 1b or any one of Tables 2a-2b, 3, 4, and 5a-5b.
    • 5.2.5.3. Preparing Probes for Microarrays
  • As noted above, the “probe” to which a particular polynucleotide molecule specifically hybridizes according to the invention contains a complementary genomic polynucleotide sequence. The probes of the microarray preferably consist of nucleotide sequences of no more than 1,000 nucleotides. In some embodiments, the probes of the array consist of nucleotide sequences of 10 to 1,000 nucleotides. In a preferred embodiment, the nucleotide sequences of the probes are in the range of 10-200 nucleotides in length and are genomic sequences of a species of organism, such that a plurality of different probes is present, with sequences complementary and thus capable of hybridizing to the genome of such a species of organism, sequentially tiled across all or a portion of such genome. In other specific embodiments, the probes are in the range of 10-30 nucleotides in length, in the range of 10-40 nucleotides in length, in the range of 20-50 nucleotides in length, in the range of 40-80 nucleotides in length, in the range of 50-150 nucleotides in length, in the range of 80-120 nucleotides in length, and most preferably are 60 nucleotides in length.
  • The probes may comprise DNA or DNA “mimics” (e.g., derivatives and analogues) corresponding to a portion of an organism's genome. In another embodiment, the probes of the microarray are complementary RNA or RNA mimics. DNA mimics are polymers composed of subunits capable of specific, Watson-Crick-like hybridization with DNA, or of specific hybridization with RNA. The nucleic acids can be modified at the base moiety, at the sugar moiety, or at the phosphate backbone. Exemplary DNA mimics include, e.g., phosphorothioates.
  • DNA can be obtained, e.g., by polymerase chain reaction (PCR) amplification of genomic DNA or cloned sequences. PCR primers are preferably chosen based on a known sequence of the genome that will result in amplification of specific fragments of genomic DNA. Computer programs that are well known in the art are useful in the design of primers with the required specificity and optimal amplification properties, such as Oligo version 5.0 (National Biosciences). Typically each probe on the microarray will be between 10 bases and 50,000 bases, usually between 300 bases and 1,000 bases in length. PCR methods are well known in the art, and are described, for example, in Innis et al., eds., PCR PROTOCOLS: A GUIDE TO METHODS AND APPLICATIONS, Academic Press Inc., San Diego, Calif. (1990). It will be apparent to one skilled in the art that controlled robotic systems are useful for isolating and amplifying nucleic acids.
  • An alternative, preferred means for generating the polynucleotide probes of the microarray is by synthesis of synthetic polynucleotides or oligonucleotides, e.g., using N-phosphonate or phosphoramidite chemistries (Froehler et al., Nucleic Acid Res. 14:5399-5407 (1986); McBride et al., Tetrahedron Lett. 24:246-248 (1983)). Synthetic sequences are typically between about 10 and about 500 bases in length, more typically between about 20 and about 100 bases, and most preferably between about 40 and about 70 bases in length. In some embodiments, synthetic nucleic acids include non-natural bases, such as, but by no means limited to, inosine. As noted above, nucleic acid analogues may be used as binding sites for hybridization. An example of a suitable nucleic acid analogue is peptide nucleic acid (see, e.g., Egholm et al., Nature 363:566-568 (1993); U.S. Pat. No. 5,539,083).
  • Probes are preferably selected using an algorithm that takes into account binding energies, base composition, sequence complexity, cross-hybridization binding energies, and secondary structure. See Friend et al., International Patent Publication WO 01/05935, published Jan. 25, 2001; Hughes et al., Nat. Biotech. 19:342-7 (2001).
  • A skilled artisan will also appreciate that positive control probes, e.g., probes known to be complementary and hybridizable to sequences in the target polynucleotide molecules, and negative control probes, e.g., probes known to not be complementary and hybridizable to sequences in the target polynucleotide molecules, should be included on the array. In one embodiment, positive controls are synthesized along the perimeter of the array. In another embodiment, positive controls are synthesized in diagonal stripes across the array. In still another embodiment, the reverse complement for each probe is synthesized next to the position of the probe to serve as a negative control. In yet another embodiment, sequences from other species of organism are used as negative controls or as “spike-in” controls.
    • 5.2.5.4. Attaching Probes to the Solid Surface
  • The probes are attached to a solid support or surface, which may be made, e.g., from glass, plastic (e.g., polypropylene, nylon), polyacrylamide, nitrocellulose, gel, or other porous or nonporous material. A preferred method for attaching the nucleic acids to a surface is by printing on glass plates, as is described generally by Schena et al, Science 270:467-470 (1995). This method is especially useful for preparing microarrays of cDNA (See also, DeRisi et al, Nature Genetics 14:457-460 (1996); Shalon et al., Genome Res. 6:639-645 (1996); and Schena et al., Proc. Natl. Acad. Sci. U.S.A. 93:10539-11286 (1995)).
  • A second preferred method for making microarrays is by making high-density oligonucleotide arrays. Techniques are known for producing arrays containing thousands of oligonucleotides complementary to defined sequences, at defined locations on a surface using photolithographic techniques for synthesis in situ (see, Fodor et al., 1991, Science 251:767-773; Pease et al., 1994, Proc. Natl. Acad. Sci. U.S.A. 91:5022-5026; Lockhart et al., 1996, Nature Biotechnology 14:1675; U.S. Pat. Nos. 5,578,832; 5,556,752; and 5,510,270) or other methods for rapid synthesis and deposition of defined oligonucleotides (Blanchard et al., Biosensors & Bioelectronics 11:687-690). When these methods are used, oligonucleotides (e.g., 60-mers) of known sequence are synthesized directly on a surface such as a derivatized glass slide. Usually, the array produced is redundant, with several oligonucleotide molecules per RNA.
  • Other methods for making microarrays, e.g., by masking (Maskos and Southern, 1992, Nuc. Acids. Res. 20:1679-1684), may also be used. In principle, and as noted supra, any type of array, for example, dot blots on a nylon hybridization membrane (see Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989)) could be used. However, as will be recognized by those skilled in the art, very small arrays will frequently be preferred because hybridization volumes will be smaller.
  • In one embodiment, the arrays of the present invention are prepared by synthesizing polynucleotide probes on a support. In such an embodiment, polynucleotide probes are attached to the support covalently at either the 3′ or the 5′ end of the polynucleotide.
  • In a particularly preferred embodiment, microarrays are manufactured by means of an ink jet printing device for oligonucleotide synthesis, e.g., using the methods and systems described by Blanchard in U.S. Pat. No. 6,028,189; Blanchard et al., 1996, Biosensors and Bioelectronics 11:687-690; Blanchard, 1998, in Synthetic DNA Arrays in Genetic Engineering, Vol. 20, J. K. Setlow, Ed., Plenum Press, New York at pages 111-123. Specifically, the oligonucleotide probes in such microarrays are preferably synthesized in arrays, e.g., on a glass slide, by serially depositing individual nucleotide bases in “microdroplets” of a high surface tension solvent such as propylene carbonate. The microdroplets have small volumes (e.g., 100 pL or less, more preferably 50 pL or less) and are separated from each other on the microarray (e.g., by hydrophobic domains) to form circular surface tension wells which define the locations of the array elements (i.e., the different probes). Microarrays manufactured by this ink-jet method are typically of high density, preferably having a density of at least about 2,500 different probes per 1 cm2. The polynucleotide probes are attached to the support covalently at either the 3′ or the 5′ end of the polynucleotide.
    • 5.2.5.5. Target Labeling and Hybridization to Microarrays
  • The polynucleotide molecules which may be analyzed by the present invention (the “target polynucleotide molecules”) may be from any clinically relevant source, but are expressed RNA or a nucleic acid derived therefrom (e.g., cDNA or amplified RNA derived from cDNA that incorporates an RNA polymerase promoter), including naturally occurring nucleic acid molecules, as well as synthetic nucleic acid molecules. In one embodiment, the target polynucleotide molecules comprise RNA, including, but by no means limited to, total cellular RNA, poly(A)+ messenger RNA (mRNA) or fraction thereof, cytoplasmic mRNA, or RNA transcribed from cDNA (i.e., cRNA; see, e.g., Linsley & Schelter, U.S. patent application Ser. No. 09/411,074, filed Oct. 4, 1999, or U.S. Pat. Nos. 5,545,522, 5,891,636, or 5,716,785). Methods for preparing total and poly(A)+ RNA are well known in the art, and are described generally, e.g., in Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989). In one embodiment, RNA is extracted from cells of the various types of interest in this invention using guanidinium thiocyanate lysis followed by CsCl centrifugation (Chirgwin et al., 1979, Biochemistry 18:5294-5299). In another embodiment, total RNA is extracted using a silica gel-based column, commercially available examples of which include RNeasy (Qiagen, Valencia, Calif.) and StrataPrep (Stratagene, La Jolla, Calif.). In an alternative embodiment, which is preferred for S. cerevisiae, RNA is extracted from cells using phenol and chloroform, as described in Ausubel et al., eds., 1989, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, Vol. III, Green Publishing Associates, Inc., John Wiley & Sons, Inc., New York, at pp. 13.12.1-13.12.5). Poly(A)+ RNA can be selected, e.g., by selection with oligo-dT cellulose or, alternatively, by oligo-dT primed reverse transcription of total cellular RNA. In one embodiment, RNA can be fragmented by methods known in the art, e.g., by incubation with ZnCl2, to generate fragments of RNA. In another embodiment, the polynucleotide molecules analyzed by the invention comprise cDNA, or PCR products of amplified RNA or cDNA.
  • In one embodiment, total RNA, mRNA, or nucleic acids derived therefrom, is isolated from a sample taken from a CML patient. Target polynucleotide molecules that are poorly expressed in particular cells may be enriched using normalization techniques (Bonaldo et al., 1996, Genome Res. 6:791-806).
  • As described above, the target polynucleotides are detectably labeled at one or more nucleotides. Any method known in the art may be used to detectably label the target polynucleotides. Preferably, this labeling incorporates the label uniformly along the length of the RNA, and more preferably, the labeling is carried out at a high degree of efficiency. One embodiment for this labeling uses oligo-dT primed reverse transcription to incorporate the label; however, conventional methods of this method are biased toward generating 3′ end fragments. Thus, in a preferred embodiment, random primers (e.g., 9-mers) are used in reverse transcription to uniformly incorporate labeled nucleotides over the full length of the target polynucleotides. Alternatively, random primers may be used in conjunction with PCR methods or T7 promoter-based in vitro transcription methods in order to amplify the target polynucleotides.
  • In a preferred embodiment, the detectable label is a luminescent label. For example, fluorescent labels, bioluminescent labels, chemiluminescent labels, and colorimetric labels may be used in the present invention. In a highly preferred embodiment, the label is a fluorescent label, such as a fluorescein, a phosphor, a rhodamine, or a polymethine dye derivative. Examples of commercially available fluorescent labels include, for example, fluorescent phosphoramidites such as FluorePrime (Amersham Pharmacia, Piscataway, N.J.), Fluoredite (Millipore, Bedford, Mass.), FAM (ABI, Foster City, Calif.), and Cy3 or Cy5 (Amersham Pharmacia, Piscataway, N.J.). In another embodiment, the detectable label is a radiolabeled nucleotide.
  • In a further preferred embodiment, target polynucleotide molecules from a patient sample are labeled differentially from target polynucleotide molecules of a reference sample. The reference can comprise target polynucleotide molecules from normal cell samples (i.e., cell sample, e.g., bone marrow or peripheral blood, from those not afflicted with CML) or from cell samples, e.g., bone marrow or peripheral blood, from chronic phase CML patients.
  • Nucleic acid hybridization and wash conditions are chosen so that the target polynucleotide molecules specifically bind or specifically hybridize to the complementary polynucleotide sequences of the array, preferably to a specific array site, wherein its complementary DNA is located.
  • Arrays containing double-stranded probe DNA situated thereon are preferably subjected to denaturing conditions to render the DNA single-stranded prior to contacting with the target polynucleotide molecules. Arrays containing single-stranded probe DNA (e.g., synthetic oligodeoxyribonucleic acids) may need to be denatured prior to contacting with the target polynucleotide molecules, e.g., to remove hairpins or dimers which form due to self complementary sequences.
  • Optimal hybridization conditions will depend on the length (e.g., oligomer versus polynucleotide greater than 200 bases) and type (e.g., RNA, or DNA) of probe and target nucleic acids. One of skill in the art will appreciate that as the oligonucleotides become shorter, it may become necessary to adjust their length to achieve a relatively uniform melting temperature for satisfactory hybridization results. General parameters for specific (i.e., stringent) hybridization conditions for nucleic acids are described in Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989), and in Ausubel et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, vol. 2, Current Protocols Publishing, New York (1994). Typical hybridization conditions for the cDNA microarrays of Schena et al. are hybridization in 5×SSC plus 0.2% SDS at 65° C. for four hours, followed by washes at 25° C. in low stringency wash buffer (1×SSC plus 0.2% SDS), followed by 10 minutes at 25° C. in higher stringency wash buffer (0.1×SSC plus 0.2% SDS) (Schena et al., Proc. Natl. Acad. Sci. U.S.A. 93:10614 (1993)). Useful hybridization conditions are also provided in, e.g., Tijessen, 1993, HYBRIDIZATION WITH NUCLEIC ACID PROBES, Elsevier Science Publishers B. V.; and Kricka, 1992, NONISOTOPIC DNA PROBE TECHNIQUES, Academic Press, San Diego, Calif.
  • Particularly preferred hybridization conditions include hybridization at a temperature at or near the mean melting temperature of the probes (e.g., within 51° C., more preferably within 21° C.) in 1 M NaCl, 50 mM MES buffer (pH 6.5), 0.5% sodium sarcosine and 30% formamide.
    • 5.2.5.6. Signal Detection and Data Analysis
  • When fluorescently labeled gene products are used, the fluorescence emissions at each site of a microarray may be, preferably, detected by scanning confocal laser microscopy. In one embodiment, a separate scan, using the appropriate excitation line, is carried out for each of the two fluorophores used. Alternatively, a laser may be used that allows simultaneous specimen illumination at wavelengths specific to the two fluorophores and emissions from the two fluorophores can be analyzed simultaneously (see Shalon et al., 1996, “A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization,” Genome Research 6:639-645, which is incorporated by reference in its entirety for all purposes). In a preferred embodiment, the arrays are scanned with a laser fluorescent scanner with a computer controlled X-Y stage and a microscope objective. Sequential excitation of the two fluorophores is achieved with a multi-line, mixed gas laser and the emitted light is split by wavelength and detected with two photomultiplier tubes. Fluorescence laser scanning devices are described in Schena et al., Genome Res. 6:639-645 (1996), and in other references cited herein. Alternatively, the fiber-optic bundle described by Ferguson et al., Nature Biotech. 14:1681-1684 (1996), may be used to monitor mRNA abundance levels at a large number of sites simultaneously.
    • 5.2.5.7. Other Assays for Detecting and Quantifying RNA
  • In addition to microarrays such as those described above any technique known to one of skill for detecting and measuring RNA can be used in accordance with the methods of the invention. Non-limiting examples of techniques include Northern blotting, nuclease protection assays, RNA fingerprinting, polymerase chain reaction, ligase chain reaction, Qbeta replicase, isothermal amplification method, strand displacement amplification, transcription based amplification systems, nuclease protection (SI nuclease or RNAse protection assays), SAGE as well as methods disclosed in International Publication Nos. WO 88/10315 and WO 89/06700, and International Applications Nos. PCT/US87/00880 and PCT/US89/01025.
  • A standard Northern blot assay can be used to ascertain an RNA transcript size, identify alternatively spliced RNA transcripts, and the relative amounts of mRNA in a sample, in accordance with conventional Northern hybridization techniques known to those persons of ordinary skill in the art. In Northern blots, RNA samples are first separated by size via electrophoresis in an agarose gel under denaturing conditions. The RNA is then transferred to a membrane, crosslinked and hybridized with a labeled probe. Nonisotopic or high specific activity radiolabeled probes can be used including random-primed, nick-translated, or PCR-generated DNA probes, in vitro transcribed RNA probes, and oligonucleotides. Additionally, sequences with only partial homology (e.g., cDNA from a different species or genomic DNA fragments that might contain an exon) may be used as probes. The labeled probe, e.g., a radiolabelled cDNA, either containing the full-length, single stranded DNA or a fragment of that DNA sequence may be at least 20, at least 30, at least 50, or at least 100 consecutive nucleotides in length. The probe can be labeled by any of the many different methods known to those skilled in this art. The labels most commonly employed for these studies are radioactive elements, enzymes, chemicals that fluoresce when exposed to ultraviolet light, and others. A number of fluorescent materials are known and can be utilized as labels. These include, but are not limited to, fluorescein, rhodamine, auramine, Texas Red, AMCA blue and Lucifer Yellow. A particular detecting material is anti-rabbit antibody prepared in goats and conjugated with fluorescein through an isothiocyanate. Proteins can also be labeled with a radioactive element or with an enzyme. The radioactive label can be detected by any of the currently available counting procedures. Non-limiting examples of isotopes include 3H, 14C, 32P, 35S, 36Cl, 51Cr, 57Co, 58Co, 59Fe, 90Y, 125I, 131I, and 186Re. Enzyme labels are likewise useful, and can be detected by any of the presently utilized colorimetric, spectrophotometric, fluorospectrophotometric, amperometric or gasometric techniques. The enzyme is conjugated to the selected particle by reaction with bridging molecules such as carbodiimides, diisocyanates, glutaraldehyde and the like. Any enzymes known to one of skill in the art can be utilized. Examples of such enzymes include, but are not limited to, peroxidase, beta-D-galactosidase, urease, glucose oxidase plus peroxidase and alkaline phosphatase. U.S. Pat. Nos. 3,654,090, 3,850,752, and 4,016,043 are referred to by way of example for their disclosure of alternate labeling material and methods.
  • Nuclease protection assays (including both ribonuclease protection assays and S1 nuclease assays) can be used to detect and quantitate specific mRNAs. In nuclease protection assays, an antisense probe (labeled with, e.g., radiolabeled or nonisotopic) hybridizes in solution to an RNA sample. Following hybridization, single-stranded, unhybridized probe and RNA are degraded by nucleases. An acrylamide gel is used to separate the remaining protected fragments. Typically, solution hybridization is more efficient than membrane-based hybridization, and it can accommodate up to 100 μg of sample RNA, compared with the 20-30 μg maximum of blot hybridizations.
  • The ribonuclease protection assay, which is the most common type of nuclease protection assay, requires the use of RNA probes. Oligonucleotides and other single-stranded DNA probes can only be used in assays containing S1 nuclease. The single-stranded, antisense probe must typically be completely homologous to target RNA to prevent cleavage of the probe:target hybrid by nuclease.
  • Serial Analysis Gene Expression (SAGE), which is described in e.g., Velculescu et al., 1995, Science 270:484-7; Carulli, et al., 1998, Journal of Cellular Biochemistry Supplements 30/31:286-96, can also be used to determine RNA abundances in a cell sample.
  • Quantitative reverse transcriptase PCR (qRT-PCR) can also be used to determine the expression profiles of marker genes (see, e.g., U.S. Patent Application Publication No. 2005/0048542A1). The first step in gene expression profiling by RT-PCR is the reverse transcription of the RNA template into cDNA, followed by its exponential amplification in a PCR reaction. The two most commonly used reverse transcriptases are avilo myeloblastosis virus reverse transcriptase (AMV-RT) and Moloney murine leukemia virus reverse transcriptase (MLV-RT). The reverse transcription step is typically primed using specific primers, random hexamers, or oligo-dT primers, depending on the circumstances and the goal of expression profiling. For example, extracted RNA can be reverse-transcribed using a GeneAmp RNA PCR kit (Perkin Elmer, Calif., USA), following the manufacturer's instructions. The derived cDNA can then be used as a template in the subsequent PCR reaction.
  • Although the PCR step can use a variety of thermostable DNA-dependent DNA polymerases, it typically employs the Taq DNA polymerase, which has a 5′-3′ nuclease activity but lacks a 3′-5′ proofreading endonuclease activity. Thus, TaqMan® PCR typically utilizes the 5′-nuclease activity of Taq or Tth polymerase to hydrolyze a hybridization probe bound to its target amplicon, but any enzyme with equivalent 5′ nuclease activity can be used. Two oligonucleotide primers are used to generate an amplicon typical of a PCR reaction. A third oligonucleotide, or probe, is designed to detect nucleotide sequence located between the two PCR primers. The probe is non-extendible by Taq DNA polymerase enzyme, and is labeled with a reporter fluorescent dye and a quencher fluorescent dye. Any laser-induced emission from the reporter dye is quenched by the quenching dye when the two dyes are located close together as they are on the probe. During the amplification reaction, the Taq DNA polymerase enzyme cleaves the probe in a template-dependent manner. The resultant probe fragments disassociate in solution, and signal from the released reporter dye is free from the quenching effect of the second fluorophore. One molecule of reporter dye is liberated for each new molecule synthesized, and detection of the unquenched reporter dye provides the basis for quantitative interpretation of the data.
  • TaqMan® RT-PCR can be performed using commercially available equipment, such as, for example, ABI PRISM 7700™. Sequence Detection System™ (Perkin-Elmer-Applied Biosystems, Foster City, Calif., USA), or Lightcycler (Roche Molecular Biochemicals, Mannheim, Germany). In a preferred embodiment, the 5′ nuclease procedure is run on a real-time quantitative PCR device such as the ABI PRISM 7700™ Sequence Detection System™. The system consists of a thermocycler, laser, charge-coupled device (CCD), camera and computer. The system includes software for running the instrument and for analyzing the data.
  • 5′-Nuclease assay data are initially expressed as Ct, or the threshold cycle. Fluorescence values are recorded during every cycle and represent the amount of product amplified to that point in the amplification reaction. The point when the fluorescent signal is first recorded as statistically significant is the threshold cycle (Ct).
  • To minimize errors and the effect of sample-to-sample variation, RT-PCR is usually performed using an internal standard. The ideal internal standard is expressed at a constant level among different tissues, and is unaffected by the experimental treatment. RNAs most frequently used to normalize patterns of gene expression are mRNAs for the housekeeping genes glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and β-actin.
  • A more recent variation of the RT-PCR technique is the real time quantitative PCR, which measures PCR product accumulation through a dual-labeled fluorogenic probe (i.e., TaqMan® probe). Real time PCR is compatible both with quantitative competitive PCR, where internal competitor for each target sequence is used for normalization, and with quantitative comparative PCR using a normalization gene contained within the sample, or a housekeeping gene for RT-PCR. For further details see, e.g. Held et al., Genome Research 6:986-994 (1996).
    • 5.2.5.8. Detection and Quantification of Protein
  • Measurement of the translational state may be performed according to several methods. For example, whole genome monitoring of protein (e.g., the “proteome,”) can be carried out by constructing a microarray in which binding sites comprise immobilized, preferably monoclonal, antibodies specific to a plurality of protein species encoded by the cell genome. Preferably, antibodies are present for a substantial fraction of the encoded proteins, or at least for those proteins relevant to the action of a drug of interest. Methods for making monoclonal antibodies are well known (see, e.g., Harlow and Lane, 1988, Antibodies: A Laboratory Manual, Cold Spring Harbor, N.Y., which is incorporated in its entirety for all purposes). In one embodiment, monoclonal antibodies are raised against synthetic peptide fragments designed based on genomic sequence of the cell. With such an antibody array, proteins from the cell are contacted to the array and their binding is assayed with assays known in the art.
  • Immunoassays known to one of skill in the art can be used to detect and quantify protein levels. For example, ELISAs can be used to detect and quantify protein levels. ELISAs comprise preparing antigen, coating the well of a 96 well microtiter plate with the antigen, adding the antibody of interest conjugated to a detectable compound such as an enzymatic substrate (e.g., horseradish peroxidase or alkaline phosphatase) to the well and incubating for a period of time, and detecting the presence of the antigen. In ELISAs the antibody of interest does not have to be conjugated to a detectable compound; instead, a second antibody (which recognizes the antibody of interest) conjugated to a detectable compound may be added to the well. Further, instead of coating the well with the antigen, the antibody may be coated to the well. In this case, a second antibody conjugated to a detectable compound may be added following the addition of the antigen of interest to the coated well. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the signal detected as well as other variations of ELISAs known in the art. In a preferred embodiment, an ELISA may be performed by coating a high binding 96-well microtiter plate (Costar) with 2 μg/ml of rhu-IL-9 in PBS overnight. Following three washes with PBS, the plate is incubated with three-fold serial dilutions of Fab at 25° C. for 1 hour. Following another three washes of PBS, 1 μg/ml anti-human kappa-alkaline phosphatase-conjugate is added and the plate is incubated for 1 hour at 25° C. Following three washes with PBST, the alkaline phosphatase activity is determined in 50 μl/AMP/PPMP substrate. The reactions are stopped and the absorbance at 560 nm is determined with a VMAX microplate reader. For further discussion regarding ELISAs see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York at 11.2.1.
  • Protein levels may be determined by Western blot analysis. Further, protein levels as well as the phosphorylation of proteins can be determined by immunoprecitation followed by Western blot analysis Immunoprecipitation protocols generally comprise lysing a population of cells in a lysis buffer such as RIPA buffer (1% NP-40 or Triton X-100, 1% sodium deoxycholate, 0.1% SDS, 0.15 M NaCl, 0.01 M sodium phosphate at pH 7.2, 1% Trasylol) supplemented with protein phosphatase and/or protease inhibitors (e.g., EDTA, PMSF, aprotinin, sodium vanadate), adding the antibody of interest to the cell lysate, incubating for a period of time (e.g., 1 to 4 hours) at 40° C., adding protein A and/or protein G sepharose beads to the cell lysate, incubating for about an hour or more at 40° C., washing the beads in lysis buffer and resuspending the beads in SDS/sample buffer. The ability of the antibody of interest to immunoprecipitate a particular antigen can be assessed by, e.g., western blot analysis. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the binding of the antibody to an antigen and decrease the background (e.g., pre-clearing the cell lysate with sepharose beads). For further discussion regarding immunoprecipitation protocols see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York at 10.16.1.
  • Western blot analysis generally comprises preparing protein samples, electrophoresis of the protein samples in a polyacrylamide gel (e.g., 8%-20% SDS-PAGE depending on the molecular weight of the antigen), transferring the protein sample from the polyacrylamide gel to a membrane such as nitrocellulose, PVDF or nylon, incubating the membrane in blocking solution (e.g., PBS with 3% BSA or non-fat milk), washing the membrane in washing buffer (e.g., PBS-Tween 20), incubating the membrane with primary antibody (the antibody of interest) diluted in blocking buffer, washing the membrane in washing buffer, incubating the membrane with a secondary antibody (which recognizes the primary antibody, e.g., an anti-human antibody) conjugated to an enzymatic substrate (e.g., horseradish peroxidase or alkaline phosphatase) or radioactive molecule (e.g., 32P or 125I) diluted in blocking buffer, washing the membrane in wash buffer, and detecting the presence of the antigen. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the signal detected and to reduce the background noise. For further discussion regarding western blot protocols see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York at 10.8.1.
  • Protein expression levels can also be separated by two-dimensional gel electrophoresis systems. Two-dimensional gel electrophoresis is well-known in the art and typically involves iso-electric focusing along a first dimension followed by SDS-PAGE electrophoresis along a second dimension. See, e.g., Hames et al., 1990, Gel Electrophoresis of Proteins: A Practical Approach, IRL Press, New York; Shevchenko et al., 1996, Proc. Natl. Acad. Sci. USA 93:1440-1445; Sagliocco et al., 1996, Yeast 12:1519-1533; Lander, 1996, Science 274:536-539. The resulting electropherograms can be analyzed by numerous techniques, including mass spectrometric techniques, Western blotting and immunoblot analysis using polyclonal and monoclonal antibodies, and internal and N-terminal micro-sequencing.
    • 5.3. Treating CML by Modulating Expression and/or Activity of CML Progression Genes and/or their Products
  • The invention provides methods and compositions for utilizing CML target genes listed in Table 3 or 5a or 5b and or imatinib resistance genes listed in Table 4 in treating CML. The methods and compositions are used for treating CML patient exhibiting aberrant regulation of one or more CML target/progression genes or IM resistance genes by modulating the expression and/or activity of such genes and/or the encoded proteins. The methods and composition can be used in conjunction with other CML treatment, e.g., imatinib mesylate. The compositions (e.g., agents that modulate expression and/or activity of the CML target gene or gene product) of the invention are preferably purified. In the following, for simplicity reasons, the methods are often described with reference to CML target gene(s). It will be understood that the methods are equally applicable to CML progression genes and IM resistance genes.
  • In one embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant up-regulation of a CML target gene by reducing the expression and/or activity of the gene, and/or its encoded protein by at least 2 fold, 3 fold, 4 fold, 6 fold, 8 fold or 9 fold.
  • In a specific embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant up-regulation of a CML target gene as listed in Table 5a or 5b by reducing the expression and/or activity of the gene, and/or its encoded protein.
  • In another embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant down-regulation of a CML target gene by enhancing the expression and/or activity of the gene, and/or its encoded protein by at least 2 fold, 3 fold, 4 fold, 6 fold, 8 fold or 9 fold.
  • In a specific embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant down-regulation of a CML target gene as listed in Table 5a or 5b by enhancing the expression and/or activity of the gene, and/or its encoded protein.
  • In a specific embodiment, the invention provides a method for treating CML by administering to a patient (i) an agent that modulates the expression and/or activity of an imatinib resistance gene and/or the encoded protein, and (ii) a therapeutically sufficient amount of imatinib mesylate.
  • In another embodiment, the invention provides methods and compositions for treating a CML patient exhibiting aberrant regulation of a plurality of different CML target gene as listed in Tables 5a and 5b by modulating the expression and/or activity of the plurality of genes, and/or its encoded proteins. In one embodiment, a CML patient exhibiting aberrant up-regulation of a plurality of CML progression gene listed in Tables 5a and 5b, e.g. 2, 3, 4, 5, 10 or more different CML target genes, is treated by administering to the patient one or more agents that reduce the expression and/or activities of these genes, and/or their encoded proteins.
  • A variety of therapeutic approaches may be used in accordance with the invention to modulate expression of a CML target gene or imatinib resistance gene and/or its encoded protein in vivo. For example, siRNA molecules may be engineered and used to silence a CML target gene in vivo. Antisense DNA molecules may also be engineered and used to block translation of a CML target mRNA in vivo. Alternatively, ribozyme molecules may be designed to cleave and destroy the mRNAs of a CML target gene in vivo. In another alternative, oligonucleotides designed to hybridize to the 5′ region of the CML target gene (including the region upstream of the coding sequence) and form triple helix structures may be used to block or reduce transcription of the CML target gene. The expression and/or activity of a CML target protein can be modulated using antibody, peptide or polypeptide molecules, and small organic or inorganic molecules. In the following, for simplicity, methods are described in reference to a CML target gene or protein. These methods are equally applicable to imatinib resistance genes.
  • In a preferred embodiment, RNAi is used to knock down the expression of a CML target gene. In one embodiment, double-stranded RNA molecules of 21-23 nucleotides which hybridize to a homologous region of mRNAs transcribed from the CML target gene are used to degrade the mRNAs, thereby “silence” the expression of the CML target gene. The method can be used to reduce expression levels of aberrantly up-regulated CML target genes. Preferably, the dsRNAs have a hybridizing region, e.g., a 19-nucleotide double-stranded region, which is complementary to a sequence of the coding sequence of the CML target gene. Any siRNA that targets an appropriate coding sequence of a CML target gene and exhibit a sufficient level of silencing can be used in the invention. As exemplary embodiments, 21-nucleotide double-stranded siRNAs targeting the coding regions of a CML target gene are designed according to selection rules known in the art (see, e.g., Elbashir et al., 2002, Methods 26:199-213; International Application No. PCT/US04/35636, filed Oct. 27, 2004, each of which is incorporated herein by reference in its entirety). In a preferred embodiment, the siRNA or siRNAs specifically inhibit the translation or transcription of a CML target protein without substantially affecting the translation or transcription of genes encoding other protein kinases in the same kinase family. In a specific embodiment, siRNAs targeting an up-regulated gene listed in Table 4 are used to silence the respective CML target genes.
  • The invention also provides methods and compositions for treating a CML patient exhibiting aberrant up-regulation of a plurality of CML target genes as listed in Tables 5a and 5b by reducing the expression and/or activities of these genes, and/or their encoded proteins. In one embodiment, a CML patient exhibiting aberrant up-regulation of a plurality of CML target gene listed in Tables 5a and 5b, e.g. 2, 3, 4, 5, 10 or more different CML target genes, is treated by administering to the patient one or more agents that reduce the expression and/or activities of these genes, and/or their encoded proteins. In a preferred embodiment, an siRNA is used to silence the plurality of different CML target genes. The sequence of the siRNA is chosen such that the transcript of each of the genes comprises a nucleotide sequence that is identical to a central contiguous nucleotide sequence of at least 11 nucleotides of the sense strand or the antisense strand of the siRNA, and/or comprises a nucleotide sequence that is identical to a contiguous nucleotide sequence of at least 9 nucleotides at the 3′ end of the sense strand or the antisense strand of the siRNA. Thus, when administrated to the patient, the siRNA silences all of the plurality of genes in cells of the patient. In preferred embodiments, the central contiguous nucleotide sequence of the siRNA that is identical to one or more CML target genes is 11-15, 14-15, 11, 12, or 13 nucleotides in length. In other preferred embodiments, the 3′ contiguous nucleotide sequence of the siRNA that is identical to one or more CML target genes is 9-15, 9-12, 11, 10, or 9 nucleotides in length. The length and nucleotide base sequence of the target sequence of each different target gene, i.e., the sequence of the gene that is identical to an appropriate sense or antisense sequence of the siRNA, can be different from gene to gene. For example, gene A may have a sequence of 11 nucleotides identical to the nucleotide sequence 3-13 of the sense strand of the siRNA, while gene B may have a sequence of 12 nucleotides identical to the nucleotide sequence 4-15 of the sense strand of the siRNA. Thus, a single siRNA may be designed to silence a large number of CML target genes in cells.
  • RNAi can be carried out using any standard method for introducing nucleic acids into cells. In one embodiment, gene silencing is induced by presenting the cell with one or more siRNAs targeting the CML target gene (see, e.g., Elbashir et al., 2001, Nature 411, 494-498; Elbashir et al., 2001, Genes Dev. 15, 188-200, all of which are incorporated by reference herein in their entirety). The siRNAs can be chemically synthesized, or derived from cleavage of double-stranded RNA by recombinant Dicer. Another method to introduce a double stranded DNA (dsRNA) for silencing of the CML target gene is shRNA, for short hairpin RNA (see, e.g., Paddison et al., 2002, Genes Dev. 16, 948-958; Brummelkamp et al., 2002, Science 296, 550-553; Sui, G. et al. 2002, Proc. Natl. Acad. Sci. USA 99, 5515-5520, all of which are incorporated by reference herein in their entirety). In this method, a siRNA targeting a CML target gene is expressed from a plasmid (or virus) as an inverted repeat with an intervening loop sequence to form a hairpin structure. The resulting RNA transcript containing the hairpin is subsequently processed by Dicer to produce siRNAs for silencing. Plasmid- or virus-based shRNAs can be expressed stably in cells, allowing long-term gene silencing in cells both in vitro and in vivo (see, McCaffrey et al. 2002, Nature 418, 38-39; Xia et al., 2002, Nat. Biotech. 20, 1006-1010; Lewis et al., 2002, Nat. Genetics 32, 107-108; Rubinson et al., 2003, Nat. Genetics 33, 401-406; Tiscornia et al., 2003, Proc. Natl. Acad. Sci. USA 100, 1844-1848, all of which are incorporated by reference herein in their entirety). Such plasmid- or virus-based shRNAs can be delivered using a gene therapy approach. SiRNAs targeting the CML target gene can also be delivered to an organ or tissue in a mammal, such a human, in vivo (see, e.g., Song et al. 2003, Nat. Medicine 9, 347-351; Sorensen et al., 2003, J. Mol. Biol. 327, 761-766; Lewis et al., 2002, Nat. Genetics 32, 107-108, all of which are incorporated by reference herein in their entirety). In this method, a solution of siRNA is injected intravenously into the mammal The siRNA can then reach an organ or tissue of interest and effectively reduce the expression of the target gene in the organ or tissue of the mammal
  • In preferred embodiments, an siRNA pool (mixture) containing at least k (k=2, 3, 4, 5, 6 or 10) different siRNAs targeting a CML target gene at different sequence regions is used to silence the gene. In a preferred embodiment, the total siRNA concentration of the pool is about the same as the concentration of a single siRNA when used individually. As used herein, the word “about” with reference to concentration means within 20%. Preferably, the total concentration of the pool of siRNAs is an optimal concentration for silencing the intended target gene. An optimal concentration is a concentration further increase of which does not increase the level of silencing substantially. In one embodiment, the optimal concentration is a concentration further increase of which does not increase the level of silencing by more than 5%, 10% or 20%. In a preferred embodiment, the composition of the pool, including the number of different siRNAs in the pool and the concentration of each different siRNA, is chosen such that the pool of siRNAs causes less than 30%, 20%, 10% or 5%, 1%, 0.1% or 0.01% of silencing of any off-target genes (e.g., as determined by standard nucleic acid assay, e.g., PCR). In another preferred embodiment, the concentration of each different siRNA in the pool of different siRNAs is about the same. In still another preferred embodiment, the respective concentrations of different siRNAs in the pool are different from each other by less than 5%, 10%, 20% or 50% of the concentration of any one siRNA or said total siRNA concentration of said different siRNAs. In still another preferred embodiment, at least one siRNA in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In still another preferred embodiment, none of the siRNAs in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In other embodiments, each siRNA in the pool has a concentration that is lower than the optimal concentration when used individually. In a preferred embodiment, each different siRNA in the pool has an concentration that is lower than the concentration of the siRNA that is effective to achieve at least 30%, 50%, 75%, 80%, 85%, 90% or 95% silencing when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In another preferred embodiment, each different siRNA in the pool has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the gene when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In a preferred embodiment, each siRNA has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the target gene when used alone, while the plurality of siRNAs causes at least 80% or 90% of silencing of the target gene. In specific embodiments, a pool containing the 3 different is used for targeting a CML target gene. More detailed descriptions of techniques for carrying out RNAi are also presented in Section 5.6.
  • In other embodiments, antisense, ribozyme, and triple helix forming nucleic acid are designed to inhibit the translation or transcription of a CML target protein or gene with minimal effects on the expression of other genes that may share one or more sequence motif with the CML target gene. To accomplish this, the oligonucleotides used should be designed on the basis of relevant sequences unique to a CML target gene. In one embodiment, the oligonucleotide used specifically inhibits the translation or transcription of a CML target protein or gene without substantially affecting the translation or transcription of other proteins in the same protein family.
  • For example, and not by way of limitation, the oligonucleotides should not fall within those regions where the nucleotide sequence of a CML target gene is most homologous to that of other genes. In the case of antisense molecules, it is preferred that the sequence be at least 18 nucleotides in length in order to achieve sufficiently strong annealing to the target mRNA sequence to prevent translation of the sequence. Izant et al., 1984, Cell, 36:1007-1015; Rosenberg et al., 1985, Nature, 313:703-706.
  • Ribozymes are RNA molecules which possess highly specific endoribonuclease activity. Hammerhead ribozymes comprise a hybridizing region which is complementary in nucleotide sequence to at least part of the target RNA, and a catalytic region which is adapted to cleave the target RNA. The hybridizing region contains nine (9) or more nucleotides. Therefore, the hammerhead ribozymes useful for targeting a CML target gene having a hybridizing region which is complementary to the sequences of the target gene and is at least nine nucleotides in length. The construction and production of such ribozymes is well known in the art and is described more fully in Haseloff et al., 1988, Nature, 334:585-591.
  • The ribozymes of the present invention also include RNA endoribonucleases (hereinafter “Cech-type ribozymes”) such as the one which occurs naturally in Tetrahymena Thermophila (known as the IVS, or L-19 IVS RNA) and which has been extensively described by Thomas Cech and collaborators (Zaug, et al., 1984, Science, 224:574-578; Zaug and Cech, 1986, Science, 231:470-475; Zaug, et al., 1986, Nature, 324:429-433; published International patent application No. WO 88/04300 by University Patents Inc.; Been et al., 1986, Cell, 47:207-216). The Cech endoribonucleases have an eight base pair active site which hybridizes to a target RNA sequence whereafter cleavage of the target RNA takes place.
  • In the case of oligonucleotides that hybridize to and form triple helix structures at the 5′ terminus of a CML target gene and can be used to block transcription, it is preferred that they be complementary to those sequences in the 5′ terminus of a CML target gene which are not present in other related genes. It is also preferred that the sequences not include those regions of the promoter of a CML target gene which are even slightly homologous to that of other related genes.
  • The foregoing compounds can be administered by a variety of methods which are known in the art including, but not limited to the use of liposomes as a delivery vehicle. Naked DNA or RNA molecules may also be used where they are in a form which is resistant to degradation such as by modification of the ends, by the formation of circular molecules, or by the use of alternate bonds including phosphothionate and thiophosphoryl modified bonds. In addition, the delivery of nucleic acid may be by facilitated transport where the nucleic acid molecules are conjugated to poly-lysine or transferrin. Nucleic acid may also be transported into cells by any of the various viral carriers, including but not limited to, retrovirus, vaccinia, AAV, and adenovirus.
  • Alternatively, a recombinant nucleic acid molecule which encodes, or is, such antisense nucleic acid, ribozyme, triple helix forming nucleic acid, or nucleic acid molecule of a CML target gene can be constructed. This nucleic acid molecule may be either RNA or DNA. If the nucleic acid encodes an RNA, it is preferred that the sequence be operatively attached to a regulatory element so that sufficient copies of the desired RNA product are produced. The regulatory element may permit either constitutive or regulated transcription of the sequence. In vivo, that is, within the cells or cells of an organism, a transfer vector such as a bacterial plasmid or viral RNA or DNA, encoding one or more of the RNAs, may be transfected into cells e.g. (Llewellyn et al., 1987, J. Mol. Biol., 195:115-123; Hanahan et al. 1983, J. Mol. Biol., 166:557-580). Once inside the cell, the transfer vector may replicate, and be transcribed by cellular polymerases to produce the RNA or it may be integrated into the genome of the host cell. Alternatively, a transfer vector containing sequences encoding one or more of the RNAs may be transfected into cells or introduced into cells by way of micromanipulation techniques such as microinjection, such that the transfer vector or a part thereof becomes integrated into the genome of the host cell.
  • The activity of a CML target protein can be modulated by modulating the interaction of a CML target protein with its binding partners. In one embodiment, agents, e.g., antibodies, peptides, aptamers, small organic or inorganic molecules, can be used to inhibit binding of a CML target protein binding partner to treat CML. In another embodiment, agents, e.g., antibodies, aptamers, small organic or inorganic molecules, can be used to inhibit the activity of a CML target protein to treat CML.
  • In other embodiments, when the CML target protein is a kinase, the invention provides small molecule inhibitors of the CML target protein. A small molecule inhibitor is a low molecular weight phosphorylation inhibitor. As used herein, a small molecule refers to an organic or inorganic molecule having a molecular weight is under 1000 Daltons, preferably in the range between 300 to 700 Daltons, which is not a nucleic acid molecule or a peptide molecule. The small molecule can be naturally occurring, e.g., extracted from plant or microorganisms, or non-naturally occurring, e.g., generated de novo by synthesis. A small molecule that is an inhibitor can be used to block a cellular process that dependent on a CML target protein. In one embodiment, the inhibitors are substrate mimics. In a preferred embodiment, the inhibitor of the CML target proteins is an ATP mimic. In one embodiment, such ATP mimics possess at least two aromatic rings. In a preferred embodiment, the ATP mimic comprises a moiety that forms extensive contacts with residues lining the ATP binding cleft of the CML target protein and/or peptide segments just outside the cleft, thereby selectively blocking the ATP binding site of the CML target protein. Minor structural differences from ATP can be introduced into the ATP mimic based on the peptide segments just outside the cleft. Such differences can lead to specific hydrogen bonding and hydrophobic interactions with the peptide segments just outside the cleft.
  • In still other embodiments, antibodies that specifically bind the CML target protein are used. In a preferred embodiment, the invention provides antibodies that specifically bind the extracellular domain of a CML target protein that is a receptor. Antibodies that specifically bind a target can be obtained using standard method known in the art, e.g., a method described in Section 5.8.
  • In one embodiment, an antibody-drug conjugate comprising an antibody that specifically binds a CML target protein is used. The efficacy of the antibodies that targets specific molecules expressed by advanced phase immature myeloid cells can be increased by attaching toxins to them. Existing immunotoxins are based on bacterial toxins like pseudomonas exotoxin, plant exotoxin like ricin or radio-nucleotides. The toxins are chemically conjugated to a specific ligand such as the variable domain of the heavy or light chain of the monoclonal antibody. Normal cells lacking the cancer specific antigens are not targeted by the targeted antibody. In a preferred embodiment, the CML target protein target is PRAME.
  • In other embodiments, a peptide and peptidomimetic that interferes with the interaction of a CML target protein with its interaction partner is used. A peptide preferably has a size of at least 5, 10, 15, 20 or 30 amino acids. Such a peptide or peptidomimetic can be designed by a person skilled in the art based on the sequence and structure of a CML target protein. In one embodiment, a peptide or peptidomimetic that interferes with substrate binding of a CML target protein is used. In another embodiment, peptide or peptidomimetic that interferes with the binding of a signal molecule to a CML target protein is used. In some embodiments of the invention, a fragment or polypeptide of at least 5, 10, 20, 50, 100 amino acids in length of a CML target protein are used. In a specific embodiment, a peptide or peptidomimetic that interferes with the interaction with PRAME is used. The peptide can be prepared by standard method known in the art.
  • In another embodiment, a dominant negative mutant of a CML target protein is used to reduce activity of a CML target protein. Such a dominant negative mutant can be designed by a person skilled in the art based on the sequence and structure of a CML target protein. In one embodiment, a dominant negative mutant that interferes with substrate binding of a CML target protein is used. In another embodiment, a dominant negative mutant that interferes with the binding of a signal molecule to a CML target protein is used. In a preferred embodiment, the invention provides a dominant negative mutant that comprises the C-terminal region of a CML target protein. In another embodiment, the invention provides a dominant negative mutant that comprises the N-terminal region of the CML target protein.
  • Gene therapy can be used for delivering any of the above described nucleic acid and protein/peptide therapeutics into target cells. Gene therapy is particularly useful for enhancing aberrantly down-regulated genes. Exemplary methods for carrying out gene therapy are described below. For general reviews of the methods of gene therapy, see Goldspiel et al., 1993, Clinical Pharmacy 12:488-505; Wu and Wu, 1991, Biotherapy 3:87-95; Tolstoshev, 1993, Ann. Rev. Pharmacol. Toxicol. 32:573-596; Mulligan, 1993, Science 260:926-932; and Morgan and Anderson, 1993, Ann. Rev. Biochem. 62:191-217; May, 1993, TIBTECH 11(5):155-215). Methods commonly known in the art of recombinant DNA technology which can be used are described in Ausubel et al. (eds.), 1993, Current Protocols in Molecular Biology, John Wiley & Sons, New York; and Kriegler, 1990, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, New York.
  • In a preferred embodiment, the therapeutic comprises a nucleic acid that is part of an expression vector that expresses a the therapeutic nucleic acid or peptide/polypeptide in a suitable host. In particular, such a nucleic acid has a promoter operably linked to the coding region, said promoter being inducible or constitutive, and, optionally, tissue-specific. In another particular embodiment, a nucleic acid molecule is used in which the coding sequences and any other desired sequences are flanked by regions that promote homologous recombination at a desired site in the genome, thus providing for intrachromosomal expression of the CML target nucleic acid (see e.g., Koller and Smithies, 1989, Proc. Natl. Acad. Sci. U.S.A. 86:8932-8935; Zijlstra et al., 1989, Nature 342:435-438).
  • Delivery of the nucleic acid into a patient may be either direct, in which case the patient is directly exposed to the nucleic acid or nucleic acid-carrying vector, or indirect, in which case, cells are first transformed with the nucleic acid in vitro, then transplanted into the patient. These two approaches are known, respectively, as in vivo or ex vivo gene therapy.
  • In a specific embodiment, the nucleic acid is directly administered in vivo, where it is expressed to produce the encoded product. This can be accomplished by any of numerous methods known in the art, e.g., by constructing it as part of an appropriate nucleic acid expression vector and administering it so that it becomes intracellular, e.g., by infection using a defective or attenuated retroviral or other viral vector (see U.S. Pat. No. 4,980,286), or by direct injection of naked DNA, or by use of microparticle bombardment (e.g., a gene gun; Biolistic, Dupont), or coating with lipids or cell-surface receptors or transfecting agents, encapsulation in liposomes, microparticles, or microcapsules, or by administering it in linkage to a peptide which is known to enter the nucleus, by administering it in linkage to a ligand subject to receptor-mediated endocytosis (see e.g., Wu and Wu, 1987, J. Biol. Chem. 262:4429-4432) (which can be used to target cell types specifically expressing the receptors), etc. In another embodiment, a nucleic acid-ligand complex can be formed in which the ligand comprises a fusogenic viral peptide to disrupt endosomes, allowing the nucleic acid to avoid lysosomal degradation. In yet another embodiment, the nucleic acid can be targeted in vivo for cell specific uptake and expression, by targeting a specific receptor (see, e.g., PCT Publications WO 92/06180 dated Apr. 16, 1992 (Wu et al.); WO 92/22635 dated Dec. 23, 1992 (Wilson et al.); WO92/20316 dated Nov. 26, 1992 (Findeis et al.); WO93/14188 dated Jul. 22, 1993 (Clarke et al.), WO 93/20221 dated Oct. 14, 1993 (Young)). Alternatively, the nucleic acid can be introduced intracellularly and incorporated within host cell DNA for expression, by homologous recombination (Koller and Smithies, 1989, Proc. Natl. Acad. Sci. U.S.A. 86:8932-8935; Zijlstra et al., 1989, Nature 342:435-438).
  • In a specific embodiment, a viral vector that contains the nucleic acid of a CML target gene is used. For example, a retroviral vector can be used (see Miller et al., 1993, Meth. Enzymol. 217:581-599). These retroviral vectors have been modified to delete retroviral sequences that are not necessary for packaging of the viral genome and integration into host cell DNA. The CML target nucleic acid to be used in gene therapy is cloned into the vector, which facilitates delivery of the gene into a patient. More detail about retroviral vectors can be found in Boesen et al., 1994, Biotherapy 6:291-302, which describes the use of a retroviral vector to deliver the mdr1 gene to hematopoietic stem cells in order to make the stem cells more resistant to chemotherapy. Other references illustrating the use of retroviral vectors in gene therapy are: Clowes et al., 1994, J. Clin. Invest. 93:644-651; Kiem et al., 1994, Blood 83:1467-1473; Salmons and Gunzberg, 1993, Human Gene Therapy 4:129-141; and Grossman and Wilson, 1993, Curr. Opin. Genet. and Devel. 3:110-114.
  • Adenoviruses are other viral vectors that can be used in gene therapy. Adenoviruses are especially attractive vehicles for delivering genes to respiratory epithelia. Adenoviruses naturally infect respiratory epithelia where they cause a mild disease. Other targets for adenovirus-based delivery systems are liver, the central nervous system, endothelial cells, and muscle. Adenoviruses have the advantage of being capable of infecting non-dividing cells. Kozarsky and Wilson (1993, Current Opinion in Genetics and Development 3:499-503) present a review of adenovirus-based gene therapy. Bout et al. (1994, Human Gene Therapy 5:3-10) demonstrated the use of adenovirus vectors to transfer genes to the respiratory epithelia of rhesus monkeys. Other instances of the use of adenoviruses in gene therapy can be found in Rosenfeld et al., 1991, Science 252:431-434; Rosenfeld et al., 1992, Cell 68:143-155; and Mastrangeli et al., 1993, J. Clin. Invest. 91:225-234.
  • Adeno-associated virus (AAV) has also been proposed for use in gene therapy (Walsh et al., 1993, Proc. Soc. Exp. Biol. Med. 204:289-300).
  • Another approach to gene therapy involves transferring a gene to cells in tissue culture by such methods as electroporation, lipofection, calcium phosphate mediated transfection, or viral infection. Usually, the method of transfer includes the transfer of a selectable marker to the cells. The cells are then placed under selection to isolate those cells that have taken up and are expressing the transferred gene. Those cells are then delivered to a patient.
  • In this embodiment, the nucleic acid is introduced into a cell prior to administration in vivo of the resulting recombinant cell. Such introduction can be carried out by any method known in the art, including but not limited to transfection, electroporation, microinjection, infection with a viral or bacteriophage vector containing the nucleic acid sequences, cell fusion, chromosome-mediated gene transfer, microcell-mediated gene transfer, spheroplast fusion, etc. Numerous techniques are known in the art for the introduction of foreign genes into cells (see e.g., Loeffler and Behr, 1993, Meth. Enzymol. 217:599-618; Cohen et al., 1993, Meth. Enzymol. 217:618-644; Cline, 1985, Pharmac. Ther. 29:69-92) and may be used in accordance with the present invention, provided that the necessary developmental and physiological functions of the recipient cells are not disrupted. The technique should provide for the stable transfer of the nucleic acid to the cell, so that the nucleic acid is expressible by the cell and preferably heritable and expressible by its cell progeny.
  • The resulting recombinant cells can be delivered to a patient by various methods known in the art. In a preferred embodiment, epithelial cells are injected, e.g., subcutaneously. In another embodiment, recombinant skin cells may be applied as a skin graft onto the patient. Recombinant blood cells (e.g., hematopoietic stem or progenitor cells) are preferably administered intravenously. The amount of cells envisioned for use depends on the desired effect, patient state, etc., and can be determined by one skilled person in the art.
  • Cells into which a nucleic acid can be introduced for purposes of gene therapy encompass any desired, available cell type, and include but are not limited to epithelial cells, endothelial cells, keratinocytes, fibroblasts, muscle cells, hepatocytes; blood cells such as T lymphocytes, B lymphocytes, monocytes, macrophages, neutrophils, eosinophils, megakaryocytes, granulocytes; various stem or progenitor cells, in particular hematopoietic stem or progenitor cells, e.g., as obtained from bone marrow, umbilical cord blood, peripheral blood, fetal liver, etc.
  • In a preferred embodiment, the cell used for gene therapy is autologous to the patient.
  • In an embodiment in which recombinant cells are used in gene therapy, a nucleic acid is introduced into the cells such that it is expressible by the cells or their progeny, and the recombinant cells are then administered in vivo for therapeutic effect. In a specific embodiment, stem or progenitor cells are used. Such stem cells can be hematopoietic stem cells (HSC).
  • Any technique which provides for the isolation, propagation, and maintenance in vitro of HSC can be used in this embodiment of the invention. Techniques by which this may be accomplished include (a) the isolation and establishment of HSC cultures from bone marrow cells isolated from the future host, or a donor, or (b) the use of previously established long-term HSC cultures, which may be allogeneic or xenogeneic. Non-autologous HSC are used preferably in conjunction with a method of suppressing transplantation immune reactions of the future host/patient. In a particular embodiment of the present invention, human bone marrow cells can be obtained from the posterior iliac crest by needle aspiration (see e.g., Kodo et al., 1984, J. Clin. Invest. 73:1377-1384). The HSCs can be made highly enriched or in substantially pure form. This enrichment can be accomplished before, during, or after long-term culturing, and can be done by any techniques known in the art. Long-term cultures of bone marrow cells can be established and maintained by using, for example, modified Dexter cell culture techniques (Dexter et al., 1977, J. Cell Physiol. 91:335) or Witlock-Witte culture techniques (Witlock and Witte, 1982, Proc. Natl. Acad. Sci. U.S.A. 79:3608-3612).
  • In a specific embodiment, the nucleic acid to be introduced for purposes of gene therapy comprises an inducible promoter operably linked to the coding region, such that expression of the nucleic acid is controllable by controlling the presence or absence of the appropriate inducer of transcription.
  • The methods and/or compositions described above for modulating the expression and/or activity of a CML target gene or CML target protein may be used to treat patients in conjunction with a chemotherapeutic agent, e.g., Gleevec™
  • The effects or benefits of administration of the compositions of the invention alone or in conjunction with a chemotherapeutic agent can be evaluated by any methods known in the art, e.g., by methods that are based on measuring the survival rate, side effects, dosage requirement of the chemotherapeutic agent, or any combinations thereof. If the administration of the compositions of the invention achieves any one or more benefits in a patient, such as increasing the survival rate, decreasing side effects, lowing the dosage requirement for the chemotherapeutic agent, the compositions of the invention are said to have augmented a chemotherapy, and the method is said to have efficacy.
    • 5.4. Diagnosis and Treatment of CML by Targeting Cell Surface Expressed PRAME
  • The present invention provides methods and compositions for diagnosis and treatment of CML by targeting PRAME (GenBank® accession no. NM—006115) on cell surfaces of advanced phase hematopoetic stem cells and immature myeloid cells. PRAME is known to be expressed in testis and to expressed at a low level in endometrium, adrenals and ovaries, and is not expressed in other normal tissues. The inventors have found that PRAME is significantly overexpressed in advanced phase CML cells as compared to chronic phase CML cells. Thus, methods and compositions that target PRAME can be used for detecting advanced phase CML cells and for treating CML by selectively targeting advanced phase CML cells.
    • 5.4.1. Methods of Detecting Advanced Phase CML
  • Antibodies or labeled antibodies directed against a PRAME (Preferentially Expressed Antigen of Melanoma) can be used for evaluating CML progression, e.g., by detecting the presence of PRAME protein on cell surface of hematopoetic stem cells and immature myeloid cells. Such diagnostic/prognostic methods are particularly useful for detecting CML progression in unsorted samples.
  • The tissue or cell type to be analyzed may include those which are known to relate to CML, e.g., bone marrow or peripheral blood. The protein isolation methods employed herein may, for example, be such as those described in Harlow and Lane (Harlow, E. and Lane, D., 1988, “Antibodies: A Laboratory Manual”, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.), which is incorporated herein by reference in its entirety. The isolated cells can be derived from cell culture or from a patient. The analysis of cells taken from culture may be a necessary step in the assessment of cells to be used as part of a cell-based gene therapy technique or, alternatively, to test the effect of compounds for CML treatment.
  • In one embodiment, the invention provides a method for diagnosing whether a patient has advanced phase chronic myeloid leukemia (CML), comprising (a) contacting a cell sample from said patient with an antibody conjugate, said antibody conjugate comprising an antibody that binds a PRAME protein conjugated with a label; and (b) detecting said label in said sample, wherein detection of said label above a predetermined threshold indicating said patient has advanced phase CML. Detection of the labeled antibody can be performed using a method described in Section 5.2.5, supra.
    • 5.4.2. Methods of Treating CML by Targeting PRAME
  • The invention provides methods and compositions for treating CML by targeting PRAME expressed on the cell surface.
  • In one embodiment, the present invention provides methods of using anti-PRAME antibodies for treatment of a CML patient. In the methods of the invention, one or more anti-PRAME antibodies are administered to the patient. The anti-PRAME antibodies bind to PRAME on the surface of advanced phase CML hematopoetic stem cells and/or immature myeloid cells. The binding of anti-PRAME antibodies to PRAME blocks the function mediated by PRAME, thereby preventing the proliferation of advanced phase hematopoetic stem cells.
  • In another embodiment, the present invention provides a method for treatment of CML using an anti-PRAME antibody that belongs to an isotype that is capable of mediating lysis of cells to which the anti-PRAME antibody is bound. In a preferred embodiment, the anti-PRAME antibody belongs to an isotype that binds a growth factor receptor and activates serum complement and/or mediates antibody dependent cellular cytotoxicity (ADCC) by activating effector cells, e.g., macrophages. In another preferred embodiment, the isotype is IgG1, IgG2a, IgG3 or IgM.
  • In still another embodiment, the anti-PRAME antibodies are used in conjunction with one or more other chemotherapeutic drugs. In such combined therapies, the anti-PRAME antibodies can be administered in a manner such as described in Section 5.10.5.
  • The dosage of the anti-PRAME antibodies can be determined by routine experiments that are familiar to one skilled in the art. The effects or benefits of administration of the anti-PRAME antibodies can be evaluated by any method known in the art.
  • In another embodiment, an antibody-drug conjugate comprising an antibody that specifically binds PRAME and a chemotherapeutic drug is used to selectively deliver the chemotherapeutic drug to advanced phase CML hematopoetic stem cells and/or immature myeloid cells. Chemotherapeutic drugs normally spread throughout the body, reaching not only the intended target but also healthy cells/organs such as the intestines and healthy bone marrow, where they kill off normal dividing cells. A drug conjugated to PRAME should be able to selectively target the advance phase CML hematopoetic stem cells and/or immature myeloid cells, thus increasing the sensitivity and specificity of the drug. For example, an anti-PRAME antibody may be conjugated to a therapeutic moiety such as a cytotoxin, e.g., a cytostatic or cytocidal agent, or a radioactive metal ion (see, e.g., Section 5.8). Any suitable antibody-drug conjugate, e.g., those described in Section 5.8.3 can be used. Normal hematopoetic stem cells and/or myeloid cells lack PRAME and are not targeted by the antibody.
  • In still another embodiment, a peptide or a peptidomimetic that interferes with the interaction of PRAME with its interaction partner is used. A peptide preferably has a size of at least 5, 10, 15, 20 or 30 amino acids. Such a peptide or peptidomimetic can be designed by a person skilled in the art based on the sequence and structure of PRAME. In some embodiments of the invention, a PRAME fragment of at least 5, 10, 20, 50, 100 amino acids in length is used. In a specific embodiment, a peptide or peptidomimetic that interferes with the interaction with PRAME is used. The peptide can be prepared by a standard method known in the art (see, e.g., Section 5.8.4).
  • The invention also provides methods for treating CML using fragments of a PRAME protein as vaccines to elicit an immunotherapeutic response in a patient, e.g., an antibody response and/or a cell mediated immune response. Antibody responses involve the production of antibodies, which are proteins called immunoglobulins. The antibodies circulate in the bloodstream and permeate the other body fluids, where they bind specifically to the foreign antigen that elicited them. Binding by antibody inactivates advanced phase CML hematopoetic stem cells and/or immature myeloid cells by blocking their functions facilitated by PRAME. Antibody binding also marks advanced phase CML hematopoetic stem cells and/or immature myeloid cells, either by making it easier for a phagocytic cell to ingest them or by activating a system of blood proteins, collectively called complement, which kills the marked target cells.
  • Cell-mediated immune responses to PRAME involve the production of specialized cells that react with PRAME antigen on the surface of advanced phase CML cells. T lymphocytes, which develop in the thymus, are responsible for cell-mediated immunity. The majority of T lymphocytes, called helper T cells and suppressor T cells, play a regulatory role in immunity, acting either to enhance or suppress the responses of other white blood cells. Other T lymphocytes, called cytotoxic T cells (CTLs), kill virus-infected cells, parasites, and cancer cells. The surface of T cells contains transmembrane proteins called T cell receptors that recognize the PRAME antigen on the surface of PRAME presenting advanced phase CML cells. T cell receptors are antibody-like proteins. The antigen must be presented to the T cell by a particular membrane protein, one encoded by a complex of genes called the major histocompatibility complex (MHC). Histocompatibility molecules are expressed on the cells of all higher vertebrates. There are two principal classes of MHC molecules, class I MHC and class II MHC. Cytotoxic T lymphocytes (CTLs) recognize foreign antigens in association with class I MHC glycoproteins on the surface of an antigen-presenting cell, whereas helper T cells recognize foreign antigens in association with class II MHC glycoproteins on the surface of an antigen-presenting cell. A cytotoxic T lymphocyte will kill an antigen-presenting cell when it recognizes antigen bound to class I MHC molecules on the surface of the antigen-presenting cell. In one embodiment, a PRAME vaccine is used to elicit production of CTLs.
  • The PRAME protein fragment or polypeptide can be prepared by a standard method known in the art. In a specific embodiment, the fragment is a human PRAME protein fragment, or its murine homolog. In another embodiment, the vaccine comprises a peptide sequence that is at least 30%, 50%, 70%, 90%, or 95% homologous (e.g., over an equal size) to such fragments of a PRAME protein, e.g., as determined by a BLAST algorithm. In some embodiments, the PRAME protein fragments or polypeptides are at least 5, 10, 20, 50, 100 amino acids in length.
  • A peptide or polypeptide which is functionally equivalent to any PRAME fragment described above can also be used. Such an equivalent PRAME fragment may contain deletions, additions or substitutions of amino acid residues within the amino acid sequence encoded by the PRAME gene sequence but which result in a silent change, thus producing a functionally equivalent PRAME protein fragment. Amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues involved. Conservative substitutions may be made from among amino acids of the same polarity. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid. “Functionally equivalent”, as utilized herein, refers to a protein fragment capable of exhibiting a substantially similar in vivo activity as the endogenous PRAME protein fragment.
  • The PRAME peptide fragments may be produced by recombinant DNA technology using techniques well known in the art (see, e.g., Section 5.8.4).
  • The PRAME peptide can be used in combination with a suitable carrier and/or adjuvant, such as Freund's complete or incomplete adjuvant, or a similar immunostimulatory agent. An oil/surfactant based adjuvant comprising one or more surfactants combined with one or more non-metabolizable mineral oil or metabolizable oil, such as the Incomplete Seppic Adjuvant (Seppic, Paris, France), may be used. An Incomplete Seppic Adjuvant has a comparable effect as Incomplete Freund's Adjuvant for antibody production, but induces a lower inflammatory response.
  • A fragment of a PRAME gene can also be used as a DNA or RNA vaccine. In a specific embodiment, the fragment of a PRAME gene is a fragment of a human PRAME gene, or its murine homolog. The invention also provides any sequence that is at least 30%, 50%, 70%, 90%, or 95% homologous (e.g., over an equal size) to such fragments of a PRAME gene. In some embodiments of the invention, the fragment of a PRAME gene is at least 20, 25, 40, 60, 80, 100, 500, 1000 bases in length. Such sequences may be useful for production of PRAME peptides.
  • In another embodiment, the present invention provides a naked DNA or RNA vaccine comprising a fragment of a PRAME gene, and uses thereof. The PRAME DNA fragment can be administered as a vaccine to elicit anti-PRAME antibodies. The DNA can be converted to RNA for example by subcloning the DNA into a transcriptional vector, such as pGEM family of plasmid vectors, or under control of a transcriptional promoter of a virus such as vaccinia, and the RNA used as a naked RNA vaccine. The naked DNA or RNA vaccine can be injected alone, or combined with one or more DNA or RNA vaccines directed to PRAME.
  • The naked DNA or RNA vaccine of the present invention can be administered for example intramuscularly, or alternatively, can be used in nose drops. The DNA or RNA fragment or a portion thereof can be injected as naked DNA or RNA, as DNA or RNA encapsulated in liposomes, as DNA or RNA entrapped in proteoliposomes containing viral envelope receptor proteins (Nicolau, C. et al. Proc. Natl. Acad. Sci. U.S.A. 1983, 80, 1068; Kanoda, Y., et al. Science 1989, 243, 375; Mannino, R. J. et al. Biotechniques 1988, 6, 682). Alternatively, the DNA can be injected along with a carrier. A carrier can be a protein or such as a cytokine, for example interleukin 2, or a polylysine-glycoprotein carrier (Wu, G. Y. and Wu, C. H. J. Biol. Chem. 1988, 263, 14621), or a nonreplicating vector, for example expression vectors containing either the Rous sarcoma virus or cytomegalovirus promoters. Such carrier proteins and vectors and methods for using same are known to a person in the art (See for example, Acsadi, G. et al. Nature 1991, 352, 815-818). In addition, the DNA or RNA could be coated onto tiny gold beads and the beads introduced into the skin with, for example, a gene gun (Cohen, J. Science 1993, 259, 1691-1692; Ulmer, J. B. et al. Science 1993, 259, 1745-1749).
    • 5.4.3. Depletion of Advanced Phase CML Hematopoetic Stem Cells and/or Immature Myeloid Cells In Vitro
  • The invention provides methods of depleting advanced phase CML hematopoetic stem cells and/or immature myeloid cells from bone marrow or blood in vitro (or ex vivo). In particular, the invention provides for methods of depleting advanced phase CML hematopoetic stem cells and/or immature myeloid cells by killing them or by separating them from bone marrow or blood. In one embodiment, anti-PRAME antibodies are combined, e.g., incubated, in vitro with bone marrow or blood from a patient, e.g., a human.
  • In one embodiment, a column containing an anti-PRAME antibody bound to a solid matrix is used to remove advanced phase hematopoetic stem cells and/or immature myeloid cells from a bone marrow or blood sample.
  • The anti-PRAME antibodies used in the in vitro depletion of advanced phase CML hematopoetic stem cells and/or immature myeloid cells from samples can be conjugated to detectable labels (e.g., various enzymes, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials) or therapeutic agents (e.g., cytostatic and cytocidal agents), which are disclosed in section 5.8.3.
  • Anti-PRAME antibodies conjugated to detectable substances can be utilized to sort advanced phase hematopoetic stem cells and/or immature myeloid cells from bone marrow or peripheral blood samples by methods known to those of skill in the art. In one embodiment, advanced phase hematopoetic stem cells and/or immature myeloid cells are sorted using a fluorescence activated cell sorter (FACS). Fluorescence activated cell sorting (FACS) is a well-known method for separating particles, including cells, based on the fluorescent properties of the particles (Kamarch, 1987, Methods Enzymol, 151:150-165). Laser excitation of fluorescent moieties in the individual particles results in a small electrical charge allowing electromagnetic separation of positive and negative particles from a mixture.
  • In one embodiment, bone marrow or peripheral blood samples, obtained from a patient, e.g., a human, are incubated with fluorescently labeled PRAME specific antibodies for a time sufficient to allow the labeled antibodies to bind to the cells. In an alternative embodiment, such cells are incubated with PRAME specific antibodies, the cells are washed, and the cells are incubated with a second labeled antibody that recognizes the PRAME specific antibodies. In accordance with these embodiments, the cells are washed and processed through the cell sorter, allowing separation of cells that bind both antibodies to be separated from hybrid cells that do not bind both antibodies. FACS sorted particles may be directly deposited into individual wells of 96-well or 384-well plates to facilitate separation.
  • In another embodiment, magnetic beads can be used to separate advanced phase immature myeloid cells from bone marrow or peripheral blood samples. Advanced phase immature myeloid cells may be sorted using a magnetic activated cell sorting (MACS) technique, a method for separating particles based on their ability to bind magnetic beads (0.5-100 nm diameter) (Dynal, 1995). A variety of useful modifications can be performed on the magnetic microspheres, including covalent addition of antibody which immunospecifically recognizes PRAME. A magnetic field is then applied, to physically manipulate the selected beads. The beads are then mixed with the cells to allow binding. Cells are then passed through a magnetic field to separate out advanced phase CML hematopoetic stem cells and/or immature myeloid cells.
  • Bone marrow or peripheral blood sample from a patient that is depleted of advanced phase CML hematopoetic stem cells and/or immature myeloid cells can be used for autologous transplant treatment of the patient. Healthy bone marrow or peripheral blood cells from a sample depleted of advanced phase CML hematopoetic stem cells and/or immature myeloid cells can be collected. These cells can then be administered to the patient to replace the abnormal cells in the patient's bone marrow. Healthy bone marrow or peripheral blood cells can also be stored, e.g., frozen, for transplant at a later time.
    • 5.5. Methods for Screening Agents that Modulate CML Progression/Target or IM Resistance Proteins
  • Agents that modulate the expression or activity of a CML progression/target gene or encoded protein (or imatinib resistance gene or encoded protein), or modulate interaction of a CML progression/target protein (or imatinib resistance protein) with other proteins or molecules can be identified using a method described in this section. Such agents are useful in treating CML patients who exhibit aberrant regulation of these genes. In the following, for simplicity, methods directed to CML progression/target gene are described. These methods are equally applicable to imatinib resistance genes.
    • 5.5.1. Screening Assays
  • The following assays are designed to identify compounds that bind to a CML progression gene or its products, bind to other cellular proteins that interact with a CML progression protein, bind to cellular constituents, e.g., proteins, that are affected by a CML progression protein, or bind to compounds that interfere with the interaction of the CML progression gene or its product with other cellular proteins and to compounds which modulate the expression or activity of a CML progression gene (i.e., modulate the expression level of the CML progression gene and/or modulate the activity level of the CML progression protein). Assays may additionally be utilized which identify compounds which bind to CML progression protein regulatory sequences (e.g., promoter sequences), see e.g., Platt, K. A., 1994, J. Biol. Chem. 269:28558-28562, which is incorporated herein by reference in its entirety, which may modulate the level of CML progression gene expression. Compounds may include, but are not limited to, small organic molecules which are able to affect expression of the CML progression gene or some other gene involved in the CML progression protein pathways, or other cellular proteins. Further, among these compounds are compounds which affect the level of CML progression gene expression and/or CML progression protein activity and which can be used in the regulation of sensitivity to the effect of a chemotherapy agent.
  • Compounds may include, but are not limited to, peptides such as, for example, soluble peptides, including but not limited to, Ig-tailed fusion peptides, and members of random peptide libraries (see, e.g., Lam, K. S. et al., 1991, Nature 354:82-84; Houghten, R. et al., 1991, Nature 354:84-86), and combinatorial chemistry-derived molecular library made of D- and/or L-configuration amino acids, phosphopeptides (including, but not limited to members of random or partially degenerate, directed phosphopeptide libraries; see, e.g., Songyang, Z. et al., 1993, Cell 72:767-778), antibodies (including, but not limited to, polyclonal, monoclonal, humanized, anti-idiotypic, chimeric or single chain antibodies, and Fab, F(ab′)2 and Fab expression library fragments, and epitope-binding fragments thereof), and small organic or inorganic molecules.
  • Compounds identified via assays such as those described herein may be useful, for example, in modulating the biological function of the CML progression protein.
  • In vitro systems may be designed to identify compounds capable of binding a CML progression protein. Compounds identified may be useful, for example, in modulating the activity of wild type and/or mutant CML progression protein, may be useful in elaborating the biological function of the CML progression protein, may be utilized in screens for identifying compounds that disrupt normal CML progression protein interactions, or may in themselves disrupt such interactions.
  • The principle of the assays used to identify compounds that bind to the CML progression protein involves preparing a reaction mixture of the CML progression protein and the test compound under conditions and for a time sufficient to allow the two components to interact and bind, thus forming a complex which can be removed and/or detected in the reaction mixture. These assays can be conducted in a variety of ways. For example, one method to conduct such an assay would involve anchoring CML progression protein or the test substance onto a solid phase and detecting CML progression protein/test compound complexes anchored on the solid phase at the end of the reaction. In one embodiment of such a method, the CML progression protein may be anchored onto a solid surface, and the test compound, which is not anchored, may be labeled, either directly or indirectly.
  • In practice, microtiter plates may conveniently be utilized as the solid phase. The anchored component may be immobilized by non-covalent or covalent attachments. Non-covalent attachment may be accomplished by simply coating the solid surface with a solution of the protein and drying. Alternatively, an immobilized antibody, preferably a monoclonal antibody, specific for the protein to be immobilized may be used to anchor the protein to the solid surface. The surfaces may be prepared in advance and stored.
  • In order to conduct the assay, the nonimmobilized component is added to the coated surface containing the anchored component. After the reaction is complete, unreacted components are removed (e.g., by washing) under conditions such that any complexes formed will remain immobilized on the solid surface. The detection of complexes anchored on the solid surface can be accomplished in a number of ways. Where the previously nonimmobilized component is pre-labeled, the detection of label immobilized on the surface indicates that complexes were formed. Where the previously nonimmobilized component is not pre-labeled, an indirect label can be used to detect complexes anchored on the surface; e.g., using a labeled antibody specific for the previously nonimmobilized component (the antibody, in turn, may be directly labeled or indirectly labeled with a labeled anti-Ig antibody).
  • Alternatively, a reaction can be conducted in a liquid phase, the reaction products separated from unreacted components, and complexes detected; e.g., using an immobilized antibody specific for a CML progression protein or the test compound to anchor any complexes formed in solution, and a labeled antibody specific for the other component of the possible complex to detect anchored complexes.
  • The CML progression gene or CML progression protein may interact in vivo with one or more intracellular or extracellular molecules, such as proteins. For purposes of this discussion, such molecules are referred to herein as “binding partners”. Compounds that disrupt CML progression protein binding may be useful in modulating the activity of the CML progression protein. Compounds that disrupt CML progression gene binding may be useful in modulating the expression of the CML progression gene, such as by modulating the binding of a regulator of CML progression gene. Such compounds may include, but are not limited to molecules such as peptides which would be capable of gaining access to the CML progression protein.
  • The basic principle of the assay systems used to identify compounds that interfere with the interaction between the CML progression protein and its intracellular or extracellular binding partner or partners involves preparing a reaction mixture containing the CML progression protein, and the binding partner under conditions and for a time sufficient to allow the two to interact and bind, thus forming a complex. In order to test a compound for inhibitory activity, the reaction mixture is prepared in the presence and absence of the test compound. The test compound may be initially included in the reaction mixture, or may be added at a time subsequent to the addition of a CML progression protein and its binding partner. Control reaction mixtures are incubated without the test compound or with a placebo. The formation of any complexes between the CML progression protein and the binding partner is then detected. The formation of a complex in the control reaction, but not in the reaction mixture containing the test compound, indicates that the compound interferes with the interaction of the CML progression protein and the interactive binding partner. Additionally, complex formation within reaction mixtures containing the test compound and a normal CML progression protein may also be compared to complex formation within reaction mixtures containing the test compound and a mutant CML progression protein. This comparison may be important in those cases where it is desirable to identify compounds that disrupt interactions of mutant but not the normal CML progression protein.
  • The assay for compounds that interfere with the interaction of the CML progression proteins and binding partners can be conducted in a heterogeneous or homogeneous format. Heterogeneous assays involve anchoring either the CML progression protein or the binding partner onto a solid phase and detecting complexes anchored on the solid phase at the end of the reaction. In homogeneous assays, the entire reaction is carried out in a liquid phase. In either approach, the order of addition of reactants can be varied to obtain different information about the compounds being tested. For example, test compounds that interfere with the interaction between the CML progression proteins and the binding partners, e.g., by competition, can be identified by conducting the reaction in the presence of the test substance; i.e., by adding the test substance to the reaction mixture prior to or simultaneously with the CML progression protein and interactive binding partner. Alternatively, test compounds that disrupt preformed complexes, e.g. compounds with higher binding constants that displace one of the components from the complex, can be tested by adding the test compound to the reaction mixture after complexes have been formed. The various formats are described briefly below.
  • In a heterogeneous assay system, either the CML progression protein or its interactive binding partner, is anchored onto a solid surface, while the non-anchored species is labeled, either directly or indirectly. In practice, microtiter plates are conveniently utilized. The anchored species may be immobilized by non-covalent or covalent attachments. Non-covalent attachment may be accomplished simply by coating the solid surface with a solution of the CML progression protein or binding partner and drying. Alternatively, an immobilized antibody specific for the species to be anchored may be used to anchor the species to the solid surface. The surfaces may be prepared in advance and stored.
  • In order to conduct the assay, the partner of the immobilized species is exposed to the coated surface with or without the test compound. After the reaction is complete, unreacted components are removed (e.g., by washing) and any complexes formed will remain immobilized on the solid surface. The detection of complexes anchored on the solid surface can be accomplished in a number of ways. Where the non-immobilized species is pre-labeled, the detection of label immobilized on the surface indicates that complexes were formed. Where the non-immobilized species is not pre-labeled, an indirect label can be used to detect complexes anchored on the surface; e.g., using a labeled antibody specific for the initially non-immobilized species (the antibody, in turn, may be directly labeled or indirectly labeled with a labeled anti-Ig antibody). Depending upon the order of addition of reaction components, test compounds which inhibit complex formation or which disrupt preformed complexes can be detected.
  • Alternatively, the reaction can be conducted in a liquid phase in the presence or absence of the test compound, the reaction products separated from unreacted components, and complexes detected; e.g., using an immobilized antibody specific for one of the binding components to anchor any complexes formed in solution, and a labeled antibody specific for the other partner to detect anchored complexes. Again, depending upon the order of addition of reactants to the liquid phase, test compounds which inhibit complex or which disrupt preformed complexes can be identified.
  • In an alternative embodiment of the invention, a homogeneous assay can be used. In this approach, a preformed complex of the CML progression protein and the interactive binding partner is prepared in which either the CML progression protein or its binding partners is labeled, but the signal generated by the label is quenched due to complex formation (see, e.g., U.S. Pat. No. 4,109,496 which utilizes this approach for immunoassays). The addition of a test substance that competes with and displaces one of the species from the preformed complex will result in the generation of a signal above background. In this way, test substances which disrupt CML progression protein/binding partner interaction can be identified.
  • In a particular embodiment, the CML progression protein can be prepared for immobilization using recombinant DNA techniques. For example, the coding region of CML progression gene can be fused to a glutathione-S-transferase (GST) gene using a fusion vector, such as pGEX-5X-1, in such a manner that its binding activity is maintained in the resulting fusion protein. The interactive binding partner can be purified and used to raise a monoclonal antibody, using methods routinely practiced in the art. This antibody can be labeled with the radioactive isotope 125I, for example, by methods routinely practiced in the art. In a heterogeneous assay, e.g., the GST-CML progression protein fusion protein can be anchored to glutathione-agarose beads. The interactive binding partner can then be added in the presence or absence of the test compound in a manner that allows interaction and binding to occur. At the end of the reaction period, unbound material can be washed away, and the labeled monoclonal antibody can be added to the system and allowed to bind to the complexed components. The interaction between the CML progression protein and the interactive binding partner can be detected by measuring the amount of radioactivity that remains associated with the glutathione-agarose beads. A successful inhibition of the interaction by the test compound will result in a decrease in measured radioactivity.
  • Alternatively, the GST-CML progression protein fusion protein and the interactive binding partner can be mixed together in liquid in the absence of the solid glutathione-agarose beads. The test compound can be added either during or after the species are allowed to interact. This mixture can then be added to the glutathione-agarose beads and unbound material is washed away. Again the extent of inhibition of the CML progression protein/binding partner interaction can be detected by adding the labeled antibody and measuring the radioactivity associated with the beads.
  • In another embodiment of the invention, these same techniques can be employed using peptide fragments that correspond to the binding domains of the CML progression protein and/or the interactive binding partner (in cases where the binding partner is a protein), in place of one or both of the full length proteins. Any number of methods routinely practiced in the art can be used to identify and isolate the binding sites. These methods include, but are not limited to, mutagenesis of the gene encoding one of the proteins and screening for disruption of binding in a co-immunoprecipitation assay. Compensating mutations in the gene encoding the second species in the complex can then be selected. Sequence analysis of the genes encoding the respective proteins will reveal the mutations that correspond to the region of the protein involved in interactive binding. Alternatively, one protein can be anchored to a solid surface using methods described in this section above, and allowed to interact with and bind to its labeled binding partner, which has been treated with a proteolytic enzyme, such as trypsin. After washing, a short, labeled peptide comprising the binding domain may remain associated with the solid material, which can be isolated and identified by amino acid sequencing. Also, once the gene coding for the binding partner is obtained, short gene segments can be engineered to express peptide fragments of the protein, which can then be tested for binding activity and purified or synthesized.
  • For example, and not by way of limitation, a CML progression protein can be anchored to a solid material as described in this section, above, by making a GST-CML progression protein fusion protein and allowing it to bind to glutathione agarose beads. The interactive binding partner can be labeled with a radioactive isotope, such as 35S, and cleaved with a proteolytic enzyme such as trypsin. Cleavage products can then be added to the anchored GST-CML progression protein fusion protein and allowed to bind. After washing away unbound peptides, labeled bound material, representing the binding partner binding domain, can be eluted, purified, and analyzed for amino acid sequence by well-known methods. Peptides so identified can be produced synthetically or fused to appropriate facilitative proteins using recombinant DNA technology.
  • Some CML progression proteins are kinases. Kinase activity of a CML progression protein can be assayed in vitro using a synthetic peptide substrate of a CML progression protein of interest, e.g., a GSK-derived biotinylated peptide substrate. The phosphopeptide product is quantitated using a Homogenous Time-Resolved Fluorescence (HTRF) assay system (Park et al., 1999, Anal. Biochem. 269:94-104). The reaction mixture contains suitable amounts of ATP, peptide substrate, and the CML progression protein. The peptide substrate has a suitable amino acid sequence and is biotinylated at the N-terminus. The kinase reaction is incubated, and then terminated with Stop/Detection Buffer and GSK3 cc anti-phosphoserine antibody (e.g., Cell Signaling Technologies, Beverly, Mass.; Cat#9338) labeled with europium-chelate (e.g., from Perkin Elmer, Boston, Mass.). The reaction is allowed to equilibrate, and relative fluorescent units are determined Inhibitor compounds are assayed in the reaction described above, to determine compound IC50s. A particular compound is added to in a half-log dilution series covering a suitable range of concentrations, e.g., from 1 nM to 100 μM. Relative phospho substrate formation, read as HTRF fluorescence units, is measured over the range of compound concentrations and a titration curve generated using a four parameter sigmoidal fit. Specific compounds having IC50 below a predetermined threshold value, e.g., ≦50 μM against a substrate, can be identified.
  • The extent of peptide phosphorylation can be determined by Homogeneous Time Resolved Fluorescence (HTRF) using a lanthanide chelate (Lance)-coupled monoclonal antibody specific for the phosphopeptide in combination with a streptavidin-linked allophycocyanin (SA-APC) fluorophore which binds to the biotin moiety on the peptide. When the Lance and APC are in proximity (i.e. bound to the same phosphopeptide molecule), a non-radiative energy transfer takes place from the Lance to the APC, followed by emission of light from APC at 665 nm. The assay can be run using various assay format, e.g., streptavidin flash plate assay, streptavidin filter plate assay.
  • A standard PKA assay can be used to assay the activity of protein kinase A (PKA). A standard PKC assay can be used to assay the activity of protein kinase C(PKC). The most common methods for assaying PKA or PKC activity involves measuring the transfer of 32P-labeled phosphate to a protein or peptide substrate that can be captured on phosphocellulose filters via weak electrostatic interactions.
  • Kinase inhibitors can be identified using fluorescence polarization to monitor kinase activity. This assay utilizes GST-CML progression protein, peptide substrate, peptide substrate tracer, an anti-phospho monoclonal IgG, and the inhibitor compound. Reactions are incubated for a period of time and then terminated. Stopped reactions are incubated and fluorescence polarization values determined.
  • In a specific embodiment, a standard SPA Filtration Assay and FlashPlate® Kinase Assay can be used to measure the activity of a CML progression protein. In these assays, GST-CML progression protein, biotinylated peptide substrate, ATP, and 33P-γ-ATP are allowed to react. After a suitable period of incubation, the reactions are terminated. In a SPA Filtration Assay, peptide substrate is allowed to bind Scintilation proximity assay (SPA) beads (Amersham Biosciences), followed by filtration on a Packard GF/B Unifilter plate and washed with phosphate buffered saline. Dried plates are sealed and the amount of 33P incorporated into the peptide substrate is determined. In a FlashPlate® Kinase Assay, a suitable amount of the reaction is transferred to streptavidin-coated FlashPlates® (NEN) and incubated. Plates are washed, dried, sealed and the amount of 33P incorporated into the peptide substrate is determined
  • A standard DELFIA® Kinase Assay can also be used. In a DELFIA® Kinase Assay, GST-CML progression protein, peptide substrate, and ATP are allowed to react. After the reactions are terminated, the biotin-peptide substrates are captured in the stopped reactions. Wells are washed and reacted with anti-phospho polyclonal antibody and europium labeled anti-rabbit-IgG. Wells are washed and europium released from the bound antibody is detected.
  • Other assays, such as those described in WO 04/080973, WO 02/070494, and WO 03/101444, may also be utilized to determine biological activity of the instant compounds.
    • 5.5.2. Screening Compounds that Modulate Expression or Activity of a Gene and/or its Products
  • For CML progression genes that are kinases, inhibitor compounds can be assayed for their ability to inhibit a CML progression protein in hematopoetic stem cells and/or immature myeloid cells by monitoring the phosphorylation or autophosphorylation in response to the compound. Cells are grown in culture medium. Cells are pooled, counted, seeded into 6 well dishes at 200,000 cells per well in 2 ml media, and incubated. Serial dilution series of compounds or control are added to each well and incubated. Following the incubation period, each well is washed and Protease Inhibitor Cocktail Complete is added to each well. Lysates are then transferred to microcentrifuge tubes and frozen at −80° C. Lysates are thawed on ice and cleared by centrifugation and the supernatants are transferred to clean tubes. Samples are electorphoresed and proteins are transferred onto PVDF. Blots are then blocked and probed using an antibody against phospho-serine or phospho threonine. Bound antibody is visualized using a horseradish peroxidase conjugated secondary antibody and enhanced chemiluminescence. After stripping of the first antibody set, blots are re-probed for total CML progression protein, using a monoclonal antibody specific for the CML progression protein. The CML progression protein monoclonal is detected using a sheep anti-mouse IgG coupled to horseradish peroxidase and enhanced chemiluminescence. ECL exposed films are scanned and the intensity of specific bands is quantitated. Titrations are evaluated for level of phosphor-Ser signal normalized to total CML progression protein and IC50 values are calculated.
  • Detection of phosphonucleolin in cell lysates can be carried out using biotinylated anti-nucleolin antibody and ruthenylated goat anti-mouse antibody. To each well of a 96-well plate is added biotynylated anti-nucleolin antibody and streptavidin coated paramagnetic beads, along with a suitable cell lysate. The antibodies and lysate are incubated. Next, another anti-phosphonucleolin antibody are added to each well of the lysate mix and incubated. Lastly, the ruthenylated goat anti-mouse antibody in antibody buffer is added to each well and incubated. The lysate antibody mixtures are read and EC50s for compound dependent increases in phosphor-nucleolin are determined.
  • The compounds identified in the screen include compounds that demonstrate the ability to selectively modulate the expression or activity of a CML progression gene or its encoded protein. These compounds include but are not limited to siRNA, antisense nucleic acid, ribozyme, triple helix forming nucleic acid, antibody, and polypeptide molecules, aptamers, and small organic or inorganic molecules.
    • 5.6. Methods of Performing RNA Interference
  • Any method known in the art for gene silencing can be used in the present invention (see, e.g., Guo et al., 1995, Cell 81:611-620; Fire et al., 1998, Nature 391:806-811; Grant, 1999, Cell 96:303-306; Tabara et al., 1999, Cell 99:123-132; Zamore et al., 2000, Cell 101:25-33; Bass, 2000, Cell 101:235-238; Petcherski et al., 2000, Nature 405:364-368; Elbashir et al., Nature 411:494-498; Paddison et al., Proc. Natl. Acad. Sci. USA 99:1443-1448). The siRNAs targeting a gene can be designed according to methods known in the art (see, e.g., International Application Publication No. WO 2005/018534, published on Mar. 3, 2005, and Elbashir et al., 2002, Methods 26:199-213, each of which is incorporated herein by reference in its entirety).
  • An siRNA having only partial sequence homology to a target gene can also be used (see, e.g., International Application Publication No. WO 2005/018534, published on Mar. 3, 2005, which is incorporated herein by reference in its entirety). In one embodiment, an siRNA that comprises a sense strand contiguous nucleotide sequence of 11-18 nucleotides that is identical to a sequence of a transcript of a gene but the siRNA does not have full length homology to any sequences in the transcript is used to silence the gene. Preferably, the contiguous nucleotide sequence is in the central region of the siRNA molecules. A contiguous nucleotide sequence in the central region of an siRNA can be any continuous stretch of nucleotide sequence in the siRNA which does not begin at the 3′ end. For example, a contiguous nucleotide sequence of 11 nucleotides can be the nucleotide sequence 2-12, 3-13, 4-14, 5-15, 6-16, 7-17, 8-18, or 9-19. In preferred embodiments, the contiguous nucleotide sequence is 11-16, 11-15, 14-15, 11, 12, or 13 nucleotides in length.
  • In another embodiment, an siRNA that comprises a 3′ sense strand contiguous nucleotide sequence of 9-18 nucleotides which is identical to a sequence of a transcript of a gene but which siRNA does not have full length sequence identity to any contiguous sequences in the transcript is used to silence the gene. In this application, a 3′ 9-18 nucleotide sequence is a continuous stretch of nucleotides that begins at the first paired base, i.e., it does not comprise the two base 3′ overhang. Thus, when it is stated that a particular nucleotide sequence is at the 3′ end of the siRNA, the 2 base overhang is not considered. In preferred embodiments, the contiguous nucleotide sequence is 9-16, 9-15, 9-12, 11, 10, or 9 nucleotides in length.
  • An siRNA having only partial sequence homology to its target genes is especially useful for silencing a plurality of different genes in a cell. In one embodiment, an siRNA is used to silence a plurality of different genes, the transcript of each of the genes comprises a nucleotide sequence that is identical to a central contiguous nucleotide sequence of at least 11 nucleotides of the sense strand or the antisense strand of the siRNA, and/or comprises a nucleotide sequence that is identical to a contiguous nucleotide sequence of at least 9 nucleotides at the 3′ end of the sense strand or the antisense strand of the siRNA. In preferred embodiments, the central contiguous nucleotide sequence is 11-15, 14-15, 11, 12, or 13 nucleotides in length. In other preferred embodiments, the 3′ contiguous nucleotide sequence is 9-15, 9-12, 11, 10, or 9 nucleotides in length.
  • In one embodiment, in vitro siRNA transfection is carried out as follows: one day prior to transfection, 100 microliters of chosen cells, e.g., cervical cancer HeLa cells (ATCC, Cat. No. CCL-2), grown in DMEM/10% fetal bovine serum (Invitrogen, Carlsbad, Calif.) to approximately 90% confluency are seeded in a 96-well tissue culture plate (Corning, Corning, N.Y.) at 1500 cells/well. For each transfection 85 microliters of OptiMEM (Invitrogen) is mixed with 5 microliter of serially diluted siRNA (Dharma on, Denver) from a 20 micro molar stock. For each transfection 5 microliter OptiMEM is mixed with 5 microliter Oligofectamine reagent (Invitrogen) and incubated 5 minutes at room temperature. The 10 microliter OptiMEM/Oligofectamine mixture is dispensed into each tube with the OptiMEM/siRNA mixture, mixed and incubated 15-20 minutes at room temperature. 10 microliter of the transfection mixture is aliquoted into each well of the 96-well plate and incubated for 4 hours at 37° C. and 5% CO2.
  • In preferred embodiments, an siRNA pool containing at least k (k=2, 3, 4, 5, 6 or 10) different siRNAs targeting the secondary target gene at different sequence regions is used to transfect the cells. In another preferred embodiment, an siRNA pool containing at least k (k=2, 3, 4, 5, 6 or 10) different siRNAs targeting two or more different target genes is used to transfect the cells.
  • In a preferred embodiment, the total siRNA concentration of the pool is about the same as the concentration of a single siRNA when used individually, e.g., 100 nM. Preferably, the total concentration of the pool of siRNAs is an optimal concentration for silencing the intended target gene. An optimal concentration is a concentration further increase of which does not increase the level of silencing substantially. In one embodiment, the optimal concentration is a concentration further increase of which does not increase the level of silencing by more than 5%, 10% or 20%. In a preferred embodiment, the composition of the pool, including the number of different siRNAs in the pool and the concentration of each different siRNA, is chosen such that the pool of siRNAs causes less than 30%, 20%, 10% or 5%, 1%, 0.1% or 0.01% of silencing of any off-target genes (e.g., as determined by standard nucleic acid assay, e.g., PCR). In another preferred embodiment, the concentration of each different siRNA in the pool of different siRNAs is about the same. In still another preferred embodiment, the respective concentrations of different siRNAs in the pool are different from each other by less than 5%, 10%, 20% or 50% of the concentration of any one siRNA or said total siRNA concentration of said different siRNAs. In still another preferred embodiment, at least one siRNA in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In still another preferred embodiment, none of the siRNAs in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In other embodiments, each siRNA in the pool has an concentration that is lower than the optimal concentration when used individually. In a preferred embodiment, each different siRNA in the pool has an concentration that is lower than the concentration of the siRNA that is effective to achieve at least 30%, 50%, 75%, 80%, 85%, 90% or 95% silencing when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In another preferred embodiment, each different siRNA in the pool has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the gene when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In a preferred embodiment, each siRNA has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the target gene when used alone, while the plurality of siRNAs causes at least 80% or 90% of silencing of the target gene.
  • Another method for gene silencing is to introduce an shRNA, for short hairpin RNA (see, e.g., Paddison et al., 2002, Genes Dev. 16, 948-958; Brummelkamp et al., 2002, Science 296, 550-553; Sui, G. et al. 2002, Proc. Natl. Acad. Sci. USA 99, 5515-5520, all of which are incorporated by reference herein in their entirety), which can be processed in the cells into siRNA. In this method, a desired siRNA sequence is expressed from a plasmid (or virus) as an inverted repeat with an intervening loop sequence to form a hairpin structure. The resulting RNA transcript containing the hairpin is subsequently processed by Dicer to produce siRNAs for silencing. Plasmid-based shRNAs can be expressed stably in cells, allowing long-term gene silencing in cells both in vitro and in vivo, e.g., in animals (see, McCaffrey et al. 2002, Nature 418, 38-39; Xia et al., 2002, Nat. Biotech. 20, 1006-1010; Lewis et al., 2002, Nat. Genetics 32, 107-108; Rubinson et al., 2003, Nat. Genetics 33, 401-406; Tiscornia et al., 2003, Proc. Natl. Acad. Sci. USA 100, 1844-1848, all of which are incorporated by reference herein in their entirety). Thus, in one embodiment, a plasmid-based shRNA is used.
  • In a preferred embodiment, shRNAs are expressed from recombinant vectors introduced either transiently or stably integrated into the genome (see, e.g., Paddison et al., 2002, Genes Dev 16:948-958; Sui et al., 2002, Proc Natl Acad Sci USA 99:5515-5520; Yu et al., 2002, Proc Natl Acad Sci USA 99:6047-6052; Miyagishi et al., 2002, Nat Biotechnol 20:497-500; Paul et al., 2002, Nat Biotechnol 20:505-508; Kwak et al., 2003, J Pharmacol Sci 93:214-217; Brummelkamp et al., 2002, Science 296:550-553; Boden et al., 2003, Nucleic Acids Res 31:5033-5038; Kawasaki et al., 2003, Nucleic Acids Res 31:700-707). The siRNA that disrupts the target gene can be expressed (via an shRNA) by any suitable vector which encodes the shRNA. The vector can also encode a marker which can be used for selecting clones in which the vector or a sufficient portion thereof is integrated in the host genome such that the shRNA is expressed. Any standard method known in the art can be used to deliver the vector into the cells. In one embodiment, cells expressing the shRNA are generated by transfecting suitable cells with a plasmid containing the vector. Cells can then be selected by the appropriate marker. Clones are then picked, and tested for knockdown. In a preferred embodiment, the expression of the shRNA is under the control of an inducible promoter such that the silencing of its target gene can be turned on when desired. Inducible expression of an siRNA is particularly useful for targeting essential genes.
  • In one embodiment, the expression of the shRNA is under the control of a regulated promoter that allows tuning of the silencing level of the target gene. This allows screening against cells in which the target gene is partially knocked out. As used herein, a “regulated promoter” refers to a promoter that can be activated when an appropriate inducing agent is present. An “inducing agent” can be any molecule that can be used to activate transcription by activating the regulated promoter. An inducing agent can be, but is not limited to, a peptide or polypeptide, a hormone, or an organic small molecule. An analogue of an inducing agent, i.e., a molecule that activates the regulated promoter as the inducing agent does, can also be used. The level of activity of the regulated promoter induced by different analogues may be different, thus allowing more flexibility in tuning the activity level of the regulated promoter. The regulated promoter in the vector can be any mammalian transcription regulation system known in the art (see, e.g., Gossen et al, 1995, Science 268:1766-1769; Lucas et al, 1992, Annu. Rev. Biochem. 61:1131; Li et al., 1996, Cell 85:319-329; Saez et al., 2000, Proc. Natl. Acad. Sci. USA 97:14512-14517; and Pollock et al., 2000, Proc. Natl. Acad. Sci. USA 97:13221-13226). In preferred embodiments, the regulated promoter is regulated in a dosage and/or analogue dependent manner. In one embodiment, the level of activity of the regulated promoter is tuned to a desired level by a method comprising adjusting the concentration of the inducing agent to which the regulated promoter is responsive. The desired level of activity of the regulated promoter, as obtained by applying a particular concentration of the inducing agent, can be determined based on the desired silencing level of the target gene.
  • In one embodiment, a tetracycline regulated gene expression system is used (see, e.g., Gossen et al, 1995, Science 268:1766-1769; U.S. Pat. No. 6,004,941). A tet regulated system utilizes components of the tet repressor/operator/inducer system of prokaryotes to regulate gene expression in eukaryotic cells. Thus, the invention provides methods for using the tet regulatory system for regulating the expression of an shRNA linked to one or more tet operator sequences. The methods involve introducing into a cell a vector encoding a fusion protein that activates transcription. The fusion protein comprises a first polypeptide that binds to a tet operator sequence in the presence of tetracycline or a tetracycline analogue operatively linked to a second polypeptide that activates transcription in cells. By modulating the concentration of a tetracycline, or a tetracycline analogue, expression of the tet operator-linked shRNA is regulated.
  • In other embodiments, an ecdyson regulated gene expression system (see, e.g., Saez et al., 2000, Proc. Natl. Acad. Sci. USA 97:14512-14517), or an MMTV glucocorticoid response element regulated gene expression system (see, e.g., Lucas et al, 1992, Annu. Rev. Biochem. 61:1131) may be used to regulate the expression of the shRNA.
  • In one embodiment, the pRETRO-SUPER (pRS) vector which encodes a puromycin-resistance marker and drives shRNA expression from an H1 (RNA Pol III) promoter is used. The pRS-shRNA plasmid can be generated by any standard method known in the art. In one embodiment, the pRS-shRNA is deconvoluted from the library plasmid pool for a chosen gene by transforming bacteria with the pool and looking for clones containing only the plasmid of interest. Preferably, a 19mer siRNA sequence is used along with suitable forward and reverse primers for sequence specific PCR. Plasmids are identified by sequence specific PCR, and confirmed by sequencing. Cells expressing the shRNA are generated by transfecting suitable cells with the pRS-shRNA plasmid. Cells are selected by the appropriate marker, e.g., puromycin, and maintained until colonies are evident. Clones are then picked, and tested for knockdown. In another embodiment, an shRNA is expressed by a plasmid, e.g., a pRS-shRNA. The knockdown by the pRS-shRNA plasmid, can be achieved by transfecting cells using Lipofectamine 2000 (Invitrogen).
  • In yet another method, siRNAs can be delivered to an organ or tissue in an animal, such a human, in vivo (see, e.g., Song et al. 2003, Nat. Medicine 9, 347-351; Sorensen et al., 2003, J. Mol. Biol. 327, 761-766; Lewis et al., 2002, Nat. Genetics 32, 107-108, all of which are incorporated by reference herein in their entirety). In this method, a solution of siRNA is injected intravenously into the animal. The siRNA can then reach an organ or tissue of interest and effectively reduce the expression of the target gene in the organ or tissue of the animal.
    • 5.7. Production of CML Progression/Target or IM Resistance Proteins and Peptides
  • CML progression proteins, or peptide fragments thereof, can be prepared for uses according to the present invention. For example, CML progression proteins, or peptide fragments thereof, can be used for the generation of antibodies, in diagnostic assays, for screening of inhibitors, or for the identification of other cellular gene products involved in the regulation of expression and/or activity of a CML progression gene.
  • The CML progression proteins or peptide fragments thereof, may be produced by recombinant DNA technology using techniques well known in the art. The amino acid sequences of the CML progression proteins are well-known and can be obtained from, e.g., GenBank®. Methods which are well known to those skilled in the art can be used to construct expression vectors containing CML progression protein coding sequences and appropriate transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. See, for example, the techniques described in Sambrook et al., 1989, supra, and Ausubel et al., 1989, supra. Alternatively, RNA capable of encoding CML progression protein sequences may be chemically synthesized using, for example, synthesizers. See, for example, the techniques described in “Oligonucleotide Synthesis”, 1984, Gait, M. J. ed., IRL Press, Oxford, which is incorporated herein by reference in its entirety.
  • A variety of host-expression vector systems may be utilized to express the CML progression gene coding sequences. Such host-expression systems represent vehicles by which the coding sequences of interest may be produced and subsequently purified, but also represent cells which may, when transformed or transfected with the appropriate nucleotide coding sequences, exhibit the CML progression protein in situ. These include but are not limited to microorganisms such as bacteria (e.g., E. coli, B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing CML progression protein coding sequences; yeast (e.g., Saccharomyces, Pichia) transformed with recombinant yeast expression vectors containing the CML progression protein coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing the CML progression protein coding sequences; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing CML progression protein coding sequences; or mammalian cell systems (e.g., COS, CHO, BHK, 293, 3T3, N2a) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter).
  • In bacterial systems, a number of expression vectors may be advantageously selected depending upon the use intended for the CML progression protein being expressed. For example, when a large quantity of such a protein is to be produced, for the generation of pharmaceutical compositions of CML progression protein protein or for raising antibodies to CML progression protein protein, for example, vectors which direct the expression of high levels of fusion protein products that are readily purified may be desirable. Such vectors include, but are not limited, to the E. coli expression vector pUR278 (Ruther et al., 1983, EMBO J. 2:1791), in which the CML progression protein coding sequence may be ligated individually into the vector in frame with the lac Z coding region so that a fusion protein is produced; pIN vectors (Inouye & Inouye, 1985, Nucleic Acids Res. 13:3101-3109; Van Heeke & Schuster, 1989, J. Biol. Chem. 264:5503-5509); and the like. pGEX vectors may also be used to express foreign polypeptides as fusion proteins with glutathione S-transferase (GST). In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption to glutathione-agarose beads followed by elution in the presence of free glutathione. The pGEX vectors are designed to include thrombin or factor Xa protease cleavage sites so that the cloned target gene product can be released from the GST moiety.
  • In an insect system, Autographa californica nuclear polyhedrosis virus (AcNPV) is used as a vector to express foreign genes. The virus grows in Spodoptera frugiperda cells. The CML progression gene coding sequence may be cloned individually into non-essential regions (for example the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (for example the polyhedrin promoter). Successful insertion of CML progression gene coding sequence will result in inactivation of the polyhedrin gene and production of non-occluded recombinant virus (i.e., virus lacking the proteinaceous coat coded for by the polyhedrin gene). These recombinant viruses are then used to infect Spodoptera frugiperda cells in which the inserted gene is expressed. (E.g., see Smith et al., 1983, J. Virol. 46: 584; Smith, U.S. Pat. No. 4,215,051).
  • In mammalian host cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, the CML progression gene coding sequence of interest may be ligated to an adenovirus transcription/translation control complex, e.g., the late promoter and tripartite leader sequence. This chimeric gene may then be inserted in the adenovirus genome by in vitro or in vivo recombination. Insertion in a non-essential region of the viral genome (e.g., region E1 or E3) will result in a recombinant virus that is viable and capable of expressing CML progression protein in infected hosts. (E.g., See Logan & Shenk, 1984, Proc. Natl. Acad. Sci. USA 81:3655-3659). Specific initiation signals may also be required for efficient translation of inserted CML progression protein coding sequences. These signals include the ATG initiation codon and adjacent sequences. In cases where an entire CML progression gene, including its own initiation codon and adjacent sequences, is inserted into the appropriate expression vector, no additional translational control signals may be needed. However, in cases where only a portion of the CML progression gene coding sequence is inserted, exogenous translational control signals, including, perhaps, the ATG initiation codon, must be provided. Furthermore, the initiation codon must be in phase with the reading frame of the desired coding sequence to ensure translation of the entire insert. These exogenous translational control signals and initiation codons can be of a variety of origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of appropriate transcription enhancer elements, transcription terminators, etc. (see Bittner et al., 1987, Methods in Enzymol. 153:516-544).
  • In addition, a host cell strain may be chosen which modulates the expression of the inserted sequences, or modifies and processes the gene product in the specific fashion desired. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products may be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins and gene products. Appropriate cell lines or host systems can be chosen to ensure the correct modification and processing of the foreign protein expressed. To this end, eukaryotic host cells which possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product may be used. Such mammalian host cells include but are not limited to CHO, VERO, BHK, HeLa, COS, MDCK, 293, 3T3, WI38.
  • For long-term, high-yield production of recombinant proteins, stable expression is preferred. For example, cell lines which stably express the CML progression protein may be engineered. Rather than using expression vectors which contain viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Following the introduction of the foreign DNA, engineered cells may be allowed to grow for 1-2 days in an enriched media, and then are switched to a selective media. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci which in turn can be cloned and expanded into cell lines. This method may advantageously be used to engineer cell lines which express the CML progression protein. Such engineered cell lines may be particularly useful in screening and evaluation of compounds that affect the endogenous activity of the CML progression protein.
  • In another embodiment, the expression characteristics of an endogenous gene (e.g., a CML progression gene) within a cell, cell line or microorganism may be modified by inserting a DNA regulatory element heterologous to the endogenous gene of interest into the genome of a cell, stable cell line or cloned microorganism such that the inserted regulatory element is operatively linked with the endogenous gene (e.g., a CML progression gene) and controls, modulates, activates, or inhibits the endogenous gene. For example, endogenous CML progression genes which are normally “transcriptionally silent”, i.e., a CML progression gene which is normally not expressed, or is expressed only at very low levels in a cell line or microorganism, may be activated by inserting a regulatory element which is capable of promoting the expression of the gene product in that cell line or microorganism. Alternatively, transcriptionally silent, endogenous CML progression genes may be activated by insertion of a promiscuous regulatory element that works across cell types.
  • A heterologous regulatory element may be inserted into a stable cell line or cloned microorganism, such that it is operatively linked with and activates or inhibits expression of endogenous CML progression genes, using techniques, such as targeted homologous recombination, which are well known to those of skill in the art, and described e.g., in Chappel, U.S. Pat. No. 5,272,071; PCT Publication No. WO 91/06667 published May 16, 1991; Skoultchi, U.S. Pat. No. 5,981,214; and Treco et al U.S. Pat. No. 5,968,502 and PCT Publication No. WO 94/12650 published Jun. 9, 1994. Alternatively, non-targeted, e.g. non-homologous recombination techniques may be used which are well-known to those of skill in the art and described, e.g., in PCT Publication No. WO 99/15650 published Apr. 1, 1999.
  • CML progression gene activation (or inactivation) may also be accomplished using designer transcription factors using techniques well known in the art. Briefly, a designer zinc finger protein transcription factor (ZFP-TF) is made which is specific for a regulatory region of the CML progression gene to be activated or inactivated. A construct encoding this designer ZFP-TF is then provided to a host cell in which the CML progression gene is to be controlled. The construct directs the expression of the designer ZFP-TF protein, which in turn specifically modulates the expression of the endogenous CML progression gene. The following references relate to various aspects of this approach in further detail: Wang & Pabo, 1999, Proc. Natl. Acad. Sci. USA 96, 9568; Berg, 1997, Nature Biotechnol. 15, 323; Greisman & Pabo, 1997, Science 275, 657; Berg & Shi, 1996, Science 271, 1081; Rebar & Pabo, 1994, Science 263, 671; Rhodes & Klug, 1993, Scientific American 269, 56; Pavletich & Pabo, 1991, Science 252, 809; Liu et al., 2001, J. Biol. Chem. 276, 11323; Zhang et al., 2000, J. Biol. Chem. 275, 33850; Beerli et al., 2000, Proc. Natl. Acad. Sci. USA 97, 1495; Kang et al., 2000, J. Biol. Chem. 275, 8742; Beerli et al., 1998, Proc. Natl. Acad. Sci. USA 95, 14628; Kim & Pabo, 1998, Proc. Natl. Acad. Sci. USA 95, 2812; Choo et al., 1997, J. Mol. Biol. 273, 525; Kim & Pabo, 1997, J. Biol. Chem. 272, 29795; Liu et al, 1997, Proc. Natl. Acad. Sci. USA 94, 5525; Kim et al, 1997, Proc. Natl. Acad. Sci. USA 94, 3616; Kikyo et al., 2000, Science 289, 2360; Robertson & Wolffe, 2000, Nature Reviews 1, 11; and Gregory, 2001, Curr. Opin. Genet. Devt. 11, 142.
  • A number of selection systems may be used, including but not limited to the herpes simplex virus thymidine kinase (Wigler, et al., 1977, Cell 11:223), hypoxanthine-guanine phosphoribosyltransferase (Szybalska & Szybalski, 1962, Proc. Natl. Acad. Sci. USA 48:2026), and adenine phosphoribosyltransferase (Lowy, et al., 1980, Cell 22:817) genes can be employed in tk−, hgprt− or aprt− cells, respectively. Also, antimetabolite resistance can be used as the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler, et al., 1980, Natl. Acad. Sci. USA 77:3567; O'Hare, et al., 1981, Proc. Natl. Acad. Sci. USA 78:1527); gpt, which confers resistance to mycophenolic acid (Mulligan & Berg, 1981, Proc. Natl. Acad. Sci. USA 78:2072); neo, which confers resistance to the aminoglycoside G-418 (Colberre-Garapin, et al., 1981, J. Mol. Biol. 150:1); and hygro, which confers resistance to hygromycin (Santerre, et al., 1984, Gene 30:147).
  • Alternatively, any fusion protein may be readily purified by utilizing an antibody specific for the fusion protein being expressed. For example, a system described by Janknecht et al. allows for the ready purification of non-denatured fusion proteins expressed in human cell lines (Janknecht, et al., 1991, Proc. Natl. Acad. Sci. USA 88: 8972-8976). In this system, the gene of interest is subcloned into a vaccinia recombination plasmid such that the gene's open reading frame is translationally fused to an amino-terminal tag consisting of six histidine residues. Extracts from cells infected with recombinant vaccinia virus are loaded onto Ni2+.nitriloacetic acid-agarose columns and histidine-tagged proteins are selectively eluted with imidazole-containing buffers.
  • In a specific embodiment, recombinant human CML progression proteins can be expressed as a fusion protein with glutathione S-transferase at the amino-terminus (GST-CML progression protein) using standard baculovirus vectors and a (Bac-to-Bac®) insect cell expression system purchased from GIBCO™ Invitrogen. Recombinant protein expressed in insect cells can be purified using glutathione sepharose (Amersham Biotech) using standard procedures described by the manufacturer.
    • 5.8. Production of Antibodies that Bind a CML Progression/Target or IM Resistance Protein
  • CML progression protein or a fragment thereof can be used to raise antibodies which bind CML progression protein. Such antibodies include but are not limited to polyclonal, monoclonal, chimeric, single chain, Fab fragments, and an Fab expression library. In a preferred embodiment, anti CML progression protein C-terminal antibodies are raised using an appropriate C-terminal fragment of a CML progression protein, e.g., the kinase domain. Such antibodies bind the kinase domain of the CML progression protein. In another preferred embodiment, anti CML progression protein N-terminal antibodies are raised using an appropriate N-terminal fragment of a CML progression protein. The N-terminal domain of a CML progression protein are less homologous to other kinases, and therefore offered a more specific target for a particular CML progression protein.
    • 5.8.1. Production of Monoclonal Antibodies Specific for a CML Progression/Target or Im Resistance Protein
  • Antibodies can be prepared by immunizing a suitable subject with a CML progression protein or a fragment thereof as an immunogen. The antibody titer in the immunized subject can be monitored over time by standard techniques, such as with an enzyme linked immunosorbent assay (ELISA) using immobilized polypeptide. If desired, the antibody molecules can be isolated from the mammal (e.g., from the blood) and further purified by well-known techniques, such as protein A chromatography to obtain the IgG fraction.
  • At an appropriate time after immunization, e.g., when the specific antibody titers are highest, antibody-producing cells can be obtained from the subject and used to prepare monoclonal antibodies by standard techniques, such as the hybridoma technique originally described by Kohler and Milstein (1975, Nature 256:495-497), the human B cell hybridoma technique by Kozbor et al. (1983, Immunol. Today 4:72), the EBV-hybridoma technique by Cole et al. (1985, Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96) or trioma techniques. The technology for producing hybridomas is well known (see Current Protocols in Immunology, 1994, John Wiley & Sons, Inc., New York, N.Y.). Hybridoma cells producing a monoclonal antibody are detected by screening the hybridoma culture supernatants for antibodies that bind the polypeptide of interest, e.g., using a standard ELISA assay.
  • Monoclonal antibodies are obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Thus, the modifier “monoclonal” indicates the character of the antibody as not being a mixture of discrete antibodies. For example, the monoclonal antibodies may be made using the hybridoma method first described by Kohler et al., 1975, Nature, 256:495, or may be made by recombinant DNA methods (U.S. Pat. No. 4,816,567). The term “monoclonal antibody” as used herein also indicates that the antibody is an immunoglobulin.
  • In the hybridoma method of generating monoclonal antibodies, a mouse or other appropriate host animal, such as a hamster, is immunized as hereinabove described to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the protein used for immunization (see, e.g., U.S. Pat. No. 5,914,112, which is incorporated herein by reference in its entirety).
  • Alternatively, lymphocytes may be immunized in vitro. Lymphocytes then are fused with myeloma cells using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103 (Academic Press, 1986)). The hybridoma cells thus prepared are seeded and grown in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells. For example, if the parental myeloma cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (HAT medium), which substances prevent the growth of HGPRT-deficient cells.
  • Preferred myeloma cells are those that fuse efficiently, support stable high-level production of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. Among these, preferred myeloma cell lines are murine myeloma lines, such as those derived from MOPC-21 and MPC-11 mouse tumors available from the Salk Institute Cell Distribution Center, San Diego, Calif. USA, and SP-2 cells available from the American Type Culture Collection, Rockville, Md. USA.
  • Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, 1984, J. Immunol., 133:3001; Brodeur et al., Monoclonal Antibody Production Techniques and Applications, pp. 51-63 (Marcel Dekker, Inc., New York, 1987)). Culture medium in which hybridoma cells are growing is assayed for production of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immuno-absorbent assay (ELISA). The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson et al., 1980, Anal. Biochem., 107:220.
  • After hybridoma cells are identified that produce antibodies of the desired specificity, affinity, and/or activity, the clones may be subcloned by limiting dilution procedures and grown by standard methods (Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103, Academic Press, 1986). Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 medium. In addition, the hybridoma cells may be grown in vivo as ascites tumors in an animal. The monoclonal antibodies secreted by the subclones are suitably separated from the culture medium, ascites fluid, or serum by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.
  • Alternative to preparing monoclonal antibody-secreting hybridomas, a monoclonal antibody directed against a CML progression protein or a fragment thereof can be identified and isolated by screening a recombinant combinatorial immunoglobulin library (e.g., an antibody phage display library) with the CML progression protein or the fragment. Kits for generating and screening phage display libraries are commercially available (e.g., Pharmacia Recombinant Phage Antibody System, Catalog No. 27-9400-01; and the Stratagene antigen SurfZAP™ Phage Display Kit, Catalog No. 240612). Additionally, examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, U.S. Pat. Nos. 5,223,409 and 5,514,548; PCT Publication No. WO 92/18619; PCT Publication No. WO 91/17271; PCT Publication No. WO 92/20791; PCT Publication No. WO 92/15679; PCT Publication No. WO 93/01288; PCT Publication No. WO 92/01047; PCT Publication No. WO 92/09690; PCT Publication No. WO 90/02809; Fuchs et al., 1991, Bio/Technology 9:1370-1372; Hay et al., 1992, Hum. Antibod. Hybridomas 3:81-85; Huse et al., 1989, Science 246:1275-1281; Griffiths et al., 1993, EMBO J. 12:725-734.
  • In addition, techniques developed for the production of “chimeric antibodies” (Morrison, et al., 1984, Proc. Natl. Acad. Sci., 81, 6851-6855; Neuberger, et al., 1984, Nature 312, 604-608; Takeda, et al., 1985, Nature, 314, 452-454) by splicing the genes from a mouse antibody molecule of appropriate antigen specificity together with genes from a human antibody molecule of appropriate biological activity can be used. A chimeric antibody is a molecule in which different portions are derived from different animal species, such as those having a variable region derived from a murine mAb and a human immunoglobulin constant region. (See, e.g., Cabilly et al., U.S. Pat. No. 4,816,567; and Boss et al., U.S. Pat. No. 4,816,397, which are incorporated herein by reference in their entirety.)
  • Humanized antibodies are antibody molecules from non-human species having one or more complementarity determining regions (CDRs) from the non-human species and a framework region from a human immunoglobulin molecule. (see e.g., U.S. Pat. No. 5,585,089, which is incorporated herein by reference in its entirety.) Such chimeric and humanized monoclonal antibodies can be produced by recombinant DNA techniques known in the art, for example using methods described in PCT Publication No. WO 87/02671; European Patent Application 184,187; European Patent Application 171,496; European Patent Application 173,494; PCT Publication No. WO 86/01533; U.S. Pat. Nos. 4,816,567 and 5,225,539; European Patent Application 125,023; Better et al., 1988, Science 240:1041-1043; Liu et al., 1987, Proc. Natl. Acad. Sci. USA 84:3439-3443; Liu et al., 1987, J. Immunol. 139:3521-3526; Sun et al., 1987, Proc. Natl. Acad. Sci. USA 84:214-218; Nishimura et al., 1987, Canc. Res. 47:999-1005; Wood et al., 1985, Nature 314:446-449; Shaw et al., 1988, J. Natl. Cancer Inst. 80:1553-1559; Morrison 1985, Science 229:1202-1207; Oi et al., 1986, Bio/Techniques 4:214; Jones et al., 1986, Nature 321:552-525; Verhoeyan et al., 1988, Science 239:1534; and Beidler et al., 1988, J. Immunol. 141:4053-4060.
  • Complementarity determining region (CDR) grafting is another method of humanizing antibodies. It involves reshaping murine antibodies in order to transfer full antigen specificity and binding affinity to a human framework (Winter et al. U.S. Pat. No. 5,225,539). CDR-grafted antibodies have been successfully constructed against various antigens, for example, antibodies against IL-2 receptor as described in Queen et al., 1989 (Proc. Natl. Acad. Sci. USA 86:10029); antibodies against cell surface receptors-CAMPATH as described in Riechmann et al. (1988, Nature, 332:323; antibodies against hepatitis B in Cole et al. (1991, Proc. Natl. Acad. Sci. USA 88:2869); as well as against viral antigens-respiratory syncitial virus in Tempest et al. (1991, Bio-Technology 9:267). CDR-grafted antibodies are generated in which the CDRs of the murine monoclonal antibody are grafted into a human antibody. Following grafting, most antibodies benefit from additional amino acid changes in the framework region to maintain affinity, presumably because framework residues are necessary to maintain CDR conformation, and some framework residues have been demonstrated to be part of the antigen binding site. However, in order to preserve the framework region so as not to introduce any antigenic site, the sequence is compared with established germline sequences followed by computer modeling.
  • Completely human antibodies are particularly desirable for therapeutic treatment of human patients. Such antibodies can be produced using transgenic mice which are incapable of expressing endogenous immunoglobulin heavy and light chain genes, but which can express human heavy and light chain genes. The transgenic mice are immunized in the normal fashion with a CML progression protein.
  • Monoclonal antibodies directed against a CML progression protein can be obtained using conventional hybridoma technology. The human immunoglobulin transgenes harbored by the transgenic mice rearrange during B cell differentiation, and subsequently undergo class switching and somatic mutation. Thus, using such a technique, it is possible to produce therapeutically useful IgG, IgA and IgE antibodies. For an overview of this technology for producing human antibodies, see Lonberg and Huszar (1995, Int. Rev. Immunol. 13:65-93). For a detailed discussion of this technology for producing human antibodies and human monoclonal antibodies and protocols for producing such antibodies, see e.g., U.S. Pat. No. 5,625,126; U.S. Pat. No. 5,633,425; U.S. Pat. No. 5,569,825; U.S. Pat. No. 5,661,016; and U.S. Pat. No. 5,545,806. In addition, companies such as Abgenix, Inc. (Freemont, Calif., see, for example, U.S. Pat. No. 5,985,615) and Medarex, Inc. (Princeton, N.J.), can be engaged to provide human antibodies directed against a CML progression protein or a fragment thereof using technology similar to that described above.
  • Completely human antibodies which recognize and bind a selected epitope can be generated using a technique referred to as “guided selection.” In this approach a selected non-human monoclonal antibody, e.g., a mouse antibody, is used to guide the selection of a completely human antibody recognizing the same epitope (Jespers et al., 1994, Bio/technology 12:899-903).
  • A pre-existing anti-CML progression protein antibody can be used to isolate additional antigens of the CML progression protein by standard techniques, such as affinity chromatography or immunoprecipitation for use as immunogens. Moreover, such an antibody can be used to detect the protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of CML progression protein. Detection can be facilitated by coupling the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125I, 131I, 35S or 3H.
    • 5.8.2. Production of Polyclonal Anti-CML Progression/Target or IM Resistance Protein Antibodies
  • The anti-CML progression protein antibodies can be produced by immunization of a suitable animal, such as but are not limited to mouse, rabbit, and horse.
  • An immunogenic preparation comprising a CML progression protein or a fragment thereof can be used to prepare antibodies by immunizing a suitable subject (e.g., rabbit, goat, mouse or other mammal). An appropriate immunogenic preparation can contain, for example, recombinantly expressed or chemically synthesized CML progression protein peptide or polypeptide. The preparation can further include an adjuvant, such as Freund's complete or incomplete adjuvant, or similar immunostimulatory agent.
  • A fragment of a CML progression protein suitable for use as an immunogen comprises at least a portion of the CML progression protein that is 8 amino acids, more preferably 10 amino acids and more preferably still, 15 amino acids long.
  • The invention also provides chimeric or fusion CML progression protein polypeptides for use as immunogens. As used herein, a “chimeric” or “fusion” CML progression protein polypeptide comprises all or part of a CML progression protein polypeptide operably linked to a heterologous polypeptide. Within the fusion CML progression protein polypeptide, the term “operably linked” is intended to indicate that the CML progression protein polypeptide and the heterologous polypeptide are fused in-frame to each other. The heterologous polypeptide can be fused to the N-terminus or C-terminus of the CML progression protein polypeptide.
  • One useful fusion CML progression protein polypeptide is a GST fusion CML progression protein polypeptide in which the CML progression protein polypeptide is fused to the C-terminus of GST sequences. Such fusion CML progression protein polypeptides can facilitate the purification of a recombinant CML progression protein polypeptide.
  • In another embodiment, the fusion CML progression protein polypeptide contains a heterologous signal sequence at its N-terminus so that the CML progression protein polypeptide can be secreted and purified to high homogeneity in order to produce high affinity antibodies. For example, the native signal sequence of an immunogen can be removed and replaced with a signal sequence from another protein. For example, the gp67 secretory sequence of the baculovirus envelope protein can be used as a heterologous signal sequence (Current Protocols in Molecular Biology, Ausubel et al., eds., John Wiley & Sons, 1992). Other examples of eukaryotic heterologous signal sequences include the secretory sequences of melittin and human placental alkaline phosphatase (Stratagene; La Jolla, Calif.). In yet another example, useful prokaryotic heterologous signal sequences include the phoA secretory signal and the protein A secretory signal (Pharmacia Biotech; Piscataway, N.J.).
  • In yet another embodiment, the fusion CML progression protein polypeptide is an immunoglobulin fusion protein in which all or part of a CML progression protein polypetide is fused to sequences derived from a member of the immunoglobulin protein family. The immunoglobulin fusion proteins can be used as immunogens to produce antibodies directed against the CML progression protein polypetide in a subject.
  • Chimeric and fusion CML progression protein polypeptide can be produced by standard recombinant DNA techniques. In one embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers which give rise to complementary overhangs between two consecutive gene fragments which can subsequently be annealed and reamplified to generate a chimeric gene sequence (e.g., Ausubel et al., supra). Moreover, many expression vectors are commercially available that already encode a fusion domain (e.g., a GST polypeptide). A nucleic acid encoding an immunogen can be cloned into such an expression vector such that the fusion domain is linked in-frame to the polypeptide.
  • The CML progression protein immunogenic preparation is then used to immunize a suitable animal. Preferably, the animal is a specialized transgenic animal that can secret human antibody. Non-limiting examples include transgenic mouse strains which can be used to produce a polyclonal population of antibodies directed to a specific pathogen (Fishwild et al., 1996, Nature Biotechnology 14:845-851; Mendez et al., 1997, Nature Genetics 15:146-156). In one embodiment of the invention, transgenic mice that harbor the unrearranged human immunoglobulin genes are immunized with the target immunogens. After a vigorous immune response against the immunogenic preparation has been elicited in the mice, the blood of the mice are collected and a purified preparation of human IgG molecules can be produced from the plasma or serum. Any method known in the art can be used to obtain the purified preparation of human IgG molecules, including but is not limited to affinity column chromatography using anti-human IgG antibodies bound to a suitable column matrix. Anti-human IgG antibodies can be obtained from any sources known in the art, e.g., from commercial sources such as Dako Corporation and ICN. The preparation of IgG molecules produced comprises a polyclonal population of IgG molecules that bind to the immunogen or immunogens at different degree of affinity. Preferably, a substantial fraction of the preparation contains IgG molecules specific to the immunogen or immunogens. Although polyclonal preparations of IgG molecules are described, it is understood that polyclonal preparations comprising any one type or any combination of different types of immunoglobulin molecules are also envisioned and are intended to be within the scope of the present invention.
  • A population of antibodies directed to a CML progression protein can be produced from a phage display library. Polyclonal antibodies can be obtained by affinity screening of a phage display library having a sufficiently large and diverse population of specificities with a CML progression protein or a fragment thereof. Examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, U.S. Pat. Nos. 5,223,409 and 5,514,548; PCT Publication No. WO 92/18619; PCT Publication No. WO 91/17271; PCT Publication No. WO 92/20791; PCT Publication No. WO 92/15679; PCT Publication No. WO 93/01288; PCT Publication No. WO 92/01047; PCT Publication No. WO 92/09690; PCT Publication No. WO 90/02809; Fuchs et al., 1991, Bio/Technology 9:1370-1372; Hay et al., 1992, Hum. Antibod. Hybridomas 3:81-85; Huse et al., 1989, Science 246:1275-1281; Griffiths et al., 1993, EMBO J. 12:725-734. A phage display library permits selection of desired antibody or antibodies from a very large population of specificities. An additional advantage of a phage display library is that the nucleic acids encoding the selected antibodies can be obtained conveniently, thereby facilitating subsequent construction of expression vectors.
  • In other preferred embodiments, the population of antibodies directed to a CML progression protein or a fragment thereof is produced by a method using the whole collection of selected displayed antibodies without clonal isolation of individual members as described in U.S. Pat. No. 6,057,098, which is incorporated by reference herein in its entirety. Polyclonal antibodies are obtained by affinity screening of a phage display library having a sufficiently large repertoire of specificities with, e.g., an antigenic molecule having multiple epitopes, preferably after enrichment of displayed library members that display multiple antibodies. The nucleic acids encoding the selected display antibodies are excised and amplified using suitable PCR primers. The nucleic acids can be purified by gel electrophoresis such that the full length nucleic acids are isolated. Each of the nucleic acids is then inserted into a suitable expression vector such that a population of expression vectors having different inserts is obtained. The population of expression vectors is then expressed in a suitable host.
    • 5.8.3 Production of Antibody-Drug Conjugates Targeting a CML Progression/Target or IM Resistance Protein
  • Cancer cells can be targeted and killed using anti-CML progression protein antibody-drug conjugates that target an advanced phase CML hematopoetic stem cell and/or immature myeloid cell expressing a CML progression protein on its surface, e.g., PRAME. For example, an antibody specific for a CML progression protein may be conjugated to a therapeutic moiety such as a cytotoxin, e.g., a cytostatic or cytocidal agent, or a radioactive metal ion. Antibody-drug conjugates can be prepared by method known in the art (see, e.g., Immunoconjugates, Vogel, ed. 1987; Targeted Drugs, Goldberg, ed. 1983; Antibody Mediated Delivery Systems, Rodwell, ed. 1988). Therapeutic drugs, such as but are not limited to, paclitaxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin and analogs or homologs thereof, can be conjugated to anti-CML progression protein antibodies. Other therapeutic agents that can be conjugated to anti-CML progression protein antibodies include, but are not limited to, antimetabolites, e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine; alkylating agents, e.g., mechlorethamine, thioepa chlorambucil, melphalan, carmustine (BSNU) and lomustine (CCNU), cyclothosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (II) (DDP) cisplatin; anthracyclines, e.g., daunorubicin (daunomycin) and doxorubicin; antibiotics, e.g., dactinomycin (actinomycin), bleomycin, mithramycin, anthramycin (AMC); and anti-mitotic agents, e.g., vincristine and vinblastine. The therapeutic agents that can be conjugated to anti-CML progression protein antibodies may also be a protein or polypeptide possessing a desired biological activity. Other chemotherapeutic agents known in the art, such as those described in Section 5.8.5, infra, can also be conjugated with such an anti-CML progression protein antibody. Such proteins may include, for example, a toxin such as abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin.
  • The drug molecules can be linked to the anti-CML progression protein antibody via a linker. Any suitable linker can be used for the preparation of such conjugates. In some embodiments, the linker can be a linker that allows the drug molecules to be released from the conjugates in unmodified form at the target site.
  • The antibodies can also be used diagnostically to, for example, monitor the presence of cancer cells as part of a clinical testing procedure to, e.g., determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, radioactive materials, positron emitting metals using various positron emission tomographies, and nonradioactive paramagnetic metal ions. See generally U.S. Pat. No. 4,741,900 for metal ions which can be conjugated to antibodies for use as diagnostics according to the present invention. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include fluorescent proteins, e.g., green fluorescent protein (GFP), umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125I, 131I, 111In, 177Lu, 90Y or 99Tc.
  • Techniques for conjugating therapeutic moieties to antibodies are well known, see, e.g., Arnon et al., “Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy”, in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., “Antibodies For Drug Delivery”, in Controlled Drug Delivery (2nd Ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, “Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review”, in Monoclonal Antibodies '84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); “Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy”, in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985), and Thorpe et al., “The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates”, Immunol. Rev., 62:119-58 (1982); each of which is incorporated herein by reference.
  • Alternatively, an antibody can be conjugated to a second antibody to form an antibody heteroconjugate as described by Segal in U.S. Pat. No. 4,676,980, which is incorporated herein by reference.
    • 5.8.4 Production of Peptides
  • A CML progression protein-binding peptide or polypeptide or peptide or polypeptide of a CML progression protein may be produced by recombinant DNA technology using techniques well known in the art. Thus, the polypeptide or peptide can be produced by expressing nucleic acid containing sequences encoding the polypeptide or peptide. Methods which are well known to those skilled in the art can be used to construct expression vectors containing coding sequences and appropriate transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. See, for example, the techniques described in Sambrook et al., 1989, supra, and Ausubel et al., 1989, supra. Alternatively, RNA capable of encoding CML progression protein polypeptide sequences may be chemically synthesized using, for example, synthesizers. See, for example, the techniques described in “Oligonucleotide Synthesis”, 1984, Gait, M. J. ed., IRL Press, Oxford, which is incorporated herein by reference in its entirety.
    • 5.8.5 Chemotherapeutic Drugs
  • The invention can be practiced with any known chemotherapeutic drugs, including but not limited to DNA damaging agents, anti-metabolites, anti-mitotic agents, or a combination of two or more of such known anti-cancer agents.
  • DNA damage agents cause chemical damage to DNA and/or RNA. DNA damage agents can disrupt DNA replication or cause the generation of nonsense DNA or RNA. DNA damaging agents include but are not limited to topoisomerase inhibitor, DNA binding agent, and ionizing radiation. A topoisomerase inhibitor that can be used in conjunction with the invention can be a topoisomerase I (Topo I) inhibitor, a topoisomerase II (Topo II) inhibitor, or a dual topoisomerase I and II inhibitor. A topo I inhibitor can be for example from any of the following classes of compounds: camptothecin analogue (e.g., karenitecin, aminocamptothecin, lurtotecan, topotecan, irinotecan, BAY 56-3722, rubitecan, GI14721, exatecan mesylate), rebeccamycin analogue, PNU 166148, rebeccamycin, TAS-103, camptothecin (e.g., camptothecin polyglutamate, camptothecin sodium), intoplicine, ecteinascidin 743, J-107088, pibenzimol Examples of preferred topo I inhibitors include but are not limited to camptothecin, topotecan (hycaptamine), irinotecan (irinotecan hydrochloride), belotecan, or an analogue or derivative of any of the foregoing.
  • A topo II inhibitor that can be used in conjunction with the invention can be for example from any of the following classes of compounds: anthracycline antibiotics (e.g., carubicin, pirarubicin, daunorubicin citrate liposomal, daunomycin, 4-iodo-4-doxydoxorubicin, doxorubicin, n,n-dibenzyl daunomycin, morpholinodoxorubicin, aclacinomycin antibiotics, duborimycin, menogaril, nogalamycin, zorubicin, epirubicin, marcellomycin, detorubicin, annamycin, 7-cyanoquinocarcinol, deoxydoxorubicin, idarubicin, GPX-100, MEN-10755, valrubicin, KRN5500), epipodophyllotoxin compound (e.g., podophyllin, teniposide, etoposide, GL331, 2-ethylhydrazide), anthraquinone compound (e.g., ametantrone, bisantrene, mitoxantrone, anthraquinone), ciprofloxacin, acridine carboxamide, amonafide, anthrapyrazole antibiotics (e.g., teloxantrone, sedoxantrone trihydrochloride, piroxantrone, anthrapyrazole, losoxantrone), TAS-103, fostriecin, razoxane, XK469R, XK469, chloroquinoxaline sulfonamide, merbarone, intoplicine, elsamitrucin, CI-921, pyrazoloacridine, elliptinium, amsacrine. Examples of preferred topo II inhibitors include but are not limited to doxorubicin (Adriamycin), etoposide phosphate (etopofos), teniposide, sobuzoxane, or an analogue or derivative of any of the foregoing.
  • DNA binding agents that can be used in conjunction with the invention include but are not limited to a DNA groove binding agent, e.g., DNA minor groove binding agent; DNA crosslinking agent; intercalating agent; and DNA adduct forming agent. A DNA minor groove binding agent can be an anthracycline antibiotic, mitomycin antibiotic (e.g., porfiromycin, KW-2149, mitomycin B, mitomycin A, mitomycin C), chromomycin A3, carzelesin, actinomycin antibiotic (e.g., cactinomycin, dactinomycin, actinomycin F1), brostallicin, echinomycin, bizelesin, duocarmycin antibiotic (e.g., KW 2189), adozelesin, olivomycin antibiotic, plicamycin, zinostatin, distamycin, MS-247, ecteinascidin 743, amsacrine, anthramycin, and pibenzimol, or an analogue or derivative of any of the foregoing.
  • DNA crosslinking agents include but are not limited to antineoplastic alkylating agent, methoxsalen, mitomycin antibiotic, psoralen. An antineoplastic alkylating agent can be a nitrosourea compound (e.g., cystemustine, tauromustine, semustine, PCNU, streptozocin, SarCNU, CGP-6809, carmustine, fotemustine, methylnitrosourea, nimustine, ranimustine, ethylnitrosourea, lomustine, chlorozotocin), mustard agent (e.g., nitrogen mustard compound, such as spiromustine, trofosfamide, chlorambucil, estramustine, 2,2,2-trichlorotriethylamine, prednimustine, novembichin, phenamet, glufosfamide, peptichemio, ifosfamide, defosfamide, nitrogen mustard, phenesterin, mannomustine, cyclophosphamide, melphalan, perfosfamide, mechlorethamine oxide hydrochloride, uracil mustard, bestrabucil, DHEA mustard, tallimustine, mafosfamide, aniline mustard, chlornaphazine; sulfur mustard compound, such as bischloroethylsulfide; mustard prodrug, such as TLK286 and ZD2767), ethylenimine compound (e.g., mitomycin antibiotic, ethylenimine, uredepa, thiotepa, diaziquone, hexamethylene bisacetamide, pentamethylmelamine, altretamine, carzinophilin, triaziquone, meturedepa, benzodepa, carboquone), alkylsulfonate compound (e.g., dimethylbusulfan, Yoshi-864, improsulfan, piposulfan, treosulfan, busulfan, hepsulfam), epoxide compound (e.g., anaxirone, mitolactol, dianhydrogalactitol, teroxirone), miscellaneous alkylating agent (e.g., ipomeanol, carzelesin, methylene dimethane sulfonate, mitobronitol, bizelesin, adozelesin, piperazinedione, VNP40101M, asaley, 6-hydroxymethylacylfulvene, EO9, etoglucid, ecteinascidin 743, pipobroman), platinum compound (e.g., ZD0473, liposomal-cisplatin analogue, satraplatin, BBR 3464, spiroplatin, ormaplatin, cisplatin, oxaliplatin, carboplatin, lobaplatin, zeniplatin, iproplatin), triazene compound (e.g., imidazole mustard, CB10-277, mitozolomide, temozolomide, procarbazine, dacarbazine), picoline compound (e.g., penclomedine), or an analogue or derivative of any of the foregoing. Examples of preferred alkylating agents include but are not limited to cisplatin, dibromodulcitol, fotemustine, ifosfamide (ifosfamid), ranimustine (ranomustine), nedaplatin (latoplatin), bendamustine (bendamustine hydrochloride), eptaplatin, temozolomide (methazolastone), carboplatin, altretamine (hexamethylmelamine), prednimustine, oxaliplatin (oxalaplatinum), carmustine, thiotepa, leusulfon (busulfan), lobaplatin, cyclophosphamide, bisulfan, melphalan, and chlorambucil, or an analogue or derivative of any of the foregoing.
  • Intercalating agents can be an anthraquinone compound, bleomycin antibiotic, rebeccamycin analogue, acridine, acridine carboxamide, amonafide, rebeccamycin, anthrapyrazole antibiotic, echinomycin, psoralen, LU 79553, BW A773U, crisnatol mesylate, benzo(a)pyrene-7,8-diol-9,10-epoxide, acodazole, elliptinium, pixantrone, or an analogue or derivative of any of the foregoing.
  • DNA adduct forming agents include but are not limited to enediyne antitumor antibiotic (e.g., dynemicin A, esperamicin A1, zinostatin, dynemicin, calicheamicin gamma 11), platinum compound, carmustine, tamoxifen (e.g., 4-hydroxy-tamoxifen), psoralen, pyrazine diazohydroxide, benzo(a)pyrene-7,8-diol-9,10-epoxide, or an analogue or derivative of any of the foregoing.
  • Anti-metabolites block the synthesis of nucleotides or deoxyribonucleotides, which are necessary for making DN, thereby preventing cells from replicating. Anti-metabolites include but are not limited to cytosine, arabinoside, floxuridine, 5-fluorouracil (5-FU), mercaptopurine, gemcitabine, hydroxyurea (HU), and methotrexate (MTX).
  • Anti-mitotic agents disrupt the development of the mitotic spindle thereby interfering with tumor cell proliferation. Anti-mitotic agents include but are not limited to Vinblastine, Vincristine, and Pacitaxel (Taxol). Anti-mitotic agents also includes agents that target the enzymes that regulate mitosis, e.g., agents that target kinesin spindle protein (KSP), e.g., L-001000962-000Y.
    • 5.9. KITS
  • The invention provides kits that are useful in determining the stage of CML in a patient. The kits of the present invention comprise one or more probes and/or primers for each of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 gene products that are encoded by the respectively marker genes listed in Tables 1a and/or 1b or functional equivalents of such genes, wherein the probes and/or primers are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total probes and/or primers in the kit. The probes of marker genes may be part of an array, or the biomarker(s) may be packaged separately and/or individually.
  • The invention provides kits that are useful in determining the progression of CML in a patient. The kits of the present invention comprise one or more probes and/or primers for each of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 gene products that are encoded by the respectively marker genes listed in Tables 2a and/or 2b or functional equivalents of such genes, wherein the probes and/or primers are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total probes and/or primers in the kit. In a preferred embodiment, the kits comprise one or more probes and/or primers for each of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 gene products that are encoded by the respectively marker genes listed in Table 4 or functional equivalents of such genes, wherein the probes and/or primers are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total probes and/or primers in the kit. The probes of marker genes may be part of an array, or the biomarker(s) may be packaged separately and/or individually.
  • In one embodiment, the invention provides kits comprising probes that are immobilized at an addressable position on a substrate, e.g., in a microarray. In a particular embodiment, the invention provides such a microarray.
  • The kits of the present invention may also contain probes that can be used to detect protein products of the marker genes of the invention. In a specific embodiment, the invention provides a kit comprises a plurality of antibodies that specifically bind a plurality of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 proteins that are encoded by the respectively marker genes listed in Tables 1a and/or 1b or any one of Tables 2a and/or 2b and 5a and/or 5b or functional equivalents of such genes, wherein the antibodies are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total antibodies in the kit. In accordance with this embodiment, the kit may comprise a set of antibodies or functional fragments or derivatives thereof (e.g., Fab, F(ab′)2, Fv, or scFv fragments). In accordance with this embodiment, the kit may include antibodies, fragments or derivatives thereof (e.g., Fab, F(ab′)2, Fv, or scFv fragments) that are specific for these proteins. In one embodiment, the antibodies may be detectably labeled.
  • The kits of the present invention may also include reagents such as buffers, or other reagents that can be used in obtaining the marker profile. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like.
  • In some embodiments of the invention, the kits of the present invention comprise a microarray. The microarray can be any of the microarrays described above, e.g., in Section 5.6.1, optionally in a sealed container. In one embodiment this microarray comprises a plurality of probe spots, wherein at least 20%, 40%, 60%, 80%, or 90% of the probe spots in the plurality of probe spots correspond to marker genes listed in Tables 1a and/or 1b or any one of Tables 2a and/or 2b and 4.
  • In still other embodiments, the kits of the invention may further comprise a computer program product for use in conjunction with a computer system, wherein the computer program product comprises a computer readable storage medium and a computer program mechanism embedded therein. In such kits, the computer program mechanism comprises instructions for prediction of prognosis using a marker profile obtained with the reagents of the kits.
  • In still other embodiments, the kits of the present invention comprise a computer having a central processing unit and a memory coupled to the central processing unit. The memory stores instructions for prediction of prognosis using a marker profile obtained with the reagents of the kits.
    • 5.10. Pharmaceutical Formulations and Routes of Administration
  • The compounds that can be used to modulate the expression of the CML progression genes or the activity of their gene products can be administered to a patient at therapeutically effective doses. A therapeutically effective dose refers to that amount of the compound sufficient to result in normal expression or activity level.
    • 5.10.1. Effective Dose
  • Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD50/ED50. Compounds which exhibit large therapeutic indices are preferred. While compounds that exhibit toxic side effects may be used, care should be taken to design a delivery system that targets such compounds to the site of affected tissue in order to minimize potential damage to uninfected cells and, thereby, reduce side effects.
  • The data obtained from the cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound used in the method of the invention, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography.
    • 5.10.2. Formulations and Use
  • Pharmaceutical compositions for use in accordance with the present invention may be formulated in conventional manner using one or more pharmaceutically acceptable carriers or excipients.
  • Thus, the compounds and their pharmaceutically acceptable salts and solvates may be formulated for administration by inhalation or insufflation (either through the mouth or the nose) or oral, buccal, parenteral or rectal administration.
  • For oral administration, the pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g., lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g., magnesium stearate, talc or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulphate). The tablets may be coated by methods well known in the art. Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol or fractionated vegetable oils); and preservatives (e.g., methyl or propyl-p-hydroxybenzoates or sorbic acid). The preparations may also contain buffer salts, flavoring, coloring and sweetening agents as appropriate.
  • Preparations for oral administration may be suitably formulated to give controlled release of the active compound.
  • For buccal administration the compositions may take the form of tablets or lozenges formulated in conventional manner.
  • For administration by inhalation, the compounds for use according to the present invention are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebuliser, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of e.g. gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.
  • The compounds may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.
  • The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides.
  • In addition to the formulations described previously, the compounds may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.
  • The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack may for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration.
    • 5.10.3. Routes of Administration
  • Suitable routes of administration may, for example, include oral, rectal, transmucosal, transdermal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections.
  • Alternately, one may administer the compound in a local rather than systemic manner, for example, via injection of the compound directly into an affected area, often in a depot or sustained release formulation.
  • Furthermore, one may administer the drug in a targeted drug delivery system, for example, in a liposome coated with an antibody specific for affected cells. The liposomes will be targeted to and taken up selectively by the cells.
    • 5.10.4. Packaging
  • The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack may for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. Compositions comprising a compound formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition. Suitable conditions indicated on the label may include treatment of a disease such as one characterized by aberrant or excessive expression or activity of a CML progression protein.
  • 5.10.5. Combination Therapy
  • In a combination therapy, one or more compositions of the present invention can be administered before, at the same time as, or after the administration of a chemotherapeutic agent. In one embodiment, the compositions of the invention are administered before the administration of an chemotherapeutic agent (i.e., the agent that modulates expression or activity of a CML progression gene or imatinib mesylate resistance gene and/or encoded protein is for sequential or concurrent use with one or more chemotherapeutic agents). In one embodiment, the composition of the invention and a chemotherapeutic agent are administered in a sequence and within a time interval such that the composition of the invention and a chemotherapeutic agent can act together to provide an increased benefit than if they were administered alone. In another embodiment, the composition of the invention and a chemotherapeutic agent are administered sufficiently close in time so as to provide the desired therapeutic outcome. The time intervals between the administration of the compositions of the invention and a chemotherapeutic agent can be determined by routine experiments that are familiar to one skilled person in the art. In one embodiment, a chemotherapeutic agent is given to the patient after the level of the CML progression gene or imatinib mesylate resistance gene and/or encoded protein reaches a desirable threshold. The level of a CML progression gene or imatinib mesylate resistance gene and/or encoded protein can be determined by using any techniques known in the art such as those described in Section 5.3., infra.
  • The composition of the invention and a chemotherapeutic agent can be administered simultaneously or separately, in any appropriate form and by any suitable route. In one embodiment, the composition of the invention and the chemotherapeutic agent are administered by different routes of administration. In an alternate embodiment, each is administered by the same route of administration. The composition of the invention and the chemotherapeutic agent can be administered at the same or different sites, e.g. arm and leg.
  • In various embodiments, such as those described above, the composition of the invention and a chemotherapeutic agent are administered less than 1 hour apart, at about 1 hour apart, 1 hour to 2 hours apart, 2 hours to 3 hours apart, 3 hours to 4 hours apart, 4 hours to 5 hours apart, 5 hours to 6 hours apart, 6 hours to 7 hours apart, 7 hours to 8 hours apart, 8 hours to 9 hours apart, 9 hours to 10 hours apart, 10 hours to 11 hours apart, 11 hours to 12 hours apart, no more than 24 hours apart or no more than 48 hours apart, or no more than 1 week or 2 weeks or 1 month or 3 months apart. As used herein, the word about means within 10%. In other embodiments, the composition of the invention and a chemotherapeutic agent are administered 2 to 4 days apart, 4 to 6 days apart, 1 week apart, 1 to 2 weeks apart, 2 to 4 weeks apart, one month apart, 1 to 2 months apart, or 2 or more months apart. In preferred embodiments, the composition of the invention and a chemotherapeutic agent are administered in a time frame where both are still active. One skilled in the art would be able to determine such a time frame by determining the half life of each administered component. In separate or in the foregoing embodiments, the composition of the invention and a chemotherapeutic agent are administered less than 2 weeks, one month, six months, 1 year or 5 years apart.
  • In another embodiment, the compositions of the invention are administered at the same time or at the same patient visit, as the chemotherapeutic agent.
  • In still another embodiment, one or more of the compositions of the invention are administered both before and after the administration of a chemotherapeutic agent. Such administration can be beneficial especially when the chemotherapeutic agent has a longer half life than that of the one or more of the compositions of the invention used in the treatment.
  • In one embodiment, the chemotherapeutic agent is administered daily and the composition of the invention is administered once a week for the first 4 weeks, and then once every other week thereafter. In one embodiment, the chemotherapeutic agent is administered daily and the composition of the invention is administered once a week for the first 8 weeks, and then once every other week thereafter.
  • In certain embodiments, the composition of the invention and the chemotherapeutic agent are cyclically administered to a subject. Cycling therapy involves the administration of the composition of the invention for a period of time, followed by the administration of a chemotherapeutic agent for a period of time and repeating this sequential administration. Cycling therapy can reduce the development of resistance to one or more of the therapies, avoid or reduce the side effects of one of the therapies, and/or improve the efficacy of the treatment. In such embodiments, the invention contemplates the alternating administration of the composition of the invention followed by the administration of a chemotherapeutic agent 4 to 6 days later, preferable 2 to 4 days, later, more preferably 1 to 2 days later, wherein such a cycle may be repeated as many times as desired.
  • In certain embodiments, the composition of the invention and a chemotherapeutic agent are alternately administered in a cycle of less than 3 weeks, once every two weeks, once every 10 days or once every week. In a specific embodiment of the invention, one cycle can comprise the administration of a chemotherapeutic agent by infusion over 90 minutes every cycle, 1 hour every cycle, or 45 minutes every cycle. Each cycle can comprise at least 1 week of rest, at least 2 weeks of rest, at least 3 weeks of rest. In an embodiment, the number of cycles administered is from 1 to 12 cycles, more typically from 2 to 10 cycles, and more typically from 2 to 8 cycles.
  • It will be apparent to one skilled person in the art that any combination of different timing of the administration of the compositions of the invention and a chemotherapeutic agent can be used. For example, when the chemotherapeutic agent has a longer half life than that of the composition of the invention, it is preferable to administer the compositions of the invention before and after the administration of the chemotherapeutic agent.
  • The frequency or intervals of administration of the compositions of the invention depends on the desired level of the CML progression gene or imatinib mesylate resistance gene and/or encoded protein, which can be determined by any of the techniques known in the art, e.g., those techniques described infra. The administration frequency of the compositions of the invention can be increased or decreased when the level of the CML progression gene or imatinib mesylate resistance gene and/or encoded protein changes either higher or lower from the desired level.
    • 5.11. Implementation Systems and Methods
  • The analytical methods of the present invention can preferably be implemented using a computer system, such as the computer system described in this section, according to the following programs and methods. Such a computer system can also preferably store and manipulate measured signals obtained in various experiments that can be used by a computer system implemented with the analytical methods of this invention. Accordingly, such computer systems are also considered part of the present invention.
  • An exemplary computer system suitable from implementing the analytic methods of this invention is illustrated in FIG. 8. Computer system 801 is illustrated here as comprising internal components and as being linked to external components. The internal components of this computer system include one or more processor elements 802 interconnected with a main memory 803. For example, computer system 801 can be an Intel Pentium IV®-based processor of 2 GHZ or greater clock rate and with 256 MB or more main memory. In a preferred embodiment, computer system 801 is a cluster of a plurality of computers comprising a head “node” and eight sibling “nodes,” with each node having a central processing unit (“CPU”). In addition, the cluster also comprises at least 128 MB of random access memory (“RAM”) on the head node and at least 256 MB of RAM on each of the eight sibling nodes. Therefore, the computer systems of the present invention are not limited to those consisting of a single memory unit or a single processor unit.
  • The external components can include a mass storage 804. This mass storage can be one or more hard disks that are typically packaged together with the processor and memory. Such hard disk are typically of 10 GB or greater storage capacity and more preferably have at least 40 GB of storage capacity. For example, in a preferred embodiment, described above, wherein a computer system of the invention comprises several nodes, each node can have its own hard drive. The head node preferably has a hard drive with at least 10 GB of storage capacity whereas each sibling node preferably has a hard drive with at least 40 GB of storage capacity. A computer system of the invention can further comprise other mass storage units including, for example, one or more floppy drives, one more CD-ROM drives, one or more DVD drives or one or more DAT drives.
  • Other external components typically include a user interface device 805, which is most typically a monitor and a keyboard together with a graphical input device 806 such as a “mouse.” The computer system is also typically linked to a network link 807 which can be, e.g., part of a local area network (“LAN”) to other, local computer systems and/or part of a wide area network (“WAN”), such as the Internet, that is connected to other, remote computer systems. For example, in the preferred embodiment, discussed above, wherein the computer system comprises a plurality of nodes, each node is preferably connected to a network, preferably an NFS network, so that the nodes of the computer system communicate with each other and, optionally, with other computer systems by means of the network and can thereby share data and processing tasks with one another.
  • Loaded into memory during operation of such a computer system are several software components that are also shown schematically in FIG. 8. The software components comprise both software components that are standard in the art and components that are special to the present invention. These software components are typically stored on mass storage such as the hard drive 804, but can be stored on other computer readable media as well including, for example, one or more floppy disks, one or more CD-ROMs, one or more DVDs or one or more DATs. Software component 810 represents an operating system which is responsible for managing the computer system and its network interconnections. The operating system can be, for example, of the Microsoft Windows™ family such as Windows 95, Window 98, Windows NT, Windows 2000 or Windows XP. Alternatively, the operating software can be a Macintosh operating system, a UNIX operating system or a LINUX operating system. Software components 811 comprises common languages and functions that are preferably present in the system to assist programs implementing methods specific to the present invention. Languages that can be used to program the analytic methods of the invention include, for example, C and C++, FORTRAN, PERL, HTML, JAVA, and any of the UNIX or LINUX shell command languages such as C shell script language. The methods of the invention can also be programmed or modeled in mathematical software packages that allow symbolic entry of equations and high-level specification of processing, including specific algorithms to be used, thereby freeing a user of the need to procedurally program individual equations and algorithms. Such packages include, e.g., Matlab from Mathworks (Natick, Mass.), Mathematica from Wolfram Research (Champaign, Ill.) or S-Plus from MathSoft (Seattle, Wash.).
  • Software component 812 comprises any analytic methods of the present invention described supra, preferably programmed in a procedural language or symbolic package. For example, software component 812 preferably includes programs that cause the processor to implement steps of accepting a plurality of measured signals and storing the measured signals in the memory. For example, the computer system can accept measured signals that are manually entered by a user (e.g., by means of the user interface). More preferably, however, the programs cause the computer system to retrieve measured signals from a database. Such a database can be stored on a mass storage (e.g., a hard drive) or other computer readable medium and loaded into the memory of the computer, or the compendium can be accessed by the computer system by means of the network 807.
  • In addition to the exemplary program structures and computer systems described herein, other, alternative program structures and computer systems will be readily apparent to the skilled artisan. Such alternative systems, which do not depart from the above described computer system and programs structures either in spirit or in scope, are therefore intended to be comprehended within the accompanying claims.
    • 6. EXAMPLES
  • The following examples are presented by way of illustration of the present invention, and are not intended to limit the present invention in any way.
    • 6.1. Identification of Phase-Specific Genes in CML
  • A set of 91 individual cases of CML, including chronic phase (N=42), accelerated phase by blast count criteria (N=9) or by the occurrence of additional clonal cytogenetic changes (N=8), blast crisis (N=28), and 4 cases of blast crisis in remission after chemotherapy were used to identify genes involved in progression from chronic phase to advanced disease (i.e., accelerated and blast phases). A pool of 200 chronic phase bone marrows was used as the reference. An ANOVA analysis revealed ˜3,000 genes differentially expressed across the different phases of disease using a minimum statistical significance cutoff of p<10−11 (Tables 1a and 1b). Sequences of polynucleotide probes used to detect these genes are listed in Table 8. This set of genes identified in the progression from chronic to blast phase is referred to here as the “phase reporter” gene set. FIG. 1 shows a “heat map” of the expression of the 3,000 phase reporter genes across the various phases of CML. This illustrates the global change of gene expression as the disease progresses from the chronic phase through the advanced phase of the disease.
  • The expression patterns were then examined to determine if progression of CML best fits a three-step model as often described in the literature (chronic phase to accelerated phase to blast crisis), or a two-step model (chronic phase to advanced phase, i.e., accelerated or blast phase). The gene expression patterns of accelerated phase cases were compared to those of the blast crisis cases (FIG. 5). The correlation between the expression profiles of accelerated cases and those of the blast phase was quite strong (r=0.81). Comparing differentially regulated genes between accelerated phase with blast phase, there are very few phase specific genes, i.e. genes only regulated in one phase but not in another. These observations suggest that the difference of gene expression changes between accelerated and blast phase is a quantitative one rather than a qualitative one that requires new gene expression or repression.
  • The biological functions of the genes associated with CML phases were also examined by applying a biological annotation program based on the GO and KEGG annotations. The functional groups most highly correlated with progression to blast crisis included increased expression of nuclear genes, mitochondrial genes, RNA binding genes, protein biosynthesis genes, and genes involved in chaperone function, all reflecting the increased proliferation and metabolism of progressive disease.
  • Progression was also associated with decreases in the expression levels of genes involved in structural integrity and adhesion, as well as decreases in the expression levels of genes involved in inflammatory and immune response. In addition, several proto-oncogenes and tumor suppressor genes were differentially expressed with progression. For example, N- and Hras, FLT3, yes, AF1q, CBFB, WT1, ORALOV1, PTNN11, and Bc1-2 demonstrated increased expression in blast crisis as compared to chronic phase. Analysis of the phase reporter genes suggested a relative decrease in MAPPK signaling in advanced phase as compared to chronic phase. The progression was also seen as associated with increases in alternative signal pathways. Thus, the cytoplasmic GTP protein Rras2 was highly over-expressed in advanced phases, as was ras signaling components RAB56 and RALGD5. Alterations of cytokine signaling were demonstrated by an increase in expression of TNF factors SF4 and 7, and SOCS2 and 4.
    • 6.2. Identification of Progression- and Response-Specific Genes
  • Next, how the phase reporter gene set was influenced by the gene expression signature of leukemia blasts and how they compared to normal immature CD34+ cells were investigated. First, the gene expression signatures of eight samples of normal CD34+ cells were compared with CML blast samples containing >70% blasts (FIG. 2 a). It was found that the gene expression pattern of CML blast cells was very similar to normal CD34+ cells, suggesting that “progression” from the chronic phase to the advanced phase is functionally similar to a block or “reversion” towards a more primitive hematopoetic cell. To uncover genes that are unique to progression, the normal CD34+ signatures were mathematically subtracted from each of the disease samples and the phase reporter signals were searched for (FIG. 2 c and FIG. 6). A set of 386 genes (p<10−8) were identified (FIG. 2 c and Tables 2a and 2b). These genes are called the “progression genes.” A set of 368 genes with ANOVA p<0.1% were identified as differentially expressed between CML blast crisis and normal immature CD34+ cells were also identified (FIG. 2 b and Tables 5a and 5b). These genes are called the “target genes.” There were 103 genes overlapping between these two sets (hypergeometric P-value: 1.3×10−99). This gene set is enriched in genes that are diagnostic markers of progression and novel targets of therapy. Table 3 shows the “top ten” genes that are associated with progression, independent of normal CD34+ expression, based on log 10 ratio of expression compared to the chronic phase pool. These genes suggest a deregulation of genes of transcriptional regulation (GLI2, WT1, FOS, FOSB), signal transduction (SOCS2, Rras2, IL8), and apoptosis (GAS2). Moreover, two HSP 70 subunits are differentially down-regulated, suggesting an alteration of this component of the chaperone system in blast crisis. Also significantly associated with progression was the surface protein PRAME, which has an unknown function, but has been associated with myeloid malignancy (van Baren et al. 1998, Br J Haematol 102:1376; Watari et al. 2000, FEBS Lett 466:367). Gene functions overrepresented in blast crisis were predominated by changes in ribosome gene expression and increased in the beta-catenin/WNT signaling pathway. More significant changes in gene function were down-regulated in progression, including nucleosome assembly and chromatin structure, sugar catabolism and metabolism, differentiation, and apoptosis.
    • 6.3. Identification of Signaling Pathways Associated with Progression
  • Multiple changes in several signaling pathways are represented in the progression gene set. Again, these genes were seen in the progression of chronic phase to advanced disease, but are differentially expressed compared to normal CD34+ cells. There was a deregulation of the betacatenin/WNT pathway. Expression of the cell surface protein cadherin was decreased, as was proto-cadhedrin, potentially leading to an activation of the beta-catenin/WNT signaling pathway by allowing more free beta-catenin to move to the cytoplasm. Moreover, the myogenesis transcription control gene MDFI (I-mfa), which complexes with axin (therefore potentially increasing free beta-catenin), was increased by approximately 7-fold. In all, 16 genes associated with the beta-catenin pathway were significantly over-expressed (e.g., PRICKLE1, CSNK1E, PLCB1, FZD2, LRP6, SMAD3, etc.). In summary, these findings strongly suggest aberrant activation of the betacatenin/WNT pathway during CML progression. Moreover, progression appears to be associated with a remodeling of several cytoskeletal and adhesion molecules, which may play a role in regulating proliferation. Thus there is an increase in CD47, Creb11, and ITGA5 expression, and a decrease in proto-cadhedrin, cadhedrin, actin, and betaactin.
  • In addition, the abl family member abl2 (ARG) was significantly associated with disease progression; by contrast, abl1, which is both expressed from the normal chromosome 9 and the t(9;22) translocation, was not differentially expressed with progression. Advanced phase disease was associated with deregulation of transcription factors, differentiation and apoptosis. Both components of the AP-1 transcription complex, Jun B and Fos, show decreased expression in progression. In addition, the Kupple-like zinc finger GLI2 is highly over-expressed in progression. The block in differentiation may be facilitated by the up-regulation of MDFI, WT1, and AF1q, and the down regulation of GADD45. Apoptosis in blast cells appears to be inhibited by the over-expression of Bcl2, DAP, and the decrease in MCL1 and Acinus. Progression was also associated with alterations in normal protein chaperone and degradation processes, with a widespread decrease in the expression of HSP70 and DNAJ families of genes. In addition, proteosome components BMA1 PSME2, and TRIP12 were all significantly increased in advanced phase CML cases.
    • 6.4. Identification of Progression-Specific Promoters
  • In order to examine if specific pathways were altered in progression, the progression and phase reporter gene sets were analyzed for aberrant expression of genes possessing known promoter sequences. Aberrant regulation of several sets of promoter controlled genes was revealed (Table 6). The most statistically significantly set of genes showing aberrant control in progression where those that contained a MZF promoter or a delta EF1 promoter sequence (p<10−15 and <10−11, respectively; FIGS. 3 a and 3 b). Also significantly associated with progression were genes bearing SPI-B, Yin Yang, and Ahr-ARNT promoter sequences (all with p values <10−9).
    • 6.5. Identification of Imatinib Responsiveness Reporter Genes
  • Gene expression profiles of patients who failed imatinib therapy were analyzed. A set of 21 cases of CML treated with the tyrosine kinase inhibitor imatinib mesylate, including 9 patients who initially achieved a complete cytogenetic remission (CCR) on imatinib therapy, but then relapsed, most back into an apparent chronic phase by morphology; 3 cases who had achieved a complete hematologic but no cytogenetic response; 3 late chronic phase patients before treatment with imatinib; and 6 cases of blast crisis was used. All but one of these the chronic phase patients who relapsed after a CCR had a point mutation in abl1, presumably abrogating imatinib activity (Table 7).
  • TABLE 7
    Characteristics of cases treated with imatinib
    Phase of Disease at Phase of disease at
    CODE Case type initiation of imatinib time of sample Cytogenetics Mutation(s)
     2 Imatinib failure chronic relapsed chronic 100% Ph+; M244V
    NEW: t(1; 12) in all
    cells
     4 Imatinib failure chronic relapsed chronic 100% Ph+ T315I
     5 Imatinib failure chronic relapsed chronic 80% Ph+ F359V
     6 Imatinib failure chronic relapsed chronic 100% Ph+ M351T,
    F317L
     8 Imatinib failure chronic relapsed chronic 100% Ph+ M351T
    10 Imatinib failure chronic relapsed chronic 100% Ph+ E255K
    11 Imatinib failure chronic post-allo relapsed chronic not available T315I
    BMT
    12 Imatinib failure chronic relapsed chronic 100% Ph+ L248V
    14 Imatinib failure chronic relapsed chronic 100% Ph+ M351T,
    H396R
    15 Pre-imatinib chronic chronic pre-treatment 50% Ph+ none
    treatment
    17 Pre-imatinib chronic chronic pre-treatment 100% Ph+ none
    treatment
    18 Pre-imatinib chronic CHR; no cytogenetic 100% Ph+ none
    treatment response
    19 Pre-imatinib chronic chronic pre-treatment 45% t(9; 13; 22); 50% none
    treatment t (9; 13; 22), −Y; 5%
    nl
    21 Pre-imatinib chronic CHR; no cytogenetic 100% Ph+ none
    treatment response
    22 (same pt as Pre-imatinib chronic CHR; no cytogenetic 100% Ph+ (3 of 18 none
    13) treatment response with additional Ph)
    23 Pre-imatinib myeloid blast crisis pre-treatment MBC 100% Ph+ none
    treatment
    24 Pre-imatinib myeloid blast crisis pre-treatment MBC 100% Ph+, t(2; 16) none
    treatment
    25 Pre-imatinib myeloid blast crisis pre-treatment MBC 100% Ph+, +8, iso none
    treatment 17q
    26 Pre-imatinib myeloid blast crisis not treated not available unknown
    treatment
    27 Pre-imatinib myeloid blast crisis relapsed MBC 100% Ph+ unknown
    treatment
    29 Pre-imatinib myeloid blast crisis relapsed MBC not available unknown
    treatment
    29 Pre-imatinib myeloid blast crisis relapsed MBC not available unknown
    treatment
  • FIG. 4 a shows the expression pattern of 15 cases of clinical chronic phase CML patients, 3 with longstanding chronic phase before imatinib treatment, the other 12 who had initially a suboptimal response (achieving only a hematological response) or relapsed after an initial CCR. The association with the progression signature can be demonstrated by segregating all CML cases by the correlation of gene expression signature between the boundaries of “most chronic” and “most advanced” gene expression for all 3,000 genes in the phase reporter gene set (FIG. 4 b). The majority of the poor response patients had gene expression profiles more consistent with advanced disease rather than chronic phase. Both cases with T315I mutations, which have been shown to have especially poor prognosis, have expression signatures more similar to advanced disease than chronic phase. However, while these imatinib failures shared much of the blast crisis signature, there were gene expression features that were unique to these cases. FIG. 4 c compares relapsed imatinib cases against blast crisis cases. Several areas (boxed) indicate genes that are expressed in reverse direction in these two states. Table 4 lists genes in the first box which are strongly associated with imatinib failure. Examples of genes unique to imatinib failure are those of serine threonine kinases (CTRL, MAP21K14, CLK3), MAP kinase (MKNK2), and the tyrosine kinase oncogene FYN. The highest genes over-expressed in imatinib resistant cases were TCF7 (a putatively T cell specific transcription factor), two guanine nucleotide binding proteins (GNAZ and GNG11), and the MAF oncogene.
    • 6.6. Discussion
  • The biology and treatment of CML is dictated by the phase of disease, since the efficacy of all therapies (transplantation, interferon, imatinib) works best in chronic phase, and worse in accelerated phase and blast crisis. Understanding the biology of progression provides clinical diagnostic markers of progression, and offer insights into new strategies for treatment. The data presented in these examples suggest that the progression of chronic phase CML to advanced phase CML is a two-step process, with progression associated with a block of differentiation and apoptosis, a shift towards turning on expression of genes involved in the nucleosome, while down-regulating histone transcription. Moreover, progression is associated with alterations in cell adhesion, and activation of alternative signaling pathways. In addition, it appears that relapse after initial successful treatment with imatinib may be associated with gene expression patterns similar to advanced phase CML, suggesting that the process of progression persists in a subpopulation of CML cells even in the background of apparent successful therapy.
  • The demonstration that the gene expression pattern between accelerated and blast phases are very similar suggests that the crucial steps in progression are at the transition of chronic to accelerated phase, before obvious morphologic, cytogenetic or clinical evidence of progression. This has obvious clinical implications, since these patients might benefit from aggressive therapy. In addition, the observation that gene signatures of blast crisis can be seen in accelerated phase patients by cytogenetic criteria only, and blast crisis cases in remission (both of which have low blast counts similar to patients with chronic phase disease), demonstrates two important points. First, it points out the difficulty of correlating morphology with the biology of the disease.
  • Secondly, the penetration of a progression gene expression signature into a “chronic phase” appearing bone marrow suggests that progression is not merely an absolute block of differentiation, but that abnormal gene expression signals “leak” from the presumably immature blast crisis precursors into more normal appearing differentiated cell. This is critically important since it provides the basis for testing for progression genes in unsorted bone marrow samples from “chronic phase” patients.
  • In addition, the finding that CML blasts share a gene expression profile with normal CD34+ cells has important biological considerations (Passegue et al., 2003, Proc Natl Acad Sci USA 100 Suppl 1:11842). First, it implies that there may be a limited number of novel pathways active in CML blasts. This finding is obviously important (and encouraging) in the era of targeted therapeutics. It also may explain the relative resistance of blast crisis CML to chemotherapy. Normal hematopoetic stem cells are remarkably resistant to chemotherapy, and thus in AML and ALL, with remission comes the return of normal hematopoiesis. Remission is rare in blast crisis CML, perhaps because the blast cells are similarly resistant to chemotherapy as their normal counterpart.
  • Bcr-Ab1 has a wholesale range of biological activities. Critical in the transformation process is the activation of the Ras/MAPK pathways, which has broad effects on changes in cell adhesion (through Rho), proliferation (MAPK pathway), and apoptosis (through Akt) (Faderl et al., 1999, N Engl J Med 341:164; Ren, 2002, Oncogene 21:8629). The efficacy of imatinib works through the blockade of these effects.
  • Imatinib works poorly on advanced phase disease, and it may be because these tumors are less reliant on the pathways that imatinib blocks than chronic phase disease. Thus, it was found that the MAPK pathway was relatively under-expressed in advanced disease compared to chronic phase, but other signaling pathways, including those involving cytokines (IL3RA, SOCS2), alternative ras pathways (Rras2), and those involved in cell adhesion (B-catenin/WNT) were activated. The activation of these pathways may allow progression even in the face of therapeutic blockade of Bcr-Ab1 activated pathways. In addition, abl2 (Ab1 related gene, or ARG) is also upregulated in progresson. As opposed to abl1 (which is a nuclear protein until involved in the chimeric Bcr-Ab1 protein, at which time it migrates to the cytoplasm), ARG is a cytoplasmic protein (Kruh et al., 1990, Proc Natl Acad Sci USA 87:5802). The signaling targets of ARG are unknown, and although broadly expressed in tissue, its only known functional role apparent from knockout mouse models appears to be in the nervous system (Koleske et al., 1998, Neuron 21:1259; Perego et al., 1991, Oncogene 6:1899). ARG has been associated with myeloid leukemia in the contest of TEL/ARG translocations (Cazzaniga et al., 1999, Blood 94:4370; Iijima et al., 2000, Blood 95:2126). ARG shares over 90% homology of its tyrosine kinase domain with abl1, and ARG tyrosine kinase activity is inhibited by imatinib at similar drug concentrations (Kruh et al., 1990, Proc Natl Acad Sci USA 87:5802; Okuda et al., 2001, Blood 97:2440). However, given that Bcr-ABL amplification is considered to play a role in imatinib resistance (le Coutre et al. 2000, Blood 95:1758; Weisberg et al., 2000, Blood 95:3498), ARG over-expression in blast crisis could theoretically contribute to the relative resistance to imatinib found with progressive disease.
  • Two recent observations on the molecular biology of progression in CML are relevant to this study. First, activation of the beta-catenin pathway was observed in primary cell samples from patients with CML (Jamieson et al., 2004, N Engl J Med 351:657). Secondly, it was recently observed that mice deficient in Jun B develop a disease much like CML (Passegue et al., 2004, Cell 119:431). The data in these examples complement these findings, as we found broad dysregulation of WNT/beta-catenin pathway as well as decreased Jun B expression. A link between these pathways may be the gene MDFI (Imfa), an inhibitor of myogenic basic H-L-H transcription factors 4. MDFI interacts with axin, which is involved in binding and modulating free beta-catenin. Thus an increase in MDFI would effectively allow for more free beta-catenin to migrate to the nucleus, where it causes gene activation (Nelson et al., 2004, Science 303:1483). An increase in MDFI could also decrease the axinmediated activation of Jun (Kusano et al., 2002, Mol Cell Biol 22:6393). Thus, MDFI may play a central role in progression by both influencing the beta-catenin and Jun B pathways. Moreover, the fact that both Jun B and Fos were down-regulated in progression suggests that there may be a wholesale deregulation in AP-1 targets, which could have broad functional affects on differentiation, apoptosis, and cell cycle control (Hess et al., 2004, J Cell Sci 117:5965).
  • The analysis suggests that genes controlled by MZF1 and delta EF1 may be particularly important in progression. MZF1 is a member of the Kruppel family of zinc finger proteins, and was originally cloned from a cDNA library from a blast crisis CML patient (Hromas et al., 1991, J Biol Chem 266:14183). MZF1 appears to play a critical role in hematopoetic stem cell differentiation, including modulation of CD34 and c-myb expression (Gaboli et al., 2001, Genes Dev 15:1625; Perrotti et al., 1995, Mol Cell Biol 15:6075). MZF1 −/− knock-out mice display an increase in hemapoetic progenitor proliferation which continues in long-term culture conditions (Gaboli et al., 2001, Genes Dev 15:1625). These data support the findings found in our human studies described about that MZF1 deregulation may disrupt normal differentiation, promoting the progression to advanced disease. Delta EF1 is related to the Smad zinc finger proteins that play an important role in TGFbeta gene regulation. Delta EF1 has been shown to compete with basic helix-loop-helix activators, and is implicated in modulation of MyoD regulated pathways (Funahashi et al., 1993, Development 119:433; Sekido et al., 1994, Mol Cell Biol 14:5692). It is not known if delta EF1 directly influences MDFI expression.
  • Of note is that both MZF1 and delta EF1 have been shown to influence cadherin expression (Guaita et al., 2002, J Biol Chem 277:39209; Le et al., 2005, Exp Cell Res 302:129; Miyoshi et al., 2004, Br J Cancer 90:1265). Thus, the further study of the control of MZF1 and delta EF1 may be particularly fruitful in understanding the molecular mechanisms of CML progression. Given that efficacy of treatment in CML (be it with interferon, imatinib, or transplantation) is so intimately associated with phase of disease, those patients who fail therapy in chronic phase may have genetic features of advanced phase invisible to routine pathological and cytogenetic exam. Imatinib failures are a reasonable setting to explore this possibility. While imatinib can cause cytogenetic remissions in the majority of chronic phase cases, treatment failure, especially secondary to point mutations, is an increasingly important problem. It has previously been demonstrated that the probability of developing a point mutation depends largely on the time from diagnosis to initiation of therapy (Branford et al., 2003, Blood 102:276). This finding implies that the genetic mechanisms that lead to point mutations are relentless, and therefore the treatment of “late” chronic phase patients (i.e., >1 year from diagnosis) may be undermined by genetic changes that have already occurred. Branford et al. demonstrated that patients who developed point mutations had a very poor outcome, with approximately half dying within a year of relapse (Branford et al., 2003, Blood 102:276). These observations are in keeping with the demonstration in these examples that many imatinib failures have gene expression changes similar to advanced disease, despite their benign pathological appearance. Thus, resistance to imatinib may be ameliorated by either targeting pathways of progression (beta-catenin, JunB/Fos, etc.), or by targeting pathways specifically found activated in imatinib resistance cases (alternative kinases, protein transporters).
  • Several of the genes found in the progression set might serve as early markers of progression in diagnostic assays, and may serve as therapeutic targets, as well. For example, PRAME (Preferentially Expressed Antigen of Melanoma) was originally identified as a tumor antigen recognized by cytotoxic T-cells against a melanoma surface antigen (Matsushita et al., 2001, Br J Haematol 112:916, 2001; van Baren et al., 1998, Br J Haematol 102:1376). Like similar antigens MAGE, BAGE, and GAGE, which are expressed in some solid tumors; unlike these other antigens, however, PRAME has been found to be overexpressed in over 25% of leukemia, and has been found to be induced by Bcr-Abl in CML cell lines (Watari et al., 2000, FEBS Lett 466:367). Indeed, PRAME over-expression has been described as one of the few features that characterize the transient myeloproliferative syndrome of Down's syndrome from the progressive acute megakaryoblastic leukemia found in that disorder (McElwaine et al., 2004, Br J Haematol 125:729). While the function of PRAME is still unknown, its expression on the cell surface might be amenable to flow cytometry assays, as well as a target for immunologic (vaccine or cell-based) therapy. CD47, an integrin-like protein, is another potential diagnostic target discovered in our analysis of progression (Motegi et al., 2003, Embo J 22:2634; Okazawa et al., 2005, J Immunol 174:2004). In addition, the demonstration of aberrant regulation of alternative signaling pathways (FLT3; Rras2; beta-catenin. SOCS2), proteosomes, and chaperone proteins suggest that the targeting of several novel pathways may be needed in the treatment of advanced CML.
  • Compared to other types of leukemia, there have been few papers exploring the use of microarrays on the biology of CML. In sum, 23 patients of various stages have been studied, 10 on unsorted samples, 13 from AC133+ isolated cells. It is difficult to make a direct comparison of these studies and ours, given the different types of samples obtained, the difference in the array platforms (these studies used platforms examining 3,000-5,000 genes, compared to ˜24,000 genes in this current study). In general, however, the functional changes of progression, e.g., changes in differentiation, apoptosis, and cell adhesion, remained as common themes across the study. In contrast to one study, no significant differences in signatures obtained from bone marrow and peripheral blood (FIG. 7) were found, which may be important in future prospective studies of this disease in patients.
  • These findings have the potential to influence therapy of CML. Patients who present with gene expression patterns suggestive of advanced phase disease might benefit to move straight to transplantation if a donor exists, or if not, other investigation therapies. Moreover, PCR assays of individual genes (or small sets of genes) may be used to monitor patients early in the course of imatinib therapy for signs of progression to advanced disease. Microarray studies of large cohorts of patients treated with imatinib will likely identify gene patterns indicative of response that can be used immediately at diagnosis to tailor therapy.
    • 6.7. Materials and Methods
  • Patient samples. All samples were obtained under the auspices of institutional review board approve protocols. Samples came from the FHCRC, the Southwest Oncology Group (SWOG) Myeloid Repository, the University of Oregon Health Sciences Center, the University of California, Los Angeles, or the University of Chicago. RNA extraction was either performed immediately, or in the case of samples stored in a liquid nitrogen repository, after thawing. All RNA samples were quality tested by analysis of ribosomal RNA peaks using an ABI Bioalyzer. The definition of chronic, accelerated and blast crisis was based on the criteria of Sokal (Sokal et al., 1984, Blood 63:789).
  • Amplification, labeling, and hybridization. The procedures of RNA amplification, labeling, and the hybridization to arrays, as well as the specifics of the array platforms, has been previously published (Hughes et al., 2001, Nat Biotechnol 19:342).
  • Analytic Methods and Results. Each individual sample was hybridized to a pool of chronic phase samples. The log10 (Ratio) of intensity of individual samples to the pool were used for the subsequent analysis. Before selecting features by ANOVA, 25,000 genes on the array were first screened for evidence of differential regulation by requiring P-value of regulation <1% in more than 3 experiments. Where P-value of regulation is based on the platform error model. Features differentiating progression stages were selected by ANOVA test.
  • Functional annotation of gene lists. Genes represented on the microarray were annotated by assignment to GO Biological Process or Molecular Function categories (at the web address www.ebi.ac.uk/GOA/), or to KEGG pathways (at the web address www.genome.jp/kegg/pathway.html). Gene lists (input sets) were queried for enrichment of members of specific functional classes or pathways relative to the background frequency. The significance (P-value) of enrichment was computed using the hypergeometric probability distribution. Reported in each case are the numbers of genes in the input set (input gene count), number of genes in a particular category or pathway in the input set (overlap gene count), number of genes in a particular category among all genes present on the array (set gene count). The total number of unique genes on the array is 24132.
  • Methods to common promote site analysis. The common promoter sites were based on the predictions derived from the database (oPOSSUM) by Wasserman et al. (www.cisreg.ca). The hypergeometric P-value for enrichment of a particular binding site was computed by comparing the number of genes with the binding site from a signature gene set to that from a background set (i.e., all genes represented on the microarray).
  • Controls. We compared the genes found associated with progression to the genes found significantly over- and under-expressed with prolonged “transit time” from sample acquisition to RNA processing (Radich et al., 2004, Genomics 83:980). There gene signatures of the two data sets were different, excluding this artifact as contributing significantly to the progression gene set.
  • Lastly, we compared gene expression signatures from the sites contributing samples to confirm that there were no site-signatures confounding the analysis. We found no evidence of site-specific signatures.
  • As some samples of blast crisis came from peripheral blood rather than bone marrow, we compared three samples in which simultaneous samples were available from bone marrow and peripheral blood. Gene expression was extremely well correlated (r=0.97 to 0.99; FIG. 7).
  • TABLE 8
    The phase reporter genes
    SEQ PROBE SEQ
    SUBS GENE DESCRIPTION SP_XREF_KEYWORD_LIST ID NO. ID NO.
    AB002301 KIAA0303 KIAA0303 protein Hypothetical protein, ATP-binding, 1 3969
    Kinase, Serine/threonine-protein
    kinase, Transferase
    AB002313 PLXNB2 plexin B2 Hypothetical protein 2 3970
    AB002314 KIAA0316 KIAA0316 gene Hypothetical protein 3 3971
    product
    AB002331 DATF1 death associated Apoptosis, Nuclear protein, Zinc- 4 3972
    transcription factor 1 finger, Alternative splicing
    AB002336 EPB41L1 erythrocyte Hypothetical protein, Structural 5 3973
    membrane protein protein, Cytoskeleton, Actin-binding
    band 4.1-like 1
    AB002337 KIAA0339 KIAA0339 gene Hypothetical protein 6 3974
    product
    AB002354 KIAA0356 pleckstrin homology Hypothetical protein 7 3975
    domain containing,
    family M (with RUN
    domain) member 1
    AB002359 PFAS phosphoribosylformylglycinamidine Purine biosynthesis, Ligase, ATP- 8 3976
    synthase (FGAR binding, Glutamine
    amidotransferase) amidotransferase, Hypothetical
    protein
    AB002360 MCF2L MCF.2 cell line Hypothetical protein, Guanine- 9 3977
    derived transforming nucleotide releasing factor, Proto-
    sequence-like oncogene
    AB002366 KIAA0368 KIAA0368 Hypothetical protein 10 3978
    AB002368 XPO6 exportin 6 Hypothetical protein 11 3979
    AB002369 MTMR3 myotubularin related Hydrolase, Zinc-finger, Alternative 12 3980
    protein 3 splicing, Hypothetical protein
    AB002373 KIAA0375 RUN and SH3 Hypothetical protein, SH3 domain 13 3981
    domain containing 2
    AB002377 KIAA0379 ankyrin repeat Hypothetical protein, Repeat, ANK 14 3982
    domain 28 repeat
    AB002379 DAAM2 dishevelled Coiled coil, Alternative splicing 15 3983
    associated activator
    of morphogenesis 2
    AB004857 SLC11A2 solute carrier family Transport, Iron transport, 16 3984
    11 (proton-coupled Transmembrane, Glycoprotein,
    divalent metal ion Alternative splicing, Polymorphism
    transporters),
    member 2
    AB006622 KIAA0284 KIAA0284 Hypothetical protein 17 3985
    AB007855 TIX1 zinc fingers and DNA-binding, Homeobox, Nuclear 18 3986
    homeoboxes 3 protein, Zinc-finger, Metal-binding,
    Repeat
    AB007863 PIP3-E phosphoinositide- Hypothetical protein 19 3987
    binding protein PIP3-E
    AB007864 KIAA0404 KIAA0404 protein Hypothetical protein, Metal-binding, 20 3988
    Oxidoreductase, Zinc
    AB007888 MBNL1 muscleblind-like Hypothetical protein, Zinc-finger, 21 3989
    (Drosophila) Repeat, Nuclear protein, RNA-
    binding, Alternative splicing
    AB007902 AUTS2 autism susceptibility Chromosomal translocation, 22 3990
    candidate 2 Polymorphism, Alternative splicing
    AB007915 KIAA0446 KIAA0446 gene Hypothetical protein 23 3991
    product
    AB007931 RBAF600 retinoblastoma- Hypothetical protein 24 3992
    associated factor
    600
    AB007941 KIAA0472 dusty protein kinase ATP-binding, Transferase, 25 3993
    Hypothetical protein, Kinase,
    Serine/threonine-protein kinase
    AB007958 KIAA0489 KIAA0792 gene Hypothetical protein 26 3994
    product
    AB007962 KIAA0493 KIAA0493 protein 27 3995
    AB007965 CYHR1 MRNA, chromosome 28 3996
    1 specific transcript
    KIAA0496.
    AB007972 PPP1R12B protein phosphatase ANK repeat, Myosin, Repeat 29 3997
    1, regulatory
    (inhibitor) subunit
    12B
    AB011093 P114-RHO- rho/rac guanine Hypothetical protein 30 3998
    GEF nucleotide exchange
    factor (GEF) 18
    AB011105 LAMA5 laminin, alpha 5 Laminin EGF-like domain, Signal, 31 3999
    Glycoprotein, Basement membrane,
    Extracellular matrix, Coiled coil, Cell
    adhesion, Repeat
    AB011112 KIAA0540 KIAA0540 protein Hypothetical protein, Repeat, WD 32 4000
    repeat
    AB011114 KIAA0542 KIAA0542 gene Hypothetical protein 33 4001
    product
    AB011133 KIAA0561 microtubule Hypothetical protein, ATP-binding, 34 4002
    associated Kinase, Serine/threonine-protein
    serine/threonine kinase, Transferase
    kinase 3
    AB011136 KIAA0564 KIAA0564 protein Hypothetical protein, ATP-binding 35 4003
    AB011153 PLCB1 phospholipase C, Hydrolase, Lipid degradation, 36 4004
    beta 1 Transducer, Phosphorylation,
    (phosphoinositide- Calcium, Alternative splicing
    specific)
    AB011154 RAB1A KIAA0582 protein Hypothetical protein 37 4005
    AB011157 PTDSR phosphatidylserine Hypothetical protein, Receptor 38 4006
    receptor
    AB011167 KIAA0595 peroxisome Hypothetical protein 39 4007
    proliferative
    activated receptor,
    gamma, coactivator-
    related 1
    AB011171 KIAA0599 KIAA0599 Hypothetical protein, Plasmid 40 4008
    AB011173 KIAA0601 amine oxidase Hypothetical protein 41 4009
    (flavin containing)
    domain 2
    AB011542 EGFL5 EGF-like-domain, Laminin EGF-like domain 42 4010
    multiple 5
    AB012692 CAC-1 beta-casein-like Hypothetical protein 43 4011
    protein
    AB014516 MECT1 Homo sapiens Transcription regulation, DNA- 44 4012
    mRNA for KIAA0616 binding, Activator, Nuclear protein,
    protein, partial cds. Phosphorylation, Cell cycle,
    Alternative splicing, 3D-structure,
    Polymorphism, Hypothetical protein
    AB014520 PLXND1 plexin D1 Hypothetical protein 45 4013
    AB014538 KIAA0638 pleckstrin homology- Hypothetical protein 46 4014
    like domain, family
    B, member 1
    AB014543 KIAA0643 KIAA0643 protein Hypothetical protein 47 4015
    AB014548 KIAA0648 KIAA0648 protein Hypothetical protein 48 4016
    AB014557 KIAA0657 KIAA0657 protein Hypothetical protein, 49 4017
    Immunoglobulin domain
    AB014558 CRY2 cryptochrome 2 Lyase, Hypothetical protein 50 4018
    (photolyase-like)
    AB014564 KIAA0664 KIAA0664 protein Hypothetical protein, Initiation factor, 51 4019
    Protein biosynthesis
    AB014566 DAAM1 dishevelled Coiled coil, Alternative splicing 52 4020
    associated activator
    of morphogenesis 1
    AB014567 TIP120B TBP-interacting Hypothetical protein 53 4021
    protein
    AB014568 UNC84B unc-84 homolog B Transmembrane, Nuclear protein, 54 4022
    (C. elegans) Coiled coil
    AB014574 KIAA0674 KIAA0674 protein Hypothetical protein 55 4023
    AB014578 KIAA0678 RME8 protein Hypothetical protein 56 4024
    AB014589 CSTF2T cleavage stimulation Hypothetical protein 57 4025
    factor, 3′ pre-RNA,
    subunit 2, 64 kDa,
    tau variant
    AB014597 GTAR ankyrin repeat Hypothetical protein, ANK repeat, 58 4026
    domain 17 Repeat
    AB014600 SIN3B SIN3 homolog B, Transcription regulation, Repressor, 59 4027
    transcriptional Repeat, Nuclear protein
    regulator (yeast)
    AB014604 OSBPL3 oxysterol binding Lipid transport, Transport, 60 4028
    protein-like 3 Alternative splicing
    AB015330 DKFZP761I2123 hypothetical protein Hypothetical protein 61 4029
    DKFZp761I2123
    AB015343 HRIHFB2122 Tara-like protein Cytoskeleton, Actin-binding, Coiled 62 4030
    coil, Nuclear protein
    AB018268 KIAA0725 SAM, WWE and Hypothetical protein 63 4031
    DDHD domain
    containing 1
    AB018325 CENTD2 centaurin, delta 2 GTPase activation, Repeat, Zinc- 64 4032
    finger, Alternative splicing
    AB018339 SYNE1 spectrin repeat Structural protein, Cytoskeleton, 65 4033
    containing, nuclear Actin-binding, Coiled coil,
    envelope 1 Transmembrane, Repeat, Alternative
    splicing, Polymorphism
    AB018348 PCNX pecanex homolog Transmembrane, Glycoprotein, 66 4034
    (Drosophila) Alternative splicing
    AB018353 UNC84A unc-84 homolog A Transmembrane, Nuclear protein, 67 4035
    (C. elegans) Coiled coil, Alternative splicing
    AB020627 KIAA0820 dynamin family Hydrolase, Motor protein, GTP- 68 4036
    member binding, Microtubule, Multigene
    family, Endocytosis
    AB020636 TIP120A TBP-interacting Hypothetical protein 69 4037
    protein
    AB020637 KIAA0830 KIAA0830 protein Hypothetical protein 70 4038
    AB020644 FACL6 acyl-CoA synthetase Ligase, Fatty acid metabolism, 71 4039
    long-chain family Magnesium, Multigene family,
    member 6 Alternative splicing, Chromosomal
    translocation, Hypothetical protein
    AB020649 KIAA0842 pleckstrin homology Hypothetical protein 72 4040
    domain containing,
    family M (with RUN
    domain) member 2
    AB020673 MYH11 myosin, heavy Myosin, Muscle protein, Coiled coil, 73 4041
    polypeptide 11, Thick filament, Actin-binding,
    smooth muscle Calmodulin-binding, ATP-binding,
    Methylation, Multigene family, Proto-
    oncogene, Chromosomal
    translocation
    AB020684 KIAA0877 KIAA0877 protein Hypothetical protein 74 4042
    AB020691 KIAA0884 GTPase activating Hypothetical protein 75 4043
    RANGAP domain-
    like 1
    AB020695 KIAA0888 KIAA0888 protein Hypothetical protein 76 4044
    AB020698 USP19 ubiquitin specific Protease, Ubl conjugation pathway, 77 4045
    protease 19 Hydrolase, Thiol protease, Multigene
    family, Zinc-finger, Metal-binding
    AB020703 DD5 progestin induced Ubl conjugation pathway, Ligase, 78 4046
    protein Nuclear protein, 3D-structure
    AB020704 PPFIA4 protein tyrosine Hypothetical protein 79 4047
    phosphatase,
    receptor type, f
    polypeptide
    (PTPRF), interacting
    protein (liprin), alpha 4
    AB023152 KIAA0935 mannosidase alpha Hydrolase, Glycosidase, Signal, 80 4048
    class 2B member 2 Glycoprotein, Hypothetical protein
    AB023154 KIAA0937 macrophage Hypothetical protein, Metal-binding, 81 4049
    expressed gene 1 Zinc, Zinc-finger
    AB023156 SLC9A8 solute carrier family Hypothetical protein 82 4050
    9 (sodium/hydrogen
    exchanger), isoform 8
    AB023164 KIAA0947 KIAA0947 protein Hypothetical protein 83 4051
    AB023210 WDFY3 WD repeat and Hypothetical protein, Repeat, WD 84 4052
    FYVE domain repeat
    containing 3
    AB023211 PADI2 peptidyl arginine Hydrolase, Calcium-binding, 85 4053
    deiminase, type II Multigene family
    AB023212 PCNX pecanex homolog Transmembrane, Glycoprotein, 86 4054
    (Drosophila) Alternative splicing
    AB023216 KIAA0999 KIAA0999 protein Hypothetical protein, ATP-binding, 87 4055
    Kinase, Serine/threonine-protein
    kinase, Transferase
    AB023230 KIAA1013 GRP1-binding Hypothetical protein, Cytoskeleton 88 4056
    protein GRSP1
    AB023233 CHDC1 calponin homology Hypothetical protein, Leucine-rich 89 4057
    (CH) domain repeat, Repeat
    containing 1
    AB025254 PCTAIRE2BP tudor repeat Hypothetical protein 90 4058
    associator with
    PCTAIRE 2
    AB026054 ZNF179 zinc finger protein Zinc-finger 91 4059
    179
    AB026436 DUSP10 dual specificity Hydrolase, Nuclear protein, 92 4060
    phosphatase 10 Hypothetical protein
    AB028972 KIAA1049 KIAA1049 protein Hypothetical protein 93 4061
    AB028978 KIAA1055 KIAA1055 protein Hypothetical protein 94 4062
    AB028980 USP24 ubiquitin specific Hypothetical protein, Ubl conjugation 95 4063
    protease 24 pathway, Hydrolase, Thiol protease,
    Multigene family
    AB028986 USP22 ubiquitin specific Hypothetical protein, Protease, Ubl 96 4064
    protease 22 conjugation pathway, Hydrolase,
    Thiol protease, Multigene family
    AB028989 MAPK8IP3 mitogen-activated Phosphorylation, Coiled coil 97 4065
    protein kinase 8
    interacting protein 3
    AB028994 AMOT angiomotin Hypothetical protein 98 4066
    AB029030 KIAA1107 KIAA1107 protein Hypothetical protein 99 4067
    AB029032 FLJ21404 hypothetical protein Hypothetical protein 100 4068
    KIAA1109
    AB029041 KIAA1118 likely ortholog of Hypothetical protein 101 4069
    mouse 5-azacytidine
    induced gene 1
    AB032952 KIAA1126 KIAA1126 protein Hypothetical protein 102 4070
    AB032965 CASKIN2 CASK interacting Hypothetical protein, ANK repeat, 103 4071
    protein 2 Repeat
    AB032973 LCHN LCHN protein Hypothetical protein 104 4072
    AB032976 P66 transcription Hypothetical protein 105 4073
    repressor p66 beta
    component of the
    MeCP1 complex
    AB032993 GRIPAP1 GRIP1 associated Hypothetical protein 106 4074
    protein 1
    AB033009 KIAA1183 KIAA1183 protein Hypothetical protein 107 4075
    AB033037 KIAA1211 KIAA1211 protein Hypothetical protein 108 4076
    AB033050 RAI17 retinoic acid induced Hypothetical protein 109 4077
    17
    AB033053 ZNF295 zinc finger protein Transcription regulation, DNA- 110 4078
    295 binding, Zinc-finger, Metal-binding,
    Nuclear protein, Repeat
    AB033055 KIAA1229 KIAA1229 protein Hypothetical protein 111 4079
    AB033068 FZR1 Fzr1 protein Hypothetical protein, Ubl conjugation 112 4080
    pathway, Cell cycle, Cell division,
    Mitosis, Repeat, WD repeat,
    Phosphorylation, Alternative splicing
    AB033070 KIAA1244 KIAA1244 Hypothetical protein 113 4081
    AB033073 KIAA1247 sulfatase 2 Hydrolase, Signal, Glycoprotein, 114 4082
    Endoplasmic reticulum, Golgi stack
    AB033085 KIAA1259 hypothetical protein Hypothetical protein, ATP-binding, 115 4083
    KIAA1259 Helicase, Hydrolase
    AB033087 TLE4 transducin-like Transcription regulation, Repressor, 116 4084
    enhancer of split 4 Nuclear protein, Repeat, WD repeat,
    (E(sp1) homolog, Phosphorylation, Wnt signaling
    Drosophila) pathway
    AB033091 KIAA1265 solute carrier family Hypothetical protein 117 4085
    39 (zinc transporter),
    member 10
    AB033092 MTA3 metastasis Hypothetical protein, Zinc-finger, 118 4086
    associated family, Nuclear protein, Alternative splicing
    member
    3
    AB033100 KIAA1274 KIAA protein (similar Hypothetical protein 119 4087
    to mouse paladin)
    AB033108 KCNH3 potassium voltage- Hypothetical protein, Transport, Ion 120 4088
    gated channel, transport, Ionic channel, Voltage-
    subfamily H (eag- gated channel, Potassium channel,
    related), member 3 Potassium transport,
    Transmembrane, Glycoprotein,
    Multigene family
    AB033112 BRPF3 bromodomain and Hypothetical protein, Zinc-finger, 121 4089
    PHD finger Bromodomain
    containing, 3
    AB033118 ZDHHC8 zinc finger, DHHC Transmembrane, Zinc-finger, 122 4090
    domain containing 8 Hypothetical protein
    AB037716 KIAA1295 KIAA1295 protein Hypothetical protein, SH3 domain 123 4091
    AB037720 SH2B SH2-B homolog Hypothetical protein 124 4092
    AB037721 STARD9 START domain Hypothetical protein 125 4093
    containing 9
    AB037722 KIAA1301 NEDD4-related E3 Hypothetical protein 126 4094
    ubiquitin ligase
    NEDL2
    AB037729 RALGDS ral guanine Guanine-nucleotide releasing factor, 127 4095
    nucleotide 3D-structure, Hypothetical protein
    dissociation
    stimulator
    AB037749 KIAA1328 KIAA1328 protein Hypothetical protein 128 4096
    AB037757 KIAA1336 WD repeat domain Hypothetical protein, Repeat, WD 129 4097
    35 repeat
    AB037760 ZNF398 zinc finger protein Transcription regulation, Activator, 130 4098
    398 DNA-binding, Zinc-finger, Metal-
    binding, Nuclear protein, Repeat,
    Alternative splicing
    AB037771 KIAA1350 ubiquitin specific Hypothetical protein 131 4099
    protease 53
    AB037787 NLGN2 neuroligin 2 Cell adhesion, Glycoprotein, Signal, 132 4100
    Transmembrane
    AB037795 KIAA1374 KIAA1374 protein Hypothetical protein, Repeat, WD 133 4101
    repeat
    AB037802 COG1 component of Transport, Protein transport, Golgi 134 4102
    oligomeric golgi stack, Membrane
    complex
    1
    AB037813 DKFZp762K222 hypothetical protein Hypothetical protein 135 4103
    DKFZp762K222
    AB037814 KIAA1393 KIAA1393 Hypothetical protein 136 4104
    AB037836 PRex1 phosphatidylinositol Guanine-nucleotide releasing factor, 137 4105
    3,4,5-trisphosphate- Repeat, Alternative splicing
    dependent RAC
    exchanger
    1
    AB037845 ARHGAP10 Rho GTPase Hypothetical protein 138 4106
    activating protein 21
    AB037851 KIAA1430 KIAA1430 protein Hypothetical protein 139 4107
    AB037855 KIAA1434 hypothetical protein Hypothetical protein 140 4108
    KIAA1434
    AB037859 MKL1 megakaryoblastic Transcription regulation, Nuclear 141 4109
    leukemia protein, Coiled coil, Repeat,
    (translocation) 1 Chromosomal translocation, Proto-
    oncogene
    AB037860 NFIA nuclear factor I/A Activator, DNA replication, DNA- 142 4110
    binding, Nuclear protein,
    Transcription, Transcription
    regulation, Multigene family
    AB037861 DKFZP586J0619 DKFZP586J0619 Hypothetical protein 143 4111
    protein
    AB040881 KIF1B kinesin family Hypothetical protein, Motor protein, 144 4112
    member 1B Microtubule, ATP-binding, Coiled
    coil, Mitochondrion, Alternative
    splicing, Disease mutation, Charcot-
    Marie-Tooth disease
    AB040900 KIAA1467 KIAA1467 protein Hypothetical protein 145 4113
    AB040907 KIAA1474 zinc finger protein Hypothetical protein, Metal-binding, 146 4114
    537 Zinc, Zinc-finger
    AB040908 VPS18 vacuolar protein Transport, Protein transport, 147 4115
    sorting protein 18 Membrane, Zinc-finger, Coiled coil,
    Alternative splicing
    AB040917 KIAA1484 leucine rich repeat Hypothetical protein, 148 4116
    and fibronectin type Immunoglobulin domain
    III domain containing 1
    AB040930 LRRN1 leucine rich repeat Hypothetical protein, 149 4117
    neuronal 1 Immunoglobulin domain
    AB040942 KIAA1509 KIAA1509 Hypothetical protein, Plasmid 150 4118
    AB040955 KIAA1522 KIAA1522 protein Hypothetical protein 151 4119
    AB040960 FLJ22670 lymphocyte alpha- Hypothetical protein, Kinase 152 4120
    kinase
    AB040961 DTX2 deltex homolog 2 Nuclear protein, Repeat, Metal- 153 4121
    (Drosophila) binding, Zinc, Zinc-finger, Alternative
    splicing, Polymorphism
    AB040968 HCN3 hyperpolarization Transport, Ion transport, Ionic 154 4122
    activated cyclic channel, Voltage-gated channel,
    nucleotide-gated Potassium channel, Potassium,
    potassium channel 3 Potassium transport, Sodium
    transport, cAMP, cAMP-binding,
    Transmembrane, Glycoprotein,
    Sodium channel
    AB040969 KIAA1536 KIAA1536 protein Hypothetical protein 155 4123
    AB040972 FLJ11560 Homo sapiens Hypothetical protein 156 4124
    mRNA for KIAA1539
    protein, partial cds.
    AF000560 hypothetical protein Metal-binding, Zinc, Zinc-finger 157 4125
    LOC126208
    AF007217 TRIP11 thyroid hormone Antigen, Golgi stack, Coiled coil, 158 4126
    receptor interactor Chromosomal translocation,
    11 Hypothetical protein
    AF011757 S100A12 S100 calcium Calcium-binding, Zinc, Metal-binding 159 4127
    binding protein A12
    (calgranulin C)
    AF016267 TNFRSF10C tumor necrosis factor Receptor, Apoptosis, Glycoprotein, 160 4128
    receptor superfamily, Repeat, GPI-anchor, Signal,
    member 10c, decoy Lipoprotein
    without an
    intracellular domain
    AF016495 AQP9 aquaporin 9 Transport, Repeat, Transmembrane 161 4129
    AF017433 ZNF213 zinc finger protein Transcription regulation, DNA- 162 4130
    213 binding, Zinc-finger, Metal-binding,
    Nuclear protein, Repeat
    AF026816 ITPA inosine Hydrolase, Nucleotide metabolism, 163 4131
    triphosphatase Disease mutation
    (nucleoside
    triphosphate
    pyrophosphatase)
    AF031166 SRP46 Splicing factor, 164 4132
    arginine/serine-rich,
    46 kD
    AF034803 PPFIBP2 PTPRF interacting Receptor, Hypothetical protein 165 4133
    protein, binding
    protein 2 (liprin beta
    2)
    AF035307 plexin C1 166 4134
    AF038193 ADP-ribosylation GTP-binding, Multigene family, 167 4135
    factor-like 3 Polymorphism
    AF038535 SYT7 synaptotagmin VII Transmembrane, Repeat, Synapse 168 4136
    AF038554 DENR density-regulated Hypothetical protein 169 4137
    protein
    AF043469 NXPH4 serine Transferase, Methyltransferase, 170 4138
    hydroxymethyltransferase 2 Pyridoxal phosphate, One-carbon
    (mitochondrial) metabolism, Mitochondrion, Transit
    peptide, Glycoprotein, Repeat,
    Signal, Hypothetical protein
    AF045229 RGS10 regulator of G- Signal transduction inhibitor, 171 4139
    protein signalling 10 Lipoprotein, Palmitate, Alternative
    splicing, Polymorphism
    AF049140 UBE2V2 ubiquitin-conjugating Ligase, Ubl conjugation pathway, 172 4140
    enzyme E2 variant 2 Vitamin D
    AF052093 NJMU-R1 protein kinase Njmu- 173 4141
    R1
    AF052117 chloride channel 4 Ionic channel, Ion transport, Chloride 174 4142
    channel, Chloride, Voltage-gated
    channel, Transmembrane, CBS
    domain, Repeat
    AF052159 protein tyrosine 175 4143
    phosphatase-like
    (proline instead of
    catalytic arginine),
    member b
    AF052167 MRS2L MRS2-like, Signal, Hypothetical protein 176 4144
    magnesium
    homeostasis factor
    (S. cerevisiae)
    AF052169 LOC115207 potassium channel Hypothetical protein 177 4145
    tetramerisation
    domain containing
    12
    AF052181 epimorphin 178 4146
    AF055006 SEC6 SEC6-like 1 (S. cerevisiae) Hypothetical protein, Exocytosis, 179 4147
    Transport, Protein transport, Coiled
    coil, Alternative splicing
    AF055012 TGIF2 TGFB-induced factor DNA-binding, Homeobox, 180 4148
    2 (TALE family Transcription regulation, Nuclear
    homeobox) protein, Phosphorylation
    AF055016 C13orf1 chromosome 13 Hypothetical protein 181 4149
    open reading frame 1
    AF055019 homeodomain Transferase, Serine/threonine- 182 4150
    interacting protein protein kinase, ATP-binding, Nuclear
    kinase
    2 protein, Alternative splicing
    AF055029 hypothetical protein 183 4151
    LOC151162
    AF055270 SFRS7 Homo sapiens heat- Nuclear protein, RNA-binding, 184 4152
    shock suppressed mRNA splicing, Alternative splicing,
    protein 1 (HSSG1) Phosphorylation, Repeat, Zinc-
    mRNA, complete finger, Hypothetical protein
    cds.
    AF059531 PRMT3 protein arginine N- Hypothetical protein, Transferase, 185 4153
    methyltransferase 3 Methyltransferase, Zinc-finger
    AF062341 CTNND1 catenin (cadherin- Cytoskeleton, Structural protein, 186 4154
    associated protein), Phosphorylation, Repeat, Cell
    delta
    1 adhesion, Coiled coil, Nuclear
    protein, Alternative splicing
    AF063020 PSIP2 PC4 and SFRS1 Receptor 187 4155
    interacting protein 1
    AF067972 DNMT3A DNA (cytosine-5-)- Methyltransferase, Transferase, 188 4156
    methyltransferase 3 Zinc-finger, Metal-binding, Nuclear
    alpha protein, Hypothetical protein
    AF068296 MRPS35 mitochondrial Hypothetical protein, Ribosomal 189 4157
    ribosomal protein protein, Mitochondrion
    S35
    AF070587 Clone 24741 mRNA 190 4158
    sequence
    AF070643 LOC55977 intraflagellar 191 4159
    transport protein
    IFT20
    AF072810 BAZ1B bromodomain Transcription regulation, 192 4160
    adjacent to zinc Bromodomain, Zinc-finger, Coiled
    finger domain, 1B coil, Nuclear protein, Alternative
    splicing, Williams-Beuren syndrome
    AF073519 SERF1A small EDRK-rich Alternative splicing 193 4161
    factor 1A (telomeric)
    AF073931 CACNA1H calcium channel, Ionic channel, Transmembrane, Ion 194 4162
    voltage-dependent, transport, Voltage-gated channel,
    alpha 1H subunit Calcium channel, Glycoprotein,
    Repeat, Multigene family, Calcium-
    binding, Phosphorylation, Alternative
    splicing
    AF077965 CLN3 ceroid-lipofuscinosis, Transmembrane, Lysosome, 195 4163
    neuronal 3, juvenile Glycoprotein, Alternative splicing,
    (Batten, Spielmeyer- Neuronal ceroid lipofuscinosis,
    Vogt disease) Disease mutation
    AF078843 LOC51202 DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 196 4164
    Asp) box polypeptide Hypothetical protein
    47
    AF085243 ZNF236 zinc finger protein Metal-binding, Nuclear protein, Zinc, 197 4165
    236 Zinc-finger, Hypothetical protein,
    Transcription regulation, DNA-
    binding, Repeat, Alternative splicing
    AF090935 C20orf3 Homo sapiens clone Transmembrane, Signal-anchor, 198 4166
    HQ0569. Glycoprotein, Polymorphism
    AF097021 GW112 differentially 199 4167
    expressed in
    hematopoietic
    lineages
    AF112213 C20orf24 chromosome 20 Alternative splicing 200 4168
    open reading frame
    24
    AF112219 ESD esterase Hydrolase, Serine esterase, 201 4169
    D/formylglutathione Polymorphism
    hydrolase
    AF113694 NF2 neurofibromin 2 Structural protein, Cytoskeleton, 202 4170
    (bilateral acoustic Anti-oncogene, Disease mutation,
    neuroma) Alternative splicing, Deafness, 3D-
    structure
    AF114264 nexilin nexilin (F actin Hypothetical protein 203 4171
    binding protein)
    AF116238 PUS1 pseudouridylate Lyase, tRNA processing, Nuclear 204 4172
    synthase 1 protein
    AF117236 MATR3 matrin 3 Nuclear protein, RNA-binding, 205 4173
    Repeat, Zinc-finger
    AF119665 PP pyrophosphatase Hydrolase, Metal-binding, 206 4174
    (inorganic) Magnesium
    AF119856 PRO1851 Homo sapiens Acute phase, Serine protease 207 4175
    mRNA for PK-120, inhibitor, Repeat, Signal, Multigene
    complete cds. family, Glycoprotein, Alternative
    splicing, Polymorphism
    AF121856 SNX6 sorting nexin 6 Hypothetical protein, Transport, 208 4176
    Protein transport
    AF126749 SCA8 SCA8 mRNA, repeat 209 4177
    region
    AF127765 CAPN3 calpain 3, (p94) Hydrolase, Thiol protease, Calcium- 210 4178
    binding, Multigene family, Repeat,
    Disease mutation, Polymorphism,
    Alternative splicing
    AF131760 LRP10 low density Hypothetical protein, Plasmid 211 4179
    lipoprotein receptor-
    related protein 10
    AF131764 MPP5 membrane protein, Hypothetical protein, SH3 domain, 212 4180
    palmitoylated 5 Membrane
    (MAGUK p55
    subfamily member 5)
    AF131768 FLJ13657 chromosome 9 open Hypothetical protein 213 4181
    reading frame 82
    AF131774 FLJ14800 hypothetical protein Hypothetical protein 214 4182
    FLJ14800
    AF131775 MGC5560 hypothetical protein Hypothetical protein 215 4183
    MGC5560
    AF131784 RAB27B, member GTP-binding, Lipoprotein, 216 4184
    RAS oncogene Prenylation
    family
    AF131803 MGC5508 hypothetical protein Hypothetical protein 217 4185
    MGC5508
    AF131812 likely ortholog of Hypothetical protein 218 4186
    mouse monocyte
    macrophage 19
    AF131838 FLJ12806 hypothetical protein Hypothetical protein 219 4187
    FLJ12806
    AF131842 KIAA1857 netrin G2 Hypothetical protein, EGF-like 220 4188
    domain, Laminin EGF-like domain,
    Neurogenesis, Glycoprotein, GPI-
    anchor, Membrane, Signal, Repeat,
    Lipoprotein
    AF131859 PA sulfide quinone Oxidoreductase, Flavoprotein, FAD, 221 4189
    reductase-like NADP, Mitochondrion, Transit
    (yeast) peptide, Polymorphism
    AF134404 FADS3 fatty acid desaturase 3 Heme 222 4190
    AF146277 CD2AP CD2-associated SH3 domain, SH3-binding, 223 4191
    protein Phosphorylation, Coiled coil, Repeat
    AF152338 PCDHGC4 protocadherin Calcium, Calcium-binding, Cell 224 4192
    gamma subfamily C, 3 adhesion, Glycoprotein,
    Transmembrane, Alternative
    splicing, Repeat, Signal, Multigene
    family
    AF152339 PCDHGC5 protocadherin Calcium, Calcium-binding, Cell 225 4193
    gamma subfamily C, 3 adhesion, Glycoprotein,
    Transmembrane, Alternative
    splicing, Repeat, Signal, Multigene
    family
    AF155107 FLJ11806 nuclear protein Plasmid, Hypothetical protein 226 4194
    UKp68
    AF156603 WBSCR14 Williams Beuren Transcription regulation, Repressor, 227 4195
    syndrome Nuclear protein, DNA-binding,
    chromosome region Williams-Beuren syndrome,
    14 Alternative splicing
    AF161339 ARHGAP9 Rho GTPase Hypothetical protein, SH3 domain 228 4196
    activating protein 9
    AF161417 DKFZp564D177 nipsnap homolog 3A Hypothetical protein 229 4197
    (C. elegans)
    AF161442 HSPC324 Similar to HSPC324 230 4198
    (LOC389811),
    mRNA
    AF167706 CRIM1 cysteine-rich motor Signal 231 4199
    neuron 1
    AF187859 HSPBP1 hsp70-interacting Hypothetical protein 232 4200
    protein
    AF202063 FGFR4 fibroblast growth ATP-binding, Immunoglobulin 233 4201
    factor receptor 4 domain, Kinase, Receptor,
    Transferase, Tyrosine-protein
    kinase, Glycoprotein,
    Phosphorylation, Transmembrane,
    Repeat, Signal, Polymorphism, 3D-
    structure
    AF209931 7h3 hypothetical protein Hypothetical protein 234 4202
    FLJ13511
    AF212842 LILRA3 leukocyte Ig-like Receptor, Repeat, Signal, Immune 235 4203
    receptor 9 response, Immunoglobulin domain,
    Glycoprotein, Antigen, Multigene
    family, Polymorphism
    AF217798 NDEL1 nudE nuclear Hypothetical protein 236 4204
    distribution gene E
    homolog like 1 (A. nidulans)
    AF220417 LGTN ligatin Membrane, Alternative splicing 237 4205
    AF222694 LGALS12 lectin, galactoside- Galectin, Lectin, Repeat, Nuclear 238 4206
    binding, soluble, 12 protein, Alternative splicing
    (galectin 12)
    AF227924 SIGLEC9 sialic acid binding Ig- Cell adhesion, Lectin, Antigen, 239 4207
    like lectin 9 Transmembrane, Signal,
    Glycoprotein, Immunoglobulin
    domain, Repeat, Polymorphism
    AF228704 GSR glutathione FAD, Flavoprotein, Oxidoreductase, 240 4208
    reductase Redox-active center, NADP,
    Acetylation, Alternative initiation,
    Mitochondrion, Transit peptide, 3D-
    structure, Polymorphism
    AF232216 PIH1 Homo sapiens 241 4209
    pregnancy-induced
    hypertension
    syndrome-related
    protein (PIH1)
    mRNA, partial cds.
    AF237413 RAP1GDS1 RAP1, GTP-GDP GTPase activation, Repeat, 242 4210
    dissociation Alternative splicing
    stimulator
    1
    AF241831 HABP4 hyaluronan binding Hypothetical protein 243 4211
    protein 4
    AF242771 Mesenchymal stem 244 4212
    cell protein DSC96
    mRNA, partial cds
    AF244088 ZNF16 zinc finger protein 16 Hypothetical protein, Metal-binding, 245 4213
    (KOX 9) Nuclear protein, Zinc, Zinc-finger,
    Transcription regulation, DNA-
    binding, Repeat
    AF246221 ITM2B integral membrane Hypothetical protein, 246 4214
    protein 2B Transmembrane, Signal-anchor,
    Disease mutation, Amyloid,
    Deafness
    AF257175 PECI peroxisomal D3,D2- Isomerase, Peroxisome, 247 4215
    enoyl-CoA Hypothetical protein
    isomerase
    AF260261 ABI-2 abl interactor 2 Kinase, SH3 domain 248 4216
    AF272357 NPDC1 neural proliferation, Signal, Transmembrane, 249 4217
    differentiation and Hypothetical protein
    control, 1
    AI076473_RC rap2 interacting Hypothetical protein 250 4218
    protein x
    AI282511_RC PTRF hypothetical protein Hypothetical protein 251 4219
    FLJ10534
    AI286310_RC HSPA5 qu91g07.x1 ATP-binding, Endoplasmic reticulum, 252 4220
    NCI_CGAP_Gas4 Signal
    Homo sapiens cDNA
    clone
    IMAGE: 1979484 3′
    similar to
    gb: M19645_cds1 78 KD
    GLUCOSE
    REGULATED
    PROTEIN
    PRECURSOR
    (HUMAN); mRNA
    sequence.
    AI339981_RC hypothetical protein 253 4221
    LOC153346
    AI347139_RC hypothetical protein 254 4222
    MGC39372
    AI355990_RC qy51g12.x1 255 4223
    NCI_CGAP_Brn23
    Homo sapiens cDNA
    clone
    IMAGE: 2015590 3′,
    mRNA sequence.
    AI434777_RC CDNA FLJ44280 fis, 256 4224
    clone
    TRACH2001684
    AI493593_RC th39c02.x1 257 4225
    NCI_CGAP_Pan1
    Homo sapiens cDNA
    clone
    IMAGE: 2120642 3′,
    mRNA sequence.
    AI668686_RC FLJ38281 hypothetical protein Hypothetical protein, Metal-binding, 258 4226
    FLJ38281 Zinc, Zinc-finger
    AI677876_RC CDNA clone 259 4227
    IMAGE: 4648334,
    partial cds
    AI695056_RC Sarcoma antigen 260 4228
    NY-SAR-79 mRNA,
    partial cds
    AI928427_RC Transcribed 261 4229
    sequences
    AJ000480 C8FW phosphoprotein ATP-binding, Receptor, Transferase 262 4230
    regulated by
    mitogenic pathways
    AJ010228 RFPL1 ret finger protein-like 1 Zinc-finger, Metal-binding 263 4231
    AJ010842 NTPBP XPA binding protein 1 GTP-binding 264 4232
    AJ011414 plexin- plexin B1 Hypothetical protein, Receptor, 265 4233
    B1/SEP Signal
    AJ133115 THG-1 TSC-22-like Hypothetical protein, Transcription 266 4234
    regulation, Repressor, Nuclear
    protein
    AJ225028 GABBR1 gamma-aminobutyric Hypothetical protein, G-protein 267 4235
    acid (GABA) B coupled receptor, Postsynaptic
    receptor, 1 membrane, Repeat, Signal,
    Transmembrane, Coiled coil, Sushi,
    Glycoprotein, Alternative splicing,
    Polymorphism, Receptor
    AJ243107 APAF1 Homo sapiens Apoptosis, ATP-binding, Repeat, 268 4236
    mRNA for apoptotic WD repeat, Alternative splicing, 3D-
    protease activating structure
    factor-1 (Apaf-1
    gene) (short form).
    AJ249377 IGHM immunoglobulin Immunoglobulin domain, 269 4237
    lambda joining 3 Immunoglobulin C region,
    Glycoprotein, Repeat, Pyrrolidone
    carboxylic acid, Polymorphism,
    Membrane, Hypothetical protein,
    Receptor, T-cell, Signal
    AJ270996 TRPM5 transient receptor Ionic channel, Transmembrane 270 4238
    potential cation
    channel, subfamily
    M, member 5
    AJ271684 CLECSF5 C-type (calcium Transmembrane, Lectin 271 4239
    dependent,
    carbohydrate-
    recognition domain)
    lectin, superfamily
    member
    5
    AJ272057 STRAIT11499 MID1 interacting Hypothetical protein 272 4240
    G12-like protein
    AK000001 FLJ00001 chromosome 9 open Hypothetical protein 273 4241
    reading frame 28
    AK000004 FGD3 FGD1 family, 274 4242
    member 3
    AK000007 FLJ00007 hypothetical protein SH3 domain 275 4243
    FLJ00007
    AK000014 HYPE Huntingtin Hypothetical protein 276 4244
    interacting protein E
    AK000035 FLJ22390 hypothetical protein Hypothetical protein 277 4245
    FLJ22390
    AK000168 KIAA1919 Homo sapiens cDNA Hypothetical protein 278 4246
    FLJ20161 fis, clone
    COL09252, highly
    similar to L33930
    Homo sapiens CD24
    signal transducer
    mRNA.
    AK000175 hypothetical protein 279 4247
    LOC93444
    AK000212 FLJ10140 tRNA (5- Hypothetical protein, Transferase, 280 4248
    methylaminomethyl- Methyltransferase, tRNA processing
    2-thiouridylate)-
    methyltransferase 1
    AK000216 FLJ20209 hypothetical protein 281 4249
    FLJ20209
    AK000242 RALGDS ral guanine Guanine-nucleotide releasing factor, 282 4250
    nucleotide 3D-structure, Hypothetical protein
    dissociation
    stimulator
    AK000260 CDK5RAP3 Homo sapiens cDNA 283 4251
    FLJ20253 fis, clone
    COLF6895.
    AK000354 KIAA1892 KIAA1892 Hypothetical protein, Repeat, WD 284 4252
    repeat
    AK000425 FLJ25555 hypothetical protein Hypothetical protein 285 4253
    FLJ25555
    AK000435 LOC90987 zinc finger protein Hypothetical protein, Metal-binding, 286 4254
    251 Nuclear protein, Zinc, Zinc-finger
    AK000539 DKFZP564K0822 hypothetical protein Hypothetical protein 287 4255
    DKFZp564K0822
    AK000552 WDR5 WD repeat domain 5 Hypothetical protein, WD repeat, 288 4256
    Repeat
    AK000617 NFRKB hypothetical protein Hypothetical protein, Ligase, Ubl 289 4257
    LOC92912 conjugation pathway
    AK000660 cyclin-dependent 290 4258
    kinase 6
    AK000684 FLJ22104 hypothetical protein Hypothetical protein 291 4259
    FLJ22104
    AK000689 CLONE24945 arrestin domain Hypothetical protein 292 4260
    containing 2
    AK000703 FLJ20696 hypothetical protein Hypothetical protein 293 4261
    FLJ20696
    AK000729 solute carrier family Hypothetical protein 294 4262
    36 (proton/amino
    acid symporter),
    member 1
    AK000757 BCL2L1 sortilin 1 Apoptosis, Mitochondrion, 295 4263
    Alternative splicing,
    Transmembrane, 3D-structure
    AK000787 CDNA FLJ20780 fis, 296 4264
    clone COL04256
    AK000803 hypothetical protein 297 4265
    LOC90624
    AK000808 MGC4796 Ser/Thr-like kinase Hypothetical protein, ATP-binding, 298 4266
    Kinase, Serine/threonine-protein
    kinase, Transferase
    AK000822 DKFZP564M182 DKFZP564M182 Hypothetical protein 299 4267
    protein
    AK000824 TCTA T-cell leukemia 300 4268
    translocation altered
    gene
    AK000838 KIAA1295 KIAA1295 protein Hypothetical protein 301 4269
    AK000933 opsin 3 Photoreceptor, Retinal protein, 302 4270
    (encephalopsin, Transmembrane, Lipoprotein,
    panopsin) Palmitate, G-protein coupled
    receptor, GTPase activation
    AK000939 hypothetical protein 303 4271
    LOC286272
    AK000967 3PAP phosphatidylinositol- Hypothetical protein 304 4272
    3-phosphate
    associated protein
    AK001022 ISL2 ISL2 transcription Homeobox, DNA-binding, 305 4273
    factor, Developmental protein, Nuclear
    LIM/homeodomain, protein, Repeat, LIM domain, Metal-
    (islet-2) binding, Zinc, Multigene family
    AK001036 MAD, mothers Transcription regulation, Multigene 306 4274
    against family, Phosphorylation
    decapentaplegic
    homolog 5
    (Drosophila)
    AK001069 UPF3A CDNA FLJ10207 fis, 307 4275
    clone
    HEMBA1005475
    AK001163 PAICS phosphoribosylaminoimidazole Multifunctional enzyme, Purine 308 4276
    carboxylase, biosynthesis, Ligase, Lyase,
    phosphoribosylaminoimidazole Decarboxylase
    succinocarboxamide
    synthetase
    AK001166 FLJ11252 HBxAg Hypothetical protein 309 4277
    transactivated
    protein 1
    AK001228 chromosome 6 open 310 4278
    reading frame 107
    AK001319 C8FW phosphoprotein ATP-binding, Receptor, Transferase 311 4279
    regulated by
    mitogenic pathways
    AK001362 ESDN endothelial and Hypothetical protein 312 4280
    smooth muscle cell-
    derived neuropilin-
    like protein
    AK001394 hypothetical protein 313 4281
    DKFZp762K222
    AK001452 FLJ10839 Homo sapiens cDNA Hypothetical protein 314 4282
    FLJ10590 fis, clone
    NT2RP2004392,
    weakly similar to
    MNN4 PROTEIN.
    AK001469 GNPNAT1 glucosamine- Hypothetical protein, Transferase 315 4283
    phosphate N-
    acetyltransferase 1
    AK001478 ARHU ras homolog gene GTP-binding, Lipoprotein, 316 4284
    family, member U Prenylation
    AK001492 FLJ10637 hypothetical protein Hypothetical protein 317 4285
    FLJ10637
    AK001499 FLJ10637 hypothetical protein Hypothetical protein 318 4286
    FLJ10637
    AK001503 CDNA FLJ10641 fis, Metal-binding, Zinc, Zinc-finger 319 4287
    clone
    NT2RP2005748
    AK001526 DKFZp667B1218 hypothetical protein Hypothetical protein 320 4288
    DKFZp667B1218
    AK001536 Human full-length Plasmid 321 4289
    cDNA 5-PRIME end
    of clone
    CS0DK007YB08 of
    HeLa cells of Homo
    sapiens (human)
    AK001539 TEM6 tensin-like SH2 Hypothetical protein 322 4290
    domain containing 1
    AK001565 AP3M1 adaptor-related Golgi stack, Protein transport, 323 4291
    protein complex 3, Transport, Hypothetical protein
    mu 1 subunit
    AK001579 ARAP3 ARF-GAP, RHO- Hypothetical protein 324 4292
    GAP, ankyrin repeat
    and plekstrin
    homology domains-
    containing protein 3
    AK001612 hypothetical protein 325 4293
    LOC90784
    AK001630 ETS1 v-ets Proto-oncogene, Nuclear protein, 326 4294
    erythroblastosis Transcription regulation, DNA-
    virus E26 oncogene binding, Phosphorylation, Alternative
    homolog 1 (avian) splicing, 3D-structure
    AK001731 MGC17943 hypothetical protein Hypothetical protein 327 4295
    MGC17943
    AK001758 THOC2 THO complex 2 Transport, mRNA transport, mRNA 328 4296
    processing, mRNA splicing, Nuclear
    protein, RNA-binding, Alternative
    splicing
    AK001822 chromosome 9 open Hypothetical protein 329 4297
    reading frame 37
    AK001913 CL25084 XTP3-transactivated Hypothetical protein 330 4298
    protein B
    AK001980 ADPRTL2 ADP- Transferase, Glycosyltransferase, 331 4299
    ribosyltransferase NAD, DNA-binding, Nuclear protein,
    (NAD+; poly(ADP- Alternative splicing
    ribose) polymerase)-
    like 2
    AK002039 MRVI1 murine retrovirus 332 4300
    integration site 1
    homolog
    AK002081 FLJ10287 hypothetical protein Hypothetical protein 333 4301
    FLJ10287
    AK002141 PIK4CA Homo sapiens cDNA Transferase, Kinase 334 4302
    FLJ11279 fis, clone
    PLACE1009444,
    highly similar to
    PHOSPHATIDYLINOSITOL
    4-KINASE
    ALPHA (EC
    2.7.1.67).
    AK002146 hypothetical protein 335 4303
    LOC153684
    AK002174 KLHL5 kelch-like 5 Cytoskeleton, Actin-binding, Repeat, 336 4304
    (Drosophila) Kelch repeat, Alternative splicing
    AL049232 Homo sapiens 337 4305
    mRNA; cDNA
    DKFZp564P1816
    (from clone
    DKFZp564P1816).
    AL049266 Homo sapiens 338 4306
    mRNA; cDNA
    DKFZp564F093
    (from clone
    DKFZp564F093).
    AL049279 MRNA; cDNA 339 4307
    DKFZp564I083
    (from clone
    DKFZp564I083)
    AL049299 DJ465N24.2.1 hypothetical protein Hypothetical protein 340 4308
    dJ465N24.2.1
    AL049309 SFRS12 splicing factor, Nuclear protein, mRNA processing, 341 4309
    arginine/serine-rich mRNA splicing, Spliceosome,
    12 Alternative splicing
    AL049365 FTL hypothetical protein Acetylation, Iron storage, Multigene 342 4310
    MGC50853 family
    AL049381 pre-B-cell leukemia Transcription regulation, DNA- 343 4311
    transcription factor 1 binding, Nuclear protein, Activator,
    Repressor, Homeobox, Proto-
    oncogene, Chromosomal
    translocation, Alternative splicing,
    Steroidogenesis, Sexual
    differentiation, 3D-structure
    AL049397 CGI-146 protein Hypothetical protein 344 4312
    AL049415 ADAM19 a disintegrin and Hydrolase, Metalloprotease, Zinc, 345 4313
    metalloproteinase Signal, Glycoprotein, Zymogen,
    domain 19 (meltrin Transmembrane, EGF-like domain,
    beta) SH3-binding, Alternative splicing,
    Hypothetical protein
    AL049431 FLJ20619 hypothetical protein Hypothetical protein 346 4314
    FLJ20619
    AL049450 hypothetical protein 347 4315
    LOC339287
    AL049471 AT rich interactive Hypothetical protein 348 4316
    domain 5B (MRF1-
    like)
    AL049962 hypothetical protein 349 4317
    LOC286148
    AL049963 LOC64116 solute carrier family Hypothetical protein 350 4318
    39 (zinc transporter),
    member 8
    AL050002 hypothetical protein Hypothetical protein 351 4319
    LOC169611
    AL050021 solute carrier family Hypothetical protein, 352 4320
    7 (cationic amino Transmembrane, Glycoprotein,
    acid transporter, y+ Transport, Amino-acid transport,
    system), member 1 Receptor
    AL050022 DKFZP564D116 DKFZP564D116 Hypothetical protein 353 4321
    protein
    AL050050 TULIP1 GTPase activating Hypothetical protein 354 4322
    RANGAP domain-
    like 2 pseudogene
    AL050060 DKFZP566H073 DKFZP566H073 Hypothetical protein, Metal-binding, 355 4323
    protein Zinc, Zinc-finger
    AL050091 GRINL1A glutamate receptor, Hypothetical protein, Receptor 356 4324
    ionotropic, N-methyl
    D-aspartate-like 1A
    AL050126 LAP1B lamina-associated Hypothetical protein 357 4325
    polypeptide 1B
    AL050148 sorting nexin 1 Transport, Protein transport, Golgi 358 4326
    stack, Alternative splicing
    AL050163 PIK3AP hematopoietic cell Hypothetical protein, 359 4327
    signal transducer Transmembrane
    AL050164 CDYL chromodomain Hypothetical protein, Nuclear protein 360 4328
    protein, Y-like
    AL050170 SLC26A6 solute carrier family Hypothetical protein, 361 4329
    26, member 6 Transmembrane, Alternative
    splicing, Polymorphism
    AL050173 C21orf25 chromosome 21 Hypothetical protein 362 4330
    open reading frame
    25
    AL050217 BRD2 dehydrogenase/reductase Oxidoreductase 363 4331
    (SDR family)
    member 1
    AL050346 C22orf3 chromosome 22 Hypothetical protein 364 4332
    open reading frame 3
    AL079294 MRNA full length Hypothetical protein 365 4333
    insert cDNA clone
    EUROIMAGE
    362780
    AL079298 MCCC2 methylcrotonoyl- Mitochondrion, Transit peptide, 366 4334
    Coenzyme A Ligase, Disease mutation,
    carboxylase 2 (beta) Alternative splicing
    AL080110 progestin and Hypothetical protein 367 4335
    adipoQ receptor
    family member III
    AL080114 chromosome 10 Hypothetical protein 368 4336
    open reading frame
    72
    AL080125 ZNF20 zinc finger protein 20 Hypothetical protein, Metal-binding, 369 4337
    (KOX 13) Nuclear protein, Zinc, Zinc-finger,
    Transcription regulation, DNA-
    binding, Repeat
    AL080156 DKFZP434J214 TCDD-inducible Hypothetical protein 370 4338
    poly(ADP-ribose)
    polymerase
    AL080169 DKFZP434C171 DKFZP434C171 Hypothetical protein 371 4339
    protein
    AL080182 N-deacetylase/N- Hypothetical protein, Transferase, 372 4340
    sulfotransferase Transmembrane, Glycoprotein, Golgi
    (heparan stack, Signal-anchor
    glucosaminyl) 2
    AL080192 hypothetical protein Hypothetical protein 373 4341
    LOC253782
    AL096745 TBCD tubulin-specific Hypothetical protein 374 4342
    chaperone d
    AL109669 IL16 interleukin 16 Cytokine, Chemotaxis, Repeat, 3D- 375 4343
    (lymphocyte structure
    chemoattractant
    factor)
    AL109693 FLJ12587 hypothetical protein Hypothetical protein 376 4344
    FLJ12587
    AL109695 solute carrier organic Transmembrane, Transport, Ion 377 4345
    anion transporter transport, Glycoprotein
    family, member 3A1
    AL109699 MRNA full length Hypothetical protein 378 4346
    insert cDNA clone
    EUROIMAGE
    375854
    AL109705 MRNA full length 379 4347
    insert cDNA clone
    EUROIMAGE 73337
    AL109786 WDR9 chromosome 21 Bromodomain, Repeat, WD repeat 380 4348
    open reading frame
    107
    AL109817 FTCD formiminotransferase Hypothetical protein, Transferase, 381 4349
    cyclodeaminase Lyase, Histidine metabolism,
    Multifunctional enzyme, Pyridoxal
    phosphate, Folate-binding,
    Alternative splicing, Disease
    mutation, Polymorphism
    AL110152 CD109 antigen (Gov Hypothetical protein 382 4350
    platelet alloantigens)
    AL110188 ZNF10 zinc finger protein 10 Hypothetical protein, Metal-binding, 383 4351
    (KOX 1) Nuclear protein, Zinc, Zinc-finger,
    Transcription regulation, DNA-
    binding, Repeat
    AL110200 Homo sapiens 384 4352
    mRNA; cDNA
    DKFZp586B0922
    (from clone
    DKFZp586B0922).
    AL110202 PORIMIN pro-oncosis receptor Hypothetical protein, Receptor, 385 4353
    inducing membrane Transmembrane
    injury gene
    AL110210 PTPN23 protein tyrosine Hydrolase, Hypothetical protein, 386 4354
    phosphatase, non- Receptor
    receptor type
    23
    AL110218 SLB selective LIM binding Hypothetical protein 387 4355
    factor, rat homolog
    AL110238 RRN3 RNA polymerase I Initiation factor, Hypothetical protein 388 4356
    transcription factor
    RRN3
    AL110262 NCBP2 nuclear cap binding Transport, mRNA transport, Nuclear 389 4357
    protein subunit 2, protein, RNA-binding, 3D-structure
    20 kDa
    AL110277 KIAA0916 protein associated Hypothetical protein 390 4358
    with Myc
    AL117415 ADAM33 Homo sapiens Hypothetical protein, Hydrolase, 391 4359
    mRNA; cDNA Metalloprotease, Zinc, Signal,
    DKFZp434K0521 Glycoprotein, Zymogen,
    (from clone Transmembrane, EGF-like domain,
    DKFZp434K0521). Alternative splicing, Integrin,
    Protease
    AL117435 DKFZP434I216 DKFZP434I216 Hypothetical protein 392 4360
    protein
    AL117448 RAB6IP1 RAB6 interacting Hypothetical protein 393 4361
    protein 1
    AL117452 FTHFSDC1 formyltetrahydrofolate Hypothetical protein 394 4362
    synthetase domain
    containing 1
    AL117457 CFL2 cofilin 2 (muscle) Nuclear protein, Actin-binding, 395 4363
    Cytoskeleton, Phosphorylation,
    Alternative splicing
    AL117458 IHPK2 inositol Hypothetical protein, Kinase 396 4364
    hexaphosphate
    kinase
    2
    AL117462 ZFP385 zinc finger protein Metal-binding, Zinc, Zinc-finger, 397 4365
    385 Hypothetical protein
    AL117478 AGS3 G-protein signalling Hypothetical protein 398 4366
    modulator 1 (AGS3-
    like, C. elegans)
    AL117519 hypothetical protein Hypothetical protein, Metal-binding, 399 4367
    LOC152485 Zinc, Zinc-finger
    AL117573 DKFZP434F2021 DKFZP434F2021 Hypothetical protein 400 4368
    protein
    AL117578 DKFZP434C128 chromosome 21 Hypothetical protein 401 4369
    open reading frame
    30
    AL117609 DKFZp564O0463 DKFZP564O0463 Hypothetical protein, Repeat, WD 402 4370
    protein repeat
    AL117639 FLJ12890 CCR4-NOT Hypothetical protein 403 4371
    transcription
    complex, subunit 10
    AL117643 activin A receptor, Receptor, Transferase, 404 4372
    type IB Serine/threonine-protein kinase,
    ATP-binding, Transmembrane,
    Glycoprotein, Signal, Alternative
    splicing, Phosphorylation,
    Polymorphism
    AL117645 EG1 endothelial-derived Hypothetical protein 405 4373
    gene 1
    AL117654 ARH LDL receptor Hypothetical protein 406 4374
    adaptor protein
    AL122053 TRIM3 tripartite motif- Zinc-finger, Coiled coil, Alternative 407 4375
    containing 3 splicing
    AL122091 LOC56965 hypothetical protein Hypothetical protein 408 4376
    from EUROIMAGE
    1977056
    AL122097 FLJ12519 hypothetical protein Hypothetical protein, Repeat, WD 409 4377
    FLJ12519 repeat
    AL122098 NICAL NEDD9 interacting Hypothetical protein, LIM domain, 410 4378
    protein with calponin Metal-binding, Zinc, Cytoskeleton
    homology and LIM
    domains
    AL122123 MRNA; cDNA 411 4379
    DKFZp434M038
    (from clone
    DKFZp434M038)
    AL133021 STAB2 stabilin 2 EGF-like domain, Laminin EGF-like 412 4380
    domain, Hypothetical protein,
    Receptor
    AL133071 DKFZp434I1117 hypothetical protein Hypothetical protein 413 4381
    DKFZp434I1117
    AL133092 DKFZp434I0428 dispatched homolog Hypothetical protein 414 4382
    1 (Drosophila)
    AL133094 PHF10 PHD finger protein Hypothetical protein 415 4383
    10
    AL133115 cytosolic ovarian Biological rhythms, Electron 416 4384
    carcinoma antigen 1 transport, Growth regulation,
    Oxidoreductase, NAD, Membrane,
    Copper, Glycoprotein
    AL133116 FKBP10 Homo sapiens Isomerase, Rotamase, Endoplasmic 417 4385
    mRNA; cDNA reticulum, Calcium-binding,
    DKFZp586I0821 Glycoprotein, Phosphorylation,
    (from clone Repeat, Signal, Hypothetical protein
    DKFZp586I0821).
    AL133117 THO complex 2 Transport, mRNA transport, mRNA 418 4386
    processing, mRNA splicing, Nuclear
    protein, RNA-binding, Alternative
    splicing
    AL133426 AKAP13 A kinase (PRKA) Kinase, Receptor, cAMP, 419 4387
    anchor protein 13 Hypothetical protein
    AL133572 DKFZp434I0535 Homo sapiens Hypothetical protein 420 4388
    mRNA; cDNA
    DKFZp434I0535
    (from clone
    DKFZp434I0535);
    partial cds.
    AL133577 MRNA; cDNA 421 4389
    DKFZp434G0972
    (from clone
    DKFZp434G0972)
    AL133580 SCOC short coiled-coil Hypothetical protein 422 4390
    protein
    AL133581 FLJ25785 solute carrier family Hypothetical protein 423 4391
    39 (zinc transporter),
    member 13
    AL133592 MGC15548 zinc finger protein Hypothetical protein, Metal-binding, 424 4392
    496 Zinc, Zinc-finger
    AL133622 KIAA0876 jumonji domain Hypothetical protein 425 4393
    containing 2B
    AL133632 DKFZp434E1818 Similar to Hypothetical protein, Metal-binding, 426 4394
    hypothetical protein Zinc, Zinc-finger
    (LOC389822),
    mRNA
    AL133645 hypothetical protein 427 4395
    LOC90133
    AL133662 KIAA0913 KIAA0913 protein Hypothetical protein 428 4396
    AL136549 CYFIP2 cytoplasmic FMR1 Hypothetical protein 429 4397
    interacting protein 2
    AL137273 DKFZP434I0714 hypothetical protein Hypothetical protein 430 4398
    DKFZP434I0714
    AL137298 DNAJB6 MRNA; cDNA Chaperone, Alternative splicing 431 4399
    DKFZp434N2116
    (from clone
    DKFZp434N2116)
    AL137302 TEX27 testis expressed Hypothetical protein 432 4400
    sequence 27
    AL137397 FLJ21820 hypothetical protein Hypothetical protein 433 4401
    FLJ21820
    AL137421 RBM10 RNA binding motif Hypothetical protein, Metal-binding, 434 4402
    protein 10 Zinc, Zinc-finger, RNA-binding,
    Nuclear protein, Repeat
    AL137423 GU2 DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 435 4403
    Asp) box polypeptide Hypothetical protein
    50
    AL137431 WBSCR17 Williams-Beuren Transferase, Hypothetical protein 436 4404
    syndrome
    chromosome region
    17
    AL137442 C20orf177 chromosome 20 Hypothetical protein 437 4405
    open reading frame
    177
    AL137473 C20orf67 Homo sapiens Alternative splicing, Hypothetical 438 4406
    mRNA; cDNA protein
    DKFZp434E1723
    (from clone
    DKFZp434E1723);
    partial cds.
    AL137477 CDH24 cadherin-like 24 Hypothetical protein, Calcium, 439 4407
    Calcium-binding, Cell adhesion,
    Glycoprotein, Transmembrane,
    Repeat, Signal, Multigene family,
    Alternative splicing, Plasmid
    AL137480 FNBP4 formin binding Hypothetical protein 440 4408
    protein 4
    AL137491 hypothetical protein 441 4409
    LOC148696
    AL137509 DKFZp761A052 hypothetical protein Hypothetical protein 442 4410
    DKFZp761A052
    AL137514 IHPK2 inositol Hypothetical protein, Kinase 443 4411
    hexaphosphate
    kinase 2
    AL137516 FLJ22059 zinc finger protein Hypothetical protein, Metal-binding, 444 4412
    574 Zinc, Zinc-finger, Nuclear protein
    AL137557 KIAA1529 KIAA1529 Hypothetical protein 445 4413
    AL137567 KIAA1238 KIAA1238 protein Hypothetical protein 446 4414
    AL137579 SNX26 sorting nexin 26 Hypothetical protein, Transport, 447 4415
    Protein transport
    AL137597 C20orf110 chromosome 20 448 4416
    open reading frame
    110
    AL137615 MKNK2 MAP kinase- Hypothetical protein, ATP-binding, 449 4417
    interacting Kinase, Serine/threonine-protein
    serine/threonine kinase, Transferase, Translation
    kinase
    2 regulation, Phosphorylation,
    Alternative splicing
    AL137631 FBXW5 Homo sapiens Hypothetical protein, Repeat, WD 450 4418
    mRNA; cDNA repeat
    DKFZp434B205
    (from clone
    DKFZp434B205);
    partial cds.
    AL137639 KIAA0721 TSPY-like 4 Hypothetical protein 451 4419
    AL137648 DKFZP434J1813 ER-resident protein Redox-active center, Hypothetical 452 4420
    ERdj5 protein
    AL137655 Homo sapiens Hypothetical protein 453 4421
    mRNA; cDNA
    DKFZp434B2016
    (from clone
    DKFZp434B2016).
    AL137662 DKFZp434P086 hypothetical protein Hypothetical protein, ATP-binding, 454 4422
    LOC340371 Transferase
    AL137663 FLJ21791 pleckstrin homology- Hypothetical protein 455 4423
    like domain, family
    B, member 2
    AL137665 TUBGCP6 tubulin, gamma Microtubule, Repeat, Alternative 456 4424
    complex associated splicing
    protein
    6
    AL137667 MAPK8 Homo sapiens Transferase, Serine/threonine- 457 4425
    mRNA; cDNA protein kinase, ATP-binding,
    DKFZp434B231 Phosphorylation, Alternative splicing
    (from clone
    DKFZp434B231).
    AL137707 LOC55901 TPTE and PTEN Signal 458 4426
    homologous inositol
    lipid phosphatase
    pseudogene
    AL137727 C14orf9 chromosome 14 Hypothetical protein, 459 4427
    open reading frame 9 Transmembrane, Alternative splicing
    AL137733 hypothetical protein Hypothetical protein 460 4428
    LOC284701
    AL137736 Rho guanine Hypothetical protein 461 4429
    nucleotide exchange
    factor (GEF) 19
    AL137764 LOC64744 hypothetical protein Hypothetical protein 462 4430
    AL133206
    AL157432 TERA chromosome 12 Hypothetical protein 463 4431
    open reading frame
    14
    AL157449 LOC84687 protein phosphatase Hypothetical protein 464 4432
    1, regulatory subunit
    9B, spinophilin
    AL157454 FLJ21313 HCV NS3- Hypothetical protein 465 4433
    transactivated
    protein 2
    AL157455 Clone 466 4434
    IMAGE: 5288750,
    mRNA
    AL157457 PP1628 PH domain- Hypothetical protein 467 4435
    containing protein
    AL157465 FLJ20186 hypothetical protein Hypothetical protein 468 4436
    FLJ20186
    AL157480 SH3BP1 lectin, galactoside- GTPase activation, SH3-binding, 469 4437
    binding, soluble, 1 Hypothetical protein, Galectin,
    (galectin 1) Lectin, Multigene family, Acetylation
    AL157484 MRNA; cDNA 470 4438
    DKFZp762M127
    (from clone
    DKFZp762M127)
    AL161960 FLJ21324 chromosome 21 Hypothetical protein 471 4439
    open reading frame
    97
    AL161972 ICAM2 hypothetical protein 3D-structure, Cell 472 4440
    FLJ11724 adhesion, Glycoprotein, Immunoglobulin
    domain, Repeat, Signal, Transmembrane
    AL161977 PCTK3 PCTAIRE protein Hypothetical protein, ATP-binding, 473 4441
    kinase 3 Kinase, Serine/threonine-protein
    kinase, Transferase
    AL161983 hypothetical protein 474 4442
    MGC39820
    AL161994 HEI10 cyclin B1 interacting Ubl conjugation pathway, Ligase, 475 4443
    protein 1 Nuclear protein, Metal-binding, Zinc,
    Coiled coil, Zinc-finger,
    Phosphorylation, Ubl conjugation
    AL162013 PLXNA1 Homo sapiens Hypothetical protein 476 4444
    mRNA; cDNA
    DKFZp761P19121
    (from clone
    DKFZp761P19121);
    partial cds.
    AL162039 MOB1, Mps One 477 4445
    Binder kinase
    activator-like 1A
    (yeast)
    AL162062 LOC91010 formin-like 3 Hypothetical protein 478 4446
    AL353934 MUS81 MUS81 Endonuclease, Hypothetical protein 479 4447
    endonuclease
    homolog (yeast)
    AL353952 PI4KII phosphatidylinositol Hypothetical protein, Kinase 480 4448
    4-kinase type II
    AL353953 FLJ13055 lipid phosphate Hypothetical protein 481 4449
    phosphatase-related
    protein type
    2
    AL355708 NEO1 neogenin homolog 1 Cell adhesion, Repeat, Signal, 482 4450
    (chicken) Transmembrane, Immunoglobulin
    domain, Glycoprotein, Alternative
    splicing
    AW190932_RC GPI xl66g09.x1 Gluconeogenesis, Glycolysis, 483 4451
    NCI_CGAP_Pan1 Isomerase, Growth factor, Cytokine,
    Homo sapiens cDNA Disease mutation, 3D-structure,
    clone Hypothetical protein
    IMAGE: 2679712 3′,
    mRNA sequence.
    AW273216_RC ring finger protein Hypothetical protein, Metal-binding, 484 4452
    149 Zinc, Zinc-finger
    AW419203_RC KIAA0601 amine oxidase Hypothetical protein 485 4453
    (flavin containing)
    domain 2
    AW673036_RC PPP1R3B hypothetical protein Hypothetical protein 486 4454
    LOC286044
    BE671663_RC EVIN2 epidermodysplasia Transmembrane, Hypothetical 487 4455
    verruciformis 2 protein
    BE672528_RC cyclin-dependent 488 4456
    kinase 6
    Contig10037_RC hypothetical protein Hypothetical protein 489 4457
    DKFZp667C165
    Contig1007_RC LOC51754 hypothetical protein Hypothetical protein 490 4458
    LOC283070
    Contig10162_RC MGC14276 hypothetical protein Hypothetical protein 491 4459
    MGC14276
    Contig1030_RC FLJ00026 dedicator of Guanine-nucleotide releasing factor 492 4460
    cytokinesis 8
    Contig10363_RC MRF2 AT rich interactive Hypothetical protein 493 4461
    domain 5B (MRF1-
    like)
    Contig10373_RC hypothetical protein Hypothetical protein 494 4462
    MGC21854
    Contig10418_RC Transcribed 495 4463
    sequences
    Contig10429_RC DKFZp434H2111 hypothetical protein Hypothetical protein 496 4464
    DKFZp434H2111
    Contig10531_RC microtubule- Microtubule, Cytoskeleton, Repeat, 497 4465
    associated protein Alternative splicing, Acetylation,
    tau Phosphorylation, Glycoprotein,
    Polymorphism, Disease mutation,
    Alzheimer's disease, 3D-structure,
    Hypothetical protein
    Contig1056_RC LOC57106 K562 cell-derived Hypothetical protein 498 4466
    leucine-zipper-like
    protein
    1
    Contig1061_RC KIAA0924 protein Hypothetical protein, Metal-binding, 499 4467
    Nuclear protein, Zinc, Zinc-finger
    Contig10629_RC PERQ1 PERQ amino acid Hypothetical protein 500 4468
    rich, with GYF
    domain
    1
    Contig1063_RC TRIM33 Homo sapiens cDNA Hypothetical protein 501 4469
    FLJ35131 fis, clone
    PLACE6008824.
    Contig10670_RC Transcribed 502 4470
    sequences
    Contig10690_RC spleen tyrosine Transferase, Tyrosine-protein 503 4471
    kinase kinase, ATP-binding,
    Phosphorylation, SH2 domain,
    Repeat, Alternative splicing, 3D-
    structure
    Contig10750_RC Transcribed 504 4472
    sequences
    Contig10844_RC CDNA FLJ31150 fis, Hypothetical protein 505 4473
    clone
    IMR322001534
    Contig11012_RC leukocyte-derived Aminopeptidase 506 4474
    arginine
    aminopeptidase
    Contig11075_RC NFASC neurofascin Cell adhesion, Repeat, Signal, 507 4475
    Transmembrane, Immunoglobulin
    domain, Glycoprotein, Alternative
    splicing, Polymorphism, Hypothetical
    protein
    Contig11266_RC Transcribed 508 4476
    sequence with
    moderate similarity
    to protein
    ref: NP_054848.1
    (H. sapiens)
    PRO0478 protein
    [Homo sapiens]
    Contig112_RC NICE-4 NICE-4 protein Hypothetical protein 509 4477
    Contig1146_RC LOC90550 chromosome 10 Hypothetical protein 510 4478
    open reading frame
    42
    Contig11_RC hypothetical protein Hypothetical protein 511 4479
    LOC90462
    Contig12140_RC Transcribed 512 4480
    sequences
    Contig12201_RC splicing factor, Nuclear protein, RNA-binding, 513 4481
    arginine/serine-rich 5 mRNA splicing, Alternative splicing,
    Repeat, Phosphorylation,
    Polymorphism, Plasmid
    Contig12540_RC Transcribed 514 4482
    sequences
    Contig12750_RC hypothetical protein Hypothetical protein 515 4483
    LOC257106
    Contig12755_RC GCN1L1 homeodomain Transferase, Serine/threonine- 516 4484
    interacting protein protein kinase, ATP-binding, Nuclear
    kinase
    2 protein, Alternative splicing
    Contig12820_RC FLJ21709 nucleotide-binding Hypothetical protein 517 4485
    oligomerization
    domains 27
    Contig12855 MAPK8IP2 MRNA; cDNA Kinase, SH3 domain, Alternative 518 4486
    DKFZp434J0428 splicing
    (from clone
    DKFZp434J0428)
    Contig1295_RC MDS033 protein F25965 Transmembrane, Golgi stack, 519 4487
    Endoplasmic reticulum
    Contig13165_RC B4GALT6 UDP- Transferase, Glycosyltransferase, 520 4488
    Gal:betaGlcNAc Glycoprotein, Transmembrane,
    beta 1,4- Signal-anchor, Golgi stack,
    galactosyltransferase, Manganese, Magnesium, Calcium,
    polypeptide 6 Multigene family
    Contig13387_RC FLJ21458 hypothetical protein Hypothetical protein 521 4489
    FLJ21458
    Contig13480_RC Transcribed 522 4490
    sequences
    Contig1351_RC zinc finger protein Hypothetical protein, Metal-binding, 523 4491
    325 Nuclear protein, Zinc, Zinc-finger,
    Transcription regulation, DNA-
    binding, Repeat
    Contig13609_RC Transcribed 524 4492
    sequences
    Contig13643_RC Transcribed 525 4493
    sequences
    Contig1366_RC DC-TM4F2 tetraspanin similar to Hypothetical protein, 526 4494
    TM4SF9 Transmembrane
    Contig13766_RC Transcribed 527 4495
    sequences
    Contig1386_RC SEMA4B sema domain, Transmembrane, Immunoglobulin 528 4496
    immunoglobulin domain, Multigene family,
    domain (Ig), Neurogenesis, Developmental
    transmembrane protein, Glycoprotein, Signal,
    domain (TM) and Polymorphism
    short cytoplasmic
    domain,
    (semaphorin) 4B
    Contig1389_RC ITPR1 mitogen-activated ATP-binding, Kinase, Transferase, 529 4497
    protein kinase 9 Serine/threonine-protein kinase,
    Phosphorylation, Alternative splicing
    Contig14039_RC FOXE3 forkhead box E3 Transcription regulation, DNA- 530 4498
    binding, Nuclear protein
    Contig1403_RC LBH likely ortholog of Hypothetical protein 531 4499
    mouse limb-bud and
    heart gene
    Contig14172 vitelliform macular Iron storage, Iron, Metal-binding, 3D- 532 4500
    dystrophy (Best structure, Transport, Ion transport,
    disease, bestrophin) Ionic channel, Chloride channel,
    Calcium, Alternative splicing,
    Disease mutation, Polymorphism,
    Vision, Transmembrane,
    Phosphorylation
    Contig14197_RC Transcribed 533 4501
    sequences
    Contig1422_RC hypothetical protein Hypothetical protein 534 4502
    FLJ38426
    Contig14282_RC Transcribed 535 4503
    sequences
    Contig14433_RC Transcribed 536 4504
    sequences
    Contig1447_RC EFG1 mitochondrial Elongation factor, Protein 537 4505
    elongation factor G1 biosynthesis, Mitochondrion, Transit
    peptide, GTP-binding
    Contig14520_RC Transcribed 538 4506
    sequences
    Contig14555_RC Transcribed 539 4507
    sequences
    Contig14581_RC Transcribed 540 4508
    sequences
    Contig14625_RC FLJ22021 hypothetical protein Repeat, WD repeat 541 4509
    FLJ22021
    Contig1462_RC C11orf15 chromosome 11 Transmembrane 542 4510
    open reading frame
    15
    Contig14658_RC zx08b09.s1 543 4511
    Soares_total_fetus_Nb2HF8_9w
    Homo
    sapiens cDNA clone
    IMAGE: 785849 3′,
    mRNA sequence.
    Contig14720_RC Transcribed 544 4512
    sequences
    Contig14797_RC Transcribed 545 4513
    sequences
    Contig14899_RC LOC146853 LOC146853 546 4514
    Contig1505_RC MGC4308 hypothetical protein 547 4515
    MGC4308
    Contig151_RC ELKS CDNA FLJ31750 fis, Hypothetical protein 548 4516
    clone
    NT2RI2007406
    Contig15267_RC Transcribed 549 4517
    sequences
    Contig15281_RC Chediak-Higashi Protein transport, Transport, Repeat, 550 4518
    syndrome 1 WD repeat, Disease mutation,
    Alternative splicing
    Contig1540_RC ACTB serine Transferase, Acyltransferase, 551 4519
    palmitoyltransferase, Transmembrane, Pyridoxal
    long chain base phosphate, Endoplasmic reticulum
    subunit
    2
    Contig15580_RC LOC401124 552 4520
    (LOC401124),
    mRNA
    Contig15607_RC Transcribed 553 4521
    sequences
    Contig15635_RC Transcribed 554 4522
    sequences
    Contig15647_RC Transcribed 555 4523
    sequences
    Contig15674_RC Transcribed 556 4524
    sequences
    Contig15898_RC Transcribed 557 4525
    sequence with weak
    similarity to protein
    ref: NP_055301.1
    (H. sapiens)
    neuronal thread
    protein [Homo
    sapiens]
    Contig16192_RC Transcribed 558 4526
    sequence with
    moderate similarity
    to protein
    ref: NP_110386.1
    (H. sapiens) nuclear
    receptor binding
    factor-2 [Homo
    sapiens]
    Contig1619_RC NAPB N-ethylmaleimide- Hypothetical protein 559 4527
    sensitive factor
    attachment protein,
    beta
    Contig1620_RC PPP1R16A protein phosphatase ANK repeat, Repeat, Coiled coil, 560 4528
    1, regulatory Lipoprotein, Prenylation, Membrane
    (inhibitor) subunit
    16A
    Contig16217_RC Transcribed 561 4529
    sequences
    Contig1632_RC MGC17921 chromosome 14 Alternative splicing 562 4530
    open reading frame
    31
    Contig16376_RC DKFZP564B1162 hypothetical protein Hypothetical protein 563 4531
    DKFZp564B1162
    Contig16437_RC Transcribed 564 4532
    sequences
    Contig16440_RC Transcribed 565 4533
    sequences
    Contig16441_RC Transcribed 566 4534
    sequences
    Contig16447_RC C16orf44 chromosome 16 Hypothetical protein 567 4535
    open reading frame
    44
    Contig16530_RC Transcribed 568 4536
    sequences
    Contig16736_RC Clone Hypothetical protein 569 4537
    IMAGE: 5561763,
    mRNA
    Contig16772_RC Transcribed 570 4538
    sequences
    Contig16786_RC Transcribed 571 4539
    sequences
    Contig1682_RC RCP Rab coupling protein Hypothetical protein 572 4540
    Contig16908_RC MGC42174 hypothetical protein Hypothetical protein 573 4541
    MGC42174
    Contig16931_RC YR-29 TGF beta-inducible Nuclear protein 574 4542
    nuclear protein 1
    Contig1699_RC FLJ12438 hypothetical protein Hypothetical protein 575 4543
    FLJ12438
    Contig17017_RC Transcribed 576 4544
    sequences
    Contig17084_RC DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 577 4545
    Asp) box polypeptide Hypothetical protein
    31
    Contig17109_RC Similar to Protein 578 4546
    C20orf27
    (LOC390690),
    mRNA
    Contig17356_RC hypothetical protein Hypothetical protein 579 4547
    FLJ13611
    Contig17607_RC Transcribed 580 4548
    sequences
    Contig1789_RC LAGY homeodomain-only Hypothetical protein, DNA-binding, 581 4549
    protein Homeobox, Nuclear protein
    Contig178_RC syntrophin, beta 2 Actin-binding, Cytoskeleton, 582 4550
    (dystrophin- Microtubule, Calcium-binding,
    associated protein Calmodulin-binding, Membrane,
    A1, 59 kDa, basic Phosphorylation, Repeat,
    component 2) Polymorphism, Multigene family,
    Alternative splicing
    Contig17982_RC hypothetical protein Hypothetical protein 583 4551
    FLJ14624
    Contig1798_RC MOX2 antigen identified by Antigen, Neurone, T-cell, Signal, 584 4552
    monoclonal antibody Transmembrane, Immunoglobulin
    MRC OX-2 domain, Glycoprotein, Alternative
    splicing
    Contig18246_RC oz78a12.x1 585 4553
    Soares_senescent_fibroblasts_NbHSF
    Homo sapiens cDNA
    clone
    IMAGE: 1681438 3′,
    mRNA sequence.
    Contig18286_RC pellino 3 alpha Alternative splicing 586 4554
    Contig18476_RC Homo sapiens, clone 587 4555
    IMAGE: 4830091,
    mRNA.
    Contig18493_RC oj35b09.s1 588 4556
    NCI_CGAP_Lu5
    Homo sapiens cDNA
    clone
    IMAGE: 1500281 3′,
    mRNA sequence.
    Contig18504_RC OR52K3P olfactory receptor, Hypothetical protein 589 4557
    family 52, subfamily
    K, member 3
    pseudogene
    Contig19023_RC yf45a10.s2 Soares 590 4558
    fetal liver spleen
    1NFLS Homo
    sapiens cDNA clone
    IMAGE: 129786 3′,
    mRNA sequence.
    Contig19064_RC hypothetical protein 591 4559
    LOC340351
    Contig19127_RC FLJ31295 hypothetical protein Metal-binding, Zinc, Zinc-finger, 592 4560
    FLJ31295 Hypothetical protein
    Contig19210_RC Transcribed 593 4561
    sequences
    Contig1924_RC C20orf11 chromosome 20 Coiled coil 594 4562
    open reading frame
    11
    Contig19333_RC Transcribed 595 4563
    sequences
    Contig1951 GNPAT MRNA; cDNA Transferase, Acyltransferase, 596 4564
    DKFZp686J23256 Peroxisome, Membrane, Rhizomelic
    (from clone chondrodysplasia punctata, Disease
    DKFZp686J23256) mutation
    Contig19700_RC Transcribed 597 4565
    sequences
    Contig19715_RC Transcribed 598 4566
    sequences
    Contig1990_RC LOC92799 hypothetical protein Repeat, WD repeat, Hypothetical 599 4567
    BC007653 protein
    Contig19918_RC Transcribed 600 4568
    sequences
    Contig1991_RC PGA5 pepsinogen 5, group Hydrolase, Aspartyl protease, 601 4569
    I (pepsinogen A) Digestion, Zymogen, Signal,
    Phosphorylation, 3D-structure,
    Polymorphism
    Contig19931_RC Transcribed 602 4570
    sequences
    Contig20370_RC Transcribed 603 4571
    sequences
    Contig20391_RC Transcribed 604 4572
    sequence with
    strong similarity to
    protein pir: EFHU1
    (H. sapiens) EFHU1
    translation
    elongation factor
    eEF-1 alpha-1 chain -
    human
    Contig20427_RC Transcribed 605 4573
    sequences
    Contig20600_RC CDNA FLJ34654 fis, 606 4574
    clone
    KIDNE2018294
    Contig20617_RC CDNA FLJ34031 fis, 607 4575
    clone
    FCBBF2003895
    Contig20830_RC Homo sapiens cDNA 608 4576
    FLJ13550 fis, clone
    PLACE1007111.
    Contig20843_RC Transcribed 609 4577
    sequences
    Contig20864_RC FLJ22529 hypothetical protein Hypothetical protein 610 4578
    FLJ22529
    Contig20913_RC FLJ12785 hypothetical protein Hypothetical protein 611 4579
    FLJ12785
    Contig20979_RC hypothetical protein 612 4580
    MGC35555
    Contig21098_RC Msx-interacting-zinc Multigene family, Zinc-finger, 613 4581
    finger Nuclear protein, DNA-binding, Metal-
    binding, Alternative splicing
    Contig21116_RC Transcribed 614 4582
    sequences
    Contig21200_RC Transcribed 615 4583
    sequences
    Contig21268_RC Similar to 616 4584
    hypothetical protein
    FLJ35867
    (LOC342357),
    mRNA
    Contig2143_RC KIAA1771 dedicator of Hypothetical protein, Guanine- 617 4585
    cytokinesis 7 nucleotide releasing factor,
    Alternative splicing
    Contig21627_RC CDNA FLJ39637 fis, Hypothetical protein 618 4586
    clone
    SMINT2003003
    Contig21787_RC Transcribed 619 4587
    sequences
    Contig2179_RC FLJ32452 hypothetical protein Hypothetical protein 620 4588
    FLJ32452
    Contig21839_RC ow70g11.s1 621 4589
    Soares_fetal_liver_spleen_1NFLS_S1
    Homo sapiens cDNA
    clone
    IMAGE: 1652228 3′,
    mRNA sequence.
    Contig21847_RC KSP37 Ksp37 protein 622 4590
    Contig21891_RC FLJ13231 hypothetical protein Hypothetical protein 623 4591
    FLJ13231
    Contig21904 immunoglobulin 624 4592
    superfamily, member 2
    Contig21997_RC Transcribed 625 4593
    sequences
    Contig22003_RC Transcribed 626 4594
    sequences
    Contig22025_RC FLJ10111 v-akt murine Hypothetical protein, ATP-binding, 627 4595
    thymoma viral Transferase, Serine/threonine-
    oncogene homolog 1 protein kinase, Phosphorylation,
    Nuclear protein, Kinase
    Contig22418_RC PTP4A3 protein tyrosine 628 4596
    phosphatase type
    IVA, member 3
    Contig22526_RC Transcribed 629 4597
    sequences
    Contig22551_RC Transcribed 630 4598
    sequences
    Contig2263_RC KIAA1949 KIAA1949 Hypothetical protein 631 4599
    Contig22844_RC DKFZp434H2111 hypothetical protein Hypothetical protein 632 4600
    DKFZp434H2111
    Contig22901_RC AGENCOURT_6640943 633 4601
    NIH_MGC_99
    Homo sapiens cDNA
    clone
    IMAGE: 5434077 5′,
    mRNA sequence.
    Contig23240_RC hypothetical protein Hypothetical protein 634 4602
    FLJ12525
    Contig23263_RC NR5A1 Homo sapiens cDNA Receptor, Transcription regulation, 635 4603
    FLJ33539 fis, clone DNA-binding, Nuclear protein, Zinc-
    BRAMY2007610, finger, Disease mutation,
    highly similar to Hypothetical protein
    STEROIDOGENIC
    FACTOR 1.
    Contig23280 lecithin-cholesterol Cholesterol metabolism, Lipid 636 4604
    acyltransferase metabolism, Transferase,
    Acyltransferase, Signal,
    Glycoprotein, Polymorphism,
    Disease mutation
    Contig23299_RC P5 BTG3 associated Hypothetical protein 637 4605
    nuclear protein
    Contig2339_RC FLJ21032 stearoyl-CoA Hypothetical protein 638 4606
    desaturase 4
    Contig23423_RC Transcribed 639 4607
    sequences
    Contig23525_RC KIAA0140 similar to CG9643- Hypothetical protein 640 4608
    PA
    Contig23547_RC Clone 641 4609
    IMAGE: 5214442,
    mRNA
    Contig23593_RC Transcribed 642 4610
    sequences
    Contig23604_RC carnitine O- Transferase, Acyltransferase, Fatty 643 4611
    octanoyltransferase acid metabolism, Transport,
    Peroxisome
    Contig23667_RC WD repeat and Nuclear protein, DNA-binding, 644 4612
    HMG-box DNA Repeat, WD repeat
    binding protein
    1
    Contig24090 CDNA FLJ37425 fis, 645 4613
    clone
    BRAWH2001530
    Contig24094_RC CDNA FLJ30598 fis, 646 4614
    clone
    BRAWH2009263
    Contig24098_RC glutamate receptor, Receptor, Signal, Transmembrane, 647 4615
    ionotropic, N-methyl Postsynaptic membrane, Calcium,
    D-aspartate 2D Glycoprotein, Ionic channel,
    Magnesium
    Contig2429_RC FLJ40142 protein Hypothetical protein 648 4616
    Contig24450_RC Transcribed 649 4617
    sequences
    Contig24453_RC Transcribed 650 4618
    sequences
    Contig24600_RC Transcribed 651 4619
    sequences
    Contig25041_RC yx89b03.s1 Soares 652 4620
    melanocyte 2NbHM
    Homo sapiens cDNA
    clone
    IMAGE: 268877 3′,
    mRNA sequence.
    Contig25058_RC Transcribed 653 4621
    sequences
    Contig2505_RC GLTP glycolipid transfer Transport, Lipid transport, Repeat, 654 4622
    protein Acetylation
    Contig25107_RC ferredoxin 1 Metal-binding, Iron-sulfur, Iron, 2Fe—2S, 655 4623
    Electron transport,
    Mitochondrion, Transit peptide
    Contig25126_RC Transcribed 656 4624
    sequences
    Contig2531_RC FLJ12484 hypothetical protein Hypothetical protein 657 4625
    FLJ12484
    Contig25332_RC GDF11 cytokine induced Nuclear protein, DNA-binding, 658 4626
    protein 29 kDa Transcription, Transcription
    regulation, Translation regulation
    Contig25362_RC DKFZP566A1524 hypothetical protein Hypothetical protein 659 4627
    DKFZp566A1524
    Contig25429_RC Transcribed 660 4628
    sequences
    Contig25435_RC FLJ10803 hypothetical protein Hypothetical protein 661 4629
    FLJ10803
    Contig2544 FLJ11526 hypothetical protein Hypothetical protein 662 4630
    FLJ11526
    Contig25546_RC CCT6A itchy homolog E3 Ubl conjugation pathway, Ligase, 663 4631
    ubiquitin protein Nuclear protein, Repeat,
    ligase (mouse) Phosphorylation, Alternative splicing
    Contig25595_RC KIAA1618 KIAA1618 Hypothetical protein 664 4632
    Contig256 PSMD11 wt73b11.x1 Proteasome 665 4633
    Soares_thymus_NHFTh
    Homo sapiens
    cDNA clone
    IMAGE: 2513085 3′
    similar to
    TR: Q26195 Q26195
    PVA1 GENE.;
    mRNA sequence.
    Contig25610_RC CDNA FLJ31796 fis, 666 4634
    clone
    NT2RI2008841
    Contig25744_RC Transcribed 667 4635
    sequences
    Contig2576_RC DKFZP564O1664 hypothetical protein Hypothetical protein 668 4636
    DKFZp564O1664
    Contig25770_RC Clone 669 4637
    IMAGE: 4817413,
    mRNA
    Contig25783_RC Clone 670 4638
    IMAGE: 5555626,
    mRNA
    Contig2578_RC ORF1-FL49 putative nuclear Nuclear protein 671 4639
    protein ORF1-FL49
    Contig25827_RC FLJ13848 hypothetical protein Hypothetical protein 672 4640
    FLJ13848
    Contig2584_RC ribonuclease P Hydrolase, Nuclear protein, tRNA 673 4641
    (14 kD) processing
    Contig25861_RC Transcribed 674 4642
    sequences
    Contig25960_RC DKFZP564B0769 chromosome 6 open Hypothetical protein 675 4643
    reading frame 111
    Contig26014_RC SYTL3 synaptotagmin-like 3 676 4644
    Contig26019_RC methionyl Aminopeptidase, Hypothetical 677 4645
    aminopeptidase 2 protein, Hydrolase, Cobalt, 3D-
    structure
    Contig26059_RC Transcribed 678 4646
    sequences
    Contig2608 SLC2A4RG SLC2A4 regulator Transcription regulation, DNA- 679 4647
    binding, Nuclear protein, Zinc-finger,
    Metal-binding, Alternative splicing
    Contig26170_RC Transcribed 680 4648
    sequences
    Contig26332_RC Transcribed 681 4649
    sequences
    Contig263_RC MGC12435 chromosome 14 682 4650
    open reading frame
    168
    Contig26405_RC TSLL2 immunoglobulin Immunoglobulin domain 683 4651
    superfamily, member
    4C
    Contig26416_RC Transcribed 684 4652
    sequences
    Contig26461_RC Transcribed 685 4653
    sequences
    Contig2647_RC BCAT1 branched chain Transferase, Aminotransferase, 686 4654
    aminotransferase 1, Hypothetical protein, Branched-chain
    cytosolic amino acid biosynthesis, Pyridoxal
    phosphate
    Contig2648_RC MGC15407 similar to RIKEN 687 4655
    cDNA 4931428D14
    gene
    Contig2657_RC MGC16207 hypothetical protein Hypothetical protein 688 4656
    MGC16207
    Contig26622_RC BIC BIC transcript 689 4657
    Contig26706_RC CDNA FLJ43676 fis, 690 4658
    clone
    SYNOV4009129
    Contig26998_RC WD repeat domain 1 Repeat, WD repeat, Actin-binding, 691 4659
    Cytoskeleton, Alternative splicing,
    Polymorphism, Hypothetical protein
    Contig27060_RC Transcribed 692 4660
    sequence with
    moderate similarity
    to protein pdb: 1LBG
    (E. coli) B Chain B,
    Lactose Operon
    Repressor Bound To
    21-Base Pair
    Symmetric Operator
    Dna, Alpha Carbons
    Only
    Contig27084_RC CDNA FLJ45493 fis, 693 4661
    clone
    BRTHA2008598
    Contig27124_RC CDNA FLJ42250 fis, 694 4662
    clone
    TKIDN2007828
    Contig27145_RC Transcribed 695 4663
    sequences
    Contig27228_RC amyloid beta (A4) Hypothetical protein 696 4664
    precursor protein-
    binding, family B,
    member 1
    interacting protein
    Contig2728_RC zinc finger protein Hypothetical protein, Metal-binding, 697 4665
    596 Zinc, Zinc-finger
    Contig27338_RC Transcribed 698 4666
    sequences
    Contig27386_RC C7orf13 chromosome 7 open 699 4667
    reading frame 13
    Contig27542_RC Transcribed 700 4668
    sequences
    Contig27558_RC FLJ13163 MRNA; cDNA Hypothetical protein, Kinase 701 4669
    DKFZp779J2459
    (from clone
    DKFZp779J2459)
    Contig27725_RC Transcribed 702 4670
    sequences
    Contig27765_RC potassium inwardly- Hypothetical protein, Ionic channel, 703 4671
    rectifying channel, Ion transport, Voltage-gated
    subfamily J, member channel, Transmembrane,
    15 Potassium transport
    Contig27776_RC hypothetical protein Hypothetical protein 704 4672
    FLJ21106
    Contig27797_RC DnaJ (Hsp40) Chaperone, Repeat, Zinc, Metal- 705 4673
    homolog, subfamily binding, Prenylation, Lipoprotein,
    A, member 2 Membrane, Multigene family
    Contig27820_RC Transcribed 706 4674
    sequences
    Contig27837_RC Transcribed 707 4675
    sequence with weak
    similarity to protein
    ref: NP_060265.1
    (H. sapiens)
    hypothetical protein
    FLJ20378 [Homo
    sapiens]
    Contig27896_RC HSPC009 protein 708 4676
    Contig27915_RC MGC40042 hypothetical protein Hypothetical protein 709 4677
    MGC40042
    Contig27977_RC Transcribed 710 4678
    sequences
    Contig28024_RC KIAA0955 caspase recruitment Apoptosis, Nuclear protein, 711 4679
    domain family, Alternative splicing, Hypothetical
    member
    8 protein
    Contig28050_RC Homo sapiens cDNA 712 4680
    FLJ35764 fis, clone
    TESTI2004906,
    weakly similar to
    H. sapiens mRNA for
    SIRP-beta1.
    Contig2811_RC C8orf2 Homo sapiens Transmembrane, Alternative splicing 713 4681
    mRNA; cDNA
    DKFZp667H242
    (from clone
    DKFZp667H242);
    complete cds.
    Contig28164_RC Transcribed 714 4682
    sequences
    Contig28181_RC ns17h07.s1 715 4683
    NCI_CGAP_GCB1
    Homo sapiens cDNA
    clone
    IMAGE: 1183933 3′,
    mRNA sequence.
    Contig28229_RC Transcribed 716 4684
    sequences
    Contig2823_RC FLJ23499 chromosome 11 Hypothetical protein 717 4685
    open reading frame 1
    Contig28286_RC Transcribed 718 4686
    sequences
    Contig28298_RC NUP62 UI-H-BI0p-abm-b- Nuclear protein, Transport, 719 4687
    04-0-UI.s1 Glycoprotein, Coiled coil, Repeat,
    NCI_CGAP_Sub2 Polymorphism
    Homo sapiens cDNA
    clone
    IMAGE: 2712150 3′,
    mRNA sequence.
    Contig28522_RC Clone 24653 mRNA 720 4688
    sequence
    Contig28567_RC Transcribed 721 4689
    sequences
    Contig2857_RC DKFZp761G2113 hypothetical protein Hypothetical protein 722 4690
    DKFZp761G2113
    Contig28707_RC ADAMTS13 a disintegrin-like and Protease, Hypothetical protein, 723 4691
    metalloprotease Signal
    (reprolysin type) with
    thrombospondin type
    1 motif, 13
    Contig28760_RC cyclin-dependent 724 4692
    kinase 6
    Contig28766_RC Transcribed 725 4693
    sequences
    Contig28787_RC hypothetical protein Hypothetical protein 726 4694
    LOC120526
    Contig2883_RC RALY Clone Ribonucleoprotein, RNA-binding, 727 4695
    IMAGE: 5285100, Nuclear protein, Antigen, Alternative
    mRNA splicing, Polymorphism
    Contig28947_RC CDC25A cell division cycle Cell division, Mitosis, Hydrolase, 728 4696
    25A Alternative splicing, Multigene family,
    3D-structure, Hypothetical protein
    Contig28949 Clone 729 4697
    IMAGE: 5268292,
    mRNA
    Contig28996_RC NHL repeat 730 4698
    containing 1
    Contig29171_RC CDNA FLJ11544 fis, 731 4699
    clone
    HEMBA1002826
    Contig29207_RC chromosome 20 732 4700
    open reading frame
    78
    Contig29284_RC Transcribed 733 4701
    sequences
    Contig292_RC FLJ22386 leucine zipper Hypothetical protein 734 4702
    domain protein
    Contig2930_RC DAB2 CDNA FLJ35517 fis, Alternative splicing, Phosphorylation 735 4703
    clone
    SPLEN2000698
    Contig29349_RC Transcribed 736 4704
    sequences
    Contig29362_RC hypothetical protein Hypothetical protein 737 4705
    LOC338692
    Contig29373_RC 24b2/STAC2 protein 738 4706
    Contig29569_RC hypothetical protein Hypothetical protein 739 4707
    MGC29898
    Contig29732_RC hypothetical protein 740 4708
    LOC338758
    Contig29749_RC LOC85028 PNAS-123 741 4709
    Contig29780_RC Transcribed 742 4710
    sequences
    Contig29802_RC programmed cell Calcium-binding, Repeat, Apoptosis 743 4711
    death 6
    Contig29860_RC NFAM1 NFAT activation Hypothetical protein, Signal, 744 4712
    molecule 1 Transmembrane, Immunoglobulin
    domain, Phosphorylation
    Contig2986_RC EEG1 C1q domain Hypothetical protein 745 4713
    containing 1
    Contig29887_RC DKFZp434J0617 hypothetical protein Hypothetical protein 746 4714
    DKFZp434J0617
    Contig29890_RC FLJ32449 ankyrin repeat Hypothetical protein, ANK repeat, 747 4715
    domain 23 Repeat
    Contig29901_RC proteasome Proteasome, Hydrolase, Protease, 748 4716
    (prosome, Acetylation, Alternative splicing,
    macropain) subunit, Phosphorylation, Threonine protease
    alpha type, 3
    Contig29921_RC FLJ22570 Dok-like protein Hypothetical protein 749 4717
    Contig29940_RC CMYA1 cardiomyopathy Hypothetical protein 750 4718
    associated 1
    Contig29954_RC CATSPER2 Clone 751 4719
    IMAGE: 5294645,
    mRNA
    Contig29955_RC zj86d08.s1 752 4720
    Soares_fetal_liver_spleen_1NFLS_S1
    Homo sapiens cDNA
    clone
    IMAGE: 461775 3′,
    mRNA sequence.
    Contig29995_RC Transcribed 753 4721
    sequences
    Contig30052_RC C18B11 C18B11 homolog Hypothetical protein 754 4722
    (44.9 kD)
    Contig30109_RC PRKWNK4 protein kinase, lysine Hypothetical protein, ATP-binding, 755 4723
    deficient 4 Transferase, Kinase,
    Serine/threonine-protein kinase
    Contig30154_RC Transcribed 756 4724
    sequence with
    moderate similarity
    to protein sp: P39194
    (H. sapiens)
    ALU7_HUMAN Alu
    subfamily SQ
    sequence
    contamination
    warning entry
    Contig3015_RC pleckstrin homology 757 4725
    domain containing,
    family A
    (phosphoinositide
    binding specific)
    member 2
    Contig30209_RC FLJ12649 hypothetical protein Hypothetical protein 758 4726
    FLJ12649
    Contig30378_RC FLJ10178 hypothetical protein Hypothetical protein 759 4727
    FLJ10178
    Contig30474_RC VIT vitrin Hypothetical protein 760 4728
    Contig30484_RC Transcribed 761 4729
    sequences
    Contig30496_RC ZNF219 LOC400176 Transcription regulation, DNA- 762 4730
    (LOC387957), binding, Zinc-finger, Metal-binding,
    mRNA Nuclear protein, Repeat
    Contig30736_RC Transcribed 763 4731
    sequences
    Contig30811_RC PRKRA MRNA; cDNA Kinase 764 4732
    DKFZp686G1498
    (from clone
    DKFZp686G1498)
    Contig30840_RC LOC63929 hypothetical protein Hypothetical protein 765 4733
    LOC63929
    Contig30934_RC MGC33993 hypothetical protein Hypothetical protein, Metal-binding, 766 4734
    MGC33993 Zinc, Zinc-finger
    Contig3094_RC PINK1 PTEN induced Hypothetical protein, ATP-binding, 767 4735
    putative kinase 1 Kinase, Serine/threonine-protein
    kinase, Transferase
    Contig30977_RC hypothetical protein 768 4736
    LOC154790
    Contig30989_RC MGC10744 hypothetical protein Hypothetical protein 769 4737
    MGC10744
    Contig31057_RC Transcribed 770 4738
    sequences
    Contig31186_RC HNRPDL heterogeneous Nucleocapsid, Ribonucleoprotein 771 4739
    nuclear
    ribonucleoprotein D-
    like
    Contig31361_RC dedicator of Hypothetical protein, Guanine- 772 4740
    cytokinesis 7 nucleotide releasing factor,
    Alternative splicing
    Contig31366_RC LNPEP hypothetical protein Hypothetical protein 773 4741
    FLJ39485
    Contig31421_RC thyroid hormone Proteasome, Ubl conjugation 774 4742
    receptor interactor pathway, Ligase
    12
    Contig31449_RC Transcribed 775 4743
    sequence with weak
    similarity to protein
    sp: P39195
    (H. sapiens)
    ALU8_HUMAN Alu
    subfamily SX
    sequence
    contamination
    warning entry
    Contig3147_RC MUM2 trafficking protein Transport, Endoplasmic reticulum, 776 4744
    particle complex 1 Golgi stack, Disease mutation
    Contig31482_RC Transcribed 777 4745
    sequences
    Contig31495 thyroid hormone Antigen, Golgi stack, Coiled coil, 778 4746
    receptor interactor Chromosomal translocation,
    11 Hypothetical protein
    Contig31513_RC Transcribed 779 4747
    sequences
    Contig31525_RC Transcribed 780 4748
    sequence with weak
    similarity to protein
    ref: NP_079364.1
    (H. sapiens)
    hypothetical protein
    FLJ13241 [Homo
    sapiens]
    Contig31587_RC Human full-length Plasmid 781 4749
    cDNA 5-PRIME end
    of clone
    CS0DK007YB08 of
    HeLa cells of Homo
    sapiens (human)
    Contig31597_RC PDE4DIP chromosome 1 Hypothetical protein 782 4750
    amplified sequence 3
    Contig31661_RC hypothetical protein Hypothetical protein, Repeat, WD 783 4751
    FLJ10385 repeat
    Contig31664_RC MGC26979 hypothetical protein Hypothetical protein 784 4752
    MGC26979
    Contig31699_RC CDNA FLJ27273 fis, 785 4753
    clone TMS00761
    Contig31740_RC PFN1 hypothetical protein Metal-binding, Zinc, Zinc-finger, 786 4754
    LOC285345 Transcription regulation, DNA-
    binding, Nuclear protein, Repeat
    Contig31864_RC FERM domain Hypothetical protein 787 4755
    containing 3
    Contig31906_RC similar to Hypothetical protein 788 4756
    hypothetical protein
    FLJ13659
    Contig31911_RC hypothetical protein Hypothetical protein 789 4757
    LOC349136
    Contig32027_RC CDNA FLJ46867 fis, 790 4758
    clone
    UTERU3012293,
    weakly similar to
    Homo sapiens zinc
    finger protein 14
    (KOX 6) (ZNF14)
    Contig32059_RC MGC17919 zinc finger and BTB Zinc, Hypothetical protein, Metal- 791 4759
    domain containing 8 binding, Zinc-finger
    Contig32081_RC Full length insert 792 4760
    cDNA clone
    YP77A07
    Contig32103_RC Clone 793 4761
    IMAGE: 4689481,
    mRNA
    Contig32123_RC Similar to ataxin 2 794 4762
    binding protein 1
    isoform gamma;
    hexaribonucleotide
    binding protein 1
    (LOC339162),
    mRNA
    Contig32185_RC intimal thickness- 795 4763
    related receptor
    Contig3228_RC VMP1 hypothetical protein Hypothetical protein 796 4764
    LOC283680
    Contig32322_RC quaking homolog, Hypothetical protein 797 4765
    KH domain RNA
    binding (mouse)
    Contig32323_RC hypothetical protein Hypothetical protein 798 4766
    FLJ13105
    Contig32335_RC Transcribed 799 4767
    sequences
    Contig32377_RC ubiquitin specific Protease 800 4768
    protease 51
    Contig32431_RC Transcribed 801 4769
    sequences
    Contig3250_RC LOC92399 mitochondrial Hypothetical protein 802 4770
    ribosome recycling
    factor
    Contig32540_RC Transcribed 803 4771
    sequences
    Contig32550_RC ZFP93 zinc finger protein Transcription regulation, DNA- 804 4772
    235 binding, Zinc-finger, Metal-binding,
    Nuclear protein, Repeat
    Contig32637_RC RAB27A, member GTP-binding, Lipoprotein, 805 4773
    RAS oncogene Prenylation, Alternative splicing,
    family Disease mutation
    Contig32757 FLJ21069 hypothetical protein Hypothetical protein, ANK repeat, 806 4774
    FLJ21069 Repeat
    Contig32825_RC polymerase (RNA) III 807 4775
    (DNA directed)
    (32 kD)
    Contig32920 FUBP1 nexilin (F actin Hypothetical protein 808 4776
    binding protein)
    Contig33062_RC chromosome 17 Hypothetical protein 809 4777
    open reading frame
    31
    Contig3311_RC MGC13186 hypothetical protein Hypothetical protein, ATP-binding 810 4778
    MGC13186
    Contig33127_RC Sequence 161 from 811 4779
    Patent WO0220754.
    Contig3313 FLJ23153 likely ortholog of Hypothetical protein 812 4780
    mouse tumor
    necrosis-alpha-
    induced adipose-
    related protein
    Contig33188_RC Transcribed 813 4781
    sequences
    Contig33207_RC Transcribed 814 4782
    sequences
    Contig33224_RC Transcribed 815 4783
    sequences
    Contig33273_RC chromodomain DNA-binding, Helicase, Hypothetical 816 4784
    helicase DNA protein, ATP-binding, Hydrolase
    binding protein 1-like
    Contig3331_RC MKI67IP MKI67 (FHA 817 4785
    domain) interacting
    nucleolar
    phosphoprotein
    Contig33334_RC Transcribed 818 4786
    sequences
    Contig33369_RC Transcribed 819 4787
    sequence with weak
    similarity to protein
    ref: NP_062553.1
    (H. sapiens)
    hypothetical protein
    FLJ11267 [Homo
    sapiens]
    Contig33394_RC FLJ37318 ubiquitin specific Hypothetical protein 820 4788
    protease 54
    Contig3344 MGC2835 DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 821 4789
    Asp) box polypeptide Hypothetical protein
    54
    Contig33442_RC MOB1, Mps One Hypothetical protein 822 4790
    Binder kinase
    activator-like 2A
    (yeast)
    Contig33464_RC Similar to bA304I5.1 823 4791
    (novel lipase)
    (LOC340654),
    mRNA
    Contig33540_RC SEMA3F ob92d09.s1 Signal, Immunoglobulin domain, 824 4792
    NCI_CGAP_GCB1 Multigene family, Glycoprotein,
    Homo sapiens cDNA Polymorphism
    clone
    IMAGE: 1338833 3′,
    mRNA sequence.
    Contig33574_RC Transcribed 825 4793
    sequences
    Contig3359_RC neuralized-like Hypothetical protein 826 4794
    (Drosophila)
    Contig33703_RC FLJ21438 hypothetical protein Hypothetical protein 827 4795
    FLJ21438
    Contig33741_RC FLJ12428 DEP domain Hypothetical protein 828 4796
    containing 6
    Contig33760_RC chromosome 9 open 829 4797
    reading frame 71
    Contig33790_RC jun dimerization DNA-binding, Nuclear protein 830 4798
    protein 2
    Contig33810_RC FLJ31528 hypothetical protein Hypothetical protein 831 4799
    FLJ31528
    Contig33831_RC Transcribed 832 4800
    sequences
    Contig33852_RC OPRL1 opiate receptor-like 1 G-protein coupled receptor, 833 4801
    Transmembrane, Glycoprotein,
    Phosphorylation, Lipoprotein,
    Palmitate, Alternative splicing
    Contig33888_RC ow44c09.x1 834 4802
    Soares_parathyroid_tumor_NbHPA
    Homo sapiens cDNA
    clone
    IMAGE: 1649680 3′,
    mRNA sequence.
    Contig3390_RC FLJ12619 chromosome 6 open Hypothetical protein 835 4803
    reading frame 62
    Contig33951_RC nuclear pore Nuclear protein, Transport 836 4804
    complex protein
    Contig33967_RC Transcribed 837 4805
    sequences
    Contig33987 hypothetical protein Hypothetical protein 838 4806
    KIAA1109
    Contig33996_RC Transcribed 839 4807
    sequences
    Contig34019_RC MGC15827 hypothetical protein Hypothetical protein 840 4808
    MGC15827
    Contig34051_RC Transcribed 841 4809
    sequences
    Contig34090_RC Transcribed 842 4810
    sequences
    Contig340_RC PPP1R15B protein phosphatase Hypothetical protein 843 4811
    1, regulatory
    (inhibitor) subunit
    15B
    Contig34118_RC Transcribed 844 4812
    sequences
    Contig34231_RC yd77f12.s1 Soares 845 4813
    fetal liver spleen
    1NFLS Homo
    sapiens cDNA clone
    IMAGE: 114287 3′,
    mRNA sequence.
    Contig34286_RC Transcribed 846 4814
    sequences
    Contig34291_RC nuclear receptor Transcription regulation, Receptor, 847 4815
    subfamily 3, group Trans-acting factor, Nuclear protein,
    C, member 1 DNA-binding, Steroid-binding, Zinc-
    (glucocorticoid finger, Phosphorylation, Ubl
    receptor) conjugation, Alternative initiation,
    Alternative splicing, Polymorphism,
    Disease mutation
    Contig34302_RC hypothetical protein 848 4816
    LOC150166
    Contig34303_RC SFXN5 sideroflexin 5 Transport, Iron transport, Iron, 849 4817
    Mitochondrion, Transmembrane
    Contig34350_RC CDNA FLJ45384 fis, 850 4818
    clone
    BRHIP3021987
    Contig34470_RC similar to kinesin Hypothetical protein 851 4819
    family member 21A;
    N-5 kinesin
    Contig34554_RC CDNA FLJ33367 fis, 852 4820
    clone
    BRACE2005661
    Contig34593_RC Transcribed 853 4821
    sequences
    Contig34607_RC ym49g02.s1 Soares 854 4822
    infant brain 1NIB
    Homo sapiens cDNA
    clone IMAGE: 51586
    3′, mRNA sequence.
    Contig34634_RC GCN1L1 homeodomain Transferase, Serine/threonine- 855 4823
    interacting protein protein kinase, ATP-binding, Nuclear
    kinase
    2 protein, Alternative splicing
    Contig34672_RC Transcribed 856 4824
    sequences
    Contig3474_RC CDNA: FLJ22541 857 4825
    fis, clone HSI00130
    Contig34768_RC chromosome 21 Hypothetical protein 858 4826
    open reading frame
    59
    Contig34779_RC SH3-domain kinase SH3 domain, Repeat, Membrane, 859 4827
    binding protein 1 Nuclear protein, Coiled coil,
    Polymorphism, Alternative splicing
    Contig34880_RC Transcribed 860 4828
    sequences
    Contig3495_RC MGC45416 hypothetical protein Hypothetical protein 861 4829
    MGC45416
    Contig34983_RC Transcribed 862 4830
    sequences
    Contig34998_RC TMLHE CDNA FLJ25895 fis, Hypothetical protein 863 4831
    clone CBR03553
    Contig34999_RC periplakin Keratinization, Repeat, Coiled coil, 864 4832
    Cytoskeleton, Structural protein
    Contig35002_RC FLJ12994 hypothetical protein Hypothetical protein 865 4833
    FLJ12994
    Contig35018_RC zr44a03.s1 866 4834
    Soares_NhHMPu_S1
    Homo sapiens
    cDNA clone
    IMAGE: 666220 3′,
    mRNA sequence.
    Contig35043 Transcribed 867 4835
    sequences
    Contig35052_RC pituitary tumor- Transmembrane, Nuclear protein 868 4836
    transforming 1
    interacting protein
    Contig35076_RC Sequence 226 from 869 4837
    Patent WO0220754.
    Contig35094_RC FLJ21478 NOD9 protein Hypothetical protein 870 4838
    Contig35163_RC Similar to 871 4839
    hypothetical protein
    MG11009.4
    (LOC285344),
    mRNA
    Contig35182_RC qb88b05.x1 872 4840
    Soares_fetal_heart_NbHH19W
    Homo
    sapiens cDNA clone
    IMAGE: 1707153 3′,
    mRNA sequence.
    Contig35187_RC ARL4 ADP-ribosylation GTP-binding, Multigene family, 873 4841
    factor-like 4 Nuclear protein
    Contig35251_RC CDNA: FLJ22719 874 4842
    fis, clone HSI14307
    Contig35425_RC hypothetical protein Hypothetical protein 875 4843
    LOC285831
    Contig35435_RC FLJ23447 hypothetical protein Hypothetical protein 876 4844
    FLJ23447
    Contig35576_RC Transcribed 877 4845
    sequences
    Contig35608_RC df54a02.y1 Morton 878 4846
    Fetal Cochlea Homo
    sapiens cDNA clone
    IMAGE: 2487051 5′,
    mRNA sequence.
    Contig35635_RC TAGAP T-cell activation Hypothetical protein 879 4847
    GTPase activating
    protein
    Contig35661_RC DSCR1L2 Down syndrome Alternative splicing 880 4848
    critical region gene
    1-like 2
    Contig35685_RC FLJ13117 spermatogenesis Hypothetical protein 881 4849
    associated, serine-
    rich 2
    Contig35700_RC CDNA clone 882 4850
    IMAGE: 6702802,
    partial cds
    Contig35713_RC FIS 883 4851
    Contig35799_RC centaurin, beta 2 GTPase activation, Repeat, ANK 884 4852
    repeat, Zinc-finger
    Contig35874_RC Transcribed 885 4853
    sequences
    Contig35896_RC signal transducer Hypothetical protein, Repeat, WD 886 4854
    and activator of repeat
    transcription
    3
    interacting protein 1
    Contig35940 KIAA1733 RPEL repeat Hypothetical protein 887 4855
    containing 1
    Contig35958_RC MGC13071 hypothetical protein Hypothetical protein, Metal-binding, 888 4856
    MGC13071 Nuclear protein, Zinc, Zinc-finger
    Contig35976_RC family with sequence Signal 889 4857
    similarity 3, member C
    Contig3597_RC LENG5 leukocyte receptor Receptor, Hypothetical protein 890 4858
    cluster (LRC)
    member 5
    Contig36020_RC MGC15634 hypothetical protein Hypothetical protein 891 4859
    MGC15634
    Contig36075_RC Transcribed 892 4860
    sequences
    Contig36104_RC CCT6A laa10b09.x1 8 5 Chaperone, ATP-binding, Multigene 893 4861
    week embryo family
    anterior tongue 8 5
    EAT Homo sapiens
    cDNA
    3′, mRNA
    sequence.
    Contig36106_RC NCL hypothetical protein Hypothetical protein 894 4862
    LOC157697
    Contig36125_RC Transcribed 895 4863
    sequences
    Contig36129_RC MGC4707 hypothetical protein Hypothetical protein 896 4864
    LOC283989
    Contig3612_RC KIAA1802 chromosome 13 Hypothetical protein, Metal-binding, 897 4865
    open reading frame 8 Zinc, Zinc-finger
    Contig36152_RC sterile alpha motif Hypothetical protein, ANK repeat, 898 4866
    domain containing 6 Repeat
    Contig36169_RC DKFZp547E052 hypothetical protein Hypothetical protein 899 4867
    DKFZp547E052
    Contig36178_RC sialyltransferase 9 Transferase, Glycosyltransferase, 900 4868
    (CMP- Glycoprotein, Transmembrane,
    NeuAc:lactosylceramide Signal-anchor, Golgi stack
    alpha-2,3-
    sialyltransferase;
    GM3 synthase)
    Contig36190_RC Transcribed 901 4869
    sequences
    Contig36193_RC inositol
    1,4,5- Receptor, Transmembrane, 902 4870
    triphosphate Phosphorylation, Ionic channel, Ion
    receptor, type 1 transport, Calcium channel
    Contig36195 Full length insert 903 4871
    cDNA clone
    ZD73D05
    Contig3626_RC FLJ13855 hypothetical protein Hypothetical protein, Ligase, Ubl 904 4872
    FLJ13855 conjugation pathway
    Contig36323_RC SFXN5 sideroflexin 5 Transport, Iron transport, Iron, 905 4873
    Mitochondrion, Transmembrane
    Contig36359_RC Transcribed 906 4874
    sequences
    Contig36369_RC we24d02.x1 907 4875
    NCI_CGAP_Lu24
    Homo sapiens cDNA
    clone
    IMAGE: 2342019 3′,
    mRNA sequence.
    Contig36409_RC Transcribed 908 4876
    sequences
    Contig36512_RC Transcribed 909 4877
    sequences
    Contig36525 ARX aristaless related Homeobox, DNA-binding, 910 4878
    homeobox Developmental protein, Nuclear
    protein, Transcription regulation,
    Disease mutation, Triplet repeat
    expansion, Epilepsy
    Contig36617_RC chromosome 6 open 911 4879
    reading frame 182
    Contig36622_RC Transcribed 912 4880
    sequences
    Contig36628 HANP1 913 4881
    Contig36634_RC FLJ39514 sec1 family domain Hypothetical protein 914 4882
    containing 2
    Contig36720_RC Transcribed 915 4883
    sequences
    Contig36761_RC FLJ23403 hypothetical protein Hypothetical protein 916 4884
    FLJ23403
    Contig36803_RC FLJ13952 sorting nexin 22 Hypothetical protein, Transport, 917 4885
    Protein transport
    Contig36805_RC MGC15435 zinc finger, BED Zinc-finger 918 4886
    domain containing 3
    Contig36810 CDNA FLJ37425 fis, 919 4887
    clone
    BRAWH2001530
    Contig36876_RC Homo sapiens cDNA 920 4888
    FLJ32044 fis, clone
    NTONG2000985.
    Contig36879_RC Clone 921 4889
    IMAGE: 4753714,
    mRNA
    Contig36888_RC suppression of Hypothetical protein 922 4890
    tumorigenicity 7 like
    Contig36939_RC Transcribed 923 4891
    sequences
    Contig3695_RC MGC17330 HGFL gene Hypothetical protein, Glycoprotein, 924 4892
    Kringle
    Contig36973_RC AGMAT Homo sapiens Putrescine biosynthesis, Spermidine 925 4893
    cDNA: FLJ23384 fis, biosynthesis, Hydrolase,
    clone HEP16468. Manganese, Mitochondrion, Transit
    peptide
    Contig36976_RC DIBD1 disrupted in bipolar Hypothetical protein 926 4894
    affective disorder 1
    Contig36997_RC bioref zinc finger protein Transcription regulation, DNA- 927 4895
    481 binding, Zinc-finger, Metal-binding,
    Nuclear protein, Repeat
    Contig37016_RC ING5 inhibitor of growth Hypothetical protein 928 4896
    family, member 5
    Contig37025_RC CDNA FLJ41484 fis, 929 4897
    clone
    BRTHA2003030
    Contig37029_RC FLJ23153 likely ortholog of Hypothetical protein 930 4898
    mouse tumor
    necrosis-alpha-
    induced adipose-
    related protein
    Contig37037_RC chromosome 13 931 4899
    open reading frame
    25
    Contig37082_RC MGC2408 hypothetical protein Hypothetical protein 932 4900
    MGC2408
    Contig37140_RC membrane protein, Hypothetical protein, SH3 domain 933 4901
    palmitoylated 7
    (MAGUK p55
    subfamily member 7)
    Contig37142_RC Homo sapiens cDNA 934 4902
    FLJ12163 fis, clone
    MAMMA1000594.
    Contig37219 MDN1 MDN1, midasin Chaperone, ATP-binding, Repeat, 935 4903
    homolog (yeast) Nuclear protein
    Contig37262 Clone Hypothetical protein 936 4904
    IMAGE: 5263527,
    mRNA
    Contig37300_RC KIAA1904 KIAA1904 protein Hypothetical protein 937 4905
    Contig37306_RC MUC16 mucin 16 Hypothetical protein 938 4906
    Contig3734_RC RPS8 Clone Ribosomal protein 939 4907
    IMAGE: 4249217,
    mRNA
    Contig37361_RC Transcribed 940 4908
    sequences
    Contig37364_RC Transcribed 941 4909
    sequences
    Contig37368_RC nemo like kinase ATP-binding, Kinase, 942 4910
    Serine/threonine-protein kinase,
    Transferase
    Contig37569_RC CDNA FLJ26339 fis, 943 4911
    clone HRT02975
    Contig37660_RC ADAM6 a disintegrin and 944 4912
    metalloproteinase
    domain
    6
    Contig37736_RC RAD1 Transcribed Hypothetical protein, Ribosome 945 4913
    sequence with biogenesis, Nuclear protein, Cell
    moderate similarity cycle, Exonuclease
    to protein
    ref: NP_060312.1
    (H. sapiens)
    hypothetical protein
    FLJ20489 [Homo
    sapiens]
    Contig37763_RC Transcribed 946 4914
    sequence with
    moderate similarity
    to protein
    ref: NP_002945.1
    (H. sapiens)
    ubiquitin and
    ribosomal protein
    S27a precursor;
    ubiquitin carboxyl
    extension protein
    80;
    40S ribosomal
    protein S27a;
    ubiquitin; ubiquitin-
    CEP80 [Homo
    sapiens]
    Contig37764_RC qa65f01.x1 947 4915
    Soares_fetal_heart_NbHH19W
    Homo
    sapiens cDNA clone
    IMAGE: 1691641 3′,
    mRNA sequence.
    Contig37895_RC yh88d01.s1 Soares 948 4916
    placenta Nb2HP
    Homo sapiens cDNA
    clone
    IMAGE: 136801 3′,
    mRNA sequence.
    Contig37950_RC qz91d12.x1 949 4917
    Soares_pregnant_uterus_NbHPU
    Homo
    sapiens cDNA clone
    IMAGE: 2041943 3′,
    mRNA sequence.
    Contig37958 KAI1 hypothetical protein Glycoprotein, Transmembrane, 950 4918
    LOC284023 Antigen
    Contig37991_RC LOC133308 hypothetical protein Hypothetical protein 951 4919
    BC009732
    Contig38043_RC hypothetical protein 952 4920
    LOC199675
    Contig38093_RC Transcribed 953 4921
    sequences
    Contig380_RC KIAA1724 selenoprotein I, 1 Hypothetical protein, Transferase, 954 4922
    Transmembrane, Selenium,
    Selenocysteine
    Contig38117_RC Transcribed 955 4923
    sequences
    Contig38155_RC Transcribed 956 4924
    sequences
    Contig38169_RC FLJ13984 hypothetical protein Hypothetical protein 957 4925
    FLJ13984
    Contig3820_RC LOC56898 dehydrogenase/reductase Oxidoreductase, Hypothetical protein 958 4926
    (SDR family)
    member 6
    Contig38285_RC FLJ10462 male sterility domain Hypothetical protein 959 4927
    containing 1
    Contig38288_RC DKFZp762A2013 quiescin Q6-like 1 Hypothetical protein, Signal 960 4928
    Contig382_RC NLI-IF CTD (carboxy- Hypothetical protein, Nuclear protein 961 4929
    terminal domain,
    RNA polymerase II,
    polypeptide A) small
    phosphatase
    1
    Contig38320_RC Transcribed 962 4930
    sequences
    Contig38321_RC Transcribed 963 4931
    sequences
    Contig3834_RC MRNA; cDNA 964 4932
    DKFZp686K14148
    (from clone
    DKFZp686K14148)
    Contig38398_RC Transcribed 965 4933
    sequences
    Contig38493_RC CDNA FLJ42010 fis, 966 4934
    clone
    SPLEN2032036
    Contig38581_RC anaphase promoting Ubl conjugation pathway, Cell cycle, 967 4935
    complex subunit 1 Cell division, Mitosis, Repeat
    Contig38603_RC Transcribed 968 4936
    sequences
    Contig38604_RC CDNA FLJ25042 fis, Hypothetical protein 969 4937
    clone CBL03351
    Contig38654_RC solute carrier family 970 4938
    28 (sodium-coupled
    nucleoside
    transporter),
    member 3
    Contig38669_RC HS2ST1 heparan sulfate 2-O- Hypothetical protein, Transferase 971 4939
    sulfotransferase 1
    Contig38714_RC Transcribed 972 4940
    sequences
    Contig38721_RC MGC35163 sterile alpha motif Hypothetical protein 973 4941
    domain containing 3
    Contig38724_RC Clone 974 4942
    IMAGE: 5275753,
    mRNA
    Contig38726_RC SWI/SNF related, Hypothetical protein 975 4943
    matrix associated,
    actin dependent
    regulator of
    chromatin, subfamily
    e, member 1
    Contig38731_RC frizzled homolog 2 Multigene family, G-protein coupled 976 4944
    (Drosophila) receptor, Transmembrane,
    Developmental protein, Wnt
    signaling pathway, Glycoprotein,
    Signal
    Contig38778 TRIM7 tripartite motif- Zinc-finger, Zinc, Coiled coil, Metal- 977 4945
    containing 7 binding, Polymorphism, Alternative
    splicing
    Contig38803_RC Rho GTPase GTPase activation, SH3-binding, 3D- 978 4946
    activating protein 1 structure
    Contig38877 zv94e09.s1 979 4947
    Soares_NhHMPu_S1
    Homo sapiens
    cDNA clone
    IMAGE: 767464 3′,
    mRNA sequence.
    Contig38944_RC Transcribed 980 4948
    sequences
    Contig39008_RC MYCL1 v-myc Nuclear protein, DNA-binding, Proto- 981 4949
    myelocytomatosis oncogene
    viral oncogene
    homolog
    1, lung
    carcinoma derived
    (avian)
    Contig39043_RC zl77f02.s1 982 4950
    Stratagene colon
    (#937204) Homo
    sapiens cDNA clone
    IMAGE: 510651 3′,
    mRNA sequence.
    Contig39048_RC TAFA2 protein Hypothetical protein 983 4951
    Contig39116_RC a1/3GTP alpha-1,3- Glycosyltransferase, Transferase 984 4952
    galactosyltransferase
    pseudogene
    Contig3920_RC SP1 Sp1 transcription Hypothetical protein, Transcription 985 4953
    factor regulation, Activator, Zinc-finger,
    Metal-binding, DNA-binding, Nuclear
    protein, Repeat, Glycoprotein, 3D-
    structure
    Contig39236 FLJ00026 Homo sapiens, Hypothetical protein, Guanine- 986 4954
    Similar to RIKEN nucleotide releasing factor
    cDNA 5830472H07
    gene, clone
    MGC: 39702
    IMAGE: 5271738,
    mRNA, complete
    cds.
    Contig39249 THBS3 thrombospondin 3 Glycoprotein, Cell adhesion, 987 4955
    Calcium-binding, Repeat, EGF-like
    domain, Signal
    Contig39287_RC Transcribed 988 4956
    sequence with
    moderate similarity
    to protein pir: E54024
    (H. sapiens) E54024
    protein kinase
    Contig39297_RC LOC148898 hypothetical protein Hypothetical protein 989 4957
    BC007899
    Contig39364_RC UPF3B UPF3 regulator of 990 4958
    nonsense transcripts
    homolog B (yeast)
    Contig39403_RC hypothetical protein Hypothetical protein 991 4959
    FLJ34790
    Contig3940_RC C9orf19 chromosome 9 open Hypothetical protein 992 4960
    reading frame 19
    Contig39448_RC N-acetylneuraminate 993 4961
    pyruvate lyase
    (dihydrodipicolinate
    synthase)
    Contig39496_RC FLJ22501 Hermansky-Pudlak Hypothetical protein 994 4962
    syndrome 6
    Contig39545_RC MTIF3 general transcription Transcription regulation, Zinc-finger, 995 4963
    factor IIIA Metal-binding, DNA-binding, RNA-
    binding, Repeat, Nuclear protein,
    Polymorphism
    Contig39603_RC CNOT3 CCR4-NOT Hypothetical protein 996 4964
    transcription
    complex, subunit 3
    Contig39626_RC STK35 serine/threonine Hypothetical protein, Transferase, 997 4965
    kinase 35 Serine/threonine-protein kinase,
    ATP-binding, Phosphorylation
    Contig39702_RC similar to Putative Hypothetical protein 998 4966
    protein C21orf56
    Contig39739_RC CDK9 Full length insert Transferase, Serine/threonine- 999 4967
    cDNA clone protein kinase, ATP-binding, Nuclear
    ZA91F08 protein, Polymorphism
    Contig39797_RC TRIPIN tripin Hypothetical protein 1000 4968
    Contig39810_RC hypothetical protein Hypothetical protein 1001 4969
    MGC43690
    Contig39878_RC BOP SET and MYND Transcription regulation, Repressor, 1002 4970
    domain containing 1 DNA-binding, Nuclear protein, Zinc-
    finger, Metal-binding
    Contig39933_RC LOC90693 Sequence 2 from Hypothetical protein 1003 4971
    Patent WO0220754.
    Contig39989_RC MGC14289 similar to RIKEN 1004 4972
    cDNA 1200014N16
    gene
    Contig40015_RC Transcribed 1005 4973
    sequence with
    moderate similarity
    to protein pdb: 1LBG
    (E. coli) B Chain B,
    Lactose Operon
    Repressor Bound To
    21-Base Pair
    Symmetric Operator
    Dna, Alpha Carbons
    Only
    Contig40026_RC CDNA FLJ12935 fis, 1006 4974
    clone
    NT2RP2004982
    Contig40053_RC HNRPD heterogeneous Nuclear protein, RNA-binding, DNA- 1007 4975
    nuclear binding, Ribonucleoprotein, Repeat,
    ribonucleoprotein D Transcription regulation, Telomere,
    (AU-rich element Alternative splicing, 3D-structure
    RNA binding protein
    1, 37 kDa)
    Contig40055_RC Transcribed 1008 4976
    sequences
    Contig40069_RC Transcribed 1009 4977
    sequences
    Contig40093_RC fatty acid binding Transport, Lipid-binding, Acetylation, 1010 4978
    protein 3, muscle Phosphorylation, 3D-structure
    and heart
    (mammary-derived
    growth inhibitor)
    Contig40094_RC DKFZp434I099 hypothetical protein Hypothetical protein 1011 4979
    DKFZp434I099
    Contig40128_RC hypoxia-inducible Transcription regulation, Activator, 1012 4980
    factor 1, alpha Nuclear protein, DNA-binding,
    subunit (basic helix- Alternative splicing, Repeat,
    loop-helix Acetylation, Hydroxylation,
    transcription factor) Phosphorylation, S-nitrosylation,
    Polymorphism, 3D-structure
    Contig40184 SLC2A1 solute carrier family Transmembrane, Sugar transport, 1013 4981
    2 (facilitated glucose Transport, Glycoprotein, Multigene
    transporter), family, Disease mutation, 3D-
    member 1 structure
    Contig40212_RC CD5 CD5 antigen (p56-62) Signal, Transmembrane, 1014 4982
    Glycoprotein, T-cell, Repeat
    Contig40237_RC FLJ12525 hypothetical protein Hypothetical protein 1015 4983
    FLJ12525
    Contig40252_RC CDNA clone Hypothetical protein 1016 4984
    IMAGE: 3462401,
    partial cds
    Contig40340_RC hypothetical protein Hypothetical protein 1017 4985
    FLJ11000
    Contig40389_RC Similar to RIKEN 1018 4986
    cDNA 3830422K02
    (LOC387755),
    mRNA
    Contig404 Mesenchymal stem 1019 4987
    cell protein DSC96
    mRNA, partial cds
    Contig40405_RC MGC10818 chromosome 6 open Hypothetical protein 1020 4988
    reading frame 148
    Contig40410 tc14e12.x1 Hypothetical protein 1021 4989
    Soares_NhHMPu_S1
    Homo sapiens
    cDNA clone
    IMAGE: 2063854 3′,
    mRNA sequence.
    Contig40450_RC THAP domain Hypothetical protein 1022 4990
    containing 9
    Contig40552_RC FLJ25348 hypothetical protein Hypothetical protein 1023 4991
    FLJ25348
    Contig40651_RC Transcribed 1024 4992
    sequences
    Contig40676_RC Sequence 60 from 1025 4993
    Patent WO0220754.
    Contig40830_RC TSGA14 testis specific, 14 Hypothetical protein 1026 4994
    Contig40832_RC Transcribed 1027 4995
    sequences
    Contig40897_RC DKFZP434J037 likely ortholog of rat Hypothetical protein, ATP-binding, 1028 4996
    SNF1/AMP-activated Kinase, Serine/threonine-protein
    protein kinase kinase, Transferase
    Contig40960_RC FLJ36991 zinc finger protein Hypothetical protein, Metal-binding, 1029 4997
    565 Nuclear protein, Zinc, Zinc-finger
    Contig40965_RC MGC4504 hypothetical protein Hypothetical protein 1030 4998
    MGC4504
    Contig40967_RC LOC389388 1031 4999
    (LOC389388),
    mRNA
    Contig41005_RC Transcribed 1032 5000
    sequence with
    strong similarity to
    protein pdb: 1BGM
    (E. coli) O Chain O,
    Beta-Galactosidase
    Contig41035 golgi phosphoprotein 4 1033 5001
    Contig41041_RC CDNA FLJ32274 fis, 1034 5002
    clone
    PROST2000036
    Contig41080_RC Transcribed 1035 5003
    sequences
    Contig41086_RC forkhead box P1 Hypothetical protein, Transcription 1036 5004
    regulation, DNA-binding, Zinc-finger,
    Metal-binding, Nuclear protein,
    Alternative splicing
    Contig41094_RC EDG8 endothelial Hypothetical protein, Receptor 1037 5005
    differentiation,
    sphingolipid G-
    protein-coupled
    receptor, 8
    Contig41121_RC FCRH3 Fc receptor-like Immunoglobulin domain, Receptor 1038 5006
    protein 3
    Contig41209_RC FLJ21432 adiponectin receptor 2 Fatty acid metabolism, Lipid 1039 5007
    metabolism, Receptor,
    Transmembrane
    Contig41226_RC MRNA; cDNA Hypothetical protein 1040 5008
    DKFZp434O232
    (from clone
    DKFZp434O232)
    Contig412_RC FLJ22233 Homo sapiens cDNA Hypothetical protein 1041 5009
    FLJ36755 fis, clone
    UTERU2018180,
    weakly similar to
    Na+/Ca2+,K+-
    exchanging protein
    homolog C13D9.8.
    Contig41301 LOC152217 hypothetical protein Hypothetical protein 1042 5010
    BC007882
    Contig41421_RC FLJ36156 piwi-like 2 Hypothetical protein 1043 5011
    (Drosophila)
    Contig41448_RC dynamin 1-like 1044 5012
    Contig41537 MGC20496 methylmalonic Transferase, Mitochondrion, Transit 1045 5013
    aciduria (cobalamin peptide, Polymorphism, Disease
    deficiency) type B mutation
    Contig41560_RC CPT1A carnitine Transferase, Acyltransferase, 1046 5014
    palmitoyltransferase Mitochondrion, Outer membrane,
    1A (liver) Fatty acid metabolism, Transport,
    Transmembrane, Multigene family
    Contig41612_RC hypothetical protein Hypothetical protein 1047 5015
    LOC132241
    Contig41618_RC Clone Hypothetical protein 1048 5016
    IMAGE: 5315196,
    mRNA
    Contig41638_RC SLC26A8 solute carrier family 1049 5017
    26, member 8
    Contig41656_RC Similar to Eph 1050 5018
    receptor A7, clone
    IMAGE: 5273054,
    mRNA
    Contig41701_RC Transcribed 1051 5019
    sequences
    Contig41748_RC ELMO3 engulfment and cell Apoptosis, Phagocytosis, 1052 5020
    motility 3 (ced-12 Cytoskeleton, Membrane, SH3-
    homolog, C. elegans) binding
    Contig41774_RC Transcribed 1053 5021
    sequences
    Contig41781_RC ARHGEF7 Rho guanine Guanine-nucleotide releasing factor, 1054 5022
    nucleotide exchange SH3 domain, Alternative splicing,
    factor (GEF) 7 3D-structure, Hypothetical protein
    Contig41828_RC Clone 1055 5023
    IMAGE: 5310874,
    mRNA
    Contig41864_RC ZFP106 zinc finger protein Hypothetical protein, Metal-binding, 1056 5024
    106 homolog Repeat, WD repeat, Zinc, Zinc-finger
    (mouse)
    Contig41869_RC SFRS3 splicing factor, Nuclear protein, RNA-binding, 1057 5025
    arginine/serine-rich 3 mRNA splicing, Alternative splicing,
    Phosphorylation, Repeat
    Contig41903_RC FLJ21657 hypothetical protein Hypothetical protein 1058 5026
    FLJ21657
    Contig41923_RC OATL1 ornithine Transferase, Aminotransferase 1059 5027
    aminotransferase-
    like 1
    Contig41936_RC MSL3L1 male-specific lethal Chromatin regulator, Nuclear 1060 5028
    3-like 1 (Drosophila) protein, Transcription regulation,
    Alternative splicing
    Contig41983_RC ym35b12.s1 Soares 1061 5029
    infant brain 1NIB
    Homo sapiens cDNA
    clone IMAGE: 50144
    3′, mRNA sequence.
    Contig42005_RC splicing factor, Nuclear protein, RNA-binding, 1062 5030
    arginine/serine-rich mRNA splicing, Repeat
    11
    Contig42006_RC RasGEF domain Hypothetical protein 1063 5031
    family, member 1B
    Contig42012_RC zinc finger, DHHC Transmembrane, Zinc-finger 1064 5032
    domain containing
    21
    Contig42014_RC RNTRE USP6 N-terminal like Hypothetical protein 1065 5033
    Contig42076_RC FLJ39091 zinc binding alcohol Hypothetical protein 1066 5034
    dehydrogenase,
    domain containing 1
    Contig42105_RC MRNA; cDNA 1067 5035
    DKFZp686P24244
    (from clone
    DKFZp686P24244)
    Contig42146_RC chromosome 19 Hypothetical protein 1068 5036
    open reading frame
    12
    Contig42154_RC FLJ11795 hypothetical protein Hypothetical protein 1069 5037
    FLJ11795
    Contig42174 FLJ33215 hypothetical protein Hypothetical protein 1070 5038
    FLJ33215
    Contig42177_RC zinc finger, DHHC Hypothetical protein, 1071 5039
    domain containing Transmembrane, Zinc-finger
    19
    Contig42185_RC TLR8 toll-like receptor 8 Hypothetical protein, Receptor, 1072 5040
    Immune response, Inflammatory
    response, Signal, Transmembrane,
    Repeat, Leucine-rich repeat,
    Glycoprotein
    Contig421_RC KIAA1821 rab11-family Hypothetical protein 1073 5041
    interacting protein 4
    Contig42256_RC Transcribed 1074 5042
    sequences
    Contig42263_RC PSMB5 ATP synthase, H+ Hydrogen ion transport, CF(0), 1075 5043
    transporting, Mitochondrion, Transit peptide,
    mitochondrial F0 Hypothetical protein
    complex, subunit s
    (factor B)
    Contig42270_RC similar to metallo- Hypothetical protein 1076 5044
    beta-lactamase
    superfamily protein
    Contig42330_RC Transcribed 1077 5045
    sequences
    Contig42342_RC CDNA FLJ39417 fis, Hypothetical protein 1078 5046
    clone
    PLACE6016942
    Contig42418_RC Transcribed 1079 5047
    sequence with weak
    similarity to protein
    ref: NP_060265.1
    (H. sapiens)
    hypothetical protein
    FLJ20378 [Homo
    sapiens]
    Contig42437_RC C1orf28 casein kinase 1, Transferase, Serine/threonine- 1080 5048
    epsilon protein kinase, ATP-binding,
    Phosphorylation, Multigene family
    Contig42459_RC FLJ22021 hypothetical protein Repeat, WD repeat 1081 5049
    FLJ22021
    Contig42566_RC FLJ14761 hypothetical protein Hypothetical protein 1082 5050
    FLJ14761
    Contig42591_RC shadow of prion 1083 5051
    protein
    Contig42593_RC Transcribed 1084 5052
    sequences
    Contig42597_RC wd88a09.x1 1085 5053
    NCI_CGAP_Lu24
    Homo sapiens cDNA
    clone
    IMAGE: 2338648 3′,
    mRNA sequence.
    Contig42615_RC AMID apoptosis-inducing Hypothetical protein 1086 5054
    factor (AIF)-
    homologous
    mitochondrion-
    associated inducer
    of death
    Contig42617_RC SNRPG Human S6 H-8 Ubiquitin conjugation, Hydrolase, 1087 5055
    mRNA expressed in Thiol protease, Multigene family,
    chromosome 6- Alternative splicing
    suppressed
    melanoma cells.
    Contig42666_RC chromosome 10 Hypothetical protein 1088 5056
    open reading frame
    47
    Contig42759_RC BCL11B B-cell B-cell, Metal-binding, Zinc, Zinc- 1089 5057
    CLL/lymphoma 11B finger
    (zinc finger protein)
    Contig42787_RC hypothetical protein Hypothetical protein 1090 5058
    MGC5509
    Contig42824_RC FLJ10785 ubiquitin specific Ubl conjugation pathway, Hydrolase, 1091 5059
    protease 40 Thiol protease, Alternative splicing,
    Polymorphism, Multigene family
    Contig42854 CDNA FLJ33578 fis, 1092 5060
    clone
    BRAMY2011639
    Contig42903_RC Transcribed 1093 5061
    sequence with
    strong similarity to
    protein
    ref: NP_002745.1
    (H. sapiens)
    mitogen-activated
    protein kinase 13;
    mitogen-activated
    protein kinase p38
    delta; stress-
    activated protein
    kianse 4 [Homo
    sapiens]
    Contig42959_RC solute carrier family Hypothetical protein 1094 5062
    5 (sodium/glucose
    cotransporter),
    member 10
    Contig42962_RC Transcribed 1095 5063
    sequence with weak
    similarity to protein
    pir: S41161
    (H. sapiens) S41161
    keratin 9,
    cytoskeletal - human
    Contig43022_RC similar to RIKEN 1096 5064
    cDNA 2610524G09
    Contig43026_RC hypothetical protein Hypothetical protein 1097 5065
    DKFZp762C1112
    Contig43096_RC Clone 1098 5066
    IMAGE: 5743799,
    mRNA
    Contig43169_RC DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 1099 5067
    Asp) box polypeptide Hypothetical protein
    51
    Contig43184_RC yg20d12.s1 Soares 1100 5068
    infant brain 1NIB
    Homo sapiens cDNA
    clone IMAGE: 329183′,
    mRNA sequence.
    Contig43189_RC Transcribed 1101 5069
    sequences
    Contig43241_RC ADCY7 adenylate cyclase 7 Lyase, cAMP biosynthesis, 1102 5070
    Transmembrane, Glycoprotein,
    Repeat, Metal-binding, Magnesium
    Contig43253_RC KIAA1858 zinc finger protein Transcription regulation, DNA- 1103 5071
    469 binding, Zinc-finger, Metal-binding,
    Nuclear protein, Repeat
    Contig43262_RC Transcribed 1104 5072
    sequences
    Contig43277_RC Similar to KIAA1726 1105 5073
    protein
    (LOC340554),
    mRNA
    Contig43289_RC hypothetical protein 1106 5074
    LOC170371
    Contig43385_RC DKFZp762O076 hypothetical protein Hypothetical protein 1107 5075
    DKFZp762O076
    Contig43436_RC FLJ32028 hypothetical protein Hypothetical protein 1108 5076
    FLJ32028
    Contig43486_RC DRB1 developmentally Hypothetical protein 1109 5077
    regulated RNA-
    binding protein 1
    Contig43506_RC GLI pathogenesis- 1110 5078
    related 1 (glioma)
    Contig43513_RC TIGD7 Homo sapiens cDNA 1111 5079
    FLJ13533 fis, clone
    PLACE1006371.
    Contig43534 ankyrin repeat Hypothetical protein, ANK repeat, 1112 5080
    domain 10 Repeat
    Contig43540_RC GRIM19 FLJ44968 protein Oxidoreductase, Ubiquinone, NAD, 1113 5081
    Apoptosis, Mitochondrion,
    Transmembrane, Acetylation,
    Hypothetical protein
    Contig43542_RC KIAA1718 protein Hypothetical protein 1114 5082
    Contig43549_RC SNX5 Homo sapiens, clone Hypothetical protein, Transport, 1115 5083
    MGC: 3411 Protein transport
    IMAGE: 3629947,
    mRNA, complete
    cds.
    Contig43586_RC hypothetical protein 1116 5084
    LOC134218
    Contig43645_RC hypothetical protein Hypothetical protein 1117 5085
    LOC129607
    Contig43655_RC NAG14 leucine rich repeat Immunoglobulin domain, 1118 5086
    containing 4 Hypothetical protein, Signal
    Contig43658_RC likely ortholog of 1119 5087
    mouse cancer
    related gene - liver 2
    Contig4365_RC TGOLN2 trans-golgi network Hypothetical protein, Signal, 1120 5088
    protein 2 Transmembrane, Glycoprotein,
    Repeat, Golgi stack, Alternative
    splicing
    Contig43673_RC FLJ20481 calpain small subunit 2 Hypothetical protein 1121 5089
    Contig43679_RC MEF-2 myelin expression Hypothetical protein 1122 5090
    factor 2
    Contig43694_RC TSPAN-2 tetraspan 2 Glycoprotein, Transmembrane 1123 5091
    Contig43703_RC CDH13 CDNA FLJ25967 fis, Cell adhesion, Glycoprotein, 1124 5092
    clone CBR01929 Calcium-binding, Repeat, GPI-
    anchor, Signal
    Contig43724_RC FLJ13213 hypothetical protein Hypothetical protein 1125 5093
    FLJ13213
    Contig43746_RC CDNA FLJ41107 fis, 1126 5094
    clone
    BLADE2007923
    Contig43749_RC MGC14258 Rho GTPase Hypothetical protein 1127 5095
    activating protein 19
    Contig43750_RC cleavage and 1128 5096
    polyadenylation
    specific factor 6,
    68 kDa
    Contig43817_RC RINZF zinc finger and BTB Hypothetical protein, Metal-binding, 1129 5097
    domain containing Zinc, Zinc-finger
    10
    Contig438_RC hypothetical protein EGF-like domain, Hypothetical 1130 5098
    MGC61716 protein
    Contig4399_RC MYH9 myosin, heavy Myosin, ATP-binding, Calmodulin- 1131 5099
    polypeptide 9, non- binding, Actin-binding, Coiled coil,
    muscle Multigene family, Disease mutation,
    Deafness, Hypothetical protein
    Contig440 MGC3165 Homo sapiens, H2A Acetylation, Chromosomal 1132 5100
    histone family, protein, DNA-binding, Multigene
    member L, clone family, Nuclear protein, Nucleosome
    MGC: 3165 core
    IMAGE: 3355200,
    mRNA, complete
    cds.
    Contig44059_RC hypothetical protein Hypothetical protein 1133 5101
    DKFZp564B1162
    Contig44078 TA-WDRP T-cell activation WD Hypothetical protein, Repeat, WD 1134 5102
    repeat protein repeat
    Contig44105 OSBPL11 oxysterol binding Hypothetical protein, Lipid transport, 1135 5103
    protein-like 11 Transport
    Contig44124_RC CDNA FLJ30906 fis, Hypothetical protein 1136 5104
    clone
    FEBRA2006055
    Contig44133_RC FLJ11362 hypothetical protein Hypothetical protein, ANK repeat, 1137 5105
    FLJ11362 Repeat
    Contig44192_RC Cas-Br-M (murine) Hypothetical protein, Ligase, Ubl 1138 5106
    ecotropic retroviral conjugation pathway, Proto-
    transforming oncogene, Zinc-finger, SH2 domain,
    sequence Phosphorylation, Calcium-binding,
    3D-structure
    Contig44226_RC TIGD2 tigger transposable 1139 5107
    element derived 2
    Contig44265_RC ATPase, Hydrolase, Transmembrane, 1140 5108
    aminophospholipid Phosphorylation, Magnesium, ATP-
    transporter (APLT), binding, Alternative splicing,
    Class I, type 8A, Multigene family
    member
    1
    Contig44278_RC DKFZp434K114 WD repeat domain Repeat, WD repeat, Hypothetical 1141 5109
    21 protein, Plasmid
    Contig44343 CDNA FLJ26676 fis, 1142 5110
    clone MPG03726
    Contig44358_RC DKFZp434N035 Hypothetical Hypothetical protein 1143 5111
    LOC284874
    (LOC284874),
    mRNA
    Contig44409 similar to LL5 beta Hypothetical protein 1144 5112
    Contig44414_RC SLC30A1 solute carrier family Zinc transport, Transport, 1145 5113
    30 (zinc transporter), Transmembrane, Multigene family
    member
    1
    Contig44492_RC Transcribed 1146 5114
    sequences
    Contig44518_RC FAM11A family with sequence Antigen, Multigene family, Tumor 1147 5115
    similarity 11, antigen, Hypothetical protein
    member A
    Contig44521_RC LSM8 homolog, U6 Nuclear protein, Ribonucleoprotein, 1148 5116
    small nuclear RNA mRNA splicing, mRNA processing,
    associated (S. cerevisiae) RNA-binding, Acetylation
    Contig44548_RC hypothetical protein 1149 5117
    LOC283508
    Contig44593_RC retinoblastoma Hypothetical protein, Metal-binding, 1150 5118
    binding protein 6 Zinc, Zinc-finger
    Contig44595_RC hypothetical protein Hypothetical protein 1151 5119
    MGC45840
    Contig44596_RC PPIL3 peptidylprolyl Isomerase, Rotamase, Hypothetical 1152 5120
    isomerase protein
    (cyclophilin)-like 3
    Contig44708_RC BCAT1 Homo sapiens Hypothetical protein, Transferase, 1153 5121
    cDNA: FLJ21270 fis, Aminotransferase, Branched-chain
    clone COL01749. amino acid biosynthesis, Pyridoxal
    phosphate
    Contig44713 transducin-like Transcription regulation, Repressor, 1154 5122
    enhancer of split 4 Nuclear protein, Repeat, WD repeat,
    (E(sp1) homolog, Phosphorylation, Wnt signaling
    Drosophila) pathway
    Contig44720_RC FKSG32 hypothetical protein Hypothetical protein 1155 5123
    FKSG32
    Contig44723_RC Human cAMP- 1156 5124
    binding guanine
    nucleotide exchange
    factor IV (cAMP-
    GEFIV) mRNA,
    clone W15, partial
    sequence
    Contig44757_RC VIM Transcribed Hypothetical protein, Coiled coil, 1157 5125
    sequence with Intermediate filament,
    strong similarity to Phosphorylation, 3D-structure
    protein pir: A25074
    (H. sapiens) A25074
    vimentin - human
    Contig44817_RC C20orf147 chromosome 20 Hydrolase 1158 5126
    open reading frame
    147
    Contig44874_RC LOC57805 p30 DBC protein Hypothetical protein 1159 5127
    Contig44877_RC KIAA1877 beta-galactoside Hypothetical protein, Transferase, 1160 5128
    alpha-2,6- Glycosyltransferase
    sialyltransferase II
    Contig44964_RC hypothetical gene 1161 5129
    supported by
    BC017510;
    BC046919
    Contig45004_RC hypothetical protein 1162 5130
    LOC283129
    Contig45080_RC CUL5 cullin 5 Ubl conjugation pathway, Ubl 1163 5131
    conjugation, Receptor
    Contig45085_RC ATP6V0A2 Homo sapiens cDNA Hydrogen ion transport, 1164 5132
    FLJ32238 fis, clone Transmembrane, Glycoprotein,
    PLACE6004993. Hypothetical protein
    Contig45135 CDNA: FLJ22382 1165 5133
    fis, clone HRC07514
    Contig45201_RC C1QTNF2 C1q and tumor Collagen, Signal 1166 5134
    necrosis factor
    related protein 2
    Contig45290_RC Similar to RIKEN 1167 5135
    cDNA 3010021M21
    (LOC388185),
    mRNA
    Contig45304_RC DEPC-1 prostate cancer 1168 5136
    antigen-1
    Contig45305_RC MGC3130 hypothetical protein Hypothetical protein 1169 5137
    MGC3130
    Contig45328_RC Similar to Ab2-183 1170 5138
    (LOC158830),
    mRNA
    Contig45338_RC CSNK2A1 casein kinase 2, Transferase, Serine/threonine- 1171 5139
    alpha 1 polypeptide protein kinase, ATP-binding, Wnt
    signaling pathway, 3D-structure
    Contig45377_RC C10orf2 progressive external Hypothetical protein, Helicase 1172 5140
    ophthalmoplegia 1
    Contig45381_RC hypothetical protein 1173 5141
    LOC283663
    Contig45396_RC FLJ13197 hypothetical protein Hypothetical protein 1174 5142
    FLJ13197
    Contig45397_RC FLJ34299 zinc finger protein 92 Hypothetical protein, Metal-binding, 1175 5143
    (HTF12) Nuclear protein, Zinc, Zinc-finger,
    Transcription regulation, DNA-
    binding, Repeat
    Contig45437 similar to RNA Hypothetical protein 1176 5144
    polymerase B
    transcription factor
    3
    Contig45440_RC Similar to RIKEN 1177 5145
    cDNA 9330196J05
    (LOC340075),
    mRNA
    Contig45455_RC soluble liver 1178 5146
    antigen/liver
    pancreas antigen
    Contig45457_RC CYP4F12 cytochrome P450, Oxidoreductase, Monooxygenase, 1179 5147
    family 4, subfamily Electron transport, Membrane,
    F, polypeptide 12 Heme, Microsome, Endoplasmic
    reticulum, Polymorphism
    Contig45540_RC G protein-coupled Receptor 1180 5148
    receptor 114
    Contig45544_RC protein kinase, Hypothetical protein, Kinase 1181 5149
    interferon-inducible
    double stranded
    RNA dependent
    activator
    Contig45569_RC CDC14B CDC14 cell division Hydrolase 1182 5150
    cycle 14 homolog B
    (S. cerevisiae)
    Contig45624_RC HAKAI Cas-Br-M (murine) Hypothetical protein, Metal-binding, 1183 5151
    ecotropic retroviral Zinc, Zinc-finger
    transforming
    sequence-like 1
    Contig45634_RC Similar to FLJ46354 Hypothetical protein 1184 5152
    protein
    (LOC389694),
    mRNA
    Contig45642_RC mitogen-activated ATP-binding, Kinase, Transferase, 1185 5153
    protein kinase Serine/threonine-protein kinase,
    kinase kinase 2 Hypothetical protein
    Contig45790_RC KIAA0187 ESTs, Moderately 1186 5154
    similar to KIAA0187
    gene product [Homo
    sapiens] [H. sapiens]
    Contig45800_RC MTX1 metaxin 1 Mitochondrion, Outer membrane, 1187 5155
    Transmembrane, Transport, Protein
    transport
    Contig45816_RC MGC4832 chromosome 13 Hypothetical protein 1188 5156
    open reading frame 3
    Contig45821_RC ADCY4 adenylate cyclase 4 Hypothetical protein, Lyase, cAMP 1189 5157
    biosynthesis, Transmembrane,
    Glycoprotein, Repeat, Metal-binding,
    Magnesium
    Contig45847_RC DKFZP761I2123 hypothetical protein Hypothetical protein 1190 5158
    DKFZp761I2123
    Contig45879_RC KIAA1145 KIAA1145 protein Hypothetical protein, 1191 5159
    Transmembrane
    Contig45891_RC CDNA FLJ37509 fis, 1192 5160
    clone
    BRCAN1000065
    Contig45944_RC ZNF335 zinc finger protein Transcription regulation, Zinc-finger, 1193 5161
    335 Metal-binding, Nuclear protein, DNA-
    binding, Repeat
    Contig45945_RC Transcribed 1194 5162
    sequences
    Contig4595 hypothetical Hypothetical protein 1195 5163
    LOC387763
    Contig45975_RC Transcribed 1196 5164
    sequences
    Contig45984 USP7 ubiquitin specific Ubl conjugation pathway, Hydrolase, 1197 5165
    protease 7 (herpes Thiol protease, Multigene family,
    virus-associated) Nuclear protein, 3D-structure
    Contig46052_RC ectonucleoside Hydrolase, Transmembrane, 1198 5166
    triphosphate Antigen, Glycoprotein, Calcium,
    diphosphohydrolase 1 Magnesium, Alternative splicing,
    Lipoprotein, Palmitate
    Contig46178_RC Homo sapiens, clone 1199 5167
    IMAGE: 5276307,
    mRNA.
    Contig461_RC KIAA1836 KIAA1836 protein Hypothetical protein 1200 5168
    Contig46202 MAD MAX dimerization Nuclear protein, DNA-binding, 1201 5169
    protein 1 Transcription regulation, Repressor,
    3D-structure
    Contig46218_RC Similar to 1202 5170
    diaphanous homolog
    3 (Drosophila), clone
    IMAGE: 5277415,
    mRNA
    Contig46244_RC Clone 1203 5171
    IMAGE: 111705
    mRNA sequence
    Contig46262_RC Similar to 1204 5172
    2010300C02Rik
    protein
    (LOC343990),
    mRNA
    Contig46265_RC LOH11CR1J gene, 1205 5173
    loss of
    heterozygosity, 11,
    chromosomal region
    1 gene J product
    Contig46294_RC Transcribed 1206 5174
    sequence with weak
    similarity to protein
    ref: NP_060312.1
    (H. sapiens)
    hypothetical protein
    FLJ20489 [Homo
    sapiens]
    Contig46306_RC CDNA FLJ36097 fis, 1207 5175
    clone
    TESTI2020956
    Contig46343_RC SPP1 suppressor of SH2 domain, Growth regulation, 1208 5176
    cytokine signaling 7 Signal transduction inhibitor
    Contig46375_RC CDNA FLJ26349 fis, 1209 5177
    clone HRT04618
    Contig46376_RC zinc finger and BTB Hypothetical protein, Metal-binding, 1210 5178
    domain containing Zinc, Zinc-finger
    10
    Contig46399_RC Transcribed 1211 5179
    sequences
    Contig46416_RC MGC33212 hypothetical protein 1212 5180
    MGC33212
    Contig46421_RC Transcribed 1213 5181
    sequence with
    moderate similarity
    to protein
    ref: NP_005496.1
    (H. sapiens) CD36
    antigen
    Contig46437_RC synaptotagmin Transport, Protein transport 1214 5182
    binding, cytoplasmic
    RNA interacting
    protein
    Contig46443_RC solute carrier family Hypothetical protein 1215 5183
    26, member 11
    Contig46464_RC Transcribed 1216 5184
    sequences
    Contig46482_RC MRNA; cDNA 1217 5185
    DKFZp434C1435
    (from clone
    DKFZp434C1435)
    Contig46506_RC MRNA; cDNA 1218 5186
    DKFZp686C18110
    (from clone
    DKFZp686C18110)
    Contig46536_RC LGI3 leucine-rich repeat Repeat, Leucine-rich repeat, Signal, 1219 5187
    LGI family, member 3 Hypothetical protein
    Contig46563_RC Transcribed 1220 5188
    sequences
    Contig46567 Transcribed 1221 5189
    sequences
    Contig46586 UBE2D3 ubiquitin-conjugating Hypothetical protein, Ligase, Ubl 1222 5190
    enzyme E2D 3 conjugation pathway, Multigene
    (UBC4/5 homolog, family
    yeast)
    Contig46590 RAD50 CDNA FLJ46914 fis, Hypothetical protein 1223 5191
    clone
    SPLEN2027852
    Contig46591_RC hypothetical protein 1224 5192
    LOC90639
    Contig46601_RC CDNA FLJ42198 fis, 1225 5193
    clone
    THYMU2034338
    Contig46602_RC zinc finger, CCHC Hypothetical protein 1226 5194
    domain containing 6
    Contig46634 Transcribed 1227 5195
    sequences
    Contig46700_RC LSP1 small proline rich Phosphorylation, T-cell 1228 5196
    protein 4
    Contig46709_RC FLJ23045 chromosome 20 Transport, Protein transport, 1229 5197
    open reading frame Hypothetical protein
    23
    Contig46732_RC zinc finger protein Hypothetical protein, Zinc-finger, 1230 5198
    207 Metal-binding, DNA-binding, Nuclear
    protein, Alternative splicing
    Contig46747_RC parvin, gamma Cell adhesion, Cytoskeleton, Actin- 1231 5199
    binding, Repeat, Alternative splicing
    Contig46860_RC FLJ20758 protein Hypothetical protein 1232 5200
    Contig46881_RC Transcribed 1233 5201
    sequences
    Contig46954_RC PNMA3 paraneoplastic Hypothetical protein 1234 5202
    antigen MA3
    Contig46999_RC CDNA FLJ26950 fis, 1235 5203
    clone RCT08544
    Contig47014_RC MGC24180 hypothetical protein Hypothetical protein 1236 5204
    MGC24180
    Contig47015_RC hypothetical protein Hypothetical protein 1237 5205
    FLJ21439
    Contig47025_RC Hypothetical gene 1238 5206
    supported by
    AK094796
    (LOC400764),
    mRNA
    Contig47042 FLJ20069 Abelson helper Hypothetical protein, Repeat, SH3 1239 5207
    integration site domain, WD repeat
    Contig47081_RC LOC392751 1240 5208
    (LOC392751),
    mRNA
    Contig47096_RC PFKFB4 6-phosphofructo-2- Multifunctional enzyme, Transferase, 1241 5209
    kinase/fructose-2,6- Kinase, Hydrolase, ATP-binding,
    biphosphatase 4 Phosphorylation, Multigene family,
    3D-structure
    Contig47184_RC LOC400813 1242 5210
    (LOC400813),
    mRNA
    Contig47203_RC sortilin-related Endocytosis, Receptor, 1243 5211
    receptor, L(DLR Transmembrane, EGF-like domain,
    class) A repeats- Repeat, Glycoprotein, LDL, Lipid
    containing transport, Cholesterol metabolism,
    Signal
    Contig47221_RC VCP valosin-containing ATP-binding, Transport, 1244 5212
    protein Phosphorylation, Repeat, Golgi
    stack, Endoplasmic reticulum,
    Hypothetical protein
    Contig47368_RC LOC92691 hypothetical protein Hypothetical protein 1245 5213
    BC008604
    Contig47441_RC ubiquitin-conjugating Ligase, Ubl conjugation pathway, 1246 5214
    enzyme E2 variant 2 Vitamin D
    Contig47464_RC ZNF335 zinc finger protein Transcription regulation, Zinc-finger, 1247 5215
    335 Metal-binding, Nuclear protein, DNA-
    binding, Repeat
    Contig47495_RC IDI2 GTP binding protein 4 GTP-binding, Nuclear protein 1248 5216
    Contig47498_RC TMPRSS5 transmembrane Hydrolase, Serine protease, 1249 5217
    protease, serine 5 Transmembrane, Signal-anchor,
    (spinesin) Glycoprotein
    Contig47539_RC SGT1, suppressor of Ubl conjugation pathway, Repeat, 1250 5218
    G2 allele of SKP1 TPR repeat
    (S. cerevisiae)
    Contig47582_RC FLJ22757 family with sequence Hypothetical protein 1251 5219
    similarity 31,
    member C
    Contig47732_RC EPS8R3 EPS8-like 3 SH3 domain, Hypothetical protein, 1252 5220
    Receptor
    Contig47770_RC LY6G6C lymphocyte antigen Signal 1253 5221
    6 complex, locus
    G6C
    Contig47793_RC FLJ23311 FLJ23311 protein Hypothetical protein 1254 5222
    Contig47801_RC CDNA FLJ45814 fis, 1255 5223
    clone
    NT2RP7018126
    Contig47810_RC IMMP2L IMP2 inner Coated pits 1256 5224
    mitochondrial
    membrane protease-
    like (S. cerevisiae)
    Contig47814_RC HHGP phosphoribosyl Transferase 1257 5225
    transferase domain
    containing 1
    Contig47835_RC similar to RIKEN Hypothetical protein 1258 5226
    cDNA 2600017H02
    Contig47863_RC FLJ11939 latrophilin 1 Hypothetical protein, Receptor, 1259 5227
    Transmembrane
    Contig47889_RC COPS7B COP9 constitutive Hypothetical protein 1260 5228
    photomorphogenic
    homolog subunit 7B
    (Arabidopsis)
    Contig47900_RC FLJ12604 hypothetical protein Hypothetical protein 1261 5229
    FLJ12604
    Contig47912_RC NR1D2 nuclear receptor Hypothetical protein, Receptor, 1262 5230
    subfamily 1, group Transcription regulation, DNA-
    D, member 2 binding, Nuclear protein, Zinc-finger,
    Repressor
    Contig47922_RC BRAP BRCA1 associated Metal-binding, Zinc, Zinc-finger 1263 5231
    protein
    Contig47926_RC FLJ13057 germ cell-less Hypothetical protein 1264 5232
    homolog 1
    (Drosophila)
    Contig47942_RC LOC91893 hypothetical protein Hypothetical protein 1265 5233
    BC006136
    Contig47975_RC CDNA clone 1266 5234
    IMAGE: 5757380,
    partial cds
    Contig47982_RC hypothetical protein 1267 5235
    LOC112868
    Contig48059 FLJ12788 hypothetical protein Hypothetical protein 1268 5236
    FLJ12788
    Contig48144_RC FLJ11152 chromosome 6 open Hypothetical protein 1269 5237
    reading frame 70
    Contig48156_RC proprotein Cholesterol metabolism, Lipid 1270 5238
    convertase metabolism, Hydrolase, Protease,
    subtilisin/kexin type 9 Serine protease, Calcium, Signal,
    Autocatalytic cleavage, Zymogen,
    Glycoprotein, Alternative splicing,
    Polymorphism, Disease mutation
    Contig48168_RC LOC113246 CDNA FLJ46484 fis, Hypothetical protein 1271 5239
    clone
    THYMU3026350
    Contig48215_RC FLJ35801 hypothetical protein Hypothetical protein 1272 5240
    FLJ35801
    Contig48249_RC FLJ10849 hypothetical protein Hypothetical protein 1273 5241
    FLJ10849
    Contig48270_RC LOC144097 hypothetical protein Hypothetical protein 1274 5242
    BC007540
    Contig48277_RC FLJ36175 hypothetical protein Repeat, WD repeat, Hypothetical 1275 5243
    FLJ36175 protein
    Contig48290_RC MN7 CDNA FLJ43285 fis, Hypothetical protein 1276 5244
    clone
    MESAN2000067
    Contig48355_RC methionine 1277 5245
    aminopeptidase 1D
    Contig48371 malate Oxidoreductase, Tricarboxylic acid 1278 5246
    dehydrogenase 1, cycle, NAD
    NAD (soluble)
    Contig48406_RC chromosome 12 Hypothetical protein 1279 5247
    open reading frame 6
    Contig48466_RC FLJ12649 hypothetical protein Hypothetical protein 1280 5248
    FLJ12649
    Contig48472_RC MAD3 MAX dimerization Hypothetical protein 1281 5249
    protein 3
    Contig48480_RC ring finger protein 24 Zinc-finger 1282 5250
    Contig48489_RC similar to Hypothetical protein 1283 5251
    K06A9.1b.p
    Contig48506_RC KIAA1799 KIAA1799 protein Hypothetical protein 1284 5252
    Contig48529_RC CKLFSF2 chemokine-like Chemotaxis, Cytokine, 1285 5253
    factor super family 2 Transmembrane
    Contig48588_RC KIAA1706 KIAA1706 protein Hypothetical protein 1286 5254
    Contig48697_RC PFKFB2 6-phosphofructo-2- Multifunctional enzyme, Transferase, 1287 5255
    kinase/fructose-2,6- Kinase, Hydrolase, ATP-binding,
    biphosphatase 2 Phosphorylation, Alternative splicing,
    Multigene family
    Contig48722_RC Clone 1288 5256
    IMAGE: 5729395,
    mRNA
    Contig48764_RC CDNA clone Hypothetical protein 1289 5257
    MGC: 71984
    IMAGE: 4280819,
    complete cds
    Contig48806_RC Similar to RIKEN 1290 5258
    cDNA E130012A19
    (LOC390789),
    mRNA
    Contig48830_RC RPL13 ribosomal protein Ribosomal protein 1291 5259
    L13
    Contig48834_RC YR-29 KIAA0888 protein Nuclear protein 1292 5260
    Contig48914_RC hypothetical protein Hypothetical protein 1293 5261
    MGC24133
    Contig48944_RC Transcribed 1294 5262
    sequences
    Contig48951_RC chromosome 9 open Hypothetical protein 1295 5263
    reading frame 85
    Contig48983_RC CDNA FLJ14294 fis, 1296 5264
    clone
    PLACE1008181
    Contig48988_RC LOC51099 abhydrolase domain Hypothetical protein 1297 5265
    containing 5
    Contig49000_RC CDNA FLJ30257 fis, 1298 5266
    clone
    BRACE2002467
    Contig49012_RC hypothetical protein Hypothetical protein 1299 5267
    DKFZp434J0617
    Contig49063_RC A1BG alpha-1-B Hypothetical protein, 1300 5268
    glycoprotein Immunoglobulin domain,
    Glycoprotein, Plasma, Repeat,
    Signal
    Contig49169_RC SUV39H2 suppressor of Hypothetical protein, Transferase, 1301 5269
    variegation 3-9 Methyltransferase, Chromatin
    homolog 2 regulator, Nuclear protein,
    (Drosophila) Alternative splicing
    Contig49185_RC MGC2744 hypothetical protein Hypothetical protein 1302 5270
    MGC2744
    Contig49233_RC NRBF-2 nuclear receptor Receptor, Hypothetical protein 1303 5271
    binding factor 2
    Contig49254_RC RAD53 Homo sapiens, clone Hypothetical protein, ATP-binding, 1304 5272
    MGC: 2637 Kinase, Serine/threonine-protein
    IMAGE: 3505128, kinase, Transferase, Cell cycle,
    mRNA, complete Phosphorylation, Nuclear protein,
    cds. Disease mutation, Li-Fraumeni
    syndrome, 3D-structure
    Contig49255_RC leucine-rich PPR- Hypothetical protein, Repeat 1305 5273
    motif containing
    Contig49279_RC hypothetical protein Hypothetical protein 1306 5274
    FLJ25461
    Contig49306_RC DKFZP586K0717 ligand of numb- Zinc-finger, Repeat, Alternative 1307 5275
    protein X splicing
    Contig49344 FLJ22474 growth hormone Hypothetical protein 1308 5276
    regulated TBC
    protein
    1
    Contig49353_RC MGC41917 zinc finger protein Hypothetical protein, Metal-binding, 1309 5277
    550 Nuclear protein, Zinc, Zinc-finger
    Contig49409 ty82g05.x1 1310 5278
    NCI_CGAP_Kid11
    Homo sapiens cDNA
    clone
    IMAGE: 2285624 3′,
    mRNA sequence.
    Contig49468_RC MRNA; cDNA 1311 5279
    DKFZp667N1113
    (from clone
    DKFZp667N1113)
    Contig49509_RC KIAA1673 cytoplasmic Hypothetical protein 1312 5280
    polyadenylation
    element binding
    protein
    4
    Contig49522_RC hypothetical protein Hypothetical protein 1313 5281
    FLJ13105
    Contig49578_RC FLJ20274 xj92d05.x1 Hypothetical protein 1314 5282
    Soares_NFL_T_GBC_S1
    Homo sapiens
    cDNA clone
    IMAGE: 2664681 3′,
    mRNA sequence.
    Contig49591_RC activating Hypothetical protein 1315 5283
    transcription factor 7
    interacting protein 2
    Contig49631_RC ATP11C ATPase, Class VI, Hydrolase, Transmembrane, 1316 5284
    type 11C Phosphorylation, Magnesium, Metal-
    binding, ATP-binding, Multigene
    family, Alternative splicing
    Contig49667_RC deaminase domain 1317 5285
    containing 1
    Contig49673_RC AD034 RIO kinase 1 (yeast) Kinase, Hypothetical protein 1318 5286
    Contig49725_RC LOC51611 CDNA clone Transferase, Methyltransferase, 1319 5287
    IMAGE: 4821863, Alternative splicing, Hypothetical
    partial cds protein
    Contig49738_RC ATIC aj25f09.s1 Purine biosynthesis, Transferase, 1320 5288
    Soares_testis_NHT Hydrolase, Multifunctional enzyme
    Homo sapiens cDNA
    clone 1391369 3′,
    mRNA sequence.
    Contig49744_RC FLJ14166 hypothetical protein Hypothetical protein 1321 5289
    FLJ14166
    Contig49756_RC Transcribed 1322 5290
    sequences
    Contig49849_RC C6orf1 hypothetical protein Hypothetical protein 1323 5291
    MGC57858
    Contig49855 MGC33338 hypothetical protein Hypothetical protein 1324 5292
    MGC33338
    Contig49875 Full length insert 1325 5293
    cDNA YN61C04
    Contig49948_RC MGC27385 potassium channel Hypothetical protein 1326 5294
    tetramerisation
    domain containing 6
    Contig49966_RC CDNA FLJ31683 fis, 1327 5295
    clone
    NT2RI2005353
    Contig49983_RC MGC3121 hypothetical protein Hypothetical protein 1328 5296
    MGC3121
    Contig49991_RC Transcribed 1329 5297
    sequence with weak
    similarity to protein
    ref: NP_062553.1
    (H. sapiens)
    hypothetical protein
    FLJ11267 [Homo
    sapiens]
    Contig50039_RC KIAA0140 similar to CG9643- Hypothetical protein 1330 5298
    PA
    Contig50106_RC KIAA1708 kinesin family Hypothetical protein 1331 5299
    member 21A
    Contig50117_RC Transcribed 1332 5300
    sequences
    Contig50134_RC BITE p10-binding protein Hypothetical protein 1333 5301
    Contig50137_RC MGC12992 hypothetical protein GTP-binding, Microtubules, Multigene 1334 5302
    MGC12992 family
    Contig50177_RC MBLR ring finger protein Hypothetical protein, Metal-binding, 1335 5303
    134 Zinc, Zinc-finger
    Contig50190_RC LOC51005 MRNA; cDNA Glycoprotein, Ion transport, Ionic 1336 5304
    DKFZp313E2215 channel, Transmembrane
    (from clone
    DKFZp313E2215)
    Contig50194_RC C9orf16 chromosome 9 open Hypothetical protein, Coiled coil 1337 5305
    reading frame 16
    Contig50211_RC MGC35392 hypothetical protein Hypothetical protein 1338 5306
    MGC35392
    Contig50220_RC FLJ13231 hypothetical protein Hypothetical protein 1339 5307
    FLJ13231
    Contig50232_RC DDX31 DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 1340 5308
    Asp) box polypeptide Hypothetical protein
    31
    Contig50249_RC MGC23908 similar to RNA Hypothetical protein 1341 5309
    polymerase B
    transcription factor
    3
    Contig50272_RC Transcribed 1342 5310
    sequences
    Contig50273_RC hypothetical protein Hypothetical protein 1343 5311
    LOC255783
    Contig50275_RC gm117 gm117 1344 5312
    Contig50293_RC EGFR-RS rhomboid family 1 Hypothetical protein, Receptor 1345 5313
    (Drosophila)
    Contig50295_RC FLJ12541 stimulated by Hypothetical protein 1346 5314
    retinoic acid gene 6
    Contig50298_RC FLJ32370 hypothetical protein Hypothetical protein 1347 5315
    FLJ32370
    Contig50324_RC LOC51044 CDNA FLJ25011 fis, 1348 5316
    clone CBL01244
    Contig50337_RC MGC4645 hypothetical protein Hypothetical protein, Repeat, WD 1349 5317
    MGC4645 repeat
    Contig50381_RC CD109 CD109 antigen (Gov Hypothetical protein 1350 5318
    platelet alloantigens)
    Contig50391_RC Transcribed 1351 5319
    sequence with
    moderate similarity
    to protein
    ref: NP_060312.1
    (H. sapiens)
    hypothetical protein
    FLJ20489 [Homo
    sapiens]
    Contig50436_RC CDNA FLJ37094 fis, 1352 5320
    clone
    BRACE2018337
    Contig50465_RC Transcribed 1353 5321
    sequences
    Contig50483 KIAA1718 KIAA1718 protein Hypothetical protein 1354 5322
    Contig50490_RC LOC90678 leucine rich repeat Hypothetical protein 1355 5323
    and sterile alpha
    motif containing 1
    Contig50501_RC coronin, actin Actin-binding, Repeat, WD repeat, 1356 5324
    binding protein, 2A Coiled coil
    Contig50595_RC hypothetical protein Hypothetical protein 1357 5325
    LOC147111
    Contig50605_RC wj49g02.x1 1358 5326
    NCI_CGAP_Lu19
    Homo sapiens cDNA
    clone
    IMAGE: 2406194 3′,
    mRNA sequence.
    Contig50669_RC KIF9 kinesin family Hypothetical protein, Motor protein, 1359 5327
    member 9 Microtubule, ATP-binding, Coiled
    coil, Alternative splicing
    Contig50675 BA108L7.2 similar to rat Hypothetical protein, Transport, Iron 1360 5328
    tricarboxylate transport, Mitochondrion,
    carrier-like protein Transmembrane
    Contig50687_RC MINA53 hypothetical protein Hypothetical protein 1361 5329
    DKFZp667G2110
    Contig506_RC KIAA1821 rab11-family Hypothetical protein 1362 5330
    interacting protein 4
    Contig50728_RC Transcribed 1363 5331
    sequence with weak
    similarity to protein
    ref: NP_071385.1
    (H. sapiens)
    hypothetical protein
    FLJ20958 [Homo
    sapiens]
    Contig50747_RC MGC23427 BTB (POZ) domain 1364 5332
    containing 14A
    Contig50759 DKFZp761P1121 hypothetical protein Hypothetical protein, RNA-binding, 1365 5333
    DKFZp761P1121 Repeat, Alternative splicing
    Contig50787_RC FLJ31528 hypothetical protein Hypothetical protein 1366 5334
    FLJ31528
    Contig50814_RC MGC27027 immune associated Hypothetical protein 1367 5335
    nucleotide
    Contig50831_RC LOC389865 1368 5336
    (LOC389865),
    mRNA
    Contig50838_RC LOC120224 hypothetical protein Hypothetical protein 1369 5337
    BC016153
    Contig50846_RC zinc finger CCCH Hypothetical protein 1370 5338
    type domain
    containing 5
    Contig50848_RC KIAA1705 DDHD domain Lipid degradation, Hydrolase, 1371 5339
    containing 1 Alternative splicing
    Contig50891_RC Homo sapiens, ATP-binding, Kinase, 1372 5340
    p21/Cdc42/Rac1- Serine/threonine-protein kinase,
    activated kinase 1 Transferase, Apoptosis,
    (STE20 homolog, Phosphorylation, 3D-structure
    yeast), clone
    MGC: 51883
    IMAGE: 5763796,
    mRNA, complete
    cds.
    Contig50905_RC CDNA FLJ42250 fis, 1373 5341
    clone
    TKIDN2007828
    Contig50920_RC KIAA1847 Homo sapiens Hypothetical protein, Zinc-finger, 1374 5342
    mRNA for KIAA1847 Alternative splicing
    protein, partial cds.
    Contig51020_RC MGC21874 transcriptional Hypothetical protein 1375 5343
    adaptor 2 (ADA2
    homolog, yeast)-
    beta
    Contig51026_RC DKFZp762A2013 quiescin Q6-like 1 Hypothetical protein, Signal 1376 5344
    Contig51068_RC CDNA clone 1377 5345
    IMAGE: 5286843,
    partial cds
    Contig51070_RC FLJ25005 FLJ25005 protein Hypothetical protein 1378 5346
    Contig51087_RC NPEPL1 aminopeptidase-like 1 Hydrolase, Aminopeptidase, Zinc, 1379 5347
    Manganese, Alternative splicing
    Contig51103_RC JFC1 NADPH oxidase- Hypothetical protein, Repeat, 1380 5348
    related, C2 domain- Alternative splicing
    containing protein
    Contig51105_RC Transcribed 1381 5349
    sequence with weak
    similarity to protein
    ref: NP_062553.1
    (H. sapiens)
    hypothetical protein
    FLJ11267 [Homo
    sapiens]
    Contig51128_RC MGC35182 hypothetical protein Hypothetical protein 1382 5350
    MGC35182
    Contig51151_RC ASP AKAP-associated 1383 5351
    sperm protein
    Contig51163_RC hypothetical protein Hypothetical protein 1384 5352
    MGC45871
    Contig51170_RC bruno-like 4, RNA Hypothetical protein 1385 5353
    binding protein
    (Drosophila)
    Contig51254_RC CLG likely ortholog of Hypothetical protein 1386 5354
    mouse common-site
    lymphoma/leukemia
    GEF
    Contig51288_RC NR2C2 nuclear receptor Receptor, Transcription regulation, 1387 5355
    subfamily 2, group DNA-binding, Nuclear protein, Zinc-
    C, member 2 finger
    Contig51291_RC KIAA1977 KIAA1977 protein Hypothetical protein, ANK repeat, 1388 5356
    Repeat
    Contig51297_RC FLJ33817 hypothetical protein Hypothetical protein, Repeat, WD 1389 5357
    FLJ33817 repeat
    Contig51311_RC KDELC1 KDEL (Lys-Asp-Glu- Hypothetical protein 1390 5358
    Leu) containing 1
    Contig51373_RC KIAA1688 KIAA1688 protein Repeat 1391 5359
    Contig51414_RC FLJ23441 hypothetical protein Hypothetical protein 1392 5360
    FLJ23441
    Contig51417_RC SHANK3 SH3 and multiple SH3-binding, Coiled coil, 1393 5361
    ankyrin repeat Chromosomal translocation
    domains
    3
    Contig51449_RC RAB15, member Hypothetical protein, Plasmid 1394 5362
    RAS onocogene
    family
    Contig51519_RC spastic paraplegia 6 Hypothetical protein 1395 5363
    (autosomal
    dominant)
    Contig51526_RC RAB39B RAB39B, member GTP-binding, Lipoprotein, 1396 5364
    RAS oncogene Prenylation, Transport, Protein
    family transport
    Contig51553_RC MGC3200 hypothetical protein Hypothetical protein 1397 5365
    MGC3200
    Contig51567_RC hypothetical protein Hypothetical protein 1398 5366
    MGC33371
    Contig51621_RC ubiquitin specific Hypothetical protein, Ubl conjugation 1399 5367
    protease 13 pathway, Hydrolase, Thiol protease,
    (isopeptidase T-3) Multigene family, Repeat
    Contig51625_RC Clone Hypothetical protein 1400 5368
    IMAGE: 3868989,
    mRNA, partial cds
    Contig51660_RC IFRG28 28 kD interferon Transmembrane 1401 5369
    responsive protein
    Contig51687_RC KRTDAP KIPV467 1402 5370
    Contig51723_RC Splicing factor, 1403 5371
    arginine/serine-rich,
    46 kD
    Contig51726_RC FLJ20739 Transcribed Hypothetical protein 1404 5372
    sequence with weak
    similarity to protein
    pir: S41161
    (H. sapiens) S41161
    keratin
    9,
    cytoskeletal - human
    Contig51737_RC CDNA FLJ38931 fis, 1405 5373
    clone
    NT2NE2013189
    Contig51740_RC FLJ33282 amyotrophic lateral Hypothetical protein 1406 5374
    sclerosis 2 (juvenile)
    chromosome region,
    candidate 4
    Contig51742_RC RISC likely homolog of rat Hydrolase, Carboxypeptidase, 1407 5375
    and mouse retinoid- Signal, Glycoprotein, Alternative
    inducible serine splicing
    carboxypeptidase
    Contig51757 lin-7 homolog A (C. elegans) 1408 5376
    Contig51795_RC TGFBI CDNA FLJ37830 fis, Extracellular matrix, Signal, Repeat, 1409 5377
    clone Cell adhesion, Disease mutation,
    BRSSN2009395 Amyloid, Vision
    Contig51800 Transcribed 1410 5378
    sequence with
    strong similarity to
    protein pdb: 1BGM
    (E. coli) O Chain O,
    Beta-Galactosidase
    Contig51809_RC C21orf63 chromosome 21 Signal, Transmembrane, Repeat, 1411 5379
    open reading frame Glycoprotein, Lectin, Alternative
    63 splicing
    Contig51821_RC TAF4B TAF4b RNA Transcription regulation, Nuclear 1412 5380
    polymerase II, TATA protein
    box binding protein
    (TBP)-associated
    factor, 105 kDa
    Contig51882_RC MGC11335 hypothetical protein Hypothetical protein 1413 5381
    MGC11335
    Contig51888_RC pannexin 1 Gap junction, Transmembrane, 1414 5382
    Polymorphism
    Contig51896_RC HT021 HT021 1415 5383
    Contig51917_RC WBSCR14 Full length insert Transcription regulation, Repressor, 1416 5384
    cDNA clone Nuclear protein, DNA-binding,
    YI46G04 Williams-Beuren syndrome,
    Alternative splicing
    Contig51929 PAI-1 mRNA-binding Hypothetical protein 1417 5385
    protein
    Contig51964_RC FLJ40629 hypothetical protein Hypothetical protein 1418 5386
    FLJ40629
    Contig51967_RC solute carrier family Transport, Symport, 1419 5387
    16 (monocarboxylic Transmembrane, Multigene family
    acid transporters),
    member 6
    Contig51974_RC Transcribed Hypothetical protein, Phospholipid 1420 5388
    sequences biosynthesis, Transferase,
    Acyltransferase, Transmembrane
    Contig52062_RC FLJ31978 hypothetical protein Hypothetical protein 1421 5389
    FLJ31978
    Contig52099_RC CDNA FLJ41881 fis, 1422 5390
    clone
    OCBBF2021833
    Contig52186_RC zinc finger protein 67 Metal-binding, Zinc, Zinc-finger 1423 5391
    homolog (mouse)
    Contig52199_RC CDNA FLJ12540 fis, 1424 5392
    clone
    NT2RM4000425
    Contig52220_RC CDNA FLJ25573 fis, 1425 5393
    clone JTH06531
    Contig52232_RC DERMO1 twist homolog 2 Differentiation, Developmental 1426 5394
    (Drosophila) protein, Nuclear protein, DNA-
    binding, Repressor, Transcription
    regulation
    Contig52242_RC CDNA FLJ12345 fis, Hypothetical protein 1427 5395
    clone
    MAMMA1002294
    Contig52312_RC TFEB transcription factor Transcription regulation, DNA- 1428 5396
    EB binding, Nuclear protein, Alternative
    splicing
    Contig52317_RC hypothetical protein Hypothetical protein, Ubiquinone 1429 5397
    LOC91942
    Contig52320 Full length insert 1430 5398
    cDNA clone
    YX81F03
    Contig52336_RC MGC2488 homolog of yeast Hypothetical protein 1431 5399
    Mis12
    Contig52358_RC Transcribed 1432 5400
    sequences
    Contig52405_RC EDG3 endothelial G-protein coupled receptor, 1433 5401
    differentiation, Transmembrane, Glycoprotein
    sphingolipid G-
    protein-coupled
    receptor, 3
    Contig52414_RC CAMTA1 calmodulin binding Hypothetical protein, ANK repeat, 1434 5402
    transcription Repeat
    activator 1
    Contig52443 hypothetical protein 1435 5403
    INM01
    Contig52482_RC PNPASE polyribonucleotide Hypothetical protein, Exonuclease, 1436 5404
    nucleotidyltransferase 1 Nucleotidyltransferase, Transferase
    Contig52486_RC PPARAL CDNA FLJ31089 fis, 1437 5405
    clone
    IMR321000092
    Contig52520_RC MRNA full length 1438 5406
    insert cDNA clone
    EUROIMAGE
    2068962
    Contig52544_RC MGC17515 hypothetical protein Hypothetical protein 1439 5407
    MGC17515
    Contig52553_RC LOC197336 similar to RIKEN Hypothetical protein, Repeat, WD 1440 5408
    cDNA 3230401M21 repeat
    [Mus musculus]
    Contig52561_RC Cas-Br-M (murine) Hypothetical protein, Ligase, Ubl 1441 5409
    ecotropic retroviral conjugation pathway, Proto-
    transforming oncogene, Zinc-finger, SH2 domain,
    sequence Phosphorylation, Calcium-binding,
    3D-structure
    Contig52565_RC MAX dimerization Nuclear protein, DNA-binding, 1442 5410
    protein 1 Transcription regulation, Repressor,
    3D-structure
    Contig52570_RC CDNA FLJ41853 fis, 1443 5411
    clone
    NT2RI3004161
    Contig52579_RC breast cancer 1444 5412
    membrane protein
    101
    Contig52609_RC hypothetical protein Hypothetical protein 1445 5413
    FLJ33814
    Contig52623_RC FLJ12888 chromosome 9 open Hypothetical protein 1446 5414
    reading frame 76
    Contig52648_RC MGC2404 acyl-Coenzyme A ANK repeat, Repeat 1447 5415
    binding domain
    containing 6
    Contig52659_RC hypothetical protein Hypothetical protein 1448 5416
    LOC255104
    Contig52715_RC Transcribed 1449 5417
    sequences
    Contig52720_RC MGC2714 hypothetical protein Hypothetical protein 1450 5418
    MGC2714
    Contig52722_RC MGC3020 hypothetical protein Hypothetical protein 1451 5419
    MGC3020
    Contig5274_RC C21orf91 chromosome 21 Polymorphism 1452 5420
    open reading frame
    91
    Contig52777_RC Transcribed 1453 5421
    sequence with
    strong similarity to
    protein
    ref: NP_286085.1 (E. coli)
    beta-D-
    galactosidase
    [Escherichia coli
    O157:H7 EDL933]
    Contig52786_RC ZNF198 zinc finger protein Hypothetical protein, Transcription 1454 5422
    198 regulation, Nuclear protein,
    Chromosomal translocation, Repeat,
    Zinc-finger
    Contig52792_RC MGC3062 phosducin-like 3 1455 5423
    Contig52814_RC Transcribed 1456 5424
    sequences
    Contig52891_RC membrane Hypothetical protein 1457 5425
    associated
    guanylate kinase
    interacting protein-
    like 1
    Contig52914_RC MGC4663 cytochrome P450, Hypothetical protein 1458 5426
    family 2, subfamily
    R, polypeptide 1
    Contig52924_RC FLJ14827 hypothetical protein Hypothetical protein 1459 5427
    FLJ14827
    Contig52932_RC DKFZP566D1346 hypothetical protein Hypothetical protein, ANK repeat, 1460 5428
    DKFZp566D1346 Repeat
    Contig52945_RC KIAA1946 KIAA1946 protein Hypothetical protein 1461 5429
    Contig52971_RC SCAMP5 secretory carrier Hypothetical protein 1462 5430
    membrane protein 5
    Contig52993_RC MAP3K3 mitogen-activated Hypothetical protein, ATP-binding, 1463 5431
    protein kinase Transferase, Serine/threonine-
    kinase kinase 3 protein kinase
    Contig52994_RC Transcribed 1464 5432
    sequence with weak
    similarity to protein
    ref: NP_055301.1
    (H. sapiens)
    neuronal thread
    protein [Homo
    sapiens]
    Contig53047_RC TTYH1 tweety homolog 1 1465 5433
    (Drosophila)
    Contig53066_RC ARL5 ADP-ribosylation GTP-binding, Multigene family 1466 5434
    factor-like 5
    Contig53072_RC KIAA1474 zinc finger protein Hypothetical protein, Metal-binding, 1467 5435
    537 Zinc, Zinc-finger
    Contig53080_RC CDNA FLJ31655 fis, 1468 5436
    clone
    NT2RI2004284
    Contig53149_RC RIN3 Ras and Rab GTPase activation, SH2 domain, 1469 5437
    interactor 3 Alternative splicing, Plasmid
    Contig53177_RC CDNA FLJ90571 fis, 1470 5438
    clone
    OVARC1001725,
    highly similar to
    Homo sapiens
    patched related
    protein TRC8
    (TRC8) gene.
    Contig53211_RC FLJ11588 hypothetical protein Hypothetical protein 1471 5439
    FLJ11588
    Contig53223 PPP1R15B protein phosphatase Hypothetical protein 1472 5440
    1, regulatory
    (inhibitor) subunit
    15B
    Contig53226_RC hypothetical protein Hypothetical protein 1473 5441
    DKFZp762C1112
    Contig53243_RC hypothetical protein Hypothetical protein 1474 5442
    LOC257106
    Contig53253_RC WWP2 Nedd-4-like Ubl conjugation pathway, Ligase, 1475 5443
    ubiquitin-protein Repeat
    ligase
    Contig53260_RC hypothetical protein Hypothetical protein 1476 5444
    LOC196264
    Contig53307_RC LOC51184 Homo sapiens Hypothetical protein 1477 5445
    mRNA full length
    insert cDNA clone
    EUROIMAGE
    1635059.
    Contig53323 KIAA1608 KIAA1608 Hypothetical protein 1478 5446
    Contig53342_RC Transcribed 1479 5447
    sequences
    Contig53349_RC FLJ12287 hypothetical protein Hypothetical protein, Signal, 1480 5448
    FLJ12287 similar to Transmembrane, Immunoglobulin
    semaphorins domain, Multigene family,
    Neurogenesis, Developmental
    protein, Glycoprotein
    Contig53355_RC MGC10870 hypothetical protein 1481 5449
    MGC10870
    Contig53410_RC FLJ14596 chromosome 9 open Hypothetical protein 1482 5450
    reading frame 54
    Contig53439_RC FLJ22457 hypothetical protein Hypothetical protein 1483 5451
    FLJ22457
    Contig53460_RC CDNA FLJ30010 fis, 1484 5452
    clone
    3NB692000154
    Contig5348_RC Transcribed 1485 5453
    sequence with weak
    similarity to protein
    sp: Q13892
    (H. sapiens)
    BT33_HUMAN
    Transcription factor
    BTF3 homolog
    3
    Contig53517_RC PJA1 praja 1 Ubl conjugation pathway, Ligase, 1486 5454
    Zinc-finger, Alternative splicing
    Contig53555_RC myotubularin related Hydrolase, Zinc-finger, Alternative 1487 5455
    protein 3 splicing, Hypothetical protein
    Contig53566_RC LANCL2 LanC lantibiotic Hypothetical protein 1488 5456
    synthetase
    component C-like 2
    (bacterial)
    Contig53585_RC CG005 phosphonoformate Hypothetical protein 1489 5457
    immuno-associated
    protein 5
    Contig53615_RC MGC4692 hypothetical protein 1490 5458
    LOC283871
    Contig53635_RC FLJ39514 sec1 family domain Hypothetical protein 1491 5459
    containing 2
    Contig53641_RC MAGE-E1 melanoma antigen, Hypothetical protein 1492 5460
    family D, 4
    Contig53696_RC MDS006 x 006 protein 1493 5461
    Contig53709_RC adaptor-related Golgi stack, Protein transport, 1494 5462
    protein complex 1, Transport, Coated pits, Endocytosis,
    gamma 1 subunit Polymorphism, 3D-structure,
    Hypothetical protein
    Contig53719_RC FLJ30596 hypothetical protein Hypothetical protein 1495 5463
    FLJ30596
    Contig53746_RC DRLM nucleosome Hypothetical protein 1496 5464
    assembly protein 1-
    like 5
    Contig53819_RC MGC11296 breast cancer 1497 5465
    metastasis-
    suppressor 1-like
    Contig53823_RC FLJ31295 hypothetical protein Metal-binding, Zinc, Zinc-finger, 1498 5466
    FLJ31295 Hypothetical protein
    Contig53829 MGC3123 hypothetical protein Hypothetical protein 1499 5467
    MGC3123
    Contig53852_RC KIAA1577 zinc finger, SWIM Hypothetical protein 1500 5468
    domain containing 6
    Contig53884_RC LOC59346 PDZ and LIM Hypothetical protein, LIM domain, 1501 5469
    domain 2 (mystique) Metal-binding, Zinc
    Contig53909_RC MGC23947 hypothetical protein Hypothetical protein 1502 5470
    MGC23947
    Contig5392_RC Transcribed 1503 5471
    sequences
    Contig53944_RC MI-ER1 putative NFkB Hypothetical protein 1504 5472
    activating protein
    373
    Contig53985_RC FLJ30596 hypothetical protein Hypothetical protein 1505 5473
    FLJ30596
    Contig54010_RC MDS024 chromosome 6 open 1506 5474
    reading frame 75
    Contig54012_RC SAS10 MRNA; cDNA Hypothetical protein 1507 5475
    DKFZp686C2051
    (from clone
    DKFZp686C2051)
    Contig54048_RC GC1 solute carrier family Mitochondrion, Inner membrane, 1508 5476
    25 (mitochondrial Repeat, Transmembrane, Transport,
    carrier: glutamate), Symport
    member 22
    Contig54066_RC DEDD2 death effector DNA-binding, Hypothetical protein 1509 5477
    domain containing 2
    Contig54110_RC splicing factor, mRNA processing, mRNA splicing, 1510 5478
    arginine/serine-rich 1 Nuclear protein, RNA-binding,
    (splicing factor 2, Repeat, Alternative splicing,
    alternate splicing Acetylation, Phosphorylation
    factor)
    Contig54113_RC FLJ11785 Rad50-interacting Hypothetical protein 1511 5479
    protein 1
    Contig54137_RC zinc finger protein 84 Transcription regulation, DNA- 1512 5480
    (HPF2) binding, Zinc-finger, Metal-binding,
    Nuclear protein, Repeat
    Contig54184_RC MGC955 hypothetical protein Hypothetical protein 1513 5481
    MGC955
    Contig54317_RC MGC29956 hypothetical protein Hypothetical protein 1514 5482
    MGC29956
    Contig54321_RC DDX33 DEAH (Asp-Glu-Ala- Hypothetical protein, ATP-binding, 1515 5483
    His) box polypeptide Helicase, Hydrolase
    33
    Contig54342_RC MGC13096 hypothetical protein Cytokine, Disease 1516 5484
    MGC13096 mutation, Gluconeogenesis, Glycolysis,
    Growth factor, Isomerase, Neurone
    Contig54371_RC GKAP42 protein kinase Hypothetical protein, Kinase 1517 5485
    anchoring protein
    GKAP42
    Contig54463_RC CDNA FLJ12874 fis, 1518 5486
    clone
    NT2RP2003769
    Contig54503_RC kelch-like 11 Hypothetical protein 1519 5487
    (Drosophila)
    Contig54531_RC Homo sapiens cDNA 1520 5488
    FLJ38849 fis, clone
    MESAN2008936.
    Contig54559_RC ankyrin repeat and ANK repeat, Repeat 1521 5489
    BTB (POZ) domain
    containing 1
    Contig54563_RC KNSL5 kinesin family Motor protein, Cell division, 1522 5490
    member 23 Microtubule, ATP-binding, Coiled
    coil, Mitosis, Cell cycle, Nuclear
    protein
    Contig54581_RC tumor suppressor 1523 5491
    TSBF1
    Contig54609_RC PANK3 pantothenate kinase 3 Transferase, Kinase, ATP-binding, 1524 5492
    Coenzyme A biosynthesis
    Contig54614_RC FLJ14007 hypothetical protein Hypothetical protein 1525 5493
    FLJ14007
    Contig54659_RC HCCA2 HCCA2 protein Hypothetical protein 1526 5494
    Contig54667_RC ERAP140 nuclear receptor Receptor, Hypothetical protein 1527 5495
    coactivator 7
    Contig54680_RC nucleotide-binding Hypothetical protein 1528 5496
    oligomerization
    domains 27
    Contig54686_RC zinc finger protein Hypothetical protein 1529 5497
    598
    Contig54716_RC KIAA0863 KIAA0863 protein Hypothetical protein, Metal-binding, 1530 5498
    Zinc, Zinc-finger
    Contig54718_RC FLJ37562 hypothetical protein Hypothetical protein 1531 5499
    FLJ37562
    Contig54729_RC chromosome 10 Hypothetical protein 1532 5500
    open reading frame
    30
    Contig54751_RC VIK vav-1 interacting Metal-binding, Zinc, Zinc-finger, 1533 5501
    Kruppel-like protein Hypothetical protein
    Contig54757_RC hypothetical protein Hypothetical protein 1534 5502
    LOC129293
    Contig54802_RC GPR108 G protein-coupled Hypothetical protein 1535 5503
    receptor 108
    Contig54829_RC TJP3 tight junction protein Hypothetical protein 1536 5504
    3 (zona occludens 3)
    Contig54893_RC APOBEC3G apolipoprotein B Hypothetical protein 1537 5505
    mRNA editing
    enzyme, catalytic
    polypeptide-like 3G
    Contig54915_RC DR1 Hypothetical gene Transcription, Phosphorylation, 1538 5506
    supported by Nuclear protein, 3D-structure
    AL832786
    (LOC400762),
    mRNA
    Contig54932_RC BIVM basic, Hypothetical protein 1539 5507
    immunoglobulin-like
    variable motif
    containing
    Contig54961_RC lemur tyrosine Hypothetical protein, ATP-binding, 1540 5508
    kinase 2 Kinase, Transferase, Tyrosine-
    protein kinase
    Contig5498_RC C17orf26 solute carrier family Hypothetical protein 1541 5509
    39 (metal ion
    transporter),
    member 11
    Contig54999_RC FLJ12994 hypothetical protein Hypothetical protein 1542 5510
    FLJ12994
    Contig55004 DKFZP564O0463 mitochondrial folate Mitochondrion, Inner membrane, 1543 5511
    transporter/carrier Repeat, Transmembrane, Transport
    Contig55022_RC ALP asparaginase like 1 Hypothetical protein 1544 5512
    Contig55038_RC MCOLN1 mucolipin 1 Ionic channel, Transmembrane, 1545 5513
    Hypothetical protein
    Contig55044_RC DECR2 2,4-dienoyl CoA Oxidoreductase, Hypothetical protein 1546 5514
    reductase 2,
    peroxisomal
    Contig55069_RC Hypothetical gene 1547 5515
    supported by
    BC040598
    (LOC400960),
    mRNA
    Contig55079_RC FLJ21613 corneal wound Hypothetical protein 1548 5516
    healing-related
    protein
    Contig55114_RC chromosome 6 open Hypothetical protein 1549 5517
    reading frame 89
    Contig55121_RC P5326 hypothetical protein Hypothetical protein 1550 5518
    p5326
    Contig5513_RC Transcribed 1551 5519
    sequences
    Contig55181_RC LOC115509 hypothetical protein Hypothetical protein, Metal-binding, 1552 5520
    BC014000 Zinc, Zinc-finger
    Contig55193_RC HS6ST1 heparan sulfate 6-O- Transferase 1553 5521
    sulfotransferase 1
    Contig55254_RC LOC220074 Hypothetical 55.1 kDa 1554 5522
    protein F09G8.5
    in chromosome III
    Contig55265_RC ets variant gene 6 Transcription regulation, Repressor, 1555 5523
    (TEL oncogene) Nuclear protein, DNA-binding,
    Phosphorylation, Proto-oncogene,
    Chromosomal translocation, 3D-
    structure
    Contig55334_RC DKFZp547C195 hypothetical protein Hypothetical protein 1556 5524
    DKFZp547C195
    Contig55337_RC MGC2454 chromosome 2 open Hypothetical protein, 1557 5525
    reading frame 8 Methyltransferase, Transferase
    Contig55351_RC hypothetical protein Hypothetical protein 1558 5526
    MGC45871
    Contig55365_RC CDNA clone 1559 5527
    IMAGE: 6702802,
    partial cds
    Contig55375_RC C1QTNF6 C1q and tumor Collagen, Signal 1560 5528
    necrosis factor
    related protein 6
    Contig55377_RC DKFZp761H0421 RUN domain Hypothetical protein 1561 5529
    containing 1
    Contig55397_RC CSPG6 sterile alpha motif Hypothetical protein, ANK repeat, 1562 5530
    domain containing 6 Repeat
    Contig55468_RC solute carrier family Hypothetical protein 1563 5531
    9 (sodium/hydrogen
    exchanger), isoform 9
    Contig55487_RC solute carrier family Hypothetical protein 1564 5532
    39 (zinc transporter),
    member 10
    Contig55522 LOC400236 1565 5533
    (LOC400236),
    mRNA
    Contig55539_RC GAAI470 Hypothetical protein 1566 5534
    Contig55574_RC KIAA1940 KIAA1940 protein Hypothetical protein 1567 5535
    Contig55575_RC SDS3 likely ortholog of Hypothetical protein 1568 5536
    mouse Sds3
    Contig55618_RC MGC4825 hypothetical protein Hypothetical protein 1569 5537
    MGC4825
    Contig55671_RC nuclear factor of Transcription regulation, Activator, 1570 5538
    activated T-cells, Nuclear protein, DNA-binding,
    cytoplasmic, Alternative splicing, Phosphorylation,
    calcineurin- Repeat, 3D-structure
    dependent 2
    Contig55674_RC DUSP16 LOC387840 Hydrolase, Nuclear protein, 1571 5539
    (LOC387840), Hypothetical protein
    mRNA
    Contig55709_RC chromosome 14 1572 5540
    open reading frame
    35
    Contig55712_RC hypothetical protein Hypothetical protein 1573 5541
    LOC286257
    Contig55744_RC DIRC2 disrupted in renal Hypothetical protein 1574 5542
    carcinoma 2
    Contig55759_RC hypothetical protein Repeat, ANK repeat, Alternative 1575 5543
    LOC145758 splicing
    Contig55766_RC TOMM70A hypothetical protein Mitochondrion, Outer membrane, 1576 5544
    LOC348801 Transmembrane, Repeat, TPR
    repeat
    Contig55767_RC FLJ22662 hypothetical protein Hypothetical protein 1577 5545
    FLJ22662
    Contig55814_RC protein containing 1578 5546
    single MORN motif
    in testis
    Contig55886_RC zinc finger protein 1579 5547
    181 (HHZ181)
    Contig55940_RC MGC13010 hypothetical protein Hypothetical protein 1580 5548
    MGC13010
    Contig55944_RC FLJ20958 MRNA; cDNA Hypothetical protein 1581 5549
    DKFZp686A1197
    (from clone
    DKFZp686A1197)
    Contig55950_RC FLJ22329 hypothetical protein Hypothetical protein 1582 5550
    FLJ22329
    Contig55966_RC DKFZP762N2316 zinc finger protein Hypothetical protein, Metal-binding, 1583 5551
    462 Zinc, Zinc-finger
    Contig55979_RC MGC14136 chromosome 21 Hypothetical protein 1584 5552
    open reading frame
    119
    Contig55_RC protein kinase, AMP- Fatty acid biosynthesis, 1585 5553
    activated, beta 2 Phosphorylation
    non-catalytic subunit
    Contig56036_RC CD47 CD47 antigen (Rh- Integrin, Cell adhesion, Antigen, 1586 5554
    related antigen, Signal, Transmembrane,
    integrin-associated Glycoprotein, Alternative splicing
    signal transducer)
    Contig56052_RC hypothetical protein 1587 5555
    LOC203547
    Contig56056_RC TRUB1 TruB pseudouridine 1588 5556
    (psi) synthase
    homolog 1 (E. coli)
    Contig56061_RC DEF6 differentially 1589 5557
    expressed in FDCP
    6 homolog (mouse)
    Contig56082_RC RNU2 Homo sapiens Hypothetical protein 1590 5558
    mRNA; cDNA
    DKFZp666D074
    (from clone
    DKFZp666D074).
    Contig56147_RC hypothetical protein Hypothetical protein 1591 5559
    LOC338799
    Contig56167_RC BAALC brain and acute Hypothetical protein 1592 5560
    leukemia,
    cytoplasmic
    Contig56179_RC MGC15523 hypothetical protein Hypothetical protein 1593 5561
    MGC15523
    Contig56229 likely ortholog of Hypothetical protein 1594 5562
    mouse zinc finger
    protein EZI
    Contig56234_RC IMAGE3451454 SVAP1 protein Hypothetical protein 1595 5563
    Contig56242_RC FLJ23221 hypothetical protein Hypothetical protein 1596 5564
    FLJ23221
    Contig56253_RC FLJ21087 brix domain Nuclear protein 1597 5565
    containing 1
    Contig56263_RC FLJ21080 SET and MYND Zinc-finger, Hypothetical protein 1598 5566
    domain containing 3
    Contig56298_RC FLJ13154 hypothetical protein Hypothetical protein 1599 5567
    FLJ13154
    Contig56303_RC LOC51112 v-abl Abelson Transferase, Tyrosine-protein 1600 5568
    murine leukemia kinase, Proto-oncogene, ATP-
    viral oncogene binding, Phosphorylation, SH2
    homolog 2 (arg, domain, SH3 domain, Alternative
    Abelson-related splicing
    gene)
    Contig56334_RC RAI16 retinoic acid induced Hypothetical protein 1601 5569
    16
    Contig56350_RC MGC4607 cerebral cavernous Hypothetical protein 1602 5570
    malformation 2
    Contig56390_RC MGC26847 sushi domain 1603 5571
    containing 3
    Contig56395_RC FLJ14624 hypothetical protein Hypothetical protein 1604 5572
    FLJ14624
    Contig5639_RC phosphorylase, Transferase, Glycosyltransferase, 1605 5573
    glycogen; liver (Hers Carbohydrate metabolism, Glycogen
    disease, glycogen metabolism, Allosteric enzyme,
    storage disease type Pyridoxal phosphate,
    VI) Phosphorylation, Glycogen storage
    disease, Disease mutation,
    Polymorphism, 3D-structure
    Contig56503_RC MGC9753 CAB2 protein Hypothetical protein 1606 5574
    Contig56527_RC FLJ20758 protein Hypothetical protein 1607 5575
    Contig56541_RC LSFR2 dolichyl 1608 5576
    pyrophosphate
    phosphatase
    1
    Contig56544_RC H3F3A hypothetical protein Nuclear protein, Chromosomal 1609 5577
    FLJ20403 protein, DNA-binding, Nucleosome
    core, Multigene family
    Contig56572_RC DKFZP564B1162 hypothetical protein Hypothetical protein 1610 5578
    DKFZp564B1162
    Contig56583_RC PF20 PF20 Repeat, WD repeat, Hypothetical 1611 5579
    protein
    Contig56587_RC HDAC10 histone deacetylase Hydrolase, Nuclear protein, 1612 5580
    10 Chromatin regulator, Transcription
    regulation, Repressor,
    Polymorphism, Alternative splicing
    Contig565_RC CDNA FLJ31683 fis, 1613 5581
    clone
    NT2RI2005353
    Contig56623_RC Cas-Br-M (murine) Hypothetical protein, Ligase, Ubl 1614 5582
    ecotropic retroviral conjugation pathway, Proto-
    transforming oncogene, Zinc-finger, SH2 domain,
    sequence Phosphorylation, Calcium-binding,
    3D-structure
    Contig56662_RC MGC10963 THAP domain Zinc-finger, DNA-binding 1615 5583
    containing 7
    Contig56671_RC FLJ12761 mSin3A-associated Hypothetical protein 1616 5584
    protein 130
    Contig56716_RC KIAA1754 KIAA1754 Hypothetical protein 1617 5585
    Contig56735_RC CDNA FLJ90790 fis, Hypothetical protein 1618 5586
    clone
    THYRO1001529,
    weakly similar to
    SERINE
    PALMITOYLTRANSFERASE
    2 (EC
    2.3.1.50).
    Contig56781_RC MGC11349 hypothetical protein Hypothetical protein, Metal-binding, 1619 5587
    MGC11349 Zinc, Zinc-finger
    Contig56823_RC Transcribed 1620 5588
    sequence with
    moderate similarity
    to protein
    ref: NP_060265.1
    (H. sapiens)
    hypothetical protein
    FLJ20378 [Homo
    sapiens]
    Contig56944_RC ASH1 ash1 (absent, small, Hypothetical protein 1621 5589
    or homeotic)-like
    (Drosophila)
    Contig57011_RC CDA11 CDA11 protein Hypothetical protein 1622 5590
    Contig57017_RC TFB2M transcription factor Hypothetical protein 1623 5591
    B2, mitochondrial
    Contig57036_RC hypothetical protein Fatty acid biosynthesis, Biotin, 1624 5592
    LOC283445 Ligase, Multifunctional enzyme,
    ATP-binding, Phosphorylation,
    Alternative splicing
    Contig57057_RC MAP3K3 hypothetical protein Hypothetical protein, LIM domain, 1625 5593
    MGC10986 Metal-binding, Zinc
    Contig57076_RC FBXO32 F-box only protein Ubl conjugation pathway 1626 5594
    32
    Contig57081_RC MSI2 musashi homolog 2 Hypothetical protein 1627 5595
    (Drosophila)
    Contig57090_RC Full length insert 1628 5596
    cDNA clone
    YZ93G08
    Contig5716_RC CDNA FLJ38396 fis, 1629 5597
    clone
    FEBRA2007957
    Contig57173_RC KIAA1737 KIAA1737 Hypothetical protein 1630 5598
    Contig571_RC ST6GALNAC6 CMP-NeuAC:(beta)- Glycosyltransferase, Transferase, 1631 5599
    N- Hypothetical protein
    acetylgalactosaminide
    (alpha)2,6-
    sialyltransferase
    member VI
    Contig57226_RC tubulin, beta, 2 GTP-binding, Hypothetical protein, 1632 5600
    Microtubule, Multigene family
    Contig57239_RC EPI64 KIAA0114 gene Hypothetical protein 1633 5601
    product
    Contig57270_RC ABCC4 ATP-binding ATP-binding, Glycoprotein, 1634 5602
    cassette, sub-family Transmembrane, Transport, Repeat
    C (CFTR/MRP),
    member 4
    Contig57290_RC hypothetical protein 1635 5603
    LOC286334
    Contig57417 LOC80298 transcription Hypothetical protein 1636 5604
    termination factor-
    like protein
    Contig57436_RC PPP2R5E protein phosphatase Phosphorylation, Multigene family 1637 5605
    2, regulatory subunit
    B (B56), epsilon
    isoform
    Contig57458_RC IL6R interleukin 6 receptor Receptor, Transmembrane, 1638 5606
    Glycoprotein, Immunoglobulin
    domain, Repeat, Alternative splicing,
    Signal, 3D-structure
    Contig57493_RC MGC4399 mitochondrial carrier 1639 5607
    protein
    Contig57562_RC M11S1 membrane GPI-anchor 1640 5608
    component,
    chromosome 11,
    surface marker 1
    Contig57579 ABTB1 ankyrin repeat and ANK repeat, Repeat 1641 5609
    BTB (POZ) domain
    containing 1
    Contig57625_RC FLJ14225 polycystic kidney Hypothetical protein 1642 5610
    disease 1-like
    Contig57822_RC CDNA clone 1643 5611
    IMAGE: 5286019,
    partial cds
    Contig57825_RC MGC18216 hypothetical protein Hypothetical protein 1644 5612
    MGC18216
    Contig57840_RC MBP CDNA clone Hypothetical protein, Myelin, 1645 5613
    MGC: 70813 Structural protein, Acetylation,
    IMAGE: 6060520, Methylation, Phosphorylation,
    complete cds Citrullination, Autoimmune
    encephalomyelitis, 3D-structure,
    Alternative splicing
    Contig57957_RC COL5A2 similar to RIKEN Hypothetical protein 1646 5614
    cDNA 5730578N08
    gene
    Contig58042_RC CDNA FLJ39602 fis, 1647 5615
    clone
    SKNSH2005061
    Contig58113_RC FLJ14005 hypothetical protein Hypothetical protein 1648 5616
    LOC286044
    Contig58123_RC NFYB nuclear transcription Transcription regulation, DNA- 1649 5617
    factor Y, beta binding, Activator, Nuclear protein,
    3D-structure
    Contig58145_RC YEA solute carrier family Hypothetical protein 1650 5618
    35, member B4
    Contig58156_RC C20orf167 deoxynucleotidyltransferase, Nuclear protein, Polymorphism 1651 5619
    terminal,
    interacting protein 1
    Contig58193_RC TCF7L2 transcription factor Transcription regulation, Activator, 1652 5620
    7-like 2 (T-cell Repressor, Trans-acting factor,
    specific, HMG-box) Nuclear protein, DNA-binding, Wnt
    signaling pathway, Alternative
    splicing, 3D-structure, Hypothetical
    protein
    Contig58212_RC PPARBP PPAR binding DNA-binding, Transcription 1653 5621
    protein regulation, Activator, Repeat,
    Nuclear protein, Alternative splicing
    Contig58249_RC moblak MOB1, Mps One Hypothetical protein 1654 5622
    Binder kinase
    activator-like 2A
    (yeast)
    Contig58260_RC DGAT2 diacylglycerol O- Hypothetical protein, 1655 5623
    acyltransferase Acyltransferase, Transferase
    homolog 2 (mouse)
    Contig58275_RC general transcription 1656 5624
    factor IIIC,
    polypeptide 4,
    90 kDa
    Contig58288_RC LOC89941 ras homolog gene Hypothetical protein, GTP-binding 1657 5625
    family, member T2
    Contig58339_RC FLJ21616 MRNA; cDNA Hypothetical protein 1658 5626
    DKFZp686E1648
    (from clone
    DKFZp686E1648)
    Contig58353_RC FLJ13089 hypothetical protein Hypothetical protein 1659 5627
    FLJ13089
    Contig58491_RC TRIP11 ah24a06.s1 Hypothetical protein, Antigen, Golgi 1660 5628
    Soares_parathyroid_tumor_NbHPA stack, Coiled coil, Chromosomal
    Homo sapiens cDNA translocation
    clone 1239730 3′,
    mRNA sequence.
    Contig58530_RC KIAA1560 glycerol 3-phosphate Hypothetical protein, Phospholipid 1661 5629
    acyltransferase, biosynthesis, Transferase,
    mitochondrial Acyltransferase, Transmembrane,
    Mitochondrion, Transit peptide
    Contig58595_RC AP1M1 adaptor-related Golgi stack, Protein transport, 1662 5630
    protein complex 1, Transport, Coated pits, Endocytosis,
    mu 1 subunit Phosphorylation
    Contig58613 VPS4B vacuolar protein ATP-binding 1663 5631
    sorting 4B (yeast)
    Contig58966_RC HLA-F major MHC 1664 5632
    histocompatibility
    complex, class I, F
    Contig59120_RC FLJ37080 adhesion molecule Hypothetical protein 1665 5633
    AMICA
    Contig59127_RC PCF11 pre-mRNA cleavage mRNA processing, Nuclear protein 1666 5634
    complex II protein
    Pcf11
    Contig59134_RC hypothetical protein 1667 5635
    LOC283481
    Contig59136_RC qp75d05.x1 1668 5636
    Soares_fetal_lung_NbHL19W
    Homo
    sapiens cDNA clone
    IMAGE: 1928841 3′
    similar to gb: D14531
    60S RIBOSOMAL
    PROTEIN L9
    (HUMAN); mRNA
    sequence.
    Contig59187_RC NUDT3 nudix (nucleoside Hydrolase 1669 5637
    diphosphate linked
    moiety X)-type motif 3
    Contig5954_RC similar to RIKEN Hypothetical protein, Iron, Iron-sulfur 1670 5638
    cDNA B230118G17
    gene
    Contig60075 FLJ32468 ESTs 1671 5639
    Contig60315_RC MGC39807 organic solute Hypothetical protein 1672 5640
    transporter alpha
    Contig6041_RC Transcribed 1673 5641
    sequences
    Contig60509_RC GL004 protein Hypothetical protein 1674 5642
    Contig60612_RC xylosyltransferase I Transferase, Glycosyltransferase 1675 5643
    Contig6064_RC Colorectal cancer- 1676 5644
    related mRNA
    sequence
    Contig60981_RC p10-binding protein Hypothetical protein 1677 5645
    Contig61061_RC RASGRP4 RAS guanyl Hypothetical protein 1678 5646
    releasing protein 4
    Contig6113_RC CDNA FLJ30090 fis, 1679 5647
    clone
    BNGH41000015
    Contig61227_RC hypothetical protein Hypothetical protein, Repeat, WD 1680 5648
    FLJ10055 repeat
    Contig61254_RC MGC5352 hypothetical protein Hypothetical protein 1681 5649
    MGC5352
    Contig61264_RC KIAA1833 hypothetical protein Hypothetical protein 1682 5650
    KIAA1833
    Contig61267_RC C20orf126 chromosome 20 Hypothetical protein 1683 5651
    open reading frame
    126
    Contig61815 LOC51063 hypothetical protein Hypothetical protein 1684 5652
    LOC51063
    Contig61848_RC Transcribed 1685 5653
    sequence with weak
    similarity to protein
    ref: NP_060312.1
    (H. sapiens)
    hypothetical protein
    FLJ20489 [Homo
    sapiens]
    Contig61915_RC MGC2803 hypothetical protein Hypothetical protein 1686 5654
    MGC2803
    Contig61975 MGC11242 hypothetical protein Hypothetical protein 1687 5655
    MGC11242
    Contig62149_RC chromosome 22 Hypothetical protein 1688 5656
    open reading frame
    23
    Contig6254_RC Transcribed 1689 5657
    sequences
    Contig62568_RC MRPL24 mitochondrial Ribosomal protein, Hypothetical 1690 5658
    ribosomal protein protein
    L24
    Contig62588_RC hypothetical protein DNA-binding, Metal-binding, Nuclear 1691 5659
    LOC284323 protein, Zinc-finger
    Contig62628_RC EIF3S9 eukaryotic Hypothetical protein, Initiation factor, 1692 5660
    translation initiation Protein biosynthesis, RNA-binding
    factor
    3, subunit 9
    eta, 116 kDa
    Contig62675_RC similar to RIKEN Hypothetical protein 1693 5661
    1810056O20
    Contig62923_RC FLJ12697 ubiquitin specific Ubl conjugation pathway, Hydrolase, 1694 5662
    protease 42 Thiol protease, Multigene family
    Contig63026 hypothetical protein 1695 5663
    LOC285958
    Contig63079 FLJ32332 likely ortholog of Hypothetical protein 1696 5664
    mouse protein
    phosphatase 2C eta
    Contig6323_RC FLJ12581 Nanog homeobox DNA-binding, Homeobox, Nuclear 1697 5665
    protein, Hypothetical protein
    Contig63304 LOC113444 hypothetical protein Hypothetical protein 1698 5666
    BC011880
    Contig63667_RC MCPR hypothetical protein Ubl conjugation pathway, Cell cycle, 1699 5667
    LOC285069 Cell division, Mitosis, Repeat
    Contig6382_RC Transcribed 1700 5668
    sequences
    Contig63913_RC MGC13016 coiled-coil-helix- 1701 5669
    coiled-coil-helix
    domain containing 6
    Contig64214_RC MGC19604 similar to RIKEN Hypothetical protein 1702 5670
    cDNA B230118G17
    gene
    Contig64297_RC KIAA1416 KIAA1416 protein Hypothetical protein, Transcription 1703 5671
    regulation, Hydrolase, Helicase,
    Chromatin regulator, Nuclear
    protein, ATP-binding, DNA-binding,
    Repeat
    Contig64390 C20orf92 COMM domain Hypothetical protein 1704 5672
    containing 7
    Contig64477 Clone 1705 5673
    IMAGE: 5742072,
    mRNA
    Contig64502 KIAA0303 KIAA0303 protein Hypothetical protein, ATP-binding, 1706 5674
    Kinase, Serine/threonine-protein
    kinase, Transferase
    Contig64691 UBB ubiquitin B Hypothetical protein 1707 5675
    Contig64794 FLJ21156 Homo sapiens Hypothetical protein 1708 5676
    cDNA: FLJ21156 fis,
    clone CAS09878.
    Contig64940_RC ORAOV1 oral cancer Hypothetical protein 1709 5677
    overexpressed 1
    Contig65300_RC CDNA FLJ41454 fis, 1710 5678
    clone
    BRSTN2011597
    Contig65404 CKLFSF3 chemokine-like Chemotaxis, Cytokine, 1711 5679
    factor super family 3 Transmembrane, Alternative splicing
    Contig65439 C20orf178 chromosome 20 Hypothetical protein 1712 5680
    open reading frame
    178
    Contig65459_RC formin binding Hypothetical protein, SH3 domain 1713 5681
    protein 1
    Contig65478_RC phosphoglucomutase Hypothetical protein 1714 5682
    2-like 1
    Contig65900 HMGN3 high mobility group Nuclear protein, DNA-binding, 1715 5683
    nucleosomal binding Hypothetical protein
    domain
    3
    Contig65934_RC hypothetical gene Hypothetical protein 1716 5684
    supported by
    BC031661
    Contig66003_RC MY038 retinoblastoma Hypothetical protein, Metal-binding, 1717 5685
    binding protein 6 Zinc, Zinc-finger
    Contig66028_RC reversion-inducing- Signal, Glycoprotein, GPI-anchor, 1718 5686
    cysteine-rich protein Serine protease inhibitor,
    with kazal motifs Membrane, Anti-oncogene, Repeat,
    Lipoprotein
    Contig66129_RC CDNA FLJ13276 fis, 1719 5687
    clone
    OVARC1001040
    Contig66573_RC FLJ12567 Clone Hypothetical protein 1720 5688
    IMAGE: 5538723,
    mRNA
    Contig66615_RC USP9Y Human S6 H-8 Ubiquitin conjugation, Hydrolase, 1721 5689
    mRNA expressed in Thiol protease, Multigene family,
    chromosome 6- Alternative splicing
    suppressed
    melanoma cells.
    Contig66632_RC hypothetical protein 1722 5690
    LOC339324
    Contig66759_RC MGC16028 MGC16028 similar 1723 5691
    to RIKEN cDNA
    1700019E19 gene
    Contig667_RC ADAM17 hypothetical protein Hydrolase, Metalloprotease, Zinc, 1724 5692
    LOC285148 Signal, Glycoprotein, Zymogen,
    Transmembrane, SH3-binding,
    Phosphorylation, Alternative splicing,
    3D-structure
    Contig66868_RC ze63e05.s1 Soares 1725 5693
    retina N2b4HR
    Homo sapiens cDNA
    clone
    IMAGE: 363680 3′,
    mRNA sequence.
    Contig66904_RC MGC4368 hypothetical protein Hypothetical protein 1726 5694
    MGC4368
    Contig684_RC RPS3A ring finger protein 12 Transcription regulation, Zinc-finger, 1727 5695
    Hypothetical protein, Metal-binding
    Contig693_RC NFIA nuclear factor I/A Activator, DNA replication, DNA- 1728 5696
    binding, Nuclear protein,
    Transcription, Transcription
    regulation, Multigene family
    Contig706_RC CDNA FLJ32401 fis, 1729 5697
    clone
    SKMUS2000339
    Contig726_RC FLJ13725 hypothetical protein Hypothetical protein 1730 5698
    FLJ13725
    Contig732_RC FTH1 transducer of Hypothetical protein 1731 5699
    regulated cAMP
    response element-
    binding protein
    (CREB) 2
    Contig7401_RC FLJ22756 PDZ domain Hypothetical protein 1732 5700
    containing 2
    Contig75_RC RPS6KA2 ribosomal protein S6 ATP-binding, Kinase, 1733 5701
    kinase, 90 kDa, Serine/threonine-protein kinase,
    polypeptide 2 Transferase, Repeat, Multigene
    family, Phosphorylation, Nuclear
    protein
    Contig773 FLJ20989 hypothetical protein Hypothetical protein 1734 5702
    FLJ20989
    Contig8210_RC DJ467N11.1 dJ467N11.1 protein ATP-binding, Helicase, Hydrolase, 1735 5703
    Hypothetical protein
    Contig830_RC C1orf13 N-acetylneuraminate 1736 5704
    pyruvate lyase
    (dihydrodipicolinate
    synthase)
    Contig8371_RC Transcribed 1737 5705
    sequences
    Contig842_RC human T-cell Transcription regulation, DNA- 1738 5706
    leukemia virus binding, Nuclear protein
    enhancer factor
    Contig844_RC DKFZP566M1046 hypothetical protein Hypothetical protein 1739 5707
    DKFZp566M1046
    Contig8547_RC Transcribed 1740 5708
    sequences
    Contig883_RC KIAA1813 KIAA1813 protein Hypothetical protein 1741 5709
    Contig8885_RC HCS cytochrome c, Mitochondrion, Electron transport, 1742 5710
    somatic Respiratory chain, Heme,
    Acetylation, Polymorphism,
    Apoptosis
    Contig8909_RC MGC45404 TAK1-binding Hypothetical protein 1743 5711
    protein 3
    Contig8956_RC FLJ13158 chromosome 6 open Hypothetical protein 1744 5712
    reading frame 134
    Contig8963_RC wi72b03.x1 1745 5713
    NCI_CGAP_Kid12
    Homo sapiens cDNA
    clone
    IMAGE: 2398829 3′,
    mRNA sequence.
    Contig8980_RC DKFZP564B1162 hypothetical protein Hypothetical protein 1746 5714
    DKFZp564B1162
    Contig9042_RC Transcribed 1747 5715
    sequences
    Contig9059_RC FLJ12118 hypothetical protein Hypothetical protein 1748 5716
    FLJ12118
    Contig9136_RC CDNA FLJ43053 fis, 1749 5717
    clone
    BRTHA3006856
    Contig9380_RC Transcribed 1750 5718
    sequences
    Contig9514_RC Transcribed 1751 5719
    sequences
    Contig9518_RC ZNF287 zinc finger protein Metal-binding, Zinc, Zinc-finger, 1752 5720
    287 Transcription regulation, Nuclear
    protein, DNA-binding, Repeat
    Contig964_RC MGC10433 hypothetical protein Hypothetical protein 1753 5721
    MGC10433
    Contig9714_RC MRNA for Hypothetical protein 1754 5722
    hypothetical protein
    (ORF1), clone 00275
    Contig973_RC MRPL45 mitochondrial Ribosomal protein, Mitochondrion, 1755 5723
    ribosomal protein Transit peptide
    L45
    Contig9810_RC KCNE1 potassium voltage- Transport, Ion transport, Ionic 1756 5724
    gated channel, lsk- channel, Voltage-gated channel,
    related family, Potassium channel, Potassium,
    member 1 Potassium transport,
    Transmembrane, Phosphorylation,
    Glycoprotein, Polymorphism,
    Disease mutation, Long QT
    syndrome, Deafness
    Contig9965_RC DHODH dihydroorotate Pyrimidine biosynthesis, 1757 5725
    dehydrogenase Oxidoreductase, Flavoprotein, FAD,
    Transit peptide, Mitochondrion, 3D-
    structure
    D10040 FACL2 acyl-CoA synthetase Ligase, Fatty acid metabolism, 1758 5726
    long-chain family Magnesium, Multigene family,
    member 1 Hypothetical protein
    D13642 SF3B3 splicing factor 3b, Spliceosome, mRNA processing, 1759 5727
    subunit 3, 130 kDa mRNA splicing, Nuclear protein,
    Hypothetical protein
    D16816 REG1B regenerating islet- Glycoprotein, Signal, Lectin, 1760 5728
    derived 1 beta Pyrrolidone carboxylic acid
    (pancreatic stone
    protein, pancreatic
    thread protein)
    D21064 INPP5E peptidase Hypothetical protein, Hydrolase, 1761 5729
    (mitochondrial Metalloprotease, Mitochondrion,
    processing) alpha Transit peptide
    D25218 RRS1 RRS1 ribosome Ribosome biogenesis, Nuclear 1762 5730
    biogenesis regulator protein
    homolog (S. cerevisiae)
    D25328 PFKP phosphofructokinase, Kinase, Transferase, Glycolysis, 1763 5731
    platelet Repeat, Allosteric enzyme,
    Phosphorylation, Magnesium,
    Multigene family
    D26070 ITPR1 inositol 1,4,5- Receptor, Transmembrane, 1764 5732
    triphosphate Phosphorylation, Endoplasmic
    receptor, type 1 reticulum, Ionic channel, Ion
    transport, Calcium channel,
    Alternative splicing, Repeat
    D26362 BRD3 bromodomain Bromodomain, Repeat, Nuclear 1765 5733
    containing 3 protein
    D26488 KIAA0007 KIAA0007 protein Hypothetical protein, Repeat, WD 1766 5734
    repeat
    D29954 KIAA0056 KIAA0056 protein Hypothetical protein 1767 5735
    D29958 KIAA0116 KIAA0116 protein Exosome, Hydrolase, Nuclease, 1768 5736
    Exonuclease, rRNA processing,
    Nuclear protein, RNA-binding,
    Polymorphism, Hypothetical protein
    D31886 RAB3GAP RAB3 GTPase- Hypothetical protein 1769 5737
    ACTIVATING
    PROTEIN
    D31887 KIAA0062 solute carrier family Hypothetical protein 1770 5738
    39 (zinc transporter),
    member 14
    D38435 PMS2L1 postmeiotic Hypothetical protein, DNA repair, 1771 5739
    segregation Anti-oncogene, Nuclear protein,
    increased 2-like 6 Polymorphism, Disease mutation,
    Hereditary nonpolyposis colorectal
    cancer, 3D-structure
    D38522 SYT11 Homo sapiens Transmembrane, Repeat, Synapse, 1772 5740
    KIAA0080 mRNA, Hypothetical protein
    partial cds.
    D38549 CYFIP1 cytoplasmic FMR1 Hypothetical protein 1773 5741
    interacting protein 1
    D42043 KIAA0084 raft-linking protein Hypothetical protein 1774 5742
    D42084 METAP1 methionyl Hydrolase, Aminopeptidase, Cobalt 1775 5743
    aminopeptidase 1
    D43948 KIAA0097 KIAA0097 gene Hypothetical protein, Repeat 1776 5744
    product
    D43949 KIAA0082 KIAA0082 Hypothetical protein 1777 5745
    D50402 SLC11A1 solute carrier family Transport, Iron transport, 1778 5746
    11 (proton-coupled Transmembrane, Glycoprotein,
    divalent metal ion Macrophage, Polymorphism
    transporters),
    member 1
    D50911 GSA7 KIAA0121 gene Hypothetical protein 1779 5747
    product
    D50918 6-Sep septin 6 Cell division, GTP-binding, Coiled 1780 5748
    coil, Alternative splicing
    D63487 KIAA0153 KIAA0153 protein Hypothetical protein 1781 5749
    D79998 KCTD2 potassium channel Hypothetical protein 1782 5750
    tetramerisation
    domain containing 2
    D80007 PDCD11 programmed cell Nuclear protein, rRNA processing, 1783 5751
    death 11 Repeat, Polymorphism
    D80010 LPIN1 lipin 1 Nuclear protein, Polymorphism 1784 5752
    D83781 NUP160 nucleoporin 160 kDa Nuclear protein, Transport, 1785 5753
    Alternative splicing, Hypothetical
    protein
    D84294 TTC3 tetratricopeptide Repeat, TPR repeat, Zinc-finger, 1786 5754
    repeat domain 3 Alternative splicing, Polymorphism,
    Metal-binding
    D86964 DOCK2 dedicator of Guanine-nucleotide releasing factor, 1787 5755
    cytokinesis 2 Membrane, Cytoskeleton, SH3
    domain, Alternative splicing,
    Polymorphism
    D86973 GCN1L1 GCN1 general Hypothetical protein 1788 5756
    control of amino-acid
    synthesis 1-like 1
    (yeast)
    D86976 HA-1 minor 1789 5757
    histocompatibility
    antigen HA-1
    D87442 NCSTN nicastrin Transmembrane, Glycoprotein, 1790 5758
    Signal, Alternative splicing
    D87449 SLC35D1 solute carrier family Transport, Sugar transport, 1791 5759
    35 (UDP-glucuronic Transmembrane, Endoplasmic
    acid/UDP-N- reticulum
    acetylgalactosamine
    dual transporter),
    member D1
    D87453 MRPS27 mitochondrial Hypothetical protein, Ribosomal 1792 5760
    ribosomal protein protein, Mitochondrion
    S27
    D87466 KIAA0276 KIAA0276 protein Hypothetical protein 1793 5761
    G26403 C9orf19 chromosome 9 open Hypothetical protein 1794 5762
    reading frame 19
    J03077 PSAP prosaposin (variant Signal, Glycoprotein, Lysosome, 1795 5763
    Gaucher disease Sphingolipid metabolism, Repeat,
    and variant Gaucher disease, GM2-
    metachromatic gangliosidosis, Disease mutation,
    leukodystrophy) Metachromatic leukodystrophy,
    Alternative splicing, 3D-structure
    J03796 EPB41 erythrocyte Structural protein, Alternative 1796 5764
    membrane protein splicing, Cytoskeleton, Actin-binding,
    band 4.1 Phosphorylation, Pyropoikilocytosis,
    (elliptocytosis 1, RH- Glycoprotein, Elliptocytosis,
    linked) Hereditary hemolytic anemia,
    Polymorphism, 3D-structure
    J04162 FCGR3A Fc fragment of IgG, Receptor, IgG-binding protein, 1797 5765
    low affinity IIIa, Transmembrane, Glycoprotein,
    receptor for (CD16) Signal, Immunoglobulin domain,
    Repeat, Multigene family,
    Polymorphism, GPI-anchor, 3D-
    structure, Lipoprotein
    J04178 HEXA hexosaminidase A Hydrolase, Glycosidase, Lysosome, 1798 5766
    (alpha polypeptide) GM2-gangliosidosis, Signal,
    Zymogen, Glycoprotein, Disease
    mutation, Polymorphism, 3D-
    structure
    K02276 MYC v-myc Proto-oncogene, Nuclear protein, 1799 5767
    myelocytomatosis DNA-binding, Phosphorylation,
    viral oncogene Transcription regulation, Activator,
    homolog (avian) Glycoprotein, Polymorphism, 3D-
    structure
    K02403 C4A complement Complement pathway, Plasma, 1800 5768
    component 4A Glycoprotein, Sulfation, Signal,
    Inflammatory response,
    Polymorphism, Disease mutation,
    Blood group antigen, Thioester bond
    L00635 FNTB farnesyltransferase, Plasmid, Transferase, 1801 5769
    CAAX box, beta Prenyltransferase, Repeat, Zinc
    L08246 MCL1 myeloid cell Apoptosis, Transmembrane, 1802 5770
    leukemia sequence Differentiation, Alternative splicing
    1 (BCL2-related)
    L20688 ARHGDIB Rho GDP GTPase activation, 3D-structure 1803 5771
    dissociation inhibitor
    (GDI) beta
    L21961 IGL@ Human Ig Immunoglobulin domain, 1804 5772
    rearranged lambda- Hypothetical protein,
    chain mRNA, Immunoglobulin C region, 3D-
    subgroup VL3, V-J structure
    region, partial cds.
    L22005 CDC34 cell division cycle 34 Ubl conjugation pathway, Ligase, 1805 5773
    Multigene family, Hypothetical
    protein, Cell division
    L27943 CDA cytidine deaminase Hydrolase, Zinc 1806 5774
    L35035 RPIA ribose 5-phosphate Isomerase 1807 5775
    isomerase A (ribose
    5-phosphate
    epimerase)
    L39061 TAF1B TATA box binding Hypothetical protein 1808 5776
    protein (TBP)-
    associated factor,
    RNA polymerase I,
    B, 63 kDa
    L40027 GSK3A glycogen synthase Transferase, Serine/threonine- 1809 5777
    kinase 3 alpha protein kinase, ATP-binding,
    Multigene family, Phosphorylation
    M12679 HLA-C major Glycoprotein, Signal, 1810 5778
    histocompatibility Transmembrane, Hypothetical
    complex, class I, C protein, MHC, MHC I,
    Polymorphism, 3D-structure,
    Alternative splicing
    M12758 HLA-C Human MHC class I Glycoprotein, Transmembrane 1811 5779
    HLA-A cell surface
    antigen mRNA,
    (HLA-A2,-B7,-C),
    clone JY103.
    M17733 TMSB4X thymosin, beta 4, X- Actin-binding, Cytoskeleton, 1812 5780
    linked Acetylation
    M26383 IL8 interleukin 8 Cytokine, Chemotaxis, Inflammatory 1813 5781
    response, Signal, Alternative
    splicing, 3D-structure
    M31212 MYL6 myosin, light Myosin, Muscle protein, Acetylation, 1814 5782
    polypeptide 6, alkali, Alternative splicing, Multigene family
    smooth muscle and
    non-muscle
    M31523 TCF3 transcription factor 3 Transcription regulation, DNA- 1815 5783
    (E2A binding, Nuclear protein, Proto-
    immunoglobulin oncogene, Chromosomal
    enhancer binding translocation, Alternative splicing,
    factors E12/E47) Phosphorylation, 3D-structure
    M33552 LSP1 lymphocyte-specific T-cell, Phosphorylation, 1816 5784
    protein 1 Polymorphism
    M34671 CD59 CD59 antigen p18-20 Antigen, Glycoprotein, GPI-anchor, 1817 5785
    (antigen identified Signal, 3D-structure, Lipoprotein
    by monoclonal
    antibodies 16.3A5,
    EJ16, EJ30, EL32
    and G344)
    M37712 CDC2L2 Homo sapiens Apoptosis, Transferase, 1818 5786
    p58/GTA protein Serine/threonine-protein kinase,
    kinase mRNA, ATP-binding, Cell cycle,
    complete cds. Phosphorylation, Alternative splicing,
    Alternative initiation
    M60721 HLX1 H2.0-like homeo box DNA-binding, Homeobox, Nuclear 1819 5787
    1 (Drosophila) protein, Transcription regulation
    M63438 IGKC Immunoglobulin Hypothetical protein 1820 5788
    kappa light chain
    mRNA, partial cds
    M65292 HFL1 H factor Repeat, Glycoprotein, Sushi, Signal, 1821 5789
    (complement)-like 1 Polymorphism
    M74782 IL3RA interleukin 3 Receptor, Transmembrane, 1822 5790
    receptor, alpha (low Glycoprotein, Signal
    affinity)
    M83822 LRBA LPS-responsive Repeat, WD repeat 1823 5791
    vesicle trafficking,
    beach and anchor
    containing
    M90657 TM4SF1 Human tumor Glycoprotein, Antigen, 1824 5792
    antigen (L6) mRNA, Transmembrane
    complete cds.
    M91211 AGER advanced Immunoglobulin domain, 1825 5793
    glycosylation end Glycoprotein, Transmembrane,
    product-specific Repeat, Signal, Alternative splicing,
    receptor Polymorphism, Receptor
    M92439 LRPPRC leucine-rich PPR- Hypothetical protein, Repeat 1826 5794
    motif containing
    M92642 COL16A1 collagen, type XVI, Extracellular matrix, Connective 1827 5795
    alpha 1 tissue, Collagen, Hydroxylation,
    Repeat, Signal
    M94362 LMNB2 Human lamin B2 Intermediate filament, Coiled coil, 1828 5796
    (LAMB2) mRNA, Nuclear protein, Lipoprotein,
    partial cds. Prenylation, Phosphorylation,
    Hypothetical protein
    NM_000016 ACADM acyl-Coenzyme A Oxidoreductase, Flavoprotein, FAD, 1829 5797
    dehydrogenase, C-4 Fatty acid metabolism,
    to C-12 straight Mitochondrion, Transit peptide,
    chain Disease mutation, 3D-structure
    NM_000018 ACADVL acyl-Coenzyme A Oxidoreductase, Flavoprotein, FAD, 1830 5798
    dehydrogenase, very Fatty acid metabolism,
    long chain Mitochondrion, Transit peptide,
    Alternative splicing, Disease
    mutation, Polymorphism,
    Cardiomyopathy
    NM_000021 PSEN1 presenilin 1 Transmembrane, Phosphorylation, 1831 5799
    (Alzheimer disease Endoplasmic reticulum, Golgi stack,
    3) Alzheimer's disease, Disease
    mutation, Polymorphism, Alternative
    splicing
    NM_000022 ADA adenosine Hydrolase, Nucleotide metabolism, 1832 5800
    deaminase SCID, Hereditary hemolytic anemia,
    Disease mutation, Polymorphism
    NM_000026 ADSL adenylosuccinate Purine biosynthesis, Lyase, 1833 5801
    lyase Alternative splicing, Disease
    mutation, Epilepsy
    NM_000030 AGXT alanine-glyoxylate Aminotransferase, Transferase, 1834 5802
    aminotransferase Pyridoxal phosphate, Peroxisome,
    (oxalosis I; Mitochondrion, Disease mutation,
    hyperoxaluria I; Polymorphism
    glycolicaciduria;
    serine-pyruvate
    aminotransferase)
    NM_000034 ALDOA aldolase A, fructose- Lyase, Schiff base, Glycolysis, 1835 5803
    bisphosphate Multigene family, 3D-structure,
    Disease mutation
    NM_000045 ARG1 arginase, liver Urea cycle, Arginine metabolism, 1836 5804
    Hydrolase, Manganese, Disease
    mutation, Polymorphism
    NM_000056 BCKDHB branched chain keto Oxidoreductase, Mitochondrion, 1837 5805
    acid dehydrogenase Transit peptide, Disease mutation,
    E1, beta polypeptide Maple syrup urine disease, 3D-
    (maple syrup urine structure
    disease)
    NM_000070 CAPN3 calpain 3, (p94) Hydrolase, Thiol protease, Calcium- 1838 5806
    binding, Multigene family, Repeat,
    Disease mutation, Polymorphism,
    Alternative splicing
    NM_000073 CD3G CD3G antigen, Immunoglobulin domain, T-cell, 1839 5807
    gamma polypeptide Receptor, Transmembrane,
    (TiT3 complex) Glycoprotein, Signal
    NM_000074 TNFSF5 tumor necrosis factor Cytokine, Transmembrane, 1840 5808
    (ligand) superfamily, Glycoprotein, Signal-anchor,
    member 5 (hyper- Antigen, Disease mutation,
    IgM syndrome) Polymorphism, 3D-structure
    NM_000081 CHS1 Chediak-Higashi Protein transport, Transport, Repeat, 1841 5809
    syndrome 1 WD repeat, Disease mutation,
    Alternative splicing
    NM_000082 CKN1 Cockayne syndrome Nuclear protein, Repeat, WD repeat, 1842 5810
    1 (classical) Transcription regulation,
    Polymorphism, Cockayne's
    syndrome, Deafness, Dwarfism
    NM_000095 COMP cartilage oligomeric Hypothetical protein, Glycoprotein, 1843 5811
    matrix protein Cell adhesion, Calcium-binding,
    (pseudoachondroplasia, Repeat, EGF-like domain, Signal,
    epiphyseal Disease mutation, Polymorphism
    dysplasia
    1, multiple)
    NM_000099 CST3 cystatin C (amyloid Thiol protease inhibitor, Amyloid, 1844 5812
    angiopathy and Signal, Disease mutation,
    cerebral Polymorphism, 3D-structure
    hemorrhage)
    NM_000100 CSTB cystatin B (stefin B) Thiol protease inhibitor, Nuclear 1845 5813
    protein, Acetylation, Disease
    mutation, Epilepsy, 3D-structure
    NM_000101 CYBA cytochrome b-245, Oxidoreductase, NADP, Electron 1846 5814
    alpha polypeptide transport, Membrane, Heme,
    Polymorphism, Disease mutation,
    Chronic granulomatous disease,
    Hypothetical protein
    NM_000116 TAZ tafazzin Alternative splicing, 1847 5815
    (cardiomyopathy, Transmembrane, Disease mutation
    dilated 3A (X-linked);
    endocardial
    fibroelastosis
    2;
    Barth syndrome)
    NM_000120 EPHX1 epoxide hydrolase 1, Hydrolase, Endoplasmic reticulum, 1848 5816
    microsomal Detoxification, Transmembrane,
    (xenobiotic) Aromatic hydrocarbons catabolism,
    Microsome, Polymorphism
    NM_000121 EPOR erythropoietin Receptor, Transmembrane, 1849 5817
    receptor Glycoprotein, Signal,
    Phosphorylation, 3D-structure
    NM_000126 ETFA electron-transfer- Electron transport, Flavoprotein, 1850 5818
    flavoprotein, alpha FAD, Mitochondrion, Transit peptide,
    polypeptide (glutaric Disease mutation, Glutaricaciduria,
    aciduria II) Polymorphism, 3D-structure
    NM_000130 F5 coagulation factor V Blood coagulation, Glycoprotein, 1851 5819
    (proaccelerin, labile Sulfation, Calcium, Signal, Zymogen,
    factor) Repeat, Polymorphism, Disease
    mutation, Thrombophilia, 3D-
    structure
    NM_000143 FH fumarate hydratase Lyase, Tricarboxylic acid cycle, 1852 5820
    Mitochondrion, Transit peptide,
    Acetylation, Alternative initiation,
    Anti-oncogene, Disease mutation
    NM_000146 FTL ferritin, light Hypothetical protein, Iron storage, 1853 5821
    polypeptide Metal-binding, Acetylation
    NM_000151 G6PC glucose-6- Glycogen biosynthesis, Hydrolase, 1854 5822
    phosphatase, Transmembrane, Glycoprotein,
    catalytic (glycogen Endoplasmic reticulum, Glycogen
    storage disease type storage disease, Disease mutation,
    I, von Gierke Polymorphism
    disease)
    NM_000156 GAMT guanidinoacetate N- Transferase, Methyltransferase 1855 5823
    methyltransferase
    NM_000157 GBA glucosidase, beta; Glycosidase, Hydrolase, Signal, 1856 5824
    acid (includes Hypothetical protein, Sphingolipid
    glucosylceramidase) metabolism, Glycoprotein,
    Lysosome, Membrane, Gaucher
    disease, Disease mutation,
    Polymorphism, Alternative initiation,
    Pharmaceutical
    NM_000175 GPI glucose phosphate Gluconeogenesis, Glycolysis, 1857 5825
    isomerase Isomerase, Growth factor, Cytokine,
    Disease mutation, 3D-structure,
    Hypothetical protein
    NM_000177 GSN gelsolin Cytoskeleton, Actin-binding, Repeat, 1858 5826
    (amyloidosis, Finnish Calcium, Alternative initiation,
    type) Signal, Amyloid, Disease mutation,
    3D-structure, Phosphorylation, Actin
    capping
    NM_000181 GUSB glucuronidase, beta Hydrolase, Glycosidase, Lysosome, 1859 5827
    Glycoprotein, Signal,
    Mucopolysaccharidosis, Disease
    mutation, 3D-structure, Alternative
    splicing, Polymorphism
    NM_000183 HADHB hydroxyacyl- Fatty acid metabolism, Transferase, 1860 5828
    Coenzyme A Acyltransferase, Mitochondrion,
    dehydrogenase/3- Transit peptide, Disease mutation,
    ketoacyl-Coenzyme Hypothetical protein
    A thiolase/enoyl-
    Coenzyme A
    hydratase
    (trifunctional
    protein), beta
    subunit
    NM_000186 HF1 H factor 1 Complement alternate pathway, 1861 5829
    (complement) Plasma, Glycoprotein, Repeat,
    Sushi, Signal, 3D-structure,
    Polymorphism, Alternative splicing
    NM_000206 IL2RG interleukin 2 Receptor, Transmembrane, 1862 5830
    receptor, gamma Glycoprotein, Signal, Disease
    (severe combined mutation, SCID, 3D-structure
    immunodeficiency)
    NM_000211 ITGB2 integrin, beta 2 Integrin, Cell adhesion, Receptor, 1863 5831
    (antigen CD18 (p95), Transmembrane, Glycoprotein,
    lymphocyte function- Repeat, Signal, Disease mutation,
    associated antigen Pyrrolidone carboxylic acid, 3D-
    1; macrophage structure
    antigen 1 (mac-1)
    beta subunit)
    NM_000229 LCAT lecithin-cholesterol Cholesterol metabolism, Lipid 1864 5832
    acyltransferase metabolism, Transferase,
    Acyltransferase, Signal,
    Glycoprotein, Polymorphism,
    Disease mutation
    NM_000235 LIPA lipase A, lysosomal Hydrolase, Lipid degradation, 1865 5833
    acid, cholesterol Glycoprotein, Signal, Lysosome,
    esterase (Wolman Disease mutation, Polymorphism
    disease)
    NM_000239 LYZ lysozyme (renal Hydrolase, Glycosidase, 1866 5834
    amyloidosis) Bacteriolytic enzyme, Signal,
    Amyloid, 3D-structure, Disease
    mutation, Polymorphism
    NM_000243 MEFV Mediterranean fever Inflammatory response, Actin- 1867 5835
    binding, Metal-binding, Cytoskeleton,
    Microtubule, Nuclear protein, Zinc-
    finger, Zinc, Polymorphism, Disease
    mutation, Alternative splicing
    NM_000249 MLH1 mutL homolog 1, DNA repair, Nuclear protein, 1868 5836
    colon cancer, Disease mutation, Anti-oncogene,
    nonpolyposis type 2 Polymorphism, Hereditary
    (E. coli) nonpolyposis colorectal cancer
    NM_000250 MPO myeloperoxidase Oxidoreductase, Peroxidase, Iron, 1869 5837
    Heme, Calcium-binding,
    Glycoprotein, Signal, Oxidation,
    Lysosome, Alternative splicing,
    Polymorphism, Disease mutation,
    3D-structure
    NM_000254 MTR 5- Transferase, Methyltransferase, 1870 5838
    methyltetrahydrofolate- Methionine biosynthesis, Vitamin
    homocysteine B12, Cobalt, Disease mutation,
    methyltransferase Polymorphism
    NM_000265 NCF1 neutrophil cytosolic SH3 domain, Repeat, 1871 5839
    factor 1 (47 kDa, Polymorphism, Disease mutation,
    chronic Chronic granulomatous disease, 3D-
    granulomatous structure
    disease, autosomal
    1)
    NM_000269 NME1 non-metastatic cells Transferase, Kinase, ATP-binding, 1872 5840
    1, protein (NM23A) Nuclear protein, Anti-oncogene,
    expressed in Disease mutation, 3D-structure
    NM_000270 NP nucleoside Hypothetical protein, Transferase, 1873 5841
    phosphorylase Glycosyltransferase, Polymorphism,
    Disease mutation, 3D-structure
    NM_000285 PEPD peptidase D Collagen degradation, Hydrolase, 1874 5842
    Dipeptidase, Metalloprotease,
    Manganese, Acetylation,
    Polymorphism, Disease mutation
    NM_000288 PEX7 peroxisomal Repeat, WD repeat, Peroxisome, 1875 5843
    biogenesis factor 7 Transport, Protein transport,
    Rhizomelic chondrodysplasia
    punctata, Disease mutation,
    Polymorphism
    NM_000289 PFKM phosphofructokinase, Glycolysis, Kinase, Transferase, 1876 5844
    muscle Repeat, Allosteric enzyme,
    Phosphorylation, Magnesium,
    Multigene family, Alternative splicing,
    Disease mutation, Glycogen storage
    disease
    NM_000291 PGK1 phosphoglycerate Transferase, Kinase, Multigene 1877 5845
    kinase 1 family, Glycolysis, Acetylation,
    Disease mutation, Polymorphism,
    Hereditary hemolytic anemia
    NM_000295 SERPINA1 serine (or cysteine) Serpin, Serine protease inhibitor, 1878 5846
    proteinase inhibitor, Glycoprotein, Plasma,
    clade A (alpha-1 Polymorphism, Acute phase, Signal,
    antiproteinase, 3D-structure, Disease mutation,
    antitrypsin), member 1 Protease inhibitor
    NM_000297 PKD2 polycystic kidney Ionic channel, Glycoprotein, Coiled 1879 5847
    disease 2 coil, Transmembrane, Calcium-
    (autosomal binding, Disease mutation,
    dominant) Polymorphism
    NM_000302 PLOD procollagen-lysine, Oxidoreductase, Dioxygenase, 1880 5848
    2-oxoglutarate 5- Signal, Iron, Vitamin C, Glycoprotein,
    dioxygenase (lysine Endoplasmic reticulum, Membrane,
    hydroxylase, Ehlers- Polymorphism, Disease mutation,
    Danlos syndrome Ehlers-Danlos syndrome
    type VI)
    NM_000305 PON2 paraoxonase 2 Hydrolase, Glycoprotein, Signal, 1881 5849
    Membrane, Multigene family,
    Polymorphism, Alternative splicing
    NM_000307 POU3F4 POU domain, class Transcription regulation, Nuclear 1882 5850
    3, transcription factor 4 protein, DNA-binding, Homeobox,
    Disease mutation, Deafness
    NM_000320 QDPR quinoid Tetrahydrobiopterin biosynthesis, 1883 5851
    dihydropteridine Oxidoreductase, NADP, 3D-
    reductase structure, Polymorphism,
    Phenylketonuria, Disease mutation
    NM_000321 RB1 retinoblastoma 1 Transcription regulation, DNA- 1884 5852
    (including binding, Nuclear protein,
    osteosarcoma) Phosphorylation, Anti-oncogene,
    Disease mutation, 3D-structure
    NM_000327 ROM1 retinal outer Vision, Cell adhesion, 1885 5853
    segment membrane Photoreceptor, Transmembrane,
    protein 1 Polymorphism, Disease mutation,
    Retinitis pigmentosa
    NM_000376 VDR vitamin D (1,25- Receptor, Transcription regulation, 1886 5854
    dihydroxyvitamin D3) DNA-binding, Nuclear protein, Zinc-
    receptor finger, Phosphorylation, Disease
    mutation, 3D-structure
    NM_000377 WAS Wiskott-Aldrich Repeat, Disease mutation, 1887 5855
    syndrome (eczema- Phosphorylation, 3D-structure
    thrombocytopenia)
    NM_000380 XPA xeroderma DNA repair, DNA-binding, Zinc- 1888 5856
    pigmentosum, finger, Nuclear protein, Xeroderma
    complementation pigmentosum, Disease mutation,
    group A Polymorphism, 3D-structure
    NM_000386 BLMH bleomycin hydrolase Hydrolase, Thiol protease, 1889 5857
    Polymorphism, 3D-structure,
    Hypothetical protein
    NM_000392 ABCC2 ATP-binding ATP-binding, Glycoprotein, 1890 5858
    cassette, sub-family Transmembrane, Transport, Repeat,
    C (CFTR/MRP), Disease mutation, Polymorphism
    member 2
    NM_000394 CRYAA crystallin, alpha A Eye lens protein, Acetylation, 1891 5859
    Glycoprotein, Disease mutation,
    Vision
    NM_000397 CYBB cytochrome b-245, Oxidoreductase, NADP, Electron 1892 5860
    beta polypeptide transport, Transmembrane, FAD,
    (chronic Heme, Glycoprotein, Voltage-gated
    granulomatous channel, Ionic channel, Disease
    disease) mutation, Chronic granulomatous
    disease
    NM_000399 EGR2 early growth Transcription regulation, Activator, 1893 5861
    response 2 (Krox-20 DNA-binding, Nuclear protein,
    homolog, Repeat, Zinc-finger, Metal-binding,
    Drosophila) Alternative splicing, Disease
    mutation, Charcot-Marie-Tooth
    disease, Dejerine-Sottas syndrome
    NM_000401 EXT2 exostoses (multiple) 2 Transferase, Glycosyltransferase, 1894 5862
    Endoplasmic reticulum, Golgi stack,
    Transmembrane, Signal-anchor,
    Glycoprotein, Anti-oncogene,
    Disease mutation, Hereditary
    multiple exostoses, Alternative
    splicing
    NM_000402 G6PD glucose-6-phosphate Oxidoreductase, NADP, Glucose 1895 5863
    dehydrogenase metabolism, Disease mutation,
    Polymorphism, Hereditary hemolytic
    anemia, Alternative splicing,
    Acetylation
    NM_000404 GLB1 galactosidase, beta 1 Hydrolase, Glycosidase, Lysosome, 1896 5864
    Signal, Alternative splicing,
    Glycoprotein, Polymorphism,
    Disease mutation
    NM_000405 GM2A GM2 ganglioside Signal, Glycoprotein, Lysosome, 1897 5865
    activator protein Sphingolipid metabolism, GM2-
    gangliosidosis, Disease mutation,
    Polymorphism, 3D-structure
    NM_000407 GP1BB glycoprotein Ib Hypothetical protein, Cell division, 1898 5866
    (platelet), beta GTP-binding, Coiled coil, Platelet,
    polypeptide Transmembrane, Glycoprotein,
    Hemostasis, Blood coagulation,
    Signal, Phosphorylation, Cell
    adhesion, Leucine-rich repeat
    NM_000418 IL4R interleukin 4 receptor Receptor, Transmembrane, 1899 5867
    Glycoprotein, Signal, Disease
    mutation, Polymorphism, 3D-
    structure
    NM_000425 L1CAM L1 cell adhesion Neurogenesis, Cell adhesion, 1900 5868
    molecule Developmental protein,
    (hydrocephalus, Glycoprotein, Transmembrane,
    stenosis of aqueduct Repeat, Antigen, Immunoglobulin
    of Sylvius 1, MASA domain, Signal, Disease mutation,
    (mental retardation, Alternative splicing
    aphasia, shuffling
    gait and adducted
    thumbs) syndrome,
    spastic paraplegia 1)
    NM_000433 NCF2 neutrophil cytosolic SH3 domain, Repeat, TPR repeat, 1901 5869
    factor 2 (65 kDa, Chronic granulomatous disease,
    chronic Disease mutation, 3D-structure
    granulomatous
    disease, autosomal
    2)
    NM_000434 NEU1 sialidase 1 Hydrolase, Glycosidase, Signal, 1902 5870
    (lysosomal sialidase) Repeat, Glycoprotein, Disease
    mutation, Polymorphism,
    Phosphorylation
    NM_000436 OXCT 3-oxoacid CoA Mitochondrion, Transferase, Transit 1903 5871
    transferase peptide, Disease mutation,
    Polymorphism
    NM_000445 PLEC1 plectin 1, Coiled coil, Repeat, Structural 1904 5872
    intermediate filament protein, Cytoskeleton, Actin-binding,
    binding protein Phosphorylation, Alternative splicing,
    500 kDa Epidermolysis bullosa, Disease
    mutation
    NM_000454 SOD1 superoxide Antioxidant, Oxidoreductase, Metal- 1905 5873
    dismutase 1, soluble binding, Copper, Zinc, Acetylation,
    (amyotrophic lateral 3D-structure, Amyotrophic lateral
    sclerosis 1 (adult)) sclerosis, Disease mutation
    NM_000456 SUOX sulfite oxidase Oxidoreductase, Mitochondrion, 1906 5874
    Heme, Molybdenum, Transit peptide,
    Disease mutation, 3D-structure
    NM_000462 UBE3A ubiquitin protein Ligase, Nuclear protein, Ubl 1907 5875
    ligase E3A (human conjugation pathway, Alternative
    papilloma virus E6- splicing, Disease mutation,
    associated protein, Polymorphism, 3D-structure,
    Angelman Hypothetical protein
    syndrome)
    NM_000476 AK1 adenylate kinase 1 Transferase, Kinase, ATP-binding, 1908 5876
    Acetylation, Disease mutation
    NM_000480 AMPD3 adenosine Hydrolase, Nucleotide metabolism, 1909 5877
    monophosphate Multigene family, Polymorphism,
    deaminase (isoform Alternative splicing
    E)
    NM_000481 AMT aminomethyltransferase Hypothetical protein, Transferase, 1910 5878
    (glycine Aminotransferase, Mitochondrion,
    cleavage system Transit peptide, Disease mutation
    protein T)
    NM_000487 ARSA arylsulfatase A Hydrolase, Signal, Glycoprotein, 1911 5879
    Lysosome, Disease mutation,
    Metachromatic leukodystrophy,
    Sphingolipid metabolism,
    Polymorphism, 3D-structure
    NM_000497 CYP11B1 cytochrome P450, Steroidogenesis, Electron transport, 1912 5880
    family 11, subfamily Steroid metabolism, Oxidoreductase,
    B, polypeptide 1 Monooxygenase, Mitochondrion,
    Membrane, Heme, Transit peptide,
    Polymorphism, Disease mutation
    NM_000502 EPX eosinophil Oxidoreductase, Peroxidase, Iron, 1913 5881
    peroxidase Heme, Glycoprotein, Signal, Disease
    mutation
    NM_000507 FBP1 fructose-1,6- Hydrolase, Carbohydrate 1914 5882
    bisphosphatase 1 metabolism, Gluconeogenesis, Zinc,
    Allosteric enzyme, Disease mutation,
    Polymorphism, 3D-structure,
    Hypothetical protein
    NM_000512 GALNS galactosamine (N- Hypothetical protein 1915 5883
    acetyl)-6-sulfate
    sulfatase (Morquio
    syndrome,
    mucopolysaccharidosis
    type IVA)
    NM_000517 HBA2 hemoglobin, alpha 2 Heme, Oxygen transport, Transport, 1916 5884
    Erythrocyte, Disease mutation,
    Polymorphism, Acetylation, 3D-
    structure
    NM_000525 KCNJ11 potassium inwardly- Ionic channel, Ion transport, Voltage- 1917 5885
    rectifying channel, gated channel, Transmembrane,
    subfamily J, member Potassium transport, Polymorphism,
    11 Disease mutation, Diabetes mellitus
    NM_000528 MAN2B1 mannosidase, alpha, Glycosidase, Hydrolase, 1918 5886
    class 2B, member 1 Glycoprotein, Lysosome, Zymogen,
    Signal, Disease mutation,
    Polymorphism
    NM_000532 PCCB propionyl Coenzyme Hypothetical protein, Mitochondrion, 1919 5887
    A carboxylase, beta Transit peptide, Ligase, Disease
    polypeptide mutation
    NM_000542 SFTPB surfactant, Surface film, Gaseous exchange, 1920 5888
    pulmonary- Glycoprotein, Repeat,
    associated protein B Polymorphism, 3D-structure
    NM_000558 HBA1 hemoglobin, alpha 2 Heme, Oxygen transport, Transport, 1921 5889
    Erythrocyte, Disease mutation,
    Polymorphism, Acetylation, 3D-
    structure
    NM_000565 IL6R interleukin 6 receptor Receptor, Transmembrane, 1922 5890
    Glycoprotein, Immunoglobulin
    domain, Repeat, Alternative splicing,
    Signal, 3D-structure
    NM_000569 FCGR3A Fc fragment of IgG, IgG-binding protein, Receptor, 1923 5891
    low affinity IIIa, Transmembrane, Glycoprotein,
    receptor for (CD16) Signal, Immunoglobulin domain,
    Repeat, Multigene family,
    Polymorphism, GPI-anchor, 3D-
    structure, Lipoprotein
    NM_000573 CR1 complement Complement pathway, Glycoprotein, 1924 5892
    component (3b/4b) Transmembrane, Repeat, Signal,
    receptor 1, including Receptor, Sushi, Blood group
    Knops blood group antigen, Polymorphism, Pyrrolidone
    system carboxylic acid, 3D-structure
    NM_000578 SLC11A1 solute carrier family Transport, Iron transport, 1925 5893
    11 (proton-coupled Transmembrane, Glycoprotein,
    divalent metal ion Macrophage, Polymorphism
    transporters),
    member 1
    NM_000581 GPX1 glutathione Oxidoreductase, Peroxidase, 1926 5894
    peroxidase 1 Selenium, Selenocysteine,
    Erythrocyte, Polymorphism,
    Hypothetical protein
    NM_000584 IL8 interleukin 8 Cytokine, Chemotaxis, Inflammatory 1927 5895
    response, Signal, Alternative
    splicing, 3D-structure
    NM_000591 CD14 CD14 antigen Immune response, Inflammatory 1928 5896
    response, Signal, GPI-anchor,
    Repeat, Leucine-rich repeat,
    Glycoprotein, Antigen, Lipoprotein
    NM_000607 ORM1 orosomucoid 1 Glycoprotein, Plasma, Acute phase, 1929 5897
    Signal, Lipocalin, Polymorphism,
    Multigene family, Pyrrolidone
    carboxylic acid
    NM_000608 ORM2 orosomucoid 1 Glycoprotein, Plasma, Acute phase, 1930 5898
    Signal, Lipocalin, Multigene family,
    Polymorphism, Pyrrolidone
    carboxylic acid
    NM_000631 NCF4 neutrophil cytosolic SH3 domain, Alternative splicing, 1931 5899
    factor 4, 40 kDa 3D-structure
    NM_000632 ITGAM integrin, alpha M Integrin, Cell adhesion, Receptor, 1932 5900
    (complement Glycoprotein, Transmembrane,
    component receptor Signal, 3D-structure, Repeat,
    3, alpha; also known Magnesium, Calcium
    as CD11b (p170),
    macrophage antigen
    alpha polypeptide)
    NM_000633 BCL2 B-cell Proto-oncogene, Apoptosis, 1933 5901
    CLL/lymphoma 2 Alternative splicing,
    Transmembrane, Mitochondrion,
    Phosphorylation, Chromosomal
    translocation, Polymorphism,
    Disease mutation, 3D-structure
    NM_000634 IL8RA interleukin 8 G-protein coupled receptor, 1934 5902
    receptor, alpha Transmembrane, Glycoprotein,
    Chemotaxis, Polymorphism, 3D-
    structure, Receptor
    NM_000651 CR1 complement Complement pathway, Glycoprotein, 1935 5903
    component (3b/4b) Transmembrane, Repeat, Signal,
    receptor 1, including Receptor, Sushi, Blood group
    Knops blood group antigen, Polymorphism, Pyrrolidone
    system carboxylic acid, 3D-structure
    NM_000655 SELL selectin L EGF-like domain, Cell adhesion, 1936 5904
    (lymphocyte Transmembrane, Glycoprotein,
    adhesion molecule Lectin, Selectin, Signal, Sushi,
    1) Repeat, 3D-structure
    NM_000671 ADH5 alcohol Oxidoreductase, Zinc, Metal-binding, 1937 5905
    dehydrogenase 5 NAD, Multigene family, Acetylation,
    (class III), chi 3D-structure
    polypeptide
    NM_000675 ADORA2A adenosine A2a G-protein coupled receptor, 1938 5906
    receptor Transmembrane, Glycoprotein, 3D-
    structure, Polymorphism
    NM_000688 ALAS1 aminolevulinate, Heme biosynthesis, Transferase, 1939 5907
    delta-, synthase 1 Acyltransferase, Mitochondrion,
    Transit peptide, Pyridoxal
    phosphate, Multigene family
    NM_000690 ALDH2 aldehyde Oxidoreductase, NAD, 1940 5908
    dehydrogenase 2 Mitochondrion, Transit peptide,
    family Polymorphism, 3D-structure
    (mitochondrial)
    NM_000694 ALDH3B1 aldehyde Oxidoreductase, NAD 1941 5909
    dehydrogenase 3
    family, member B1
    NM_000698 ALOX5 arachidonate 5- Oxidoreductase, Dioxygenase, Iron, 1942 5910
    lipoxygenase Leukotriene biosynthesis, Calcium
    NM_000701 ATP1A1 ATPase, Na+/K+ Hydrolase, Sodium/potassium 1943 5911
    transporting, alpha 1 transport, Transmembrane,
    polypeptide Phosphorylation, Magnesium, Metal-
    binding, ATP-binding, Multigene
    family, Alternative splicing
    NM_000712 BLVRA biliverdin reductase A Oxidoreductase, NAD, NADP, Zinc, 1944 5912
    Polymorphism
    NM_000714 BZRP benzodiazapine Mitochondrion, Receptor, 1945 5913
    receptor (peripheral) Transmembrane, Polymorphism
    NM_000717 CA4 carbonic anhydrase GPI-anchor, Membrane, Lyase, Zinc, 1946 5914
    IV Signal, 3D-structure, Lipoprotein
    NM_000718 CACNA1B calcium channel, Ionic channel, Transmembrane, Ion 1947 5915
    voltage-dependent, transport, Voltage-gated channel,
    L type, alpha 1B Calcium channel, Glycoprotein,
    subunit Repeat, Multigene family, Calcium-
    binding, Phosphorylation, ATP-
    binding, Alternative splicing
    NM_000732 CD3D CD3D antigen, delta Immunoglobulin domain, T-cell, 1948 5916
    polypeptide (TiT3 Receptor, Transmembrane,
    complex) Glycoprotein, Signal
    NM_000734 CD3Z CD3Z antigen, zeta T-cell, Receptor, Transmembrane, 1949 5917
    polypeptide (TiT3 Signal, Repeat, Alternative splicing,
    complex) Phosphorylation, 3D-structure
    NM_000748 CHRNB2 cholinergic receptor, Postsynaptic membrane, Ionic 1950 5918
    nicotinic, beta channel, Glycoprotein, Signal,
    polypeptide 2 Transmembrane, Multigene family,
    (neuronal) Disease mutation, Epilepsy
    NM_000749 CHRNB3 cholinergic receptor, Postsynaptic membrane, Ionic 1951 5919
    nicotinic, beta channel, Glycoprotein, Signal,
    polypeptide 3 Transmembrane, Multigene family
    NM_000752 LTB4R leukotriene B4 Apoptosis, 3D-structure, RNA- 1952 5920
    receptor 2 binding, Repeat, G-protein coupled
    receptor, Transmembrane,
    Glycoprotein
    NM_000757 CSF1 colony stimulating Cytokine, Growth factor, 1953 5921
    factor 1 Glycoprotein, Proteoglycan,
    (macrophage) Transmembrane, Signal, Alternative
    splicing, 3D-structure
    NM_000760 CSF3R colony stimulating Cell adhesion, Receptor, Repeat, 1954 5922
    factor 3 receptor Signal, Transmembrane,
    (granulocyte) Immunoglobulin domain,
    Glycoprotein, Alternative splicing,
    Polymorphism, 3D-structure
    NM_000778 CYP4A11 cytochrome P450, Heme, Monooxygenase, 1955 5923
    family 4, subfamily Oxidoreductase, Electron transport,
    A, polypeptide 11 Membrane, Microsome,
    Endoplasmic reticulum,
    Polymorphism
    NM_000801 FKBP1A FK506 binding Isomerase, Rotamase, 3D-structure 1956 5924
    protein 1A, 12 kDa
    NM_000804 FOLR3 folate receptor 3 Receptor, Glycoprotein, Signal, 1957 5925
    (gamma) Folate-binding, Multigene family,
    Alternative splicing
    NM_000819 GART phosphoribosylglycin Multifunctional enzyme, Purine 1958 5926
    amide biosynthesis, Ligase, Transferase,
    formyltransferase, Alternative splicing, Polymorphism
    phosphoribosylglycin
    amide synthetase,
    phosphoribosylaminoimidazole
    synthetase
    NM_000846 GSTA2 glutathione S- Transferase, Multigene family, 1959 5927
    transferase A2 Polymorphism, 3D-structure
    NM_000856 GUCY1A3 guanylate cyclase 1, Lyase, cGMP biosynthesis, 1960 5928
    soluble, alpha 3 Multigene family
    NM_000857 GUCY1B3 guanylate cyclase 1, Lyase, cGMP biosynthesis, 1961 5929
    soluble, beta 3 Alternative splicing
    NM_000871 HTR6 5-hydroxytryptamine G-protein coupled receptor, 1962 5930
    (serotonin) receptor 6 Transmembrane, Glycoprotein,
    Multigene family
    NM_000876 IGF2R insulin-like growth Transmembrane, Transport, 1963 5931
    factor 2 receptor Glycoprotein, Repeat, Receptor,
    Lysosome, Signal, Polymorphism,
    3D-structure
    NM_000877 IL1R1 interleukin 1 Receptor, Repeat, Signal, 1964 5932
    receptor, type I Transmembrane, Immunoglobulin
    domain, Glycoprotein,
    Phosphorylation, 3D-structure
    NM_000878 IL2RB interleukin 2 Receptor, Transmembrane, 1965 5933
    receptor, beta Glycoprotein, Signal, 3D-structure
    NM_000883 IMPDH1 IMP (inosine Oxidoreductase, NAD, GMP 1966 5934
    monophosphate) biosynthesis, Purine biosynthesis,
    dehydrogenase 1 Multigene family, Repeat, CBS
    domain, Alternative splicing, Vision,
    Retinitis pigmentosa, Disease
    mutation
    NM_000895 LTA4H leukotriene A4 Multifunctional enzyme, Hydrolase, 1967 5935
    hydrolase Leukotriene biosynthesis,
    Metalloprotease, Metal-binding, Zinc,
    3D-structure
    NM_000903 NQO1 NAD(P)H Oxidoreductase, NAD, NADP, 1968 5936
    dehydrogenase, Flavoprotein, FAD, Multigene family,
    quinone 1 Polymorphism, 3D-structure
    NM_000904 NQO2 NAD(P)H Oxidoreductase, Flavoprotein, FAD, 1969 5937
    dehydrogenase, Multigene family, Zinc, 3D-structure
    quinone
    2
    NM_000918 P4HB procollagen-proline, Redox-active center, Isomerase, 1970 5938
    2-oxoglutarate 4- Endoplasmic reticulum, Repeat,
    dioxygenase (proline Signal, 3D-structure, Hypothetical
    4-hydroxylase), beta protein
    polypeptide (protein
    disulfide isomerase;
    thyroid hormone
    binding protein p55)
    NM_000952 PTAFR platelet-activating G-protein coupled receptor, 1971 5939
    factor receptor Transmembrane, Glycoprotein,
    Chemotaxis, Polymorphism,
    Hypothetical protein
    NM_000954 PTGDS prostaglandin D2 Isomerase, Prostaglandin 1972 5940
    synthase 21 kDa biosynthesis, Transport,
    (brain) Glycoprotein, Signal, Membrane,
    Lipocalin, Polymorphism
    NM_000963 PTGS2 prostaglandin- Oxidoreductase, Dioxygenase, 1973 5941
    endoperoxide Peroxidase, Glycoprotein,
    synthase 2 Prostaglandin biosynthesis, Heme,
    (prostaglandin G/H Iron, Signal, Membrane,
    synthase and Polymorphism
    cyclooxygenase)
    NM_000966 RARG retinoic acid Receptor, Transcription regulation, 1974 5942
    receptor, gamma DNA-binding, Nuclear protein, Zinc-
    finger, Multigene family, Alternative
    splicing, 3D-structure
    NM_000969 RPL5 ribosomal protein L5 Ribosomal protein, rRNA-binding, 1975 5943
    Hydrolase, Metalloprotease,
    Aminopeptidase, Zinc, Nuclear
    protein
    NM_000985 RPL17 ribosomal protein Hypothetical protein, Ribosomal 1976 5944
    L17 protein
    NM_000992 RPL29 ribosomal protein Methylation, Ribosomal protein, 1977 5945
    L29 Repeat, Heparin-binding
    NM_000995 RPL34 ribosomal protein Ribosomal protein 1978 5946
    L34
    NM_001006 RPS3A ribosomal protein Ribosomal protein 1979 5947
    S3A
    NM_001017 RPS13 ribosomal protein Ribosomal protein 1980 5948
    S13
    NM_001048 SST somatostatin Cleavage on pair of basic residues, 1981 5949
    Hormone, Signal, Pharmaceutical
    NM_001051 SSTR3 somatostatin G-protein coupled receptor, 1982 5950
    receptor 3 Transmembrane, Glycoprotein,
    Multigene family, Polymorphism
    NM_001052 SSTR4 somatostatin G-protein coupled receptor, 1983 5951
    receptor 4 Transmembrane, Glycoprotein,
    Multigene family, Lipoprotein,
    Palmitate, Phosphorylation,
    Polymorphism
    NM_001054 SULT1A2 sulfotransferase Transferase, Steroid metabolism, 1984 5952
    family, cytosolic, 1A, Polymorphism
    phenol-preferring,
    member 2
    NM_001055 SULT1A1 sulfotransferase Transferase, Catecholamine 1985 5953
    family, cytosolic, 1A, metabolism, Steroid metabolism,
    phenol-preferring, Polymorphism
    member 1
    NM_001060 TBXA2R thromboxane A2 G-protein coupled receptor, 1986 5954
    receptor Transmembrane, Glycoprotein,
    Disease mutation, Alternative
    splicing, Polymorphism, 3D-
    structure, Hypothetical protein,
    Metal-binding, Nuclear protein, Zinc,
    Zinc-finger
    NM_001062 TCN1 transcobalamin I Transport, Cobalt transport, 1987 5955
    (vitamin B12 binding Glycoprotein, Signal
    protein, R binder
    family)
    NM_001064 TKT transketolase Transferase, Thiamine 1988 5956
    (Wernicke-Korsakoff pyrophosphate, Calcium-binding
    syndrome)
    NM_001065 TNFRSF1A tumor necrosis factor Receptor, Apoptosis, 1989 5957
    receptor superfamily, Transmembrane, Glycoprotein,
    member 1A Repeat, Signal, Disease mutation,
    Polymorphism, 3D-structure
    NM_001066 TNFRSF1B tumor necrosis factor Receptor, Apoptosis, 1990 5958
    receptor superfamily, Transmembrane, Glycoprotein,
    member 1B Repeat, Signal, Phosphorylation,
    Pharmaceutical, Polymorphism, 3D-
    structure
    NM_001082 CYP4F2 cytochrome P450, Heme, Monooxygenase, 1991 5959
    family 4, subfamily Oxidoreductase, Electron transport,
    F, polypeptide 2 Membrane, Microsome,
    Endoplasmic reticulum,
    Polymorphism, NADP
    NM_001087 AAMP angio-associated, Repeat, WD repeat 1992 5960
    migratory cell protein
    NM_001089 ABCA3 ATP-binding ATP-binding, Transport, 1993 5961
    cassette, sub-family Transmembrane
    A (ABC1), member 3
    NM_001090 ABCF1 ATP-binding ATP-binding 1994 5962
    cassette, sub-family
    F (GCN20), member 1
    NM_001091 ABP1 amiloride binding Signal, Glycoprotein, 1995 5963
    protein 1 (amine Oxidoreductase, Copper, Heparin-
    oxidase (copper- binding, TPQ, Alternative splicing,
    containing)) Polymorphism, Metal-binding
    NM_001099 ACPP acid phosphatase, Hydrolase, Glycoprotein, Signal, 3D- 1996 5964
    prostate structure
    NM_001101 ACTB actin, beta Hypothetical protein, Structural 1997 5965
    protein, Multigene family,
    Methylation, Acetylation,
    Cytoskeleton, 3D-structure
    NM_001102 ACTN1 actinin, alpha 1 Cytoskeleton, Actin-binding, 1998 5966
    Calcium-binding, Repeat, Multigene
    family, Phosphorylation
    NM_001105 ACVR1 activin A receptor, Receptor, Transferase, 1999 5967
    type I Serine/threonine-protein kinase,
    ATP-binding, Transmembrane,
    Glycoprotein, Signal
    NM_001107 ACYP1 acylphosphatase 1, Hydrolase, Acetylation, Multigene 2000 5968
    erythrocyte family
    (common) type
    NM_001109 ADAM8 a disintegrin and Hydrolase, Metalloprotease, Zinc, 2001 5969
    metalloproteinase Signal, Glycoprotein,
    domain 8 Transmembrane, Antigen, EGF-like
    domain
    NM_001120 TETRAN tetracycline Transmembrane 2002 5970
    transporter-like
    protein
    NM_001129 AEBP1 AE binding protein 1 Carboxypeptidase 2003 5971
    NM_001140 ALOX15 arachidonate 15- Oxidoreductase, Dioxygenase, Iron, 2004 5972
    lipoxygenase Leukotriene biosynthesis
    NM_001150 ANPEP alanyl (membrane) Angiogenesis, Hydrolase, 2005 5973
    aminopeptidase Aminopeptidase, Metalloprotease,
    (aminopeptidase N, Zinc, Signal-anchor,
    aminopeptidase M, Transmembrane, Glycoprotein,
    microsomal Sulfation, Polymorphism
    aminopeptidase,
    CD13, p150)
    NM_001152 SLC25A5 solute carrier family Mitochondrion, Inner membrane, 2006 5974
    25 (mitochondrial Repeat, Transmembrane, Transport,
    carrier; adenine Multigene family
    nucleotide
    translocator),
    member 5
    NM_001153 ANXA4 annexin A4 Annexin, Calcium/phospholipid- 2007 5975
    binding, Repeat
    NM_001155 ANXA6 annexin A6 Annexin, Calcium/phospholipid- 2008 5976
    binding, Repeat, Acetylation,
    Phosphorylation, 3D-structure
    NM_001157 ANXA11 annexin A11 Annexin, Calcium/phospholipid- 2009 5977
    binding, Repeat, Polymorphism
    NM_001172 ARG2 arginase, type II Urea cycle, Arginine metabolism, 2010 5978
    Hydrolase, Manganese, Transit
    peptide, Mitochondrion, Receptor,
    Transmembrane, Transport, Protein
    transport, Coiled coil, Alternative
    splicing
    NM_001175 ARHGDIB Rho GDP GTPase activation, 3D-structure 2011 5979
    dissociation inhibitor
    (GDI) beta
    NM_001181 ASGR2 asialoglycoprotein Lectin, Glycoprotein, Receptor, 2012 5980
    receptor 2 Endocytosis, Transmembrane,
    Calcium, Signal-anchor,
    Phosphorylation, Alternative splicing
    NM_001182 ALDH7A1 aldehyde Oxidoreductase, NAD 2013 5981
    dehydrogenase 7
    family, member A1
    NM_001183 ATP6IP1 ATPase, H+ Hypothetical protein, ATP synthesis, 2014 5982
    transporting, Hydrogen ion transport, Hydrolase,
    lysosomal accessory ATP-binding, Transmembrane,
    protein 1 Glycoprotein, Signal
    NM_001184 ATR ataxia telangiectasia Kinase, Transferase 2015 5983
    and Rad3 related
    NM_001196 BID BH3 interacting Apoptosis, 3D-structure 2016 5984
    domain death
    agonist
    NM_001199 BMP1 bone morphogenetic Growth factor, Cytokine, Repeat, 2017 5985
    protein 1 Osteogenesis, Chondrogenesis,
    Hydrolase, Metalloprotease, EGF-
    like domain, Zinc, Calcium, Signal,
    Glycoprotein, Zymogen, Alternative
    splicing, Collagen
    NM_001206 BTEB1 basic transcription Transcription regulation, DNA- 2018 5986
    element binding binding, Nuclear protein, Repeat,
    protein 1 Zinc-finger, Metal-binding
    NM_001207 BTF3 basic transcription Transcription regulation, Nuclear 2019 5987
    factor 3 protein, Alternative splicing
    NM_001208 BTF3L1 basic transcription Transcription regulation, Nuclear 2020 5988
    factor 3, like 1 protein
    NM_001212 C1QBP complement Mitochondrion, Transit peptide, 3D- 2021 5989
    component 1, q structure, Hypothetical protein
    subcomponent
    binding protein
    NM_001222 CAMK2G calcium/calmodulin- Alternative splicing 2022 5990
    dependent protein
    kinase (CaM kinase)
    II gamma
    NM_001237 CCNA2 cyclin A2 Cyclin, Cell cycle, Cell division, 2023 5991
    Mitosis, 3D-structure
    NM_001252 TNFSF7 tumor necrosis factor Cytokine, Transmembrane, 2024 5992
    (ligand) superfamily, Glycoprotein, Signal-anchor, Antigen
    member 7
    NM_001256 CDC27 cell division cycle 27 Repeat, TPR repeat, Nuclear 2025 5993
    protein, Polymorphism
    NM_001259 CDK6 cyclin-dependent Transferase, Serine/threonine- 2026 5994
    kinase 6 protein kinase, ATP-binding, Cell
    cycle, Cell division, Phosphorylation,
    3D-structure
    NM_001266 CES1 carboxylesterase 1 Glycoprotein, Hydrolase, Serine 2027 5995
    (monocyte/macrophage esterase, Endoplasmic reticulum,
    serine esterase Signal, Multigene family,
    1) Polymorphism, Hypothetical protein
    NM_001276 CHI3L1 chitinase 3-like 1 Glycoprotein, Signal, 3D-structure 2028 5996
    (cartilage
    glycoprotein-39)
    NM_001282 AP2B1 adaptor-related Hypothetical protein, Coated pits, 2029 5997
    protein complex 2, 3D-structure
    beta
    1 subunit
    NM_001284 AP3S1 adaptor-related Golgi stack, Protein transport, 2030 5998
    protein complex 3, Transport
    sigma 1 subunit
    NM_001286 CLCN6 chloride channel 6 Ionic channel, Ion transport, Chloride 2031 5999
    channel, Chloride, Voltage-gated
    channel, Transmembrane, CBS
    domain, Repeat, Alternative splicing
    NM_001288 CLIC1 chloride intracellular Ionic channel, Ion transport, Chloride 2032 6000
    channel 1 channel, Chloride, Voltage-gated
    channel, Nuclear protein, 3D-
    structure
    NM_001292 CLK3 CDC-like kinase 3 Transferase, Serine/threonine- 2033 6001
    protein kinase, ATP-binding,
    Tyrosine-protein kinase,
    Phosphorylation, Nuclear protein,
    Alternative splicing
    NM_001293 CLNS1A chloride channel, Nuclear protein, Polymorphism 2034 6002
    nucleotide-sensitive,
    1A
    NM_001294 CLPTM1 cleft lip and palate Transmembrane 2035 6003
    associated
    transmembrane
    protein
    1
    NM_001305 CLDN4 claudin 4 Tight junction, Transmembrane, 2036 6004
    Williams-Beuren syndrome
    NM_001313 CRMP1 collapsin response Repeat, WD repeat 2037 6005
    mediator protein 1
    NM_001315 MAPK14 mitogen-activated ATP-binding, Kinase, Transferase, 2038 6006
    protein kinase 14 Serine/threonine-protein kinase,
    Phosphorylation, Alternative splicing,
    3D-structure
    NM_001317 CSH1 chorionic Chorion, Hormone, Placenta, 2039 6007
    somatomammotropin Multigene family, Signal
    hormone 1
    (placental lactogen)
    NM_001325 CSTF2 cleavage stimulation RNA-binding, Repeat, 2040 6008
    factor, 3′ pre-RNA, Phosphorylation, Nuclear protein
    subunit
    2, 64 kDa
    NM_001331 CTNND1 catenin (cadherin- Cytoskeleton, Structural protein, 2041 6009
    associated protein), Phosphorylation, Repeat, Cell
    delta
    1 adhesion, Coiled coil, Nuclear
    protein, Alternative splicing
    NM_001338 CXADR coxsackie virus and Immunoglobulin domain, Receptor, 2042 6010
    adenovirus receptor Transmembrane, Glycoprotein,
    Signal, Repeat, 3D-structure
    NM_001346 DGKG diacylglycerol Transferase, Kinase, Calcium- 2043 6011
    kinase, gamma binding, Phorbol-ester binding,
    90 kDa Repeat, Multigene family, Alternative
    splicing
    NM_001357 DDX9 DEAH (Asp-Glu-Ala- Helicase, RNA-binding, DNA- 2044 6012
    His) box polypeptide 9 binding, Repeat, Nuclear protein,
    ATP-binding
    NM_001358 DDX15 DEAH (Asp-Glu-Ala- mRNA processing, mRNA splicing, 2045 6013
    His) box polypeptide Helicase, ATP-binding, Nuclear
    15 protein
    NM_001363 DKC1 dyskeratosis Telomere, RNA-binding, Nuclear 2046 6014
    congenita 1, protein, Disease mutation
    dyskerin
    NM_001381 DOK1 docking protein 1, Phosphorylation, Alternative splicing 2047 6015
    62 kDa (downstream
    of tyrosine kinase 1)
    NM_001383 DPH2L1 diptheria toxin 2048 6016
    resistance protein
    required for
    diphthamide
    biosynthesis-like 1
    (S. cerevisiae)
    NM_001388 DRG2 developmentally GTP-binding 2049 6017
    regulated GTP
    binding protein
    2
    NM_001406 EFNB3 ephrin-B3 Developmental protein, 2050 6018
    Neurogenesis, Transmembrane,
    Glycoprotein, Signal, Polymorphism
    NM_001415 EIF2S3 eukaryotic Initiation factor, Protein biosynthesis, 2051 6019
    translation initiation GTP-binding, Polymorphism
    factor 2, subunit 3
    gamma, 52 kDa
    NM_001419 ELAVL1 ELAV (embryonic RNA-binding, Repeat 2052 6020
    lethal, abnormal
    vision, Drosophila)-
    like 1 (Hu antigen R)
    NM_001421 ELF4 E74-like factor 4 (ets 2053 6021
    domain transcription
    factor)
    NM_001423 EMP1 epithelial membrane Transmembrane, Glycoprotein 2054 6022
    protein 1
    NM_001431 EPB41L2 erythrocyte Hypothetical protein, Structural 2055 6023
    membrane protein protein, Cytoskeleton, Actin-binding
    band 4.1-like 2
    NM_001432 EREG epiregulin Angiogenesis, Growth factor, 2056 6024
    Mitogen, Glycoprotein, EGF-like
    domain, Transmembrane, Signal
    NM_001440 EXTL3 exostoses (multiple)- Transferase, Glycosyltransferase, 2057 6025
    like 3 Endoplasmic reticulum,
    Transmembrane, Signal-anchor,
    Glycoprotein
    NM_001444 FABP5 fatty acid binding Transport, Lipid-binding, 3D- 2058 6026
    protein 5 (psoriasis- structure
    associated)
    NM_001449 FHL1 four and a half LIM Coiled coil, Transcription regulation, 2059 6027
    domains 1 Nuclear protein, Disease mutation,
    Anhidrotic ectodermal dysplasia,
    Repeat, LIM domain, Metal-binding,
    Zinc, Developmental protein,
    Differentiation, Zinc-finger
    NM_001455 FOXO3A forkhead box O3A Transcription regulation, DNA- 2060 6028
    binding, Nuclear protein, Apoptosis,
    Chromosomal translocation, Proto-
    oncogene, Phosphorylation
    NM_001456 FLNA filamin A, alpha Cytoskeleton, Actin-binding, Repeat, 2061 6029
    (actin binding protein Phosphorylation, Polymorphism,
    280) Disease mutation, Multigene family,
    Hypothetical protein
    NM_001462 FPRL1 formyl peptide G-protein coupled receptor, 2062 6030
    receptor-like 1 Transmembrane, Glycoprotein,
    Chemotaxis, Repeat, WD repeat
    NM_001465 FYB FYN binding protein SH3 domain, Phosphorylation, 2063 6031
    (FYB-120/130) Nuclear protein, Coiled coil,
    Alternative splicing
    NM_001467 G6PT1 solute carrier family Transmembrane, Transport, Sugar 2064 6032
    37 (glycerol-6- transport, Endoplasmic reticulum,
    phosphate Alternative splicing, Glycogen
    transporter), storage disease, Disease mutation
    member
    4
    NM_001469 G22P1 thyroid autoantigen Helicase, Nuclear protein, DNA- 2065 6033
    70 kDa (Ku antigen) binding, Phosphorylation, Antigen,
    Systemic lupus erythematosus,
    Acetylation, 3D-structure
    NM_001478 GALGT UDP-N-acetyl-alpha- Hypothetical protein, Transferase, 2066 6034
    D-galactosamine:(N- Glycosyltransferase,
    acetylneuraminyl)- Transmembrane, Signal-anchor,
    galactosylglucosylceramide Golgi stack, Glycoprotein,
    N- Polymorphism
    acetylgalactosaminyl
    transferase
    (GalNAc-T)
    NM_001482 GATM glycine Transferase, Mitochondrion, Transit 2067 6035
    amidinotransferase peptide, 3D-structure, Alternative
    (L-arginine:glycine splicing
    amidinotransferase)
    NM_001483 GBAS glioblastoma 2068 6036
    amplified sequence
    NM_001487 GCN5L1 GCN5 general 2069 6037
    control of amino-acid
    synthesis 5-like 1
    (yeast)
    NM_001493 GDI1 GDP dissociation GTPase activation, Disease 2070 6038
    inhibitor 1 mutation
    NM_001500 GMDS GDP-mannose 4,6- Lyase, NADP 2071 6039
    dehydratase
    NM_001503 GPLD1 glycosylphosphatidyl Hydrolase, Glycoprotein, Signal, 2072 6040
    inositol specific Hypothetical protein
    phospholipase D1
    NM_001504 CXCR3 chemokine (C—X—C G-protein coupled receptor, 2073 6041
    motif) receptor 3 Transmembrane, Glycoprotein,
    Antigen, Polymorphism
    NM_001517 GTF2H4 general transcription Transcription regulation, DNA repair, 2074 6042
    factor IIH, Nuclear protein
    polypeptide
    4,
    52 kDa
    NM_001518 GTF2I general transcription Transcription regulation, DNA- 2075 6043
    factor II, i binding, Nuclear protein,
    Phosphorylation, Repeat, Williams-
    Beuren syndrome, Alternative
    splicing
    NM_001519 BRF1 BRF1 homolog, Transcription regulation, Activator, 2076 6044
    subunit of RNA Nuclear protein, Repeat, Zinc-finger,
    polymerase III Metal-binding, Zinc, Alternative
    transcription splicing, Hypothetical protein
    initiation factor IIIB
    (S. cerevisiae)
    NM_001520 GTF3C1 general transcription 2077 6045
    factor IIIC,
    polypeptide 1, alpha
    220 kDa
    NM_001528 HGFAC HGF activator Hydrolase, Glycoprotein, Plasma, 2078 6046
    Serine protease, Kringle, Signal,
    EGF-like domain, Repeat, Zymogen
    NM_001531 MR1 major MHC, Glycoprotein, Transmembrane 2079 6047
    histocompatibility
    complex, class I-
    related
    NM_001536 HRMT1L2 HMT1 hnRNP Transferase, Methyltransferase, 2080 6048
    methyltransferase- Nuclear protein, Alternative splicing
    like 2 (S. cerevisiae)
    NM_001538 HSF4 F-box and leucine- Transcription regulation, Nuclear 2081 6049
    rich repeat protein 8 protein, DNA-binding, Activator,
    Repressor, Heat shock, Multigene
    family, Alternative splicing
    NM_001539 DNAJA1 DnaJ (Hsp40) Chaperone, Repeat, Zinc, Metal- 2082 6050
    homolog, subfamily binding, Prenylation, Lipoprotein,
    A, member 1 Multigene family
    NM_001550 IFRD1 interferon-related 2083 6051
    developmental
    regulator
    1
    NM_001551 IGBP1 immunoglobulin B-cell activation, Phosphorylation 2084 6052
    (CD79A) binding
    protein 1
    NM_001554 CYR61 cysteine-rich, Plasmid, Chemotaxis, Cell adhesion, 2085 6053
    angiogenic inducer, Growth factor binding, Heparin-
    61 binding, Signal
    NM_001557 IL8RB interleukin 8 G-protein coupled receptor, 2086 6054
    receptor, beta Transmembrane, Glycoprotein,
    Chemotaxis, Polymorphism,
    Receptor
    NM_001558 IL10RA interleukin 10 Receptor, Transmembrane, 2087 6055
    receptor, alpha Glycoprotein, Signal, Polymorphism,
    3D-structure
    NM_001567 INPPL1 inositol DNA repair 2088 6056
    polyphosphate
    phosphatase-like 1
    NM_001572 IRF7 interferon regulatory Transcription regulation, DNA- 2089 6057
    factor 7 binding, Nuclear protein, Activator,
    Alternative splicing, Collagen
    NM_001607 ACAA1 acetyl-Coenzyme A Acyltransferase, Transferase, Fatty 2090 6058
    acyltransferase 1 acid metabolism, Peroxisome,
    (peroxisomal 3- Transit peptide, Polymorphism
    oxoacyl-Coenzyme
    A thiolase)
    NM_001618 ADPRT ADP- Transferase, Glycosyltransferase, 2091 6059
    ribosyltransferase NAD, DNA-binding, Nuclear protein,
    (NAD+; poly (ADP- ADP-ribosylation, Zinc-finger, Zinc,
    ribose) polymerase) Polymorphism
    NM_001619 ADRBK1 adrenergic, beta, Kinase, Receptor, Transferase, 2092 6060
    receptor kinase 1 Serine/threonine-protein kinase,
    ATP-binding, Multigene family, 3D-
    structure
    NM_001621 AHR aryl hydrocarbon Cell cycle, Transcription regulation, 2093 6061
    receptor Activator, Receptor, DNA-binding,
    Nuclear protein, Repeat,
    Polymorphism
    NM_001628 AKR1B1 aldo-keto reductase Oxidoreductase, NADP, Acetylation, 2094 6062
    family 1, member B1 3D-structure, Polymorphism
    (aldose reductase)
    NM_001629 ALOX5AP arachidonate 5- Transmembrane, Leukotriene 2095 6063
    lipoxygenase- biosynthesis
    activating protein
    NM_001632 ALPP alkaline Hydrolase, Zinc, Magnesium, 2096 6064
    phosphatase, Phosphorylation, Transmembrane,
    placental (Regan Placenta, Multigene family,
    isozyme) Glycoprotein, GPI-anchor, Signal,
    3D-structure, Lipoprotein
    NM_001634 AMD1 adenosylmethionine Spermidine biosynthesis, Lyase, 2097 6065
    decarboxylase 1 Decarboxylase, Pyruvate, Zymogen,
    3D-structure
    NM_001637 AOAH acyloxyacyl Hydrolase, Signal, Transmembrane, 2098 6066
    hydrolase Glycoprotein
    (neutrophil)
    NM_001643 APOA2 apolipoprotein A-II Transport, Lipid transport, HDL, 2099 6067
    Signal, Pyrrolidone carboxylic acid,
    3D-structure
    NM_001654 ARAF1 v-raf murine Transferase, Serine/threonine- 2100 6068
    sarcoma 3611 viral protein kinase, Proto-oncogene,
    oncogene homolog 1 Metal-binding, Zinc, ATP-binding,
    Phorbol-ester binding, Kinase
    NM_001657 AREG amphiregulin Glycoprotein, Cytokine, Growth 2101 6069
    (schwannoma- factor, EGF-like domain, Signal,
    derived growth Transmembrane
    factor)
    NM_001662 ARF5 ADP-ribosylation GTP-binding, Multigene family, 2102 6070
    factor 5 Myristate, Protein transport, Golgi
    stack, Lipoprotein
    NM_001665 ARHG ras homolog gene GTP-binding, Prenylation, 2103 6071
    family, member G Lipoprotein
    (rho G)
    NM_001667 ARL2 sorting nexin 15 GTP-binding, Multigene family, 2104 6072
    Hypothetical protein, Transport,
    Protein transport, Alternative splicing
    NM_001670 ARVCF armadillo repeat Hypothetical protein, Cell adhesion, 2105 6073
    gene deletes in Cytoskeleton, Structural protein,
    velocardiofacial Repeat, Coiled coil, Alternative
    syndrome splicing
    NM_001671 ASGR1 asialoglycoprotein Lectin, Glycoprotein, Receptor, 2106 6074
    receptor 1 Endocytosis, Transmembrane,
    Calcium, Signal-anchor,
    Phosphorylation, 3D-structure
    NM_001677 ATP1B1 ATPase, Na+/K+ Transferase, Kinase, ATP-binding, 2107 6075
    transporting, beta 1 Sodium/potassium transport,
    polypeptide Transmembrane, Glycoprotein,
    Multigene family, Signal-anchor,
    Alternative splicing
    NM_001678 ATP1B2 ATPase, Na+/K+ Sodium/potassium transport, 2108 6076
    transporting, beta 2 Transmembrane, Glycoprotein,
    polypeptide Multigene family, Signal-anchor
    NM_001679 ATP1B3 ATPase, Na+/K+ Sodium/potassium transport, 2109 6077
    transporting, beta 3 Transmembrane, Glycoprotein,
    polypeptide Multigene family, Signal-anchor
    NM_001681 ATP2A2 ATPase, Ca++ Hydrolase, Calcium transport, 2110 6078
    transporting, cardiac Transmembrane, Phosphorylation,
    muscle, slow twitch 2 ATP-binding, Metal-binding,
    Magnesium, Calcium-binding,
    Multigene family, Alternative splicing,
    Disease mutation, Epilepsy
    NM_001693 ATP6V1B2 ATPase, H+ Hydrolase, ATP synthesis, Hydrogen 2111 6079
    transporting, ion transport, Multigene family
    lysosomal 56/58 kDa,
    V1 subunit B,
    isoform 2
    NM_001706 BCL6 B-cell Nuclear protein, Transcription 2112 6080
    CLL/lymphoma 6 regulation, Activator, DNA-binding,
    (zinc finger protein Zinc-finger, Metal-binding, Repeat,
    51) Proto-oncogene, Chromosomal
    translocation, Polymorphism
    NM_001712 CEACAM1 carcinoembryonic Alternative splicing, Immunoglobulin 2113 6081
    antigen-related cell domain, Signal, Transmembrane,
    adhesion molecule 1 Glycoprotein, Repeat, Pyrrolidone
    (biliary glycoprotein) carboxylic acid, Hypothetical protein
    NM_001714 BICD1 Bicaudal D homolog Golgi stack, Coiled coil, Alternative 2114 6082
    1 (Drosophila) splicing
    NM_001716 BLR1 Burkitt lymphoma B-cell activation, G-protein coupled 2115 6083
    receptor 1, GTP receptor, Transmembrane,
    binding protein Glycoprotein, Alternative splicing,
    (chemokine (C—X—C Polymorphism
    motif) receptor 5)
    NM_001721 BMX BMX non-receptor Transferase, Tyrosine-protein 2116 6084
    tyrosine kinase kinase, Phosphorylation, ATP-
    binding, SH3 domain, SH2 domain
    NM_001725 BPI bactericidal/permeability- Antibiotic, Signal, Transmembrane, 2117 6085
    increasing Glycoprotein, 3D-structure
    protein
    NM_001728 BSG basigin (OK blood Immunoglobulin domain, 2118 6086
    group) Transmembrane, Glycoprotein,
    Signal, Antigen, Blood group
    antigen, Polymorphism
    NM_001730 KLF5 Kruppel-like factor 5 Transcription regulation, DNA- 2119 6087
    (intestinal) binding, Nuclear protein, Repeat,
    Zinc-finger, Metal-binding, Activator
    NM_001731 BTG1 B-cell translocation Proto-oncogene, Chromosomal 2120 6088
    gene 1, anti- translocation
    proliferative
    NM_001736 C5R1 complement G-protein coupled receptor, 2121 6089
    component 5 Transmembrane, Glycoprotein,
    receptor 1 (C5a Sulfation, Chemotaxis
    ligand)
    NM_001745 CAMLG calcium modulating Transmembrane 2122 6090
    ligand
    NM_001747 CAPG capping protein Nuclear protein, Actin-binding, 2123 6091
    (actin filament), Repeat, 3D-structure, Actin capping
    gelsolin-like
    NM_001749 CAPNS1 calpain, small Calcium-binding, Repeat, 3D- 2124 6092
    subunit 1 structure
    NM_001750 CAST calpastatin Repeat, Thiol protease inhibitor, 2125 6093
    Alternative splicing, Phosphorylation,
    Signal transduction inhibitor
    NM_001767 CD2 CD2 antigen (p50), Immunoglobulin domain, T-cell, 2126 6094
    sheep red blood cell Glycoprotein, Antigen,
    receptor Transmembrane, Cell adhesion,
    Repeat, Signal, Polymorphism, 3D-
    structure
    NM_001769 CD9 CD9 antigen (p24) Glycoprotein, Antigen, 2127 6095
    Transmembrane, Lipoprotein,
    Phosphorylation
    NM_001771 CD22 CD22 antigen Cell adhesion, Lectin, Antigen, 2128 6096
    Transmembrane, Signal,
    Glycoprotein, Immunoglobulin
    domain, Repeat, Phosphorylation,
    Alternative splicing, Polymorphism
    NM_001773 CD34 CD34 antigen Cell adhesion, Antigen, Signal, 2129 6097
    Transmembrane, Glycoprotein,
    Phosphorylation, Alternative splicing
    NM_001774 CD37 CD37 antigen Glycoprotein, Antigen, 2130 6098
    Transmembrane, Hypothetical
    protein
    NM_001776 ENTPD1 ectonucleoside Hydrolase, Transmembrane, 2131 6099
    triphosphate Antigen, Glycoprotein, Calcium,
    diphosphohydrolase 1 Magnesium, Alternative splicing,
    Lipoprotein, Palmitate
    NM_001777 CD47 CD47 antigen (Rh- Cell adhesion, Antigen, Signal, 2132 6100
    related antigen, Transmembrane, Glycoprotein,
    integrin-associated Alternative splicing
    signal transducer)
    NM_001780 CD63 CD63 antigen Glycoprotein, Antigen, 2133 6101
    (melanoma 1 Transmembrane, Lysosome
    antigen)
    NM_001781 CD69 CD69 antigen (p60, Antigen, Signal-anchor, 2134 6102
    early T-cell Transmembrane, Lectin,
    activation antigen) Glycoprotein, Phosphorylation, 3D-
    structure
    NM_001800 CDKN2D cyclin-dependent Cell cycle, Anti-oncogene, Repeat, 2135 6103
    kinase inhibitor 2D ANK repeat, 3D-structure
    (p19, inhibits CDK4)
    NM_001803 CDW52 CDW52 antigen Antigen, Signal, Glycoprotein, GPI- 2136 6104
    (CAMPATH-1 anchor, Membrane, Polymorphism,
    antigen) Lipoprotein
    NM_001805 CEBPE CCAAT/enhancer Transcription regulation, Activator, 2137 6105
    binding protein DNA-binding, Nuclear protein,
    (C/EBP), epsilon Phosphorylation
    NM_001806 CEBPG CCAAT/enhancer Transcription regulation, Activator, 2138 6106
    binding protein DNA-binding, Nuclear protein
    (C/EBP), gamma
    NM_001808 CELL carboxyl ester lipase 2139 6107
    pseudogene
    NM_001815 CEACAM3 carcinoembryonic Immunoglobulin domain, Antigen, 2140 6108
    antigen-related cell Signal, Glycoprotein,
    adhesion molecule 3 Transmembrane, Alternative
    splicing, Polymorphism
    NM_001816 CEACAM8 carcinoembryonic Immunoglobulin domain, Antigen, 2141 6109
    antigen-related cell Signal, Glycoprotein, GPI-anchor,
    adhesion molecule 8 Repeat, Polymorphism, Lipoprotein
    NM_001817 CEACAM4 carcinoembryonic Antigen 2142 6110
    antigen-related cell
    adhesion molecule
    4
    NM_001828 CLC Charot-Leyden Hydrolase, Serine esterase, Lipid 2143 6111
    crystal protein degradation, Galectin, Acetylation,
    3D-structure, Polymorphism
    NM_001835 CLTCL1 clathrin, heavy Coated pits, Alternative splicing 2144 6112
    polypeptide-like 1
    NM_001838 CCR7 chemokine (C-C G-protein coupled receptor, 2145 6113
    motif) receptor 7 Transmembrane, Glycoprotein,
    Signal
    NM_001839 CNN3 calponin 3, acidic Calmodulin-binding, Actin-binding, 2146 6114
    Multigene family, Repeat
    NM_001853 COL9A3 collagen, type IX, Hypothetical protein, Collagen, 2147 6115
    alpha 3 Extracellular matrix, Connective
    tissue, Repeat, Hydroxylation,
    Glycoprotein, Signal, Polymorphism
    NM_001882 CRHBP corticotropin Glycoprotein, Signal 2148 6116
    releasing hormone
    binding protein
    NM_001889 CRYZ crystallin, zeta Oxidoreductase, NADP, Zinc 2149 6117
    (quinone reductase)
    NM_001894 CSNK1E casein kinase 1, Transferase, Serine/threonine- 2150 6118
    epsilon protein kinase, ATP-binding,
    Phosphorylation, Multigene family
    NM_001907 CTRL chymotrypsin-like Hydrolase, Protease, Serine 2151 6119
    protease, Transferase,
    Serine/threonine-protein kinase,
    ATP-binding, Phosphorylation, Golgi
    stack, Nuclear protein, Glycoprotein,
    Zymogen, Signal
    NM_001909 CTSD cathepsin D Hydrolase, Aspartyl protease, 2152 6120
    (lysosomal aspartyl Glycoprotein, Lysosome, Signal,
    protease) Zymogen, Polymorphism,
    Alzheimer's disease, 3D-structure
    NM_001911 CTSG cathepsin G Hydrolase, Serine protease, 2153 6121
    Zymogen, Glycoprotein, Signal,
    Polymorphism, 3D-structure
    NM_001921 DCTD dCMP deaminase Hydrolase, Allosteric enzyme, 2154 6122
    Nucleotide biosynthesis, Zinc
    NM_001925 DEFA4 defensin, alpha 4, Defensin, Antibiotic, Fungicide, 2155 6123
    corticostatin Signal
    NM_001939 DRP2 dystrophin related Structural protein, Cytoskeleton, 2156 6124
    protein 2 Repeat, Zinc-finger
    NM_001940 DRPLA dentatorubral- Triplet repeat expansion, 2157 6125
    pallidoluysian Polymorphism, Epilepsy
    atrophy (atrophin-1)
    NM_001946 DUSP6 dual specificity Hydrolase, Polymorphism, 2158 6126
    phosphatase 6 Alternative splicing, 3D-structure
    NM_001951 E2F5 E2F transcription Transcription regulation, Activator, 2159 6127
    factor 5, p130- DNA-binding, Nuclear protein,
    binding Polymorphism
    NM_001953 ECGF1 endothelial cell Transferase, Glycosyltransferase, 2160 6128
    growth factor 1 Growth factor, Chemotaxis,
    (platelet-derived) Angiogenesis, Repeat,
    Polymorphism, Disease mutation
    NM_001964 EGR1 early growth Transcription regulation, Activator, 2161 6129
    response 1 DNA-binding, Nuclear protein,
    Repeat, Zinc-finger, Metal-binding
    NM_001965 EGR4 early growth Nuclear protein, Transcription 2162 6130
    response 4 regulation, DNA-binding, Zinc-finger,
    Metal-binding, Repeat
    NM_001970 EIF5A eukaryotic Protein biosynthesis, Initiation factor, 2163 6131
    translation initiation Hypusine, 3D-structure
    factor 5A
    NM_001972 ELA2 elastase 2, Hydrolase, Serine protease, 2164 6132
    neutrophil Glycoprotein, Signal, 3D-structure,
    Disease mutation
    NM_001992 F2R coagulation factor II G-protein coupled receptor, 2165 6133
    (thrombin) receptor Transmembrane, Glycoprotein,
    Signal, Blood coagulation,
    Phosphorylation, Polymorphism, 3D-
    structure, Receptor
    NM_001995 FACL1 fatty-acid-Coenzyme Ligase, Fatty acid metabolism, 2166 6134
    A ligase, long-chain 2 Magnesium, Multigene family,
    Hypothetical protein
    NM_001996 FBLN1 fibulin 1 Signal, Alternative splicing, 2167 6135
    Glycoprotein, Extracellular matrix,
    Repeat, EGF-like domain, Calcium-
    binding, Chromosomal translocation,
    Polymorphism, Hypothetical protein
    NM_001999 FBN2 fibrillin 2 (congenital Hypothetical protein, EGF-like 2168 6136
    contractural domain, Extracellular matrix,
    arachnodactyly) Calcium-binding, Glycoprotein,
    Repeat, Signal, Multigene family,
    Disease mutation, Polymorphism
    NM_002000 FCAR Fc fragment of IgA, Receptor, Glycoprotein, 2169 6137
    receptor for Transmembrane, IgA-binding
    protein, Immunoglobulin domain,
    Repeat, Signal, Alternative splicing
    NM_002003 FCN1 ficolin Lectin, Collagen, Repeat, 2170 6138
    (collagen/fibrinogen Glycoprotein, Signal, Multigene
    domain containing) 1 family
    NM_002005 FES feline sarcoma Transferase, Tyrosine-protein 2171 6139
    oncogene kinase, Proto-oncogene, ATP-
    binding, Phosphorylation, SH2
    domain
    NM_002010 FGF9 fibroblast growth Growth factor, Differentiation, 2172 6140
    factor 9 (glia- Mitogen, Heparin-binding,
    activating factor) Glycoprotein, 3D-structure
    NM_002013 FKBP3 FK506 binding Isomerase, Rotamase, Nuclear 2173 6141
    protein 3, 25 kDa protein, 3D-structure
    NM_002014 FKBP4 FK506 binding Isomerase, Rotamase, Repeat, TPR 2174 6142
    protein 4, 59 kDa repeat, Nuclear protein,
    Phosphorylation, 3D-structure
    NM_002017 FLI1 Friend leukemia Transcription regulation, Activator, 2175 6143
    virus integration 1 DNA-binding, Nuclear protein,
    Alternative splicing, Proto-oncogene,
    Chromosomal translocation, 3D-
    structure
    NM_002018 FLII flightless I homolog Developmental protein, Repeat, 2176 6144
    (Drosophila) Leucine-rich repeat
    NM_002029 FPR1 formyl peptide G-protein coupled receptor, 2177 6145
    receptor 1 Transmembrane, Glycoprotein,
    Chemotaxis, Polymorphism
    NM_002032 FTH1 ferritin, heavy Transport, Ion transport, Ionic 2178 6146
    polypeptide 1 channel, Chloride channel, Chloride,
    Calcium, Alternative splicing,
    Disease mutation, Polymorphism,
    Vision, Transmembrane,
    Phosphorylation, Iron storage, Metal-
    binding, 3D-structure
    NM_002033 FUT4 fucosyltransferase 4 Transferase, Glycosyltransferase, 2179 6147
    (alpha (1,3) Transmembrane, Glycoprotein,
    fucosyltransferase, Signal-anchor, Golgi stack
    myeloid-specific)
    NM_002035 FVT1 follicular lymphoma Proto-oncogene, Chromosomal 2180 6148
    variant translocation 1 translocation, Oxidoreductase,
    Signal
    NM_002037 FYN FYN oncogene Hypothetical protein, ATP-binding, 2181 6149
    related to SRC, SH3 domain, Transferase, Kinase,
    FGR, YES Tyrosine-protein kinase, Proto-
    oncogene, Phosphorylation,
    Myristate, SH2 domain, Palmitate,
    Lipoprotein, 3D-structure,
    Polymorphism
    NM_002046 GAPD glyceraldehyde-3- Glycolysis, NAD, Oxidoreductase, 2182 6150
    phosphate Multigene family
    dehydrogenase
    NM_002051 GATA3 GATA binding Hypothetical protein, Transcription 2183 6151
    protein 3 regulation, Activator, DNA-binding,
    Zinc-finger, Nuclear protein, T-cell,
    Alternative splicing
    NM_002061 GCLM glutamate-cysteine Ligase, Glutathione biosynthesis 2184 6152
    ligase, modifier
    subunit
    NM_002064 GLRX glutaredoxin Redox-active center, Electron 2185 6153
    (thioltransferase) transport, Acetylation,
    Polymorphism, 3D-structure
    NM_002068 GNA15 guanine nucleotide GTP-binding, Transducer, Multigene 2186 6154
    binding protein (G family, ADP-ribosylation
    protein), alpha 15
    (Gq class)
    NM_002069 GNAI1 guanine nucleotide Hypothetical protein, GTP-binding, 2187 6155
    binding protein (G Transducer, ADP-ribosylation,
    protein), alpha Multigene family, Myristate,
    inhibiting activity Palmitate, Lipoprotein, 3D-structure
    polypeptide
    1
    NM_002070 GNAI2 guanine nucleotide GTP-binding, Transducer, ADP- 2188 6156
    binding protein (G ribosylation, Multigene family,
    protein), alpha Myristate, Palmitate, Lipoprotein
    inhibiting activity
    polypeptide
    2
    NM_002073 GNAZ guanine nucleotide GTP-binding, Transducer, ADP- 2189 6157
    binding protein (G ribosylation, Multigene family,
    protein), alpha z Lipoprotein, Palmitate, Myristate,
    polypeptide Membrane
    NM_002081 GPC1 glypican 1 Proteoglycan, Heparan sulfate, 2190 6158
    Glycoprotein, Signal, GPI-anchor,
    Lipoprotein
    NM_002082 GPRK6 G protein-coupled Transferase, Serine/threonine- 2191 6159
    receptor kinase 6 protein kinase, ATP-binding,
    Phosphorylation, Lipoprotein,
    Palmitate, Alternative splicing,
    Kinase, Receptor, Hypothetical
    protein
    NM_002086 GRB2 growth factor SH2 domain, SH3 domain, Repeat, 2192 6160
    receptor-bound Alternative splicing, 3D-structure
    protein
    2
    NM_002087 GRN granulin Cytokine, Repeat, Glycoprotein, 2193 6161
    Signal, Alternative splicing,
    Polymorphism, 3D-structure,
    Hypothetical protein
    NM_002092 GRSF1 G-rich RNA Hypothetical protein, RNA-binding, 2194 6162
    sequence binding Repeat
    factor 1
    NM_002093 GSK3B glycogen synthase Transferase, Serine/threonine- 2195 6163
    kinase 3 beta protein kinase, ATP-binding, Wnt
    signaling pathway, Phosphorylation,
    Multigene family, Alternative splicing,
    3D-structure
    NM_002096 GTF2F1 general transcription Transcription regulation, DNA- 2196 6164
    factor IIF, binding, Nuclear protein,
    polypeptide 1, Phosphorylation, 3D-structure
    74 kDa
    NM_002097 GTF3A general transcription Transcription regulation, Zinc-finger, 2197 6165
    factor IIIA Metal-binding, DNA-binding, RNA-
    binding, Repeat, Nuclear protein,
    Polymorphism, Initiation factor
    NM_002103 GYS1 glycogen synthase 1 Glycogen biosynthesis, Transferase, 2198 6166
    (muscle) Glycosyltransferase, Allosteric
    enzyme, Phosphorylation, Disease
    mutation, Diabetes mellitus,
    Polymorphism, Hypothetical protein
    NM_002104 GZMK granzyme K (serine Hydrolase, Serine protease, 2199 6167
    protease, granzyme Zymogen, Signal, 3D-structure
    3; tryptase II)
    NM_002105 H2AFX H2A histone family, Chromosomal protein, Nucleosome 2200 6168
    member X core, Nuclear protein, DNA-binding,
    Multigene family, Acetylation
    NM_002107 H3F3A H3 histone, family Nuclear protein, Chromosomal 2201 6169
    3A protein, DNA-binding, Nucleosome
    core, Multigene family
    NM_002108 HAL histidine ammonia- Lyase, Histidine metabolism, 2202 6170
    lyase Polymorphism
    NM_002109 HARS histidyl-tRNA Aminoacyl-tRNA synthetase, Protein 2203 6171
    synthetase biosynthesis, Ligase, ATP-binding,
    Hypothetical protein, Repeat, WD
    repeat
    NM_002110 HCK hemopoietic cell Transferase, Tyrosine-protein 2204 6172
    kinase kinase, Phosphorylation, ATP-
    binding, Lipoprotein, Myristate,
    Palmitate, SH2 domain, SH3
    domain, Alternative initiation, 3D-
    structure
    NM_002115 HK3 hexokinase 3 (white Kinase, Transferase, Glycolysis, 2205 6173
    cell) Allosteric enzyme, Repeat, ATP-
    binding, Membrane
    NM_002131 HMGA1 high mobility group Nuclear protein, Chromosomal 2206 6174
    AT-hook 1 protein, DNA-binding, Repeat,
    Transcription regulation, Alternative
    splicing, Phosphorylation,
    Acetylation, Chromosomal
    translocation, 3D-structure
    NM_002133 HMOX1 heme oxygenase Cyclin, Heme, Oxidoreductase, 2207 6175
    (decycling) 1 Microsome, Multigene family, 3D-
    structure
    NM_002134 HMOX2 heme oxygenase Heme, Oxidoreductase, Microsome, 2208 6176
    (decycling) 2 Multigene family, Repeat
    NM_002136 HNRPA1 heterogeneous Hypothetical protein, Nucleocapsid, 2209 6177
    nuclear Ribonucleoprotein, Nuclear protein,
    ribonucleoprotein A1 RNA-binding, Repeat, Methylation,
    Alternative splicing, 3D-structure,
    Polymorphism
    NM_002139 RBMX RNA binding motif Hypothetical protein, Nuclear 2210 6178
    protein, X-linked protein, RNA-binding,
    Ribonucleoprotein, Glycoprotein
    NM_002155 HSPA6 heat shock 70 kDa ATP-binding, Heat shock, Multigene 2211 6179
    protein 6 (HSP70B′) family
    NM_002156 HSPD1 heat shock 60 kDa Chaperone, ATP-binding, 2212 6180
    protein 1 Mitochondrion, Transit peptide
    (chaperonin)
    NM_002157 HSPE1 heat shock 10 kDa Chaperone, Mitochondrion, Heat 2213 6181
    protein 1 shock, Acetylation
    (chaperonin 10)
    NM_002162 ICAM3 intercellular Immunoglobulin domain, Cell 2214 6182
    adhesion molecule 3 adhesion, Glycoprotein,
    Transmembrane, Repeat, Signal,
    Phosphorylation
    NM_002180 IGHMBP2 immunoglobulin mu Hydrolase, Helicase, ATP-binding, 2215 6183
    binding protein 2 DNA-binding, Nuclear protein,
    Transcription regulation, Activator,
    3D-structure
    NM_002191 INHA inhibin, alpha Growth factor, Hormone, 2216 6184
    Glycoprotein, Signal, Polymorphism
    NM_002194 INPP1 inositol Hydrolase, Lithium 2217 6185
    polyphosphate-1-
    phosphatase
    NM_002205 ITGA5 integrin, alpha 5 Integrin, Cell adhesion, Receptor, 2218 6186
    (fibronectin receptor, Glycoprotein, Transmembrane,
    alpha polypeptide) Signal, Calcium, Repeat
    NM_002209 ITGAL integrin, alpha L Integrin, Cell adhesion, Receptor, 2219 6187
    (antigen CD11A Glycoprotein, Transmembrane,
    (p180), lymphocyte Signal, 3D-structure, Magnesium,
    function-associated Calcium, Repeat, Alternative
    antigen
    1; alpha splicing, Hypothetical protein
    polypeptide)
    NM_002218 ITIH4 inter-alpha (globulin) Acute phase, Serine protease 2220 6188
    inhibitor H4 (plasma inhibitor, Repeat, Signal, Multigene
    Kallikrein-sensitive family, Glycoprotein, Alternative
    glycoprotein) splicing, Polymorphism
    NM_002220 ITPKA inositol 1,4,5- Kinase, Transferase, Calmodulin- 2221 6189
    trisphosphate 3- binding
    kinase A
    NM_002222 ITPR1 inositol 1,4,5- Receptor, Transmembrane, 2222 6190
    triphosphate Phosphorylation, Endoplasmic
    receptor, type 1 reticulum, Ionic channel, Ion
    transport, Calcium channel,
    Alternative splicing, Repeat
    NM_002226 JAG2 jagged 2 Calcium-binding, EGF-like domain, 2223 6191
    Glycoprotein, Developmental
    protein, Repeat, Signal,
    Transmembrane, Alternative splicing
    NM_002228 JUN v-jun sarcoma virus Proto-oncogene, Transcription 2224 6192
    17 oncogene regulation, DNA-binding, 3D-
    homolog (avian) structure, Nuclear protein,
    Phosphorylation, Polymorphism
    NM_002236 KCNF1 potassium voltage- Transport, Ion transport, Ionic 2225 6193
    gated channel, channel, Voltage-gated channel,
    subfamily F, member 1 Potassium channel, Potassium,
    Potassium transport,
    Transmembrane, Multigene family
    NM_002243 KCNJ15 potassium inwardly- Hypothetical protein, Ionic channel, 2226 6194
    rectifying channel, Ion transport, Voltage-gated
    subfamily J, member channel, Transmembrane,
    15 Potassium transport
    NM_002250 KCNN4 potassium Ionic channel, Transmembrane, Ion 2227 6195
    intermediate/small transport, Calmodulin-binding
    conductance
    calcium-activated
    channel, subfamily
    N, member 4
    NM_002258 KLRB1 killer cell lectin-like 2228 6196
    receptor subfamily
    B, member 1
    NM_002267 KPNA3 karyopherin alpha 3 Hypothetical protein, Transport, 2229 6197
    (importin alpha 4) Protein transport, Repeat, Nuclear
    protein, Polymorphism
    NM_002271 KPNB3 karyopherin Hypothetical protein, Transport, 2230 6198
    (importin) beta 3 Protein transport, Repeat, Nuclear
    protein, Polymorphism
    NM_002273 KRT8 keratin 8 Intermediate filament, Coiled coil, 2231 6199
    Keratin, Phosphorylation
    NM_002275 KRT15 keratin 15 Intermediate filament, Coiled coil, 2232 6200
    Keratin
    NM_002277 KRTHA1 keratin, hair, acidic, 1 Intermediate filament, Coiled coil, 2233 6201
    Keratin
    NM_002278 KRTHA2 keratin, hair, acidic, 2 Intermediate filament, Coiled coil, 2234 6202
    Keratin
    NM_002282 KRTHB3 keratin, hair, basic, 3 Coiled coil, Intermediate filament 2235 6203
    NM_002296 LBR lamin B receptor Receptor, Transmembrane, 2236 6204
    Phosphorylation, Nuclear protein,
    DNA-binding
    NM_002298 LCP1 lymphocyte cytosolic Calcium-binding, Phosphorylation, 2237 6205
    protein 1 (L-plastin) Actin-binding, Repeat,
    Polymorphism
    NM_002299 LCT lactase Hydrolase, Glycosidase, Zymogen, 2238 6206
    Signal, Transmembrane, Repeat
    NM_002300 LDHB lactate Oxidoreductase, NAD, Glycolysis, 2239 6207
    dehydrogenase B Multigene family, Disease mutation,
    3D-structure
    NM_002306 LGALS3 lectin, galactoside- Galectin, Lectin, IgE-binding protein, 2240 6208
    binding, soluble, 3 Repeat, Phosphorylation,
    (galectin 3) Acetylation, Nuclear protein,
    Polymorphism, 3D-structure
    NM_002311 LIG3 ligase III, DNA, ATP- DNA repair, DNA replication, DNA 2241 6209
    dependent recombination, Cell division, Ligase,
    ATP-binding, Zinc-finger, Nuclear
    protein, Alternative splicing, 3D-
    structure, Hypothetical protein
    NM_002313 ABLIM1 actin binding LIM LIM domain, Metal-binding, Zinc, 2242 6210
    protein 1 Hypothetical protein
    NM_002316 LMX1B LIM homeobox DNA-binding, Homeobox, LIM 2243 6211
    transcription factor 1, domain, Metal-binding, Nuclear
    beta protein, Zinc, Developmental protein,
    Repeat, Activator, Transcription
    regulation, Alternative splicing,
    Disease mutation
    NM_002332 LRP1 low density Receptor, Transmembrane, Repeat, 2244 6212
    lipoprotein-related Endocytosis, Glycoprotein, Signal,
    protein 1 (alpha-2- Calcium-binding, EGF-like domain,
    macroglobulin Coated pits, 3D-structure,
    receptor) Polymorphism
    NM_002335 LRP5 low density Receptor, Lipoprotein 2245 6213
    lipoprotein receptor-
    related protein 5
    NM_002337 LRPAP1 low density Signal, Heparin-binding, 2246 6214
    lipoprotein receptor- Glycoprotein, Antigen, 3D-structure,
    related protein Polymorphism
    associated protein 1
    NM_002339 LSP1 lymphocyte-specific T-cell, Phosphorylation, 2247 6215
    protein 1 Polymorphism
    NM_002341 LTB lymphotoxin beta Cytokine, Transmembrane, 2248 6216
    (TNF superfamily, Glycoprotein, Signal-anchor,
    member 3) Alternative splicing, Polymorphism
    NM_002343 LTF lactotransferrin Glycoprotein, Iron transport, Metal- 2249 6217
    binding, Transport, Repeat, Signal,
    Polymorphism, 3D-structure
    NM_002357 MAD MAX dimerization Nuclear protein, DNA-binding, 2250 6218
    protein 1 Transcription regulation, Repressor,
    3D-structure
    NM_002375 MAP4 microtubule- Hypothetical protein, Microtubule, 2251 6219
    associated protein 4 Repeat, Phosphorylation, Alternative
    splicing
    NM_002382 MAX MAX protein Hypothetical protein, Transcription 2252 6220
    regulation, Activator, Repressor,
    Nuclear protein, DNA-binding,
    Phosphorylation, Alternative splicing,
    3D-structure
    NM_002394 SLC3A2 solute carrier family Glycoprotein, Transmembrane, 2253 6221
    3 (activators of Signal-anchor
    dibasic and neutral
    amino acid
    transport), member 2
    NM_002402 MEST mesoderm specific Aromatic hydrocarbons catabolism, 2254 6222
    transcript homolog Detoxification, Hydrolase,
    (mouse) Hypothetical protein
    NM_002406 MGAT1 mannosyl (alpha- Transferase, Glycosyltransferase, 2255 6223
    1,3-)-glycoprotein Transmembrane, Signal-anchor,
    beta-1,2-N- Golgi stack, Hypothetical protein
    acetylglucosaminyltransferase
    NM_002419 MAP3K11 mitogen-activated ATP-binding, Kinase, SH3 domain, 2256 6224
    protein kinase Serine/threonine-protein kinase,
    kinase kinase 11 Transferase
    NM_002424 MMP8 matrix Hydrolase, Metalloprotease, 2257 6225
    metalloproteinase 8 Glycoprotein, Calcium-binding,
    (neutrophil Metal-binding, Zinc, Zymogen,
    collagenase) Collagen degradation, Extracellular
    matrix, Signal, 3D-structure
    NM_002431 MNAT1 menage a trois 1 Transcription regulation, Cell cycle, 2258 6226
    (CAK assembly Nuclear protein, Zinc-finger, 3D-
    factor) structure
    NM_002432 MNDA myeloid cell nuclear Interferon induction, Nuclear protein, 2259 6227
    differentiation DNA-binding, Transcription
    antigen regulation, Activator, Repressor,
    Polymorphism
    NM_002435 MPI mannose phosphate Isomerase, Zinc, Disease mutation 2260 6228
    isomerase
    NM_002442 MSI1 musashi homolog 1 RNA-binding 2261 6229
    (Drosophila)
    NM_002453 MTIF2 mitochondrial Initiation factor, Protein biosynthesis, 2262 6230
    translational initiation GTP-binding, Transit peptide,
    factor 2 Mitochondrion, Polymorphism
    NM_002455 MTX1 metaxin 1 Mitochondrion, Outer membrane, 2263 6231
    Transmembrane, Transport, Protein
    transport
    NM_002475 MLC1SA myosin light chain 1 Myosin, Muscle protein, Multigene 2264 6232
    slow a family
    NM_002483 CEACAM6 carcinoembryonic Immunoglobulin domain, Signal, 2265 6233
    antigen-related cell Antigen, Glycoprotein, GPI-anchor,
    adhesion molecule 6 Repeat, Lipoprotein
    (non-specific cross
    reacting antigen)
    NM_002486 NCBP1 nuclear cap binding Transport, mRNA transport, Nuclear 2266 6234
    protein subunit 1, protein, RNA-binding, 3D-structure
    80 kDa
    NM_002492 NDUFB5 NADH Oxidoreductase, NAD, Ubiquinone, 2267 6235
    dehydrogenase Mitochondrion, Transit peptide
    (ubiquinone) 1 beta
    subcomplex, 5,
    16 kDa
    NM_002495 NDUFS4 NADH Oxidoreductase, NAD, Ubiquinone, 2268 6236
    dehydrogenase Mitochondrion, Transit peptide,
    (ubiquinone) Fe—S Polymorphism
    protein 4, 18 kDa
    (NADH-coenzyme Q
    reductase)
    NM_002499 NEO1 neogenin homolog 1 Cell adhesion, Repeat, Signal, 2269 6237
    (chicken) Transmembrane, Immunoglobulin
    domain, Glycoprotein, Alternative
    splicing
    NM_002512 NME2 non-metastatic cells Transferase, Kinase, ATP-binding, 2270 6238
    2, protein (NM23B) Nuclear protein, Anti-oncogene,
    expressed in DNA-binding, Transcription
    regulation, Activator, 3D-structure
    NM_002517 NPAS1 neuronal PAS Repeat, DNA-binding, Nuclear 2271 6239
    domain protein 1 protein, Transcription regulation
    NM_002520 NPM1 nucleophosmin Hypothetical protein, Transcription 2272 6240
    (nucleolar regulation, Nuclear protein, DNA-
    phosphoprotein B23, binding, Zinc-finger, Proto-
    numatrin) oncogene, Chromosomal
    translocation, Alternative splicing,
    Repeat, Coiled coil, 3D-structure,
    Metal-binding, Receptor, Multigene
    family, Phosphorylation, RNA-
    NM_002524 NRAS neuroblastoma RAS Hypothetical protein, RNA-binding, 2273 6241
    viral (v-ras) Repeat, Alternative splicing, Proto-
    oncogene homolog oncogene, GTP-binding, Prenylation,
    Lipoprotein, Disease mutation
    NM_002528 NTHL1 nth endonuclease III- Hydrolase, Nuclease, Endonuclease, 2274 6242
    like 1 (E. coli) Multifunctional enzyme, DNA repair,
    Glycosidase, Lyase, Iron-sulfur, 4Fe—4S,
    Nuclear protein, Polymorphism
    NM_002532 NUP88 nucleoporin 88 kDa Nuclear protein, Transport, Coiled 2275 6243
    coil
    NM_002541 OGDH oxoglutarate (alpha- Glycolysis, Oxidoreductase, 2276 6244
    ketoglutarate) Flavoprotein, Thiamine
    dehydrogenase pyrophosphate, Mitochondrion,
    (lipoamide) Transit peptide, Hypothetical protein
    NM_002543 OLR1 oxidised low density Lectin, Lipoprotein, Receptor 2277 6245
    lipoprotein (lectin-
    like) receptor 1
    NM_002553 ORC5L origin recognition DNA replication, Nuclear protein, 2278 6246
    complex, subunit 5- ATP-binding, Polymorphism
    like (yeast)
    NM_002555 SLC22A1L solute carrier family Hypothetical protein 2279 6247
    22 (organic cation
    transporter),
    member 1-like
    NM_002557 OVGP1 oviductal Glycoprotein, Fertilization, Signal, 2280 6248
    glycoprotein 1, Polymorphism
    120 kDa (mucin 9,
    oviductin)
    NM_002564 P2RY2 purinergic receptor G-protein coupled receptor, 2281 6249
    P2Y, G-protein Transmembrane, Glycoprotein
    coupled, 2
    NM_002573 PAFAH1B3 platelet-activating Hydrolase, Lipid degradation 2282 6250
    factor
    acetylhydrolase,
    isoform Ib, gamma
    subunit 29 kDa
    NM_002574 PRDX1 peroxiredoxin 1 Antioxidant, Peroxidase, 2283 6251
    Oxidoreductase, Redox-active
    center
    NM_002576 PAK1 p21/Cdc42/Rac1- Apoptosis, Transferase, 2284 6252
    activated kinase 1 Serine/threonine-protein kinase,
    (STE20 homolog, ATP-binding, Phosphorylation, 3D-
    yeast) structure, Kinase
    NM_002585 PBX1 pre-B-cell leukemia Transcription regulation, DNA- 2285 6253
    transcription factor 1 binding, Nuclear protein, Activator,
    Repressor, Homeobox, Proto-
    oncogene, Chromosomal
    translocation, Alternative splicing,
    Steroidogenesis, Sexual
    differentiation, 3D-structure,
    Phosphorylation
    NM_002587 PCDH1 protocadherin 1 Cell adhesion, Transmembrane, 2286 6254
    (cadherin-like 1) Calcium-binding, Repeat, Signal,
    Alternative splicing
    NM_002598 PDCD2 programmed cell Zinc-finger, DNA-binding, Nuclear 2287 6255
    death 2 protein, Apoptosis
    NM_002601 PDE6D phosphodiesterase Hydrolase, cGMP, Vision, 3D- 2288 6256
    6D, cGMP-specific, structure
    rod, delta
    NM_002608 PDGFB platelet-derived Mitogen, Growth factor, Proto- 2289 6257
    growth factor beta oncogene, Platelet, Signal,
    polypeptide (simian Pharmaceutical, 3D-structure,
    sarcoma viral (v-sis) Polymorphism, Chromosomal
    oncogene homolog) translocation
    NM_002611 PDK2 pyruvate Kinase, Transferase, Transit peptide, 2290 6258
    dehydrogenase Mitochondrion, Multigene family
    kinase, isoenzyme 2
    NM_002613 PDPK1 3-phosphoinositide Transferase, Serine/threonine- 2291 6259
    dependent protein protein kinase, ATP-binding,
    kinase-1 Phosphorylation, Membrane,
    Alternative splicing, Kinase
    NM_002616 PER1 period homolog 1 Transcription regulation, Nuclear 2292 6260
    (Drosophila) protein, Repeat, Biological rhythms,
    Alternative splicing
    NM_002621 PFC properdin P factor, Signal, Complement alternate 2293 6261
    complement pathway, Glycoprotein, Repeat,
    Disease mutation
    NM_002629 PGAM1 phosphoglycerate Isomerase, Hydrolase, Glycolysis, 2294 6262
    mutase 1 (brain) Acetylation, 3D-structure
    NM_002631 PGD phosphogluconate Oxidoreductase, Pentose shunt, 2295 6263
    dehydrogenase NADP
    NM_002633 PGM1 phosphoglucomutase 1 Isomerase, Phosphorylation, 2296 6264
    Magnesium, Polymorphism,
    Alternative splicing, Hypothetical
    protein
    NM_002635 SLC25A3 solute carrier family Mitochondrion, Inner membrane, 2297 6265
    25 (mitochondrial Repeat, Transit peptide,
    carrier; phosphate Transmembrane, Transport,
    carrier), member 3 Symport, Alternative splicing,
    Hypothetical protein
    NM_002640 SERPINB8 serine (or cysteine) Protease inhibitor, Serine protease 2298 6266
    proteinase inhibitor, inhibitor, Serpin
    clade B (ovalbumin),
    member 8
    NM_002649 PIK3CG phosphoinositide-3- Kinase, Transferase, Multigene 2299 6267
    kinase, catalytic, family, 3D-structure
    gamma polypeptide
    NM_002650 PIK4CA phosphatidylinositol Transferase, Kinase, Alternative 2300 6268
    4-kinase, catalytic, splicing
    alpha polypeptide
    NM_002651 PIK4CB phosphatidylinositol Transferase, Kinase, Golgi stack, 2301 6269
    4-kinase, catalytic, Phosphorylation, Alternative splicing
    beta polypeptide
    NM_002653 PITX1 paired-like Homeobox, DNA-binding, 2302 6270
    homeodomain Developmental protein, Nuclear
    transcription factor
    1 protein, Transcription regulation,
    Activator
    NM_002654 PKM2 pyruvate kinase, Transferase, Kinase, Glycolysis, 2303 6271
    muscle Multigene family, Magnesium,
    Alternative splicing, Hypothetical
    protein
    NM_002655 PLAG1 pleiomorphic Metal-binding, Zinc, Zinc-finger 2304 6272
    adenoma gene 1
    NM_002659 PLAUR plasminogen Receptor, Signal, Glycoprotein, GPI- 2305 6273
    activator, urokinase anchor, Repeat, Alternative splicing,
    receptor Polymorphism, Lipoprotein, Kinase
    NM_002661 PLCG2 phospholipase C, Hydrolase, Lipid degradation, 2306 6274
    gamma 2 Transducer, SH2 domain, SH3
    (phosphatidylinositol domain, Repeat, Calcium-binding,
    specific) Phosphorylation
    NM_002668 PLP2 proteolipid protein 2 Transmembrane, Glycoprotein, 2307 6275
    (colonic epithelium- Polymorphism
    enriched)
    NM_002676 PMM1 phosphomannomutase 1 Isomerase 2308 6276
    NM_002685 PMSCL2 polymyositis/scleroderma Hydrolase, Nuclease, Exonuclease, 2309 6277
    autoantigen 2, rRNA processing, Nuclear protein,
    100 kDa RNA-binding, Antigen, Alternative
    splicing, Hypothetical protein
    NM_002686 PNMT phenylethanolamine Transferase, Methyltransferase, 2310 6278
    N-methyltransferase Catecholamine biosynthesis, 3D-
    structure
    NM_002688 PNUTL1 peanut-like 1 Hypothetical protein, Cell division, 2311 6279
    (Drosophila) GTP-binding, Coiled coil, Platelet,
    Transmembrane, Glycoprotein,
    Hemostasis, Blood coagulation,
    Signal, Phosphorylation, Cell
    adhesion, Leucine-rich repeat
    NM_002691 POLD1 polymerase (DNA DNA replication, DNA-binding, DNA- 2312 6280
    directed), delta 1, directed DNA polymerase,
    catalytic subunit Transferase, Hydrolase,
    125 kDa Exonuclease, Zinc-finger, Nuclear
    protein, Polymorphism
    NM_002692 POLE2 polymerase (DNA Transferase, DNA-directed DNA 2313 6281
    directed), epsilon 2 polymerase, DNA replication, DNA-
    (p59 subunit) binding, Nuclear protein
    NM_002710 PPP1CC protein phosphatase Hydrolase, Metal-binding, Iron, 2314 6282
    1, catalytic subunit, Manganese, Glycogen metabolism,
    gamma isoform Multigene family, Cell division,
    Alternative splicing, 3D-structure
    NM_002720 PPP4C protein phosphatase Hydrolase, Metal-binding, Iron, 2315 6283
    4 (formerly X), Manganese
    catalytic subunit
    NM_002727 PRG1 proteoglycan 1, Glycoprotein, Proteoglycan, Repeat, 2316 6284
    secretory granule Signal
    NM_002728 PRG2 proteoglycan 2, bone Eosinophil, Signal, Immune 2317 6285
    marrow (natural killer response, Antibiotic, Lectin,
    cell activator, Proteoglycan, Glycoprotein, Heparin-
    eosinophil granule binding, 3D-structure
    major basic protein)
    NM_002731 PRKACB protein kinase, ATP-binding, Kinase, 2318 6286
    cAMP-dependent, Serine/threonine-protein kinase,
    catalytic, beta Transferase, Nuclear protein, cAMP,
    Myristate, Phosphorylation,
    Multigene family, Lipoprotein
    NM_002733 PRKAG1 protein kinase, AMP- Fatty acid biosynthesis, Repeat, 2319 6287
    activated, gamma 1 CBS domain, Hypothetical protein
    non-catalytic subunit
    NM_002738 PRKCB1 protein kinase C, Transferase, Serine/threonine- 2320 6288
    beta 1 protein kinase, Membrane, ATP-
    binding, Calcium-binding, Metal-
    binding, Zinc, Repeat, Phorbol-ester
    binding, Phosphorylation, Alternative
    splicing
    NM_002741 PRKCL1 protein kinase C-like 1 Transferase, ATP-binding, 2321 6289
    Serine/threonine-protein kinase,
    Phosphorylation, Polymorphism, 3D-
    structure
    NM_002745 MAPK1 mitogen-activated Transferase, Serine/threonine- 2322 6290
    protein kinase 1 protein kinase, ATP-binding, Cell
    cycle, Phosphorylation, 3D-structure
    NM_002748 MAPK6 mitogen-activated Kinase, Transferase, 2323 6291
    protein kinase 6 Serine/threonine-protein kinase,
    ATP-binding, Cell cycle
    NM_002749 MAPK7 mitogen-activated ATP-binding, Kinase, 2324 6292
    protein kinase 7 Serine/threonine-protein kinase,
    Transferase, Cell cycle,
    Phosphorylation, Cell adhesion,
    Extracellular matrix, Glycoprotein,
    Calcium, Signal
    NM_002756 MAP2K3 mitogen-activated Transferase, Serine/threonine- 2325 6293
    protein kinase protein kinase, Tyrosine-protein
    kinase
    3 kinase, ATP-binding,
    Phosphorylation, Alternative splicing,
    Disease mutation
    NM_002757 MAP2K5 mitogen-activated ATP-binding, Kinase, 2326 6294
    protein kinase Serine/threonine-protein kinase,
    kinase 5 Transferase
    NM_002758 MAP2K6 mitogen-activated Transferase, Serine/threonine- 2327 6295
    protein kinase protein kinase, Tyrosine-protein
    kinase
    6 kinase, ATP-binding,
    Phosphorylation, Alternative splicing
    NM_002764 PRPS1 phosphoribosyl Nucleotide biosynthesis, 2328 6296
    pyrophosphate Transferase, Kinase, Magnesium,
    synthetase 1 Multigene family, Gout, Disease
    mutation
    NM_002765 PRPS2 phosphoribosyl Nucleotide biosynthesis, 2329 6297
    pyrophosphate Transferase, Kinase, Magnesium,
    synthetase 2 Multigene family
    NM_002767 PRPSAP2 phosphoribosyl Nucleotide biosynthesis 2330 6298
    pyrophosphate
    synthetase-
    associated protein 2
    NM_002770 PRSS2 protease, serine, 2 Hydrolase, Protease, Serine 2331 6299
    (trypsin 2) protease, Digestion, Pancreas,
    Zymogen, Calcium-binding, Signal,
    Multigene family
    NM_002777 PRTN3 proteinase 3 (serine Collagen degradation, Hydrolase, 2332 6300
    proteinase, Serine protease, Signal, Zymogen,
    neutrophil, Wegener Glycoprotein, Polymorphism, 3D-
    granulomatosis structure
    autoantigen)
    NM_002782 PSG6 pregnancy specific Immunoglobulin domain, 2333 6301
    beta-1-glycoprotein 6 Glycoprotein, Signal, Multigene
    family, Repeat, Polymorphism,
    Alternative splicing, Hypothetical
    protein, Flavoprotein, Lyase,
    Thiamine pyrophosphate
    NM_002786 PSMA1 proteasome Proteasome, Hydrolase, Protease, 2334 6302
    (prosome, Acetylation, Alternative splicing,
    macropain) subunit, Threonine protease
    alpha type, 1
    NM_002788 PSMA3 proteasome Proteasome, Hydrolase, Protease, 2335 6303
    (prosome, Acetylation, Alternative splicing,
    macropain) subunit, Phosphorylation, Threonine protease
    alpha type, 3
    NM_002790 PSMA5 proteasome Proteasome, Hydrolase, Protease, 2336 6304
    (prosome, Threonine protease
    macropain) subunit,
    alpha type, 5
    NM_002793 PSMB1 proteasome Proteasome, Hydrolase, Protease, 2337 6305
    (prosome, Threonine protease
    macropain) subunit,
    beta type, 1
    NM_002794 PSMB2 proteasome Proteasome, Hydrolase, Protease, 2338 6306
    (prosome, Threonine protease
    macropain) subunit,
    beta type, 2
    NM_002796 PSMB4 proteasome Proteasome, Hydrolase, Protease, 2339 6307
    (prosome, Zymogen, Polymorphism, Threonine
    macropain) subunit, protease
    beta type, 4
    NM_002805 PSMC5 proteasome ATP-binding, Proteasome 2340 6308
    (prosome,
    macropain) 26S
    subunit, ATPase, 5
    NM_002807 PSMD1 proteasome Proteasome, Repeat 2341 6309
    (prosome,
    macropain) 26S
    subunit, non-
    ATPase, 1
    NM_002809 PSMD3 proteasome Hypothetical protein, Proteasome 2342 6310
    (prosome,
    macropain) 26S
    subunit, non-
    ATPase, 3
    NM_002815 PSMD11 proteasome Proteasome 2343 6311
    (prosome,
    macropain) 26S
    subunit, non-
    ATPase, 11
    NM_002818 PSME2 proteasome Proteasome, Interferon induction 2344 6312
    (prosome,
    macropain) activator
    subunit 2 (PA28
    beta)
    NM_002821 PTK7 PTK7 protein ATP-binding, Immunoglobulin 2345 6313
    tyrosine kinase 7 domain, Receptor, Transferase,
    Transmembrane, Signal,
    Glycoprotein, Cell adhesion, Repeat,
    Hypothetical protein, Kinase,
    Tyrosine-protein kinase
    NM_002824 PTMS parathymosin Hypothetical protein, Immune 2346 6314
    response, Acetylation
    NM_002826 QSCN6 quiescin Q6 Redox-active center 2347 6315
    NM_002831 PTPN6 protein tyrosine Hydrolase, SH2 domain, Repeat, 2348 6316
    phosphatase, non- Phosphorylation, Alternative splicing,
    receptor type 6 3D-structure
    NM_002842 PTPRH protein tyrosine Signal 2349 6317
    phosphatase,
    receptor type, H
    NM_002843 PTPRJ protein tyrosine Signal, Glycoprotein, 2350 6318
    phosphatase, Transmembrane, Repeat,
    receptor type, J Hydrolase, Disease mutation,
    Receptor
    NM_002850 PTPRS protein tyrosine Hydrolase, Receptor, Glycoprotein, 2351 6319
    phosphatase, Signal, Transmembrane, Cell
    receptor type, S adhesion, Immunoglobulin domain,
    Alternative splicing, Repeat
    NM_002852 PTX3 pentaxin-related Pentaxin, Glycoprotein, Signal 2352 6320
    gene, rapidly
    induced by IL-1 beta
    NM_002859 PXN hypothetical protein Cytoskeleton, Phosphorylation, LIM 2353 6321
    FLJ23042 domain, Repeat, Metal-binding, Zinc,
    Alternative splicing, 3D-structure,
    Hypothetical protein
    NM_002862 PYGB phosphorylase, Carbohydrate metabolism, 2354 6322
    glycogen; brain Glycosyltransferase, Pyridoxal
    phosphate, Transferase, Glycogen
    metabolism, Allosteric enzyme,
    Phosphorylation
    NM_002863 PYGL phosphorylase, Transferase, Glycosyltransferase, 2355 6323
    glycogen; liver (Hers Carbohydrate metabolism, Glycogen
    disease, glycogen metabolism, Allosteric enzyme,
    storage disease type Pyridoxal phosphate,
    VI) Phosphorylation, Glycogen storage
    disease, Disease mutation,
    Polymorphism, 3D-structure
    NM_002865 RAB2 RAB2, member RAS GTP-binding, Transport, Protein 2356 6324
    oncogene family transport, Endoplasmic reticulum,
    Golgi stack, Lipoprotein, Prenylation
    NM_002872 RAC2 ras-related C3 GTP-binding, Prenylation, 2357 6325
    botulinum toxin Lipoprotein, 3D-structure
    substrate 2 (rho
    family, small GTP
    binding protein
    Rac2)
    NM_002878 RAD51L3 RAD51-like 3 (S. cerevisiae) DNA damage, DNA repair, DNA 2358 6326
    recombination, DNA-binding, ATP-
    binding, Nuclear protein, Alternative
    splicing, Hypothetical protein
    NM_002880 RAF1 v-raf-1 murine Hypothetical protein, Metal-binding, 2359 6327
    leukemia viral Zinc, Zinc-finger, Transferase,
    oncogene homolog 1 Serine/threonine-protein kinase,
    Proto-oncogene, ATP-binding,
    Phorbol-ester binding,
    Phosphorylation, 3D-structure,
    Repeat
    NM_002881 RALB v-ral simian GTP-binding, Prenylation, 2360 6328
    leukemia viral Lipoprotein
    oncogene homolog
    B (ras related; GTP
    binding protein)
    NM_002883 RANGAP1 Ran GTPase Hypothetical protein, GTPase 2361 6329
    activating protein 1 activation, Repeat, Leucine-rich
    repeat, Ubl conjugation
    NM_002887 RARS arginyl-tRNA Aminoacyl-tRNA synthetase, Protein 2362 6330
    synthetase biosynthesis, Ligase, ATP-binding,
    Alternative initiation
    NM_002893 RBBP7 retinoblastoma Nuclear protein, Repeat, WD repeat 2363 6331
    binding protein 7
    NM_002896 RBM4 RNA binding motif Zinc-finger 2364 6332
    protein 4
    NM_002897 RBMS1 RNA binding motif, DNA-binding, DNA replication, RNA- 2365 6333
    single stranded binding, Nuclear protein,
    interacting protein 1 Phosphorylation
    NM_002901 RCN1 reticulocalbin 1, EF- Calcium-binding, Endoplasmic 2366 6334
    hand calcium reticulum, Signal, Glycoprotein,
    binding domain Repeat, Polymorphism
    NM_002902 RCN2 reticulocalbin 2, EF- Calcium-binding, Endoplasmic 2367 6335
    hand calcium reticulum, Signal, Repeat
    binding domain
    NM_002903 RCV1 recoverin Calcium-binding, Repeat, Myristate, 2368 6336
    Vision, Lipoprotein
    NM_002905 RDH5 retinol Oxidoreductase, NAD, Membrane, 2369 6337
    dehydrogenase 5 Vision, Disease mutation,
    (11-cis and 9-cis) Polymorphism
    NM_002910 RENBP renin binding protein Isomerase 2370 6338
    NM_002918 RFX1 regulatory factor X, 1 DNA-binding, Transcription 2371 6339
    (influences HLA regulation, Activator, Nuclear
    class II expression) protein, 3D-structure
    NM_002922 RGS1 regulator of G- Signal transduction inhibitor, B-cell 2372 6340
    protein signalling 1 activation, Phosphorylation
    NM_002923 RGS2 regulator of G- Signal transduction inhibitor, Cell 2373 6341
    protein signalling 2, cycle, Phosphorylation
    24 kDa
    NM_002934 RNASE2 ribonuclease, RNase Hydrolase, Nuclease, Endonuclease, 2374 6342
    A family, 2 (liver, Chemotaxis, Eosinophil,
    eosinophil-derived Glycoprotein, Signal, Polymorphism,
    neurotoxin) 3D-structure
    NM_002935 RNASE3 ribonuclease, RNase Hydrolase, Nuclease, Endonuclease, 2375 6343
    A family, 3 Eosinophil, Glycoprotein, Antibiotic,
    (eosinophil cationic Signal, Polymorphism, 3D-structure
    protein)
    NM_002936 RNASEH1 ribonuclease H1 Hydrolase, Nuclease, Endonuclease, 2376 6344
    Magnesium
    NM_002939 RNH ribonuclease/angiogenin Repeat, Leucine-rich repeat, 3D- 2377 6345
    inhibitor structure, Polymorphism,
    Hypothetical protein
    NM_002940 ABCE1 ATP-binding Capsid assembly, Chaperone, 2378 6346
    cassette, sub-family Mitochondrion, ATP-binding, Repeat
    E (OABP), member 1
    NM_002953 RPS6KA1 ribosomal protein S6 Transferase, Serine/threonine- 2379 6347
    kinase, 90 kDa, protein kinase, ATP-binding, Repeat,
    polypeptide 1 Multigene family
    NM_002957 RXRA retinoid X receptor, Receptor, Transcription regulation, 2380 6348
    alpha DNA-binding, Nuclear protein, Zinc-
    finger, Multigene family, 3D-
    structure, Polymorphism
    NM_002961 S100A4 S100 calcium Calcium-binding, 3D-structure 2381 6349
    binding protein A4
    (calcium protein,
    calvasculin,
    metastasin, murine
    placental homolog)
    NM_002964 S100A8 S100 calcium Macrophage, Calcium-binding, 3D- 2382 6350
    binding protein A8 structure
    (calgranulin A)
    NM_002965 S100A9 S100 calcium Calcium-binding, Macrophage, 2383 6351
    binding protein A9 Phosphorylation, Polymorphism, 3D-
    (calgranulin B) structure
    NM_002967 SAFB scaffold attachment Transcription regulation, Repressor, 2384 6352
    factor B Nuclear protein, DNA-binding, RNA-
    binding, Phosphorylation
    NM_002969 MAPK12 mitogen-activated Transferase, Serine/threonine- 2385 6353
    protein kinase 12 protein kinase, ATP-binding, Cell
    cycle, Phosphorylation,
    Polymorphism, 3D-structure
    NM_002978 SCNN1D sodium channel, Ion transport, Sodium transport, 2386 6354
    nonvoltage-gated 1, Ionic channel, Transmembrane,
    delta Glycoprotein, Alternative splicing,
    Sodium channel
    NM_002984 CCL4 chemokine (C-C Cytokine, Chemotaxis, Inflammatory 2387 6355
    motif) ligand 4 response, Signal, 3D-structure
    NM_002985 CCL5 chemokine (C-C Cytokine, Chemotaxis, T-cell, Signal, 2388 6356
    motif) ligand 5 Inflammatory response, 3D-structure
    NM_003003 SEC14L1 SEC14-like 1 (S. cerevisiae) 2389 6357
    NM_003006 SELPLG selectin P ligand Hypothetical protein, Cell adhesion, 2390 6358
    Glycoprotein, Transmembrane,
    Signal, Repeat, Polymorphism,
    Sulfation, 3D-structure, Lectin,
    Selectin
    NM_003011 SET SET translocation Proto-oncogene, Chromosomal 2391 6359
    (myeloid leukemia- translocation, Nuclear protein,
    associated) Phosphorylation
    NM_003021 SGT small glutamine-rich Chaperone, Repeat, TPR repeat, 2392 6360
    tetratricopeptide Hypothetical protein
    repeat (TPR)-
    containing, alpha
    NM_003040 SLC4A2 solute carrier family Transmembrane, Glycoprotein, 2393 6361
    4, anion exchanger, Transport, Antiport, Ion transport,
    member 2 Anion exchange, Lipoprotein,
    (erythrocyte Palmitate, Alternative splicing
    membrane protein
    band 3-like 1)
    NM_003044 SLC6A12 solute carrier family Neurotransmitter transport, 2394 6362
    6 (neurotransmitter Transport, Transmembrane,
    transporter, Glycoprotein, Symport
    betaine/GABA),
    member 12
    NM_003055 SLC18A3 choline Transport, Neurotransmitter 2395 6363
    acetyltransferase transport, Transmembrane,
    Glycoprotein
    NM_003056 SLC19A1 solute carrier family Folate-binding, Transport, 2396 6364
    19 (folate Transmembrane, Glycoprotein
    transporter),
    member 1
    NM_003057 SLC22A1 solute carrier family Transmembrane 2397 6365
    22 (organic cation
    transporter),
    member 1
    NM_003059 SLC22A4 solute carrier family Transmembrane 2398 6366
    22 (organic cation
    transporter),
    member 4
    NM_003064 SLPI secretory leukocyte Serine protease inhibitor, Repeat, 2399 6367
    protease inhibitor Signal
    (antileukoproteinase)
    NM_003066 SLPI secretory leukocyte Serine protease inhibitor, Repeat, 2400 6368
    protease inhibitor Signal
    (antileukoproteinase)
    NM_003071 SMARCA3 SWI/SNF related, ATP-binding, DNA-binding, Helicase, 2401 6369
    matrix associated, Hydrolase, Metal-binding, Zinc, Zinc-
    actin dependent finger
    regulator of
    chromatin, subfamily
    a, member 3
    NM_003073 SMARCB1 SWI/SNF related, Hypothetical protein, Transcription 2402 6370
    matrix associated, regulation, Activator, Nuclear
    actin dependent protein, Alternative splicing, Anti-
    regulator of oncogene
    chromatin, subfamily
    b, member 1
    NM_003074 SMARCC1 SWI/SNF related, DNA-binding, Nuclear protein 2403 6371
    matrix associated,
    actin dependent
    regulator of
    chromatin, subfamily
    c, member 1
    NM_003077 SMARCD2 SWI/SNF related, 2404 6372
    matrix associated,
    actin dependent
    regulator of
    chromatin, subfamily
    d, member 2
    NM_003079 SMARCE1 SWI/SNF related, 2405 6373
    matrix associated,
    actin dependent
    regulator of
    chromatin, subfamily
    e, member 1
    NM_003084 SNAPC3 small nuclear RNA Hypothetical protein, Transcription 2406 6374
    activating complex, regulation, DNA- binding
    polypeptide
    3,
    50 kDa
    NM_003085 SNCB synuclein, beta Phosphorylation, Repeat 2407 6375
    NM_003086 SNAPC4 small nuclear RNA DNA-binding, Nuclear protein, 2408 6376
    activating complex, Hypothetical protein
    polypeptide
    4,
    190 kDa
    NM_003088 FSCN1 fascin homolog 1, Actin-binding, Acetylation, 2409 6377
    actin-bundling Phosphorylation, 3D-structure,
    protein Hypothetical protein
    (Strongylocentrotus
    purpuratus)
    NM_003090 SNRPA1 small nuclear Nuclear protein, RNA-binding, 2410 6378
    ribonucleoprotein Ribonucleoprotein, Leucine-rich
    polypeptide A′ repeat, Repeat, 3D-structure
    NM_003092 SNRPB2 small nuclear mRNA processing, mRNA splicing, 2411 6379
    ribonucleoprotein Nuclear protein, RNA-binding,
    polypeptide B″ Ribonucleoprotein, Repeat,
    Systemic lupus erythematosus, 3D-
    structure
    NM_003093 SNRPC small nuclear Nuclear protein, RNA-binding, 2412 6380
    ribonucleoprotein Ribonucleoprotein, Zinc-finger
    polypeptide C
    NM_003094 SNRPE small nuclear Nuclear protein, Ribonucleoprotein, 2413 6381
    ribonucleoprotein Systemic lupus erythematosus,
    polypeptide E mRNA splicing, mRNA processing,
    RNA-binding
    NM_003100 SNX2 sorting nexin 2 Transport, Protein transport 2414 6382
    NM_003104 SORD sorbitol Oxidoreductase, Zinc, Metal-binding, 2415 6383
    dehydrogenase NAD, Acetylation, Polymorphism
    NM_003105 SORL1 sortilin-related Endocytosis, Receptor, 2416 6384
    receptor, L(DLR Transmembrane, EGF-like domain,
    class) A repeats- Repeat, Glycoprotein, LDL, Lipid
    containing transport, Cholesterol metabolism,
    Signal
    NM_003107 SOX4 SRY (sex DNA-binding, Nuclear protein, 2417 6385
    determining region Transcription regulation, Activator
    Y)-box 4
    NM_003120 SPI1 spleen focus forming Proto-oncogene, DNA-binding, 2418 6386
    virus (SFFV) proviral Transcription regulation, Activator,
    integration oncogene Nuclear protein
    spi1
    NM_003135 SRP19 signal recognition Signal recognition particle, RNA- 2419 6387
    particle 19 kDa binding, Ribonucleoprotein, 3D-
    structure
    NM_003141 SSA1 Sjogren syndrome Systemic lupus erythematosus, Zinc- 2420 6388
    antigen A1 (52 kDa, finger, Antigen, RNA-binding,
    ribonucleoprotein Ribonucleoprotein, DNA-binding,
    autoantigen SS- Polymorphism
    A/Ro)
    NM_003143 SSBP1 single-stranded DNA DNA-binding, DNA replication, 2421 6389
    binding protein 1 Mitochondrion, Transit peptide, 3D-
    structure
    NM_003146 SSRP1 structure specific DNA-binding, Nuclear protein 2422 6390
    recognition protein 1
    NM_003150 STAT3 signal transducer Hypothetical protein, Transcription 2423 6391
    and activator of regulation, Activator, DNA-binding,
    transcription 3 Nuclear protein, Phosphorylation,
    (acute-phase SH2 domain
    response factor)
    NM_003153 STAT6 signal transducer Transcription regulation, Repressor, 2424 6392
    and activator of Alternative splicing, Activator, DNA-
    transcription 6, binding, Nuclear protein,
    interleukin-4 induced Phosphorylation, SH2 domain,
    Polymorphism
    NM_003163 STX1B1 Human mRNA for Neurotransmitter transport, Coiled 2425 6393
    SYNTAXIN1B, coil, Transmembrane
    complete cds.
    NM_003168 SUPT4H1 suppressor of Ty 4 Nuclear protein, Transcription, Zinc- 2426 6394
    homolog 1 (S. cerevisiae) finger
    NM_003169 SUPT5H suppressor of Ty 5 2427 6395
    homolog (S. cerevisiae)
    NM_003171 SUPV3L1 suppressor of var1, ATP-binding, Helicase, Hydrolase 2428 6396
    3-like 1 (S. cerevisiae)
    NM_003174 SVIL supervillin 2429 6397
    NM_003177 SYK spleen tyrosine Transferase, Tyrosine-protein 2430 6398
    kinase kinase, ATP-binding,
    Phosphorylation, SH2 domain,
    Repeat, Alternative splicing, 3D-
    structure
    NM_003190 TAPBP TAP binding protein Immunoglobulin domain, Signal, 2431 6399
    (tapasin) Transmembrane, Endoplasmic
    reticulum, Microsome, Alternative
    splicing, Polymorphism
    NM_003191 TARS hypothetical protein Aminoacyl-tRNA synthetase, Protein 2432 6400
    MGC9344 biosynthesis, Ligase, ATP-binding
    NM_003193 TBCE tubulin-specific 2433 6401
    chaperone e
    NM_003197 TCEB1L S-phase kinase- Ubl conjugation pathway, Alternative 2434 6402
    associated protein splicing, 3D-structure
    1A (p19A)
    NM_003199 TCF4 transcription factor 4 Transcription regulation, DNA- 2435 6403
    binding, Activator, Nuclear protein,
    Alternative splicing
    NM_003201 TFAM transcription factor Transcription regulation, DNA- 2436 6404
    A, mitochondrial binding, Activator, Mitochondrion,
    Transit peptide, Repeat,
    Polymorphism
    NM_003202 TCF7 transcription factor 7 Transcription regulation, Activator, 2437 6405
    (T-cell specific, Repressor, Trans-acting factor,
    HMG-box) Nuclear protein, DNA-binding, Wnt
    signaling pathway, Alternative
    splicing, Alternative promoter usage
    NM_003203 C2orf3 chromosome 2 open 2438 6406
    reading frame 3
    NM_003205 TCF12 transcription factor Transcription regulation, DNA- 2439 6407
    12 (HTF4, helix- binding, Nuclear protein,
    loop-helix Developmental protein
    transcription factors
    4)
    NM_003217 TEGT testis enhanced Apoptosis, Transmembrane 2440 6408
    gene transcript (BAX
    inhibitor 1)
    NM_003226 TFF3 trefoil factor 3 Signal, 3D-structure 2441 6409
    (intestinal)
    NM_003227 TFR2 transferrin receptor 2 Transmembrane, Glycoprotein, 2442 6410
    Receptor, Signal-anchor, Alternative
    splicing, Disease mutation
    NM_003236 TGFA transforming growth EGF-like domain, Growth factor, 2443 6411
    factor, alpha Mitogen, Glycoprotein,
    Transmembrane, Signal, 3D-
    structure, Lipoprotein, Palmitate
    NM_003245 TGM3 transglutaminase 3 Transferase, Acyltransferase, 2444 6412
    (E polypeptide, Calcium-binding, Zymogen,
    protein-glutamine- Keratinization, 3D-structure
    gamma-
    glutamyltransferase)
    NM_003248 THBS4 thrombospondin 4 Glycoprotein, Cell adhesion, 2445 6413
    Calcium-binding, Repeat, EGF-like
    domain, Signal
    NM_003252 TIAL1 TIA1 cytotoxic RNA-binding, Apoptosis, Repeat 2446 6414
    granule-associated
    RNA binding protein-
    like 1
    NM_003255 TIMP2 tissue inhibitor of Hypothetical protein, 2447 6415
    metalloproteinase 2 Metalloprotease inhibitor, Signal, 3D-
    structure
    NM_003263 TLR1 toll-like receptor 1 Receptor, Immune response, 2448 6416
    Inflammatory response, Signal,
    Transmembrane, Repeat, Leucine-
    rich repeat, Glycoprotein, 3D-
    structure
    NM_003274 TMEM1 transmembrane Transport, Endoplasmic reticulum, 2449 6417
    protein 1 Golgi stack, Polymorphism
    NM_003281 TNNI1 troponin I, skeletal, Muscle protein, Actin-binding, Ubl 2450 6418
    slow conjugation pathway, Hydrolase,
    Thiol protease, Multigene family
    NM_003288 TPD52L2 tumor protein D52- Coiled coil, Alternative splicing 2451 6419
    like 2
    NM_003289 TPM2 tropomyosin 2 (beta) Muscle protein, Cytoskeleton, Actin- 2452 6420
    binding, Coiled coil, Alternative
    splicing, Multigene family,
    Acetylation, Disease mutation
    NM_003290 TPM4 tropomyosin 4 Muscle protein, Cytoskeleton, Actin- 2453 6421
    binding, Coiled coil, Alternative
    splicing, Multigene family
    NM_003299 TRA1 tumor rejection Chaperone, Endoplasmic reticulum, 2454 6422
    antigen (gp96) 1 Glycoprotein, Calcium-binding,
    Signal
    NM_003307 TRPM2 Homo sapiens Ionic channel, Transmembrane, Ion 2455 6423
    transient receptor transport, Calcium channel,
    potential cation Alternative splicing
    channel, subfamily
    M, member 2
    (TRPM2), mRNA.
    NM_003310 TSSC1 tumor suppressing Repeat, WD repeat 2456 6424
    subtransferable
    candidate
    1
    NM_003316 TTC3 tetratricopeptide Metal-binding, Zinc, Zinc-finger, 2457 6425
    repeat domain 3 Repeat, TPR repeat, Alternative
    splicing, Polymorphism
    NM_003326 TNFSF4 tumor necrosis factor Cytokine, Transmembrane, 2458 6426
    (ligand) superfamily, Glycoprotein, Signal-anchor
    member 4 (tax-
    transcriptionally
    activated
    glycoprotein 1,
    34 kDa)
    NM_003329 TXN thioredoxin Redox-active center, Electron 2459 6427
    transport, 3D-structure
    NM_003330 TXNRD1 thioredoxin Redox-active center, 2460 6428
    reductase 1 Oxidoreductase, NADP,
    Flavoprotein, FAD
    NM_003331 TYK2 tyrosine kinase 2 Transferase, Tyrosine-protein 2461 6429
    kinase, ATP-binding,
    Phosphorylation, SH2 domain,
    Repeat
    NM_003332 TYROBP TYRO protein Transmembrane, Signal, 2462 6430
    tyrosine kinase Phosphorylation, Polymorphism,
    binding protein Receptor
    NM_003338 UBE2D1 ubiquitin-conjugating Ubl conjugation pathway, Ligase, 2463 6431
    enzyme E2D 1 Multigene family
    (UBC4/5 homolog,
    yeast)
    NM_003341 UBE2E1 ubiquitin-conjugating Ubl conjugation pathway, Ligase, 2464 6432
    enzyme E2E 1 Multigene family
    (UBC4/5 homolog,
    yeast)
    NM_003343 UBE2G2 ubiquitin-conjugating Ubl conjugation pathway, Ligase, 2465 6433
    enzyme E2G 2 Multigene family, Hypothetical
    (UBC7 homolog, protein
    yeast)
    NM_003348 UBE2N ubiquitin-conjugating Ubl conjugation pathway, Ligase, 2466 6434
    enzyme E2N Multigene family, 3D-structure
    (UBC13 homolog,
    yeast)
    NM_003355 UCP2 uncoupling protein 2 Mitochondrion, Inner membrane, 2467 6435
    (mitochondrial, Repeat, Transmembrane, Transport,
    proton carrier) Polymorphism
    NM_003358 UGCG UDP-glucose Transferase, Glycosyltransferase, 2468 6436
    ceramide Transmembrane, Signal-anchor,
    glucosyltransferase Endoplasmic reticulum
    NM_003362 UNG uracil-DNA DNA repair, Hydrolase, Glycosidase, 2469 6437
    glycosylase Nuclear protein, Mitochondrion,
    Transit peptide, Disease mutation,
    Alternative splicing, 3D-structure
    NM_003364 UP uridine Transferase, Glycosyltransferase, 2470 6438
    phosphorylase 1 Alternative splicing
    NM_003366 UQCRC2 ubiquinol- Mitochondrion, Inner membrane, 2471 6439
    cytochrome c Electron transport, Respiratory
    reductase core chain, Oxidoreductase, Transit
    protein II peptide
    NM_003370 VASP vasodilator- Phosphorylation, Actin-binding, 3D- 2472 6440
    stimulated structure
    phosphoprotein
    NM_003374 VDAC1 voltage-dependent Outer membrane, Porin, 2473 6441
    anion channel 1 Mitochondrion, Acetylation
    NM_003375 VDAC2 voltage-dependent Outer membrane, Porin, 2474 6442
    anion channel 2 Mitochondrion, Alternative splicing,
    Polymorphism
    NM_003377 VEGFB vascular endothelial Mitogen, Growth factor, 2475 6443
    growth factor B Glycoprotein, Signal, Heparin-
    binding, Alternative splicing,
    Multigene family
    NM_003387 WASPIP Wiskott-Aldrich Actin-binding, Repeat, 2476 6444
    syndrome protein Polymorphism
    interacting protein
    NM_003389 CORO2A coronin, actin Actin-binding, Repeat, WD repeat, 2477 6445
    binding protein, 2A Coiled coil
    NM_003403 YY1 YY1 transcription Transcription regulation, Repressor, 2478 6446
    factor Activator, Nuclear protein, Zinc-
    finger, Metal-binding, DNA-binding,
    Repeat, 3D-structure
    NM_003407 ZFP36 zinc finger protein Nuclear protein, Repeat, Metal- 2479 6447
    36, C3H type, binding, Zinc-finger, DNA-binding
    homolog (mouse)
    NM_003426 ZNF74 zinc finger protein 74 Transcription regulation, DNA- 2480 6448
    (Cos52) binding, RNA-binding, Zinc-finger,
    Metal-binding, Nuclear protein,
    Repeat, Alternative splicing,
    Polymorphism
    NM_003451 ZNF177 zinc finger protein Transcription regulation, DNA- 2481 6449
    177 binding, Zinc-finger, Metal-binding,
    Nuclear protein, Repeat,
    Hypothetical protein
    NM_003457 ZNF207 zinc finger protein Zinc-finger, Metal-binding, DNA- 2482 6450
    207 binding, Nuclear protein, Alternative
    splicing, Hypothetical protein
    NM_003461 ZYX zyxin LIM domain, Metal-binding, Zinc, 2483 6451
    Repeat, Cell adhesion, Receptor
    NM_003465 CHIT1 chitinase 1 Carbohydrate metabolism, Chitin 2484 6452
    (chitotriosidase) degradation, Polysaccharide
    degradation, Hydrolase,
    Glycosidase, Chitin-binding, Signal,
    Alternative splicing, 3D-structure
    NM_003466 PAX8 paired box gene 8 DNA-binding, Developmental 2485 6453
    protein, Nuclear protein, Paired box,
    Transcription, Transcription
    regulation, Differentiation, Alternative
    splicing, Disease mutation,
    Polymorphism
    NM_003467 CXCR4 chemokine (C—X—C G-protein coupled receptor, 2486 6454
    motif) receptor 4 Receptor, Transmembrane,
    Glycoprotein, Sulfation, Antigen,
    Alternative splicing
    NM_003475 C11orf13 chromosome 11 Coiled coil, Alternative splicing 2487 6455
    open reading frame
    13
    NM_003477 PDX1 pyruvate Transit peptide, Mitochondrion, 2488 6456
    dehydrogenase Lipoyl, Hypothetical protein,
    complex, component X Acyltransferase, Transferase
    NM_003489 NRIP1 nuclear receptor Transcription regulation, Nuclear 2489 6457
    interacting protein 1 protein
    NM_003493 HIST3H3 histone 3, H3 Nuclear protein, Chromosomal 2490 6458
    protein, DNA-binding, Nucleosome
    core, Multigene family, Acetylation,
    Methylation
    NM_003494 DYSF dysferlin, limb girdle Transmembrane, Repeat, Disease 2491 6459
    muscular dystrophy mutation, Hypothetical protein
    2B (autosomal
    recessive)
    NM_003498 SNN stannin Transmembrane, Hypothetical 2492 6460
    protein
    NM_003507 FZD7 frizzled homolog 7 Multigene family, G-protein coupled 2493 6461
    (Drosophila) receptor, Transmembrane,
    Developmental protein, Wnt
    signaling pathway, Glycoprotein,
    Signal
    NM_003508 FZD9 frizzled homolog 9 Multigene family, G-protein coupled 2494 6462
    (Drosophila) receptor, Transmembrane,
    Developmental protein, Wnt
    signaling pathway, Glycoprotein,
    Signal
    NM_003530 HIST1H3D histone 1, H3d Nuclear protein, Chromosomal 2495 6463
    protein, DNA-binding, Nucleosome
    core, Multigene family, Acetylation,
    Methylation
    NM_003532 HIST1H3E histone 1, H3c Nuclear protein, Chromosomal 2496 6464
    protein, DNA-binding, Nucleosome
    core, Multigene family, Acetylation,
    Methylation
    NM_003534 HIST1H3G histone 1, H3g Nuclear protein, Chromosomal 2497 6465
    protein, DNA-binding, Nucleosome
    core, Multigene family, Acetylation,
    Methylation
    NM_003535 HIST1H3J histone 1, H3j Nuclear protein, Chromosomal 2498 6466
    protein, DNA-binding, Nucleosome
    core, Multigene family, Acetylation,
    Methylation
    NM_003549 HYAL3 hyaluronoglucosaminidase 3 EGF-like domain 2499 6467
    NM_003560 PLA2G6 phospholipase A2, Hypothetical protein, ANK repeat, 2500 6468
    group VI (cytosolic, Repeat, Hydrolase, Lipid
    calcium- degradation, Membrane, Alternative
    independent) splicing
    NM_003562 SLC25A11 solute carrier family Mitochondrion, Inner membrane, 2501 6469
    25 (mitochondrial Repeat, Transmembrane, Transport
    carrier; oxoglutarate
    carrier), member 11
    NM_003565 ULK1 unc-51-like kinase 1 Hypothetical protein, ATP-binding, 2502 6470
    (C. elegans) Transferase, Serine/threonine-
    protein kinase
    NM_003570 CMAH MRNA for CMP-N- 2503 6471
    acetylneuraminic
    acid hydroxylase,
    complete cds.
    NM_003577 UTF1 undifferentiated 2504 6472
    embryonic cell
    transcription factor
    1
    NM_003579 RAD54L RAD54-like (S. cerevisiae) ATP-binding, DNA repair, Helicase, 2505 6473
    Hydrolase
    NM_003587 DDX16 DEAH (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 2506 6474
    His) box polypeptide mRNA processing, mRNA splicing,
    16 Nuclear protein
    NM_003599 SUPT3H suppressor of Ty 3 Transcription regulation, Activator, 2507 6475
    homolog (S. cerevisiae) Nuclear protein, Alternative splicing
    NM_003601 SMARCA5 SWI/SNF related, ATP-binding, DNA-binding, Helicase, 2508 6476
    matrix associated, Hydrolase, Nuclear protein
    actin dependent
    regulator of
    chromatin, subfamily
    a, member 5
    NM_003618 MAP4K3 mitogen-activated ATP-binding, Kinase, Transferase 2509 6477
    protein kinase
    kinase kinase kinase 3
    NM_003624 RANBP3 RAN binding protein 3 Hypothetical protein 2510 6478
    NM_003634 NIPSNAP1 nipsnap homolog 1 Polymorphism 2511 6479
    (C. elegans)
    NM_003635 NDST2 N-deacetylase/N- Hypothetical protein, Transferase, 2512 6480
    sulfotransferase Transmembrane, Glycoprotein, Golgi
    (heparan stack, Signal-anchor
    glucosaminyl) 2
    NM_003636 KCNAB2 potassium voltage- Ionic channel, Ion transport, 2513 6481
    gated channel, Potassium transport, Voltage-gated
    shaker-related channel, Alternative splicing
    subfamily, beta
    member
    2
    NM_003639 IKBKG inhibitor of kappa Coiled coil, Transcription regulation, 2514 6482
    light polypeptide Nuclear protein, Disease mutation,
    gene enhancer in B- Anhidrotic ectodermal dysplasia,
    cells, kinase gamma Repeat, LIM domain, Metal-binding,
    Zinc, Developmental protein,
    Differentiation, Zinc-finger
    NM_003644 GAS7 growth arrest- Neurogenesis, Developmental 2515 6483
    specific 7 protein, Coiled coil, Proto-oncogene,
    Chromosomal translocation,
    Alternative splicing
    NM_003648 DGKD diacylglycerol Transferase, Kinase, Phorbol-ester 2516 6484
    kinase, delta 130 kDa binding, Repeat, Multigene family
    NM_003650 CST7 cystatin F Thiol protease inhibitor, 2517 6485
    (leukocystatin) Glycoprotein, Signal
    NM_003655 CBX4 chromobox homolog Chromatin regulator, Nuclear 2518 6486
    4 (Pc class homolog, protein, Transcription regulation,
    Drosophila) Repressor, Alternative splicing
    NM_003668 MAPKAPK5 mitogen-activated Hypothetical protein, ATP-binding, 2519 6487
    protein kinase- Kinase, Serine/threonine-protein
    activated protein kinase, Transferase
    kinase 5
    NM_003674 CDK10 cyclin-dependent Transferase, Serine/threonine- 2520 6488
    kinase (CDC2-like) protein kinase, ATP-binding, Kinase,
    10 Cyclin
    NM_003680 YARS tyrosyl-tRNA Aminoacyl-tRNA synthetase, Protein 2521 6489
    synthetase biosynthesis, Ligase, ATP-binding,
    RNA-binding, tRNA-binding, 3D-
    structure
    NM_003681 PDXK pyridoxal Transferase, Kinase, Alternative 2522 6490
    (pyridoxine, vitamin splicing
    B6) kinase
    NM_003682 MADD MAP-kinase Hypothetical protein, Kinase 2523 6491
    activating death
    domain
    NM_003685 KHSRP KH-type splicing Transport, mRNA transport, mRNA 2524 6492
    regulatory protein processing, mRNA splicing,
    (FUSE binding Transcription regulation, Trans-
    protein 2) acting factor, Nuclear protein, DNA-
    binding, RNA-binding, Repeat
    NM_003686 EXO1 exonuclease 1 Exonuclease, Hypothetical protein 2525 6493
    NM_003690 PRKRA protein kinase, Hypothetical protein, Kinase 2526 6494
    interferon-inducible
    double stranded
    RNA dependent
    activator
    NM_003707 RUVBL1 RuvB-like 1 (E. coli) Transcription, DNA recombination, 2527 6495
    ATP-binding, Hydrolase, Helicase,
    Nuclear protein
    NM_003709 KLF7 Kruppel-like factor 7 Transcription regulation, Activator, 2528 6496
    (ubiquitous) Zinc-finger, Metal-binding, DNA-
    binding, Nuclear protein, Repeat
    NM_003713 PPAP2B phosphatidic acid Collagen, Hydrolase, Hypothetical 2529 6497
    phosphatase type protein
    2B
    NM_003725 RODH 3-hydroxysteroid Oxidoreductase 2530 6498
    epimerase
    NM_003726 SCAP1 src family associated SH3 domain 2531 6499
    phosphoprotein 1
    NM_003730 RNASE6PL ribonuclease T2 Hydrolase, Nuclease, Endonuclease, 2532 6500
    Glycoprotein, Signal, Alternative
    splicing, Polymorphism, Hypothetical
    protein
    NM_003734 AOC3 amine oxidase, Oxidoreductase, Copper, TPQ, 2533 6501
    copper containing 3 Glycoprotein, Transmembrane,
    (vascular adhesion Signal-anchor, Cell adhesion,
    protein 1) Polymorphism, Metal-binding
    NM_003748 ALDH4A1 aldehyde Oxidoreductase, NAD, Proline 2534 6502
    dehydrogenase 4 metabolism, Mitochondrion, Transit
    family, member A1 peptide, Polymorphism, Disease
    mutation
    NM_003750 EIF3S10 eukaryotic Initiation factor, Protein biosynthesis, 2535 6503
    translation initiation Repeat, Phosphorylation
    factor
    3, subunit 10
    theta, 150/170 kDa
    NM_003754 EIF3S5 eukaryotic Initiation factor, Protein biosynthesis, 2536 6504
    translation initiation Polymorphism, Hypothetical protein
    factor
    3, subunit 5
    epsilon, 47 kDa
    NM_003755 EIF3S4 eukaryotic Initiation factor, Protein biosynthesis, 2537 6505
    translation initiation RNA-binding
    factor
    3, subunit 4
    delta, 44 kDa
    NM_003756 EIF3S3 eukaryotic Initiation factor, Protein biosynthesis 2538 6506
    translation initiation
    factor
    3, subunit 3
    gamma, 40 kDa
    NM_003758 EIF3S1 eukaryotic Hypothetical protein, Initiation factor, 2539 6507
    translation initiation Protein biosynthesis
    factor
    3, subunit 1
    alpha, 35 kDa
    NM_003764 STX11 syntaxin 11 Coiled coil, Membrane, 2540 6508
    Polymorphism
    NM_003765 STX10 syntaxin 10 Coiled coil, Transmembrane, 2541 6509
    Transport, Protein transport, Golgi
    stack, Alternative splicing
    NM_003769 SFRS9 splicing factor, Nuclear protein, RNA-binding, 2542 6510
    arginine/serine-rich 9 mRNA splicing, Repeat,
    Phosphorylation
    NM_003776 MRPL40 mitochondrial Ribosomal protein, Mitochondrion, 2543 6511
    ribosomal protein Transit peptide, Polymorphism
    L40
    NM_003782 B3GALT4 UDP- Transferase, Glycosyltransferase, 2544 6512
    Gal:betaGlcNAc Glycoprotein, Transmembrane,
    beta 1,3- Signal-anchor, Golgi stack
    galactosyltransferase,
    polypeptide 4
    NM_003786 ABCC3 ATP-binding ATP-binding, Glycoprotein, 2545 6513
    cassette, sub-family Transmembrane, Transport, Repeat,
    C (CFTR/MRP), Alternative splicing
    member
    3
    NM_003791 MBTPS1 membrane-bound Hydrolase, Protease, Serine 2546 6514
    transcription factor protease, Lipid metabolism,
    protease, site 1 Cholesterol metabolism, Signal,
    Transmembrane, Endoplasmic
    reticulum, Golgi stack, Zymogen,
    Autocatalytic cleavage, Glycoprotein,
    Calcium
    NM_003796 C19orf2 chromosome 19 Nuclear protein 2547 6515
    open reading frame 2
    NM_003801 GPAA1 GPAA1P anchor Hypothetical protein 2548 6516
    attachment protein 1
    homolog (yeast)
    NM_003805 CRADD CASP2 and RIPK1 Apoptosis, 3D-structure 2549 6517
    domain containing
    adaptor with death
    domain
    NM_003807 TNFSF14 tumor necrosis factor Cytokine, Transmembrane, 2550 6518
    (ligand) superfamily, Glycoprotein, Signal-anchor,
    member 14 Alternative splicing
    NM_003808 TNFSF13 tumor necrosis factor Cytokine, Immune response, 2551 6519
    (ligand) superfamily, Glycoprotein, Alternative splicing
    member
    13
    NM_003815 ADAM15 a disintegrin and Hydrolase, Metalloprotease, Zinc, 2552 6520
    metalloproteinase Signal, Glycoprotein, Zymogen,
    domain 15 Transmembrane, EGF-like domain,
    (metargidin) SH3-binding, Phosphorylation
    NM_003820 TNFRSF14 tumor necrosis factor Receptor, Transmembrane, 2553 6521
    receptor superfamily, Glycoprotein, Repeat, Signal,
    member 14 Polymorphism, 3D-structure
    (herpesvirus entry
    mediator)
    NM_003829 MPDZ multiple PDZ domain Hypothetical protein 2554 6522
    protein
    NM_003830 SIGLEC5 sialic acid binding Ig- Cell adhesion, Lectin, 2555 6523
    like lectin 5 Transmembrane, Signal,
    Glycoprotein, Immunoglobulin
    domain, Repeat, Antigen,
    Polymorphism
    NM_003841 TNFRSF10C tumor necrosis factor Receptor, Apoptosis, Glycoprotein, 2556 6524
    receptor superfamily, Repeat, GPI-anchor, Signal,
    member 10c, decoy Lipoprotein
    without an
    intracellular domain
    NM_003846 PEX11B peroxisomal 2557 6525
    biogenesis factor
    11B
    NM_003852 TIF1 transcriptional Elongation factor, Protein 2558 6526
    intermediary factor 1 biosynthesis, GTP-binding,
    Methylation, Multigene family,
    Transcription regulation, Repressor,
    DNA-binding, Bromodomain, Zinc-
    finger, Alternative splicing, Nuclear
    protein, Coiled coil, Repeat
    NM_003853 IL18RAP interleukin 18 Receptor 2559 6527
    receptor accessory
    protein
    NM_003866 INPP4B inositol Hypothetical protein 2560 6528
    polyphosphate-4-
    phosphatase, type II,
    105 kDa
    NM_003877 SOCS2 suppressor of SH2 domain, Growth regulation, 2561 6529
    cytokine signaling 2 Signal transduction inhibitor
    NM_003887 DDEF2 development and Hypothetical protein, ANK repeat, 2562 6530
    differentiation Repeat, SH3 domain
    enhancing factor
    2
    NM_003893 LDB1 LIM domain binding 1 DNA-binding, Homeobox, Nuclear 2563 6531
    protein
    NM_003895 SYNJ1 synaptojanin 1 Hydrolase, Alternative splicing, 2564 6532
    Repeat, Endocytosis, RNA-binding,
    Multigene family, Hypothetical
    protein
    NM_003896 SIAT9 sialyltransferase 9 Transferase, Glycosyltransferase, 2565 6533
    (CMP- Glycoprotein, Transmembrane,
    NeuAc:lactosylceramide Signal-anchor, Golgi stack
    alpha-2,3-
    sialyltransferase;
    GM3 synthase)
    NM_003897 IER3 immediate early Glycoprotein, Transmembrane, 2566 6534
    response 3 Signal-anchor
    NM_003899 ARHGEF7 Rho guanine Hypothetical protein, SH3 domain, 2567 6535
    nucleotide exchange Guanine-nucleotide releasing factor,
    factor (GEF) 7 Alternative splicing, 3D-structure
    NM_003900 SQSTM1 sequestosome 1 Hypothetical protein 2568 6536
    NM_003903 CDC16 CDC16 cell division Ubl conjugation pathway, Cell cycle, 2569 6537
    cycle 16 homolog (S. cerevisiae) Cell division, Mitosis, Repeat, TPR
    repeat, Alternative splicing
    NM_003904 ZNF259 zinc finger protein Nuclear protein, Zinc-finger 2570 6538
    259
    NM_003905 APPBP1 amyloid beta Hypothetical protein 2571 6539
    precursor protein
    binding protein
    1,
    59 kDa
    NM_003909 CPNE3 copine III Repeat, Phosphorylation, 2572 6540
    Transferase, Serine/threonine-
    protein kinase
    NM_003915 CPNE1 copine I Repeat 2573 6541
    NM_003923 FOXH1 forkhead box H1 Transcription regulation, Activator, 2574 6542
    DNA-binding, Nuclear protein,
    Polymorphism
    NM_003931 WASF1 WAS protein family, Actin-binding 2575 6543
    member 1
    NM_003938 AP3D1 adaptor-related Golgi stack, Protein transport, 2576 6544
    protein complex 3, Transport, Alternative splicing,
    delta 1 subunit Polymorphism
    NM_003940 USP13 ubiquitin specific Ubl conjugation pathway, Hydrolase, 2577 6545
    protease 13 Thiol protease, Multigene family,
    (isopeptidase T-3) Repeat, Hypothetical protein
    NM_003943 GENX- genethonin 1 2578 6546
    3414
    NM_003945 ATP6V0E ATPase, H+ Hydrolase, Hydrogen ion transport, 2579 6547
    transporting, Transmembrane
    lysosomal 9 kDa, V0
    subunit e
    NM_003951 SLC25A14 solute carrier family Mitochondrion, Repeat, 2580 6548
    25 (mitochondrial Transmembrane, Transport,
    carrier, brain), Alternative splicing
    member 14
    NM_003953 MPZL1 myelin protein zero- Hypothetical protein 2581 6549
    like 1
    NM_003954 MAP3K14 mitogen-activated Hypothetical protein, Transferase, 2582 6550
    protein kinase Serine/threonine-protein kinase,
    kinase kinase 14 ATP-binding, Phosphorylation
    NM_003967 PNR putative G-protein coupled receptor, 2583 6551
    neurotransmitter Receptor, Transmembrane
    receptor
    NM_003975 SH2D2A SH2 domain protein Angiogenesis, Phosphorylation, SH2 2584 6552
    2A domain, SH3-binding, Alternative
    splicing
    NM_003977 AIP aryl hydrocarbon Repeat, TPR repeat 2585 6553
    receptor interacting
    protein
    NM_003978 PSTPIP1 proline-serine- SH3 domain 2586 6554
    threonine
    phosphatase
    interacting protein
    1
    NM_003983 SLC7A6 solute carrier family Hypothetical protein 2587 6555
    7 (cationic amino
    acid transporter, y+
    system), member 6
    NM_004031 IRF7 interferon regulatory Transcription regulation, DNA- 2588 6556
    factor 7 binding, Nuclear protein, Activator,
    Alternative splicing, Collagen
    NM_004033 ANXA6 annexin A6 Annexin, Calcium/phospholipid- 2589 6557
    binding, Repeat, Acetylation,
    Phosphorylation, 3D-structure
    NM_004037 AMPD2 adenosine Hydrolase, Nucleotide metabolism, 2590 6558
    monophosphate Multigene family, Alternative splicing
    deaminase 2
    (isoform L)
    NM_004039 ANXA2 annexin A2 Annexin, Calcium, Calcium-binding, 2591 6559
    Calcium/phospholipid-binding,
    Repeat, Phosphorylation,
    Acetylation, Polymorphism
    NM_004044 ATIC 5-aminoimidazole-4- Purine biosynthesis, Transferase, 2592 6560
    carboxamide Hydrolase, Multifunctional enzyme
    ribonucleotide
    formyltransferase/IMP
    cyclohydrolase
    NM_004046 ATP5A1 ATP synthase, H+ ATP synthesis, ATP-binding, CF(1), 2593 6561
    transporting, Hydrogen ion transport, Hydrolase,
    mitochondrial F1 Ion transport, Transport,
    complex, alpha Mitochondrion, Transit peptide,
    subunit, isoform 1, Pyrrolidone carboxylic acid,
    cardiac muscle Hypothetical protein
    NM_004047 ATP6V0B ATPase, H+ Hydrolase, Hydrogen ion transport, 2594 6562
    transporting, ATP synthesis, Transmembrane
    lysosomal 21 kDa,
    V0 subunit c″
    NM_004049 BCL2A1 BCL2-related protein Apoptosis 2595 6563
    A1
    NM_004053 BYSL bystin-like Cell adhesion 2596 6564
    NM_004054 C3AR1 complement G-protein coupled receptor, 2597 6565
    component 3a Transmembrane, Glycoprotein,
    receptor 1 Chemotaxis
    NM_004060 CCNG1 cyclin G1 Cyclin, Cell cycle, Cell division, 2598 6566
    Mitosis, Nuclear protein
    NM_004070 CLCNKA chloride channel Ka Ionic channel, Ion transport, Chloride 2599 6567
    channel, Chloride, Voltage-gated
    channel, Transmembrane, CBS
    domain, Repeat
    NM_004073 CNK cytokine-inducible Transferase, Serine/threonine- 2600 6568
    kinase protein kinase, ATP-binding, Repeat,
    Phosphorylation, Hypothetical
    protein, Kinase
    NM_004079 CTSS cathepsin S Hydrolase, Thiol protease, 2601 6569
    Lysosome, Zymogen, Signal, 3D-
    structure
    NM_004084 DEFA1 defensin, alpha 1, Defensin, Antibiotic, Antiviral, 2602 6570
    myeloid-related Fungicide, Signal, 3D-structure
    sequence
    NM_004090 DUSP3 dual specificity Hydrolase, 3D-structure, 2603 6571
    phosphatase 3 Hypothetical protein
    (vaccinia virus
    phosphatase VH1-
    related)
    NM_004092 ECHS1 enoyl Coenzyme A Fatty acid metabolism, Lyase, 2604 6572
    hydratase, short Mitochondrion, Transit peptide
    chain, 1,
    mitochondrial
    NM_004094 EIF2S1 eukaryotic Initiation factor, Protein biosynthesis, 2605 6573
    translation initiation Translation regulation, RNA-binding,
    factor 2, subunit 1 Phosphorylation, 3D-structure
    alpha, 35 kDa
    NM_004099 STOM stomatin Erythrocyte, Transmembrane, 2606 6574
    Phosphorylation, Lipoprotein,
    Palmitate, Hypothetical protein,
    Transducer, Prenylation, Multigene
    family
    NM_004105 EFEMP1 EGF-containing Repeat, EGF-like domain, Calcium- 2607 6575
    fibulin-like binding, Glycoprotein, Signal,
    extracellular matrix Disease mutation, Polymorphism,
    protein 1 Alternative splicing
    NM_004106 FCER1G Fc fragment of IgE, IgE-binding protein, Receptor, 2608 6576
    high affinity I, Transmembrane, Signal
    receptor for; gamma
    polypeptide
    NM_004107 FCGRT Fc fragment of IgG, IgG-binding protein, Receptor, 2609 6577
    receptor, transporter, Transmembrane, Glycoprotein,
    alpha Signal, Immunoglobulin domain, 3D-
    structure
    NM_004108 FCN2 ficolin Lectin, Collagen, Repeat, 2610 6578
    (collagen/fibrinogen Glycoprotein, Signal, Multigene
    domain containing family
    lectin) 2 (hucolin)
    NM_004109 FDX1 ferredoxin 1 Metal-binding, Iron-sulfur, Iron, 2Fe—2S, 2611 6579
    Electron transport,
    Mitochondrion, Transit peptide
    NM_004115 FGF14 fibroblast growth Growth factor 2612 6580
    factor 14
    NM_004119 FLT3 fms-related tyrosine Signal, Transferase, Tyrosine- 2613 6581
    kinase 3 protein kinase, Receptor,
    Transmembrane, Glycoprotein,
    Phosphorylation, ATP-binding,
    Immunoglobulin domain
    NM_004122 GHSR growth hormone G-protein coupled receptor, 2614 6582
    secretagogue Transmembrane, Glycoprotein,
    receptor Alternative splicing
    NM_004126 GNG11 guanine nucleotide Transducer, Prenylation, Lipoprotein, 2615 6583
    binding protein (G Multigene family
    protein), gamma 11
    NM_004128 GTF2F2 general transcription Transcription regulation, DNA- 2616 6584
    factor IIF, binding, Helicase, ATP-binding,
    polypeptide 2, Nuclear protein, 3D-structure
    30 kDa
    NM_004130 GYG glycogenin Transferase, Glycogen biosynthesis, 2617 6585
    Acetylation, Phosphorylation,
    Glycoprotein, Alternative splicing,
    Hypothetical protein
    NM_004131 GZMB granzyme B Hydrolase, Serine protease, 2618 6586
    (granzyme 2, Zymogen, Signal, T-cell, Cytolysis,
    cytotoxic T- Apoptosis, Glycoprotein, 3D-
    lymphocyte- structure, Protease
    associated serine
    esterase 1)
    NM_004134 HSPA9B heat shock 70 kDa ATP-binding, Heat shock, 2619 6587
    protein 9B (mortalin- Chaperone, Mitochondrion, Transit
    2) peptide
    NM_004147 DRG1 developmentally GTP-binding, Hypothetical protein 2620 6588
    regulated GTP
    binding protein
    1
    NM_004148 NINJ1 ninjurin 1 Cell adhesion, Transmembrane, 2621 6589
    Hypothetical protein
    NM_004152 OAZ1 ornithine 2622 6590
    decarboxylase
    antizyme
    1
    NM_004168 SDHA succinate Tricarboxylic acid cycle, 2623 6591
    dehydrogenase Flavoprotein, FAD, Oxidoreductase,
    complex, subunit A, Electron transport, Mitochondrion,
    flavoprotein (Fp) Transit peptide, Disease mutation,
    Leigh syndrome
    NM_004177 STX3A syntaxin 3A Neurotransmitter transport, Coiled 2624 6592
    coil, Transmembrane, Alternative
    splicing
    NM_004178 TARBP2 TAR (HIV) RNA Hypothetical protein, RNA-binding, 2625 6593
    binding protein 2 Repeat, Nuclear protein
    NM_004180 TANK TRAF family Zinc-finger, Metal-binding, 2626 6594
    member-associated Alternative splicing, 3D-structure
    NFKB activator
    NM_004183 VMD2 vitelliform macular Transport, Ion transport, Ionic 2627 6595
    dystrophy (Best channel, Chloride channel, Chloride,
    disease, bestrophin) Calcium, Alternative splicing,
    Disease mutation, Polymorphism,
    Vision, Transmembrane,
    Phosphorylation, Iron storage, Metal-
    binding, 3D-structure
    NM_004207 SLC16A3 solute carrier family Transport, Symport, 2628 6596
    16 (monocarboxylic Transmembrane, Multigene family
    acid transporters),
    member 3
    NM_004221 NK4 natural killer cell Signal 2629 6597
    transcript 4
    NM_004225 MFHAS1 malignant fibrous GTP-binding 2630 6598
    histiocytoma
    amplified sequence 1
    NM_004235 KLF4 Kruppel-like factor 4 Transcription regulation, Activator, 2631 6599
    (gut) Zinc-finger, Metal-binding, DNA-
    binding, Nuclear protein, Repeat
    NM_004239 TRIP11 thyroid hormone Hypothetical protein, Antigen, Golgi 2632 6600
    receptor interactor stack, Coiled coil, Chromosomal
    11 translocation
    NM_004244 CD163 CD163 antigen Signal, Antigen 2633 6601
    NM_004245 TGM5 transglutaminase 5 Transferase, Acyltransferase, 2634 6602
    Calcium-binding, Polymorphism,
    Alternative splicing
    NM_004252 SLC9A3R1 solute carrier family 2635 6603
    9 (sodium/hydrogen
    exchanger), isoform
    3 regulatory factor 1
    NM_004255 COX5A cytochrome c Oxidoreductase, Heme, 2636 6604
    oxidase subunit Va Mitochondrion, Inner membrane,
    Transit peptide
    NM_004258 IGSF2 immunoglobulin 2637 6605
    superfamily, member 2
    NM_004263 SEMA4F sema domain, Signal, Transmembrane, 2638 6606
    immunoglobulin Immunoglobulin domain, Multigene
    domain (Ig), family, Neurogenesis,
    transmembrane Developmental protein,
    domain (TM) and Glycoprotein, Alternative splicing
    short cytoplasmic
    domain,
    (semaphorin) 4F
    NM_004265 FADS2 fatty acid desaturase 2 Hypothetical protein, Heme 2639 6607
    NM_004272 HOMER1 homer homolog 1 Coiled coil, Alternative splicing 2640 6608
    (Drosophila)
    NM_004279 PMPCB peptidase Chaperone, Nuclear protein, 2641 6609
    (mitochondrial Phosphorylation, Hydrolase,
    processing) beta Metalloprotease, Zinc,
    Mitochondrion, Transit peptide,
    Hypothetical protein
    NM_004295 TRAF4 TNF receptor- Apoptosis, Developmental protein, 2642 6610
    associated factor 4 Nuclear protein, Zinc-finger, Coiled
    coil, Repeat, Alternative splicing
    NM_004300 ACP1 acid phosphatase 1, Hydrolase, Acetylation, Alternative 2643 6611
    soluble splicing, Polymorphism, 3D-structure
    NM_004305 BIN1 bridging integrator 1 Alternative splicing, SH3 domain, 2644 6612
    Coiled coil, Endocytosis, Anti-
    oncogene, Differentiation,
    Phosphorylation, Hypothetical
    protein
    NM_004309 ARHGDIA Rho GDP GTPase activation, 3D-structure 2645 6613
    dissociation inhibitor
    (GDI) alpha
    NM_004313 ARRB2 arrestin, beta 2 Sensory transduction, Nuclear 2646 6614
    protein, Alternative splicing
    NM_004331 BNIP3L BCL2/adenovirus Apoptosis, Transmembrane, 2647 6615
    E1B 19 kDa Mitochondrion
    interacting protein 3-
    like
    NM_004334 BST1 bone marrow Hydrolase, NAD, Glycoprotein, GPI- 2648 6616
    stromal cell antigen 1 anchor, Signal, 3D-structure,
    Lipoprotein, Hypothetical protein
    NM_004336 BUB1 BUB1 budding Transferase, Serine/threonine- 2649 6617
    uninhibited by protein kinase, ATP-binding, Cell
    benzimidazoles
    1 cycle, Nuclear protein, Mitosis,
    homolog (yeast) Phosphorylation, Polymorphism
    NM_004337 C8orf1 chromosome 8 open Meiosis 2650 6618
    reading frame 1
    NM_004345 CAMP cathelicidin Antibiotic, Signal, Pyrrolidone 2651 6619
    antimicrobial peptide carboxylic acid
    NM_004350 RUNX3 runt-related Transcription regulation, DNA- 2652 6620
    transcription factor 3 binding, Nuclear protein, ATP-
    binding, Alternative splicing
    NM_004358 CDC25B cell division cycle Cell division, Mitosis, Hydrolase, 2653 6621
    25B Alternative splicing, Multigene family,
    3D-structure
    NM_004360 CDH1 cadherin 1, type 1, Elongation factor, Protein 2654 6622
    E-cadherin biosynthesis, GTP-binding,
    (epithelial) Methylation, Multigene family,
    Ribosomal protein, Repeat,
    Hypothetical protein, Cell adhesion,
    Glycoprotein, Transmembrane,
    Calcium-binding, Signal,
    Phosphorylation, Disease mutation,
    Polymorphism, 3D-structure
    NM_004368 CNN2 calponin 2 Calmodulin-binding, Actin-binding, 2655 6623
    Multigene family, Repeat
    NM_004374 COX6C cytochrome c Oxidoreductase, Inner membrane, 2656 6624
    oxidase subunit VIc Mitochondrion
    NM_004375 COX11 COX11 homolog, Copper, Mitochondrion, 2657 6625
    cytochrome c Transmembrane, Transit peptide,
    oxidase assembly Transport, Protein transport, SH3-
    protein (yeast) binding, Membrane, Golgi stack,
    Phosphorylation, Hypothetical
    protein
    NM_004380 CREBBP CREB binding Transferase, Transcription 2658 6626
    protein (Rubinstein- regulation, Nuclear protein,
    Taybi syndrome) Activator, Bromodomain,
    Chromosomal translocation, Zinc-
    finger, Repeat, Disease mutation,
    3D-structure
    NM_004381 CREBL1 cAMP responsive Glycoprotein, Cell adhesion, Repeat, 2659 6627
    element binding EGF-like domain, Coiled coil,
    protein-like 1 Extracellular matrix, Alternative
    splicing, Signal, Ehlers-Danlos
    syndrome, Transcription regulation,
    DNA-binding, Activator, Unfolded
    protein response, Nuclear protein,
    Endoplasmic reticu
    NM_004385 CSPG2 chondroitin sulfate Glycoprotein, Proteoglycan, Lectin, 2660 6628
    proteoglycan 2 Extracellular matrix, Sushi, Signal,
    (versican) Repeat, EGF-like domain, Calcium,
    Immunoglobulin domain, Hyaluronic
    acid, Alternative splicing
    NM_004390 CTSH cathepsin H Hydrolase, Protease, Thiol protease, 2661 6629
    Lysosome, Glycoprotein, Zymogen,
    Signal, 3D-structure
    NM_004398 DDX10 DEAD (Asp-Glu-Ala- Helicase, ATP-binding, RNA-binding 2662 6630
    Asp) box polypeptide
    10
    NM_004409 DMPK dystrophia Transferase, Serine/threonine- 2663 6631
    myotonica-protein protein kinase, ATP-binding, Coiled
    kinase coil, Alternative splicing
    NM_004417 DUSP1 dual specificity Hydrolase, Cell cycle 2664 6632
    phosphatase 1
    NM_004418 DUSP2 dual specificity Hydrolase, Nuclear protein, 3D- 2665 6633
    phosphatase 2 structure
    NM_004424 E4F1 E4F transcription Metal-binding, Zinc, Zinc-finger 2666 6634
    factor 1
    NM_004427 PHC2 polyhomeotic-like 2 Hypothetical protein 2667 6635
    (Drosophila)
    NM_004446 EPRS glutamyl-prolyl-tRNA Aminoacyl-tRNA synthetase, Protein 2668 6636
    synthetase biosynthesis, Ligase, ATP-binding,
    Multifunctional enzyme, Repeat, 3D-
    structure
    NM_004450 ERH enhancer of 2669 6637
    rudimentary
    homolog
    (Drosophila)
    NM_004453 ETFDH electron-transferring- Oxidoreductase, Electron transport, 2670 6638
    flavoprotein Flavoprotein, FAD, Iron-sulfur, 4Fe—4S,
    dehydrogenase Mitochondrion, Transit peptide,
    Ubiquinone, Transmembrane,
    Glutaricaciduria
    NM_004475 FLOT2 flotillin 2 Cell adhesion, Membrane 2671 6639
    NM_004477 FRG1 FSHD region gene 1 Multigene family 2672 6640
    NM_004479 FUT7 fucosyltransferase 7 Transferase, Glycosyltransferase, 2673 6641
    (alpha (1,3) Transmembrane, Glycoprotein,
    fucosyltransferase) Signal-anchor, Golgi stack
    NM_004480 FUT8 fucosyltransferase 8 Transferase, Glycosyltransferase, 2674 6642
    (alpha (1,6) Transmembrane, Signal-anchor,
    fucosyltransferase) Golgi stack, SH3 domain, SH3-
    binding, Alternative splicing
    NM_004482 GALNT3 UDP-N-acetyl-alpha- Transferase 2675 6643
    D-
    galactosamine:polypeptide
    N-
    acetylgalactosaminyl
    transferase 3
    (GalNAc-T3)
    NM_004483 GCSH glycine cleavage Mitochondrion, Transit peptide, 2676 6644
    system protein H Lipoyl
    (aminomethyl
    carrier)
    NM_004485 GNG4 guanine nucleotide Transducer, Prenylation, Lipoprotein, 2677 6645
    binding protein (G Multigene family
    protein), gamma 4
    NM_004489 GPS2 G protein pathway Hypothetical protein 2678 6646
    suppressor 2
    NM_004492 GTF2A2 general transcription Transcription regulation, Nuclear 2679 6647
    factor IIA, 2, 12 kDa protein
    NM_004497 FOXA3 forkhead box A3 DNA-binding, Nuclear protein, 2680 6648
    Transcription regulation, Activator,
    Polymorphism
    NM_004504 HRB HIV-1 Rev binding Nuclear protein, Transport, Repeat, 2681 6649
    protein DNA-binding, Zinc-finger
    NM_004506 HSF2 heat shock Heat shock, Transcription regulation, 2682 6650
    transcription factor 2 Nuclear protein, DNA-binding,
    Activator, Phosphorylation,
    Multigene family
    NM_004513 IL16 interleukin 16 Cytokine, Chemotaxis, Repeat, 3D- 2683 6651
    (lymphocyte structure
    chemoattractant
    factor)
    NM_004515 ILF2 interleukin enhancer 2684 6652
    binding factor 2,
    45 kDa
    NM_004516 ILF3 interleukin enhancer Hypothetical protein, Transcription 2685 6653
    binding factor 3, regulation, DNA-binding, RNA-
    90 kDa binding, Nuclear protein, Repeat,
    Phosphorylation, Methylation,
    Alternative splicing
    NM_004524 LLGL2 lethal giant larvae Repeat, WD repeat 2686 6654
    homolog 2
    (Drosophila)
    NM_004529 MLLT3 myeloid/lymphoid or Transcription regulation, Activator, 2687 6655
    mixed-lineage Nuclear protein, Chromosomal
    leukemia (trithorax translocation, Proto-oncogene
    homolog,
    Drosophila);
    translocated to, 3
    NM_004537 NAP1L1 nucleosome Nuclear protein 2688 6656
    assembly protein 1-
    like 1
    NM_004554 NFATC4 nuclear factor of Hypothetical protein, Transcription 2689 6657
    activated T-cells, regulation, Activator, Nuclear
    cytoplasmic, protein, DNA-binding, Repeat,
    calcineurin- Phosphorylation
    dependent 4
    NM_004563 PCK2 phosphoenolpyruvate Gluconeogenesis, Lyase, 2690 6658
    carboxykinase 2 Decarboxylase, GTP-binding,
    (mitochondrial) Mitochondrion, Transit peptide,
    Manganese
    NM_004566 PFKFB3 6-phosphofructo-2- Kinase, Hydrolase, Multifunctional 2691 6659
    kinase/fructose-2,6- enzyme, Transferase, ATP-binding,
    biphosphatase 3 Phosphorylation, Multigene family,
    Alternative splicing
    NM_004569 PIGH phosphatidylinositol Hypothetical protein, Transferase, 2692 6660
    glycan, class H Glycosyltransferase
    NM_004573 PLCB2 phospholipase C, Hydrolase, Lipid degradation, 2693 6661
    beta 2 Transducer, Calcium
    NM_004578 RAB4A RAB4A, member GTP-binding, Lipoprotein, 2694 6662
    RAS oncogene Prenylation, Protein transport,
    family Phosphorylation
    NM_004580 RAB27A RAB27A, member GTP-binding, Lipoprotein, 2695 6663
    RAS oncogene Prenylation, Alternative splicing,
    family Disease mutation
    NM_004583 RAB5C RAB5C, member GTP-binding, Lipoprotein, 2696 6664
    RAS oncogene Prenylation, Protein transport
    family
    NM_004603 STX1A syntaxin 1A (brain) Neurotransmitter transport, Coiled 2697 6665
    coil, Transmembrane, Antigen,
    Alternative splicing, Williams-Beuren
    syndrome
    NM_004618 TOP3A topoisomerase Isomerase, Topoisomerase, DNA- 2698 6666
    (DNA) III alpha binding, Repeat, Zinc-finger,
    Alternative splicing, Polymorphism
    NM_004629 FANCG Fanconi anemia, DNA repair, Nuclear protein 2699 6667
    complementation
    group G
    NM_004632 DAP3 death associated Apoptosis, Ribosomal protein, 2700 6668
    protein 3 Mitochondrion
    NM_004633 IL1R2 interleukin 1 Immunoglobulin domain, Receptor, 2701 6669
    receptor, type II Glycoprotein, Transmembrane,
    Signal, Repeat
    NM_004635 MAPKAPK3 mitogen-activated ATP-binding, Kinase, 2702 6670
    protein kinase- Serine/threonine-protein kinase,
    activated protein Transferase
    kinase 3
    NM_004637 RAB7 RAB7, member RAS GTP-binding, Lipoprotein, 2703 6671
    oncogene family Prenylation, Protein transport,
    Hypothetical protein
    NM_004642 CDK2AP1 CDK2-associated Anti-oncogene 2704 6672
    protein 1
    NM_004648 PTPNS1 protein tyrosine Repeat, Signal, Transmembrane, 2705 6673
    phosphatase, non- Immunoglobulin domain, SH3-
    receptor type binding, Glycoprotein,
    substrate 1 Phosphorylation, Alternative splicing,
    Polymorphism
    NM_004651 USP11 ubiquitin specific Ubl conjugation pathway, Hydrolase, 2706 6674
    protease 11 Thiol protease, Nuclear protein,
    Multigene family
    NM_004664 LIN7A lin-7 homolog A (C. elegans) 2707 6675
    NM_004665 VNN2 vanin 2 Hydrolase, Signal, Glycoprotein, 2708 6676
    GPI-anchor, Lipoprotein
    NM_004666 VNN1 vanin 1 Hydrolase, Signal, Glycoprotein, 2709 6677
    GPI-anchor, Lipoprotein
    NM_004668 MGAM maltase- Multifunctional enzyme, 2710 6678
    glucoamylase Transmembrane, Glycoprotein,
    (alpha-glucosidase) Hydrolase, Glycosidase, Repeat,
    Signal-anchor, Sulfation
    NM_004682 PSIP2 PC4 and SFRS1 2711 6679
    interacting protein 1
    NM_004689 MTA1 metastasis Zinc-finger, Nuclear protein, 2712 6680
    associated 1 Alternative splicing
    NM_004694 SLC16A6 solute carrier family Transport, Symport, 2713 6681
    16 (monocarboxylic Transmembrane, Multigene family
    acid transporters),
    member 6
    NM_004706 ARHGEF1 Rho guanine Guanine-nucleotide releasing factor, 2714 6682
    nucleotide exchange GTPase activation, Coiled coil,
    factor (GEF) 1 Alternative splicing, Phosphorylation,
    3D-structure
    NM_004708 PDCD5 programmed cell Apoptosis 2715 6683
    death 5
    NM_004712 HGS hepatocyte growth Kinase 2716 6684
    factor-regulated
    tyrosine kinase
    substrate
    NM_004720 EDG4 endothelial G-protein coupled receptor, 2717 6685
    differentiation, Transmembrane, Glycoprotein,
    lysophosphatidic Multigene family, Lipoprotein,
    acid G-protein- Palmitate
    coupled receptor, 4
    NM_004726 REPS2 RALBP1 associated Calcium-binding, Coiled coil, 2718 6686
    Eps domain Phosphorylation, Alternative splicing,
    containing 2 Repeat, 3D-structure
    NM_004727 SLC24A1 solute carrier family Vision, Transport, Antiport, Symport, 2719 6687
    24 Calcium transport, Transmembrane,
    (sodium/potassium/calcium Glycoprotein, Phosphorylation,
    exchanger), Signal, Repeat, Alternative splicing
    member
    1
    NM_004729 ALTE Ac-like transposable 2720 6688
    element
    NM_004741 NOLC1 nucleolar and coiled- Nuclear protein, Phosphorylation, 2721 6689
    body phosphoprotein 1 Repeat, GTP-binding, ATP-binding,
    Alternative splicing
    NM_004748 CPR8 cell cycle Hypothetical protein 2722 6690
    progression 8
    protein
    NM_004749 CPR2 cell cycle Hypothetical protein 2723 6691
    progression 2
    protein
    NM_004756 NUMBL numb homolog 2724 6692
    (Drosophila)-like
    NM_004757 SCYE1 small inducible Protein biosynthesis, RNA-binding, 2725 6693
    cytokine subfamily tRNA-binding, Cytokine, 3D-
    E, member 1 structure
    (endothelial
    monocyte-activating)
    NM_004762 PSCD1 pleckstrin homology, Guanine-nucleotide releasing factor, 2726 6694
    Sec7 and coiled-coil Coiled coil, Alternative splicing, 3D-
    domains 1(cytohesin structure
    1)
    NM_004774 PPARBP PPAR binding DNA-binding, Transcription 2727 6695
    protein regulation, Activator, Repeat,
    Nuclear protein, Alternative splicing
    NM_004779 CNOT8 CCR4-NOT Coiled coil, Nuclear protein, 2728 6696
    transcription Alternative splicing, Hypothetical
    complex, subunit 8 protein, Molybdenum cofactor
    biosynthesis, Disease mutation,
    Transcription regulation, Repressor
    NM_004781 VAMP3 vesicle-associated Synapse, Synaptosome, 2729 6697
    membrane protein 3 Transmembrane, Coiled coil,
    (cellubrevin) Multigene family
    NM_004786 TXNL thioredoxin-like, Redox-active center, Electron 2730 6698
    32 kDa transport, 3D-structure
    NM_004800 TM9SF2 transmembrane 9 Signal, Transmembrane 2731 6699
    superfamily member 2
    NM_004802 OTOF otoferlin Transmembrane, Repeat, Alternative 2732 6700
    splicing, Deafness
    NM_004808 NMT2 N- Transferase, Acyltransferase 2733 6701
    myristoyltransferase 2
    NM_004814 HPRP8BP U5 snRNP-specific Repeat, WD repeat, Hypothetical 2734 6702
    40 kDa protein protein
    (hPrp8-binding)
    NM_004817 TJP2 tight junction protein Tight junction, SH3 domain, Repeat, 2735 6703
    2 (zona occludens 2) Membrane, Alternative splicing,
    Alternative promoter usage, Nuclear
    protein, Phosphorylation
    NM_004834 MAP4K4 mitogen-activated ATP-binding, Serine/threonine- 2736 6704
    protein kinase protein kinase, Transferase,
    kinase kinase kinase 4 Alternative splicing
    NM_004848 C1orf38 chromosome 1 open Hypothetical protein 2737 6705
    reading frame 38
    NM_004854 CHST10 carbohydrate Transferase 2738 6706
    sulfotransferase 10
    NM_004856 KIF23 anaphase-promoting Motor protein, Cell division, 2739 6707
    complex subunit 7 Microtubule, ATP-binding, Coiled
    coil, Mitosis, Cell cycle, Nuclear
    protein
    NM_004862 LITAF lipopolysaccharide- Hypothetical protein, Transcription 2740 6708
    induced TNF factor regulation, Nuclear protein
    NM_004868 GPSN2 glycoprotein, Transmembrane, Glycoprotein, 2741 6709
    synaptic 2 Alternative splicing
    NM_004875 POLR1C polymerase (RNA) I Hypothetical protein, Transferase, 2742 6710
    polypeptide C, DNA-directed RNA polymerase,
    30 kDa Transcription, Nuclear protein,
    Alternative splicing
    NM_004877 GMFG glia maturation Growth factor, Ribosomal protein 2743 6711
    factor, gamma
    NM_004878 PTGES prostaglandin E Hypothetical protein, 2744 6712
    synthase Transmembrane
    NM_004879 EI24 etoposide induced 2745 6713
    2.4 mRNA
    NM_004889 ATP5J2 ATP synthase, H+ ATP synthesis, Hydrogen ion 2746 6714
    transporting, transport, CF(0), Mitochondrion,
    mitochondrial F0 Acetylation, Alternative splicing
    complex, subunit f,
    isoform 2
    NM_004900 APOBEC3B apolipoprotein B Hydrolase 2747 6715
    mRNA editing
    enzyme, catalytic
    polypeptide-like 3B
    NM_004902 RNPC2 RNA-binding region Transcription regulation, Activator, 2748 6716
    (RNP1, RRM) Nuclear protein, RNA-binding,
    containing 2 mRNA processing, mRNA splicing,
    Repeat, Alternative splicing,
    Polymorphism
    NM_004905 PRDX6 peroxiredoxin 6 Hydrolase, Oxidoreductase, 2749 6717
    Peroxidase, Lipid degradation,
    Antioxidant, Redox-active center,
    Multifunctional enzyme, Lysosome,
    3D-structure
    NM_004907 ETR101 immediate early ATP-binding, Coiled coil, 2750 6718
    protein Microtubules, Motor protein
    NM_004910 PITPNM1 phosphatidylinositol Hypothetical protein 2751 6719
    transfer protein,
    membrane-
    associated 1
    NM_004915 ABCG1 ATP-binding ATP-binding, Transport, Hypothetical 2752 6720
    cassette, sub-family protein, Lipid transport,
    G (WHITE), member 1 Transmembrane, Alternative
    splicing, Polymorphism
    NM_004916 WWOX Human Oxidoreductase 2753 6721
    oxidoreductase
    (HHCMA56) mRNA,
    complete cds.
    NM_004920 AATK apoptosis- Kinase, Hypothetical protein, ATP- 2754 6722
    associated tyrosine binding, Transferase
    kinase
    NM_004924 ACTN4 actinin, alpha 4 Actin-binding, Calcium-binding, 2755 6723
    Repeat, Multigene family, Disease
    mutation, Nuclear protein,
    Hypothetical protein
    NM_004928 C21orf2 chromosome 21 Alternative splicing, Polymorphism 2756 6724
    open reading frame 2
    NM_004930 CAPZB capping protein Cytoskeleton, Actin-binding, 2757 6725
    (actin filament) Alternative splicing, Actin capping
    muscle Z-line, beta
    NM_004939 DDX1 DEAD (Asp-Glu-Ala- Hydrolase, ATP-binding, Helicase, 2758 6726
    Asp) box polypeptide 1 RNA-binding
    NM_004945 DNM2 dynamin 2 Hydrolase, Motor protein, GTP- 2759 6727
    binding, Microtubule, Multigene
    family, Endocytosis, Alternative
    splicing, Hypothetical protein
    NM_004954 MARK2 MAP/microtubule ATP-binding, Kinase, 2760 6728
    affinity-regulating Serine/threonine-protein kinase,
    kinase 2 Transferase
    NM_004974 KCNA2 potassium voltage- Transport, Ion transport, Ionic 2761 6729
    gated channel, channel, Voltage-gated channel,
    shaker-related Potassium channel, Potassium
    subfamily, member 2 transport, Potassium,
    Transmembrane, Glycoprotein,
    Phosphorylation, Multigene family
    NM_004979 KCND1 potassium voltage- Transport, Ion transport, Ionic 2762 6730
    gated channel, Shal- channel, Voltage-gated channel,
    related subfamily, Potassium channel, Potassium
    member 1 transport, Potassium,
    Transmembrane, Multigene family
    NM_004994 MMP9 matrix Hydrolase, Metalloprotease, 2763 6731
    metalloproteinase 9 Glycoprotein, Zinc, Zymogen,
    (gelatinase B, 92 kDa Calcium, Collagen degradation,
    gelatinase, 92 kDa Extracellular matrix, Repeat, Signal,
    type IV collagenase) Polymorphism, 3D-structure
    NM_005000 NDUFA5 NADH Hypothetical protein, 2764 6732
    dehydrogenase Oxidoreductase, NAD, Ubiquinone,
    (ubiquinone) 1 alpha Mitochondrion, Acetylation
    subcomplex, 5,
    13 kDa
    NM_005003 NDUFAB1 NADH Fatty acid biosynthesis, 2765 6733
    dehydrogenase Phosphopantetheine, Mitochondrion,
    (ubiquinone) 1, Transit peptide, Oxidoreductase
    alpha/beta
    subcomplex, 1, 8 kDa
    NM_005009 NME4 non-metastatic cells Transferase, Kinase, ATP-binding, 2766 6734
    4, protein expressed Mitochondrion, Transit peptide, 3D-
    in structure
    NM_005011 NRF1 nuclear respiratory Transcription regulation, DNA- 2767 6735
    factor 1 binding, Activator, Nuclear protein,
    Phosphorylation, Alternative splicing
    NM_005022 PFN1 profilin 1 Actin-binding, Cytoskeleton, 2768 6736
    Multigene family, Acetylation, 3D-
    structure
    NM_005024 SERPINB10 serine (or cysteine) Serpin, Serine protease inhibitor 2769 6737
    proteinase inhibitor,
    clade B (ovalbumin),
    member 10
    NM_005025 SERPINI1 serine (or cysteine) Serpin, Serine protease inhibitor, 2770 6738
    proteinase inhibitor, Glycoprotein, Signal, Disease
    clade I mutation
    (neuroserpin),
    member 1
    NM_005026 PIK3CD phosphoinositide-3- Kinase, Transferase, Multigene 2771 6739
    kinase, catalytic, family
    delta polypeptide
    NM_005029 PITX3 paired-like Homeobox, DNA-binding, 2772 6740
    homeodomain Developmental protein, Nuclear
    transcription factor
    3 protein, Disease mutation
    NM_005030 PLK polo-like kinase Transferase, Serine/threonine- 2773 6741
    (Drosophila) protein kinase, ATP-binding, Repeat,
    Nuclear protein, Phosphorylation
    NM_005040 PRCP prolylcarboxypeptidase Hydrolase, Carboxypeptidase, 2774 6742
    (angiotensinase Glycoprotein, Zymogen, Signal,
    C) Lysosome
    NM_005044 PRKX protein kinase, X- ATP-binding, Kinase, 2775 6743
    linked Serine/threonine-protein kinase,
    Transferase, Tyrosine-protein
    kinase, cAMP
    NM_005055 RAPSN receptor-associated Synapse, Postsynaptic membrane, 2776 6744
    protein of the Cytoskeleton, Phosphorylation,
    synapse, 43 kD Myristate, Zinc-finger, Repeat, TPR
    repeat, Alternative splicing,
    Lipoprotein, Metal-binding, Receptor
    NM_005056 RBBP2 retinoblastoma Trans-acting factor, Nuclear protein, 2777 6745
    binding protein 2 Repeat, Zinc-finger
    NM_005061 RPL3L ribosomal protein Ribosomal protein 2778 6746
    L3-like
    NM_005066 SFPQ splicing factor Nuclear protein, RNA-binding, DNA- 2779 6747
    proline/glutamine binding, mRNA splicing, Repeat,
    rich (polypyrimidine Alternative splicing
    tract binding protein
    associated)
    NM_005084 PLA2G7 phospholipase A2, Hydrolase, Lipid degradation, 2780 6748
    group VII (platelet- Glycoprotein, Signal, Polymorphism,
    activating factor Disease mutation
    acetylhydrolase,
    plasma)
    NM_005085 NUP214 nucleoporin 214 kDa Hypothetical protein, Repeat, WD 2781 6749
    repeat, Nuclear protein, Transport,
    Proto-oncogene, Chromosomal
    translocation, Glycoprotein
    NM_005091 PGLYRP peptidoglycan Antibiotic, Immune response, Signal 2782 6750
    recognition protein
    NM_005096 ZNF261 zinc finger protein Hypothetical protein, Chromosomal 2783 6751
    261 translocation, Transmembrane,
    Alternative splicing
    NM_005099 ADAMTS4 a disintegrin-like and Hydrolase, Metalloprotease, Zinc, 2784 6752
    metalloprotease Signal, Glycoprotein, Zymogen,
    (reprolysin type) with Extracellular matrix, Hypothetical
    thrombospondin type protein
    1 motif, 4
    NM_005106 DLEC1 deleted in lung and Hypothetical protein 2785 6753
    esophageal cancer 1
    NM_005111 CRYZL1 crystallin, zeta Oxidoreductase, NADP, Alternative 2786 6754
    (quinone reductase)- splicing
    like 1
    NM_005112 WDR1 WD repeat domain 1 Repeat, WD repeat, Hypothetical 2787 6755
    protein, Actin-binding, Cytoskeleton,
    Alternative splicing, Polymorphism
    NM_005134 PPP4R1 protein phosphatase Hypothetical protein 2788 6756
    4, regulatory subunit 1
    NM_005137 DGCR2 DiGeorge syndrome Cell adhesion, Receptor, Signal, 2789 6757
    critical region gene 2 Transmembrane, Lectin,
    Glycoprotein
    NM_005139 ANXA3 annexin A3 Annexin, Calcium/phospholipid- 2790 6758
    binding, Repeat, Phospholipase A2
    inhibitor, 3D-structure,
    Polymorphism
    NM_005143 HP haptoglobin Glycoprotein, Serine protease 2791 6759
    homolog, Sushi, Hemoglobin-
    binding, Signal, Repeat,
    Polymorphism
    NM_005148 UNC119 unc-119 homolog (C. elegans) Vision, Alternative splicing 2792 6760
    NM_005151 USP14 ubiquitin specific Ubl conjugation pathway, Hydrolase, 2793 6761
    protease 14 (tRNA- Thiol protease, Multigene family
    guanine
    transglycosylase)
    NM_005165 ALDOC aldolase C, fructose- Lyase, Schiff base, Glycolysis, 2794 6762
    bisphosphate Multigene family
    NM_005167 ARHC hypothetical protein DNA condensation, Mitosis, Cell 2795 6763
    MGC19531 cycle, ATP-binding, Coiled coil,
    Nuclear protein, Alternative splicing,
    Hypothetical protein, Proto-
    oncogene, GTP-binding, Prenylation,
    Lipoprotein
    NM_005173 ATP2A3 ATPase, Ca++ Hydrolase, Calcium transport, 2796 6764
    transporting, Transmembrane, Phosphorylation,
    ubiquitous ATP-binding, Metal-binding,
    Magnesium, Calcium-binding,
    Multigene family, Alternative splicing
    NM_005174 ATP5C1 ATP synthase, H+ ATP synthesis, CF(1), Hydrogen ion 2797 6765
    transporting, transport, Hydrolase, Mitochondrion,
    mitochondrial F1 Transit peptide, Alternative splicing,
    complex, gamma Hypothetical protein
    polypeptide
    1
    NM_005180 BMI1 B lymphoma Mo- Chromatin regulator, Nuclear 2798 6766
    MLV insertion region protein, Transcription regulation,
    (mouse) Repressor, Zinc-finger, Proto-
    oncogene
    NM_005185 CALML3 calmodulin-like 3 Calcium-binding, Repeat, 2799 6767
    Methylation, 3D-structure
    NM_005190 CCNC cyclin C Cyclin, Cell cycle, Cell division, 2800 6768
    Nuclear protein, Transcription
    regulation
    NM_005195 CEBPD KIAA0146 protein Transcription regulation, Activator, 2801 6769
    DNA-binding, Nuclear protein
    NM_005197 CHES1 checkpoint Transcription regulation, Activator, 2802 6770
    suppressor 1 DNA-binding, Nuclear protein,
    Alternative splicing
    NM_005199 CHRNG cholinergic receptor, Receptor, Postsynaptic membrane, 2803 6771
    nicotinic, gamma Ionic channel, Glycoprotein, Signal,
    polypeptide Transmembrane
    NM_005213 CSTA cystatin A (stefin A) Thiol protease inhibitor, 3D-structure 2804 6772
    NM_005217 DEFA3 defensin, alpha 3, Defensin, Antibiotic, Antiviral, 2805 6773
    neutrophil-specific Fungicide, Signal, 3D-structure
    NM_005224 DRIL1 dead ringer-like 1 Transcription regulation, Activator, 2806 6774
    (Drosophila) DNA-binding, Nuclear protein
    NM_005231 EMS1 ems1 sequence Phosphorylation, Repeat, SH3 2807 6775
    (mammary tumor domain, Cytoskeleton
    and squamous cell
    carcinoma-
    associated (p80/85
    src substrate)
    NM_005239 ETS2 v-ets Proto-oncogene, DNA-binding, 2808 6776
    erythroblastosis Nuclear protein
    virus E26 oncogene
    homolog 2 (avian)
    NM_005248 FGR Gardner-Rasheed Transferase, Tyrosine-protein 2809 6777
    feline sarcoma viral kinase, Proto-oncogene, ATP-
    (v-fgr) oncogene binding, Phosphorylation, SH2
    homolog domain, SH3 domain
    NM_005252 FOS v-fos FBJ murine Proto-oncogene, Nuclear protein, 2810 6778
    osteosarcoma viral Phosphorylation, DNA-binding, 3D-
    oncogene homolog structure
    NM_005253 FOSL2 FOS-like antigen 2 Nuclear protein, DNA-binding 2811 6779
    NM_005255 GAK cyclin G associated Transferase, Serine/threonine- 2812 6780
    kinase protein kinase, ATP-binding, Nuclear
    protein, Endoplasmic reticulum, Cell
    cycle
    NM_005256 GAS2 growth arrest- Growth arrest, Phosphorylation, 2813 6781
    specific 2 Apoptosis, Cell cycle, Cytoskeleton
    NM_005263 GFI1 growth factor Transcription regulation, Zinc-finger, 2814 6782
    independent 1 DNA-binding, Nuclear protein, Metal-
    binding, Repeat, Disease mutation
    NM_005270 GLI2 GLI-Kruppel family Transcription regulation, Zinc-finger, 2815 6783
    member GLI2 Metal-binding, DNA-binding, Nuclear
    protein, Repeat, Alternative splicing
    NM_005271 GLUD1 glutamate Oxidoreductase, NADP, 2816 6784
    dehydrogenase 1 Mitochondrion, Transit peptide,
    Polymorphism, Disease mutation,
    Multigene family, 3D-structure
    NM_005273 GNB2 guanine nucleotide Transducer, Repeat, WD repeat, 2817 6785
    binding protein (G Multigene family
    protein), beta
    polypeptide
    2
    NM_005274 GNG5 guanine nucleotide Transducer, Prenylation, Lipoprotein, 2818 6786
    binding protein (G Multigene family
    protein), gamma 5
    NM_005286 GPR8 G protein-coupled Transcription regulation, Zinc-finger, 2819 6787
    receptor 8 DNA-binding, Nuclear protein,
    Repeat, G-protein coupled receptor,
    Transmembrane, Glycoprotein,
    Lipoprotein, Palmitate,
    Phosphorylation, Polymorphism
    NM_005291 GPR17 G protein-coupled G-protein coupled receptor, 2820 6788
    receptor 17 Transmembrane, Glycoprotein,
    Alternative splicing, Receptor
    NM_005327 HADHSC L-3-hydroxyacyl- Fatty acid metabolism, 2821 6789
    Coenzyme A Oxidoreductase, NAD,
    dehydrogenase, Mitochondrion, Transit peptide, 3D-
    short chain structure
    NM_005335 HCLS1 hematopoietic cell- Repeat, SH3 domain, 2822 6790
    specific Lyn Phosphorylation
    substrate
    1
    NM_005340 HINT1 histidine triad Hydrolase, Acetylation, 3D-structure 2823 6791
    nucleotide binding
    protein
    1
    NM_005345 HSPA1A heat shock 70 kDa ATP-binding, Chaperone, Heat 2824 6792
    protein 1A shock, Multigene family, 3D-
    structure
    NM_005346 HSPA1B heat shock 70 kDa ATP-binding, Chaperone, Heat 2825 6793
    protein 1B shock, Multigene family, 3D-
    structure
    NM_005357 LIPE lipase, hormone- Hydrolase, Lipid degradation, 2826 6794
    sensitive Phosphorylation
    NM_005358 LMO7 LIM domain only 7 LIM domain, Metal-binding, Zinc, 2827 6795
    Hypothetical protein, Zinc-finger
    NM_005360 MAF v-maf Proto-oncogene, Transcription 2828 6796
    musculoaponeurotic regulation, DNA-binding, Nuclear
    fibrosarcoma protein, Alternative splicing,
    oncogene homolog Chromosomal translocation
    (avian)
    NM_005379 MYO1A myosin IA Myosin, Actin-binding, ATP-binding, 2829 6797
    Calmodulin-binding, Repeat,
    Multigene family, Polymorphism,
    Disease mutation, Deafness
    NM_005381 NCL nucleolin Hypothetical protein 2830 6798
    NM_005402 RALA v-ral simian GTP-binding, Prenylation, 2831 6799
    leukemia viral Lipoprotein
    oncogene homolog
    A (ras related)
    NM_005428 VAV1 vav 1 oncogene Hypothetical protein, SH3 domain, 2832 6800
    Proto-oncogene, Phorbol-ester
    binding, Zinc, SH2 domain, Guanine-
    nucleotide releasing factor, Repeat,
    Phosphorylation
    NM_005433 YES1 v-yes-1 Yamaguchi Proto-oncogene, Tyrosine-protein 2833 6801
    sarcoma viral kinase, Phosphorylation,
    oncogene homolog 1 Transferase, ATP-binding, Myristate,
    SH3 domain, SH2 domain,
    Lipoprotein
    NM_005436 D10S170 DNA segment on Proto-oncogene, Chromosomal 2834 6802
    chromosome 10 translocation, SH3-binding, Repeat
    (unique) 170
    NM_005439 MLF2 myeloid leukemia Nuclear protein 2835 6803
    factor 2
    NM_005441 CHAF1B chromatin assembly DNA replication, DNA repair, Cell 2836 6804
    factor 1, subunit B cycle, Nuclear protein,
    (p60) Phosphorylation, Repeat, WD repeat
    NM_005451 ENIGMA enigma (LIM domain LIM domain, Metal-binding, Zinc 2837 6805
    protein)
    NM_005463 HNRPDL heterogeneous Nucleocapsid, Ribonucleoprotein 2838 6806
    nuclear
    ribonucleoprotein D-
    like
    NM_005466 MED6 mediator of RNA Transcription regulation, Activator, 2839 6807
    polymerase II Receptor, Nuclear protein
    transcription, subunit
    6 homolog (yeast)
    NM_005472 KCNE3 potassium voltage- Transport, Ion transport, Ionic 2840 6808
    gated channel, lsk- channel, Voltage-gated channel,
    related family, Potassium channel, Potassium,
    member 3 Potassium transport,
    Transmembrane, Glycoprotein,
    Disease mutation
    NM_005479 FRAT1 frequently Wnt signaling pathway, Proto- 2841 6809
    rearranged in oncogene, 3D-structure
    advanced T-cell
    lymphomas
    NM_005480 TROAP trophinin associated Cell adhesion, Repeat, Cytoskeleton 2842 6810
    protein (tastin)
    NM_005488 TOM1 target of myb1 Hypothetical protein, Transport, 2843 6811
    (chicken) Protein transport, Membrane, 3D-
    structure
    NM_005490 SH2D3A SH2 domain Hypothetical protein 2844 6812
    containing 3A
    NM_005498 AP1M2 adaptor-related Golgi stack, Protein transport, 2845 6813
    protein complex 1, Transport, Coated pits, Endocytosis,
    mu 2 subunit Phosphorylation, Alternative splicing
    NM_005499 UBA2 SUMO-1 activating Cyclin, Hypothetical protein 2846 6814
    enzyme subunit 2
    NM_005501 ITGA3 integrin, alpha 3 Integrin, Cell adhesion, Receptor, 2847 6815
    (antigen CD49C, Glycoprotein, Transmembrane,
    alpha 3 subunit of Signal, Phosphorylation, Repeat,
    VLA-3 receptor) Alternative splicing, Calcium
    NM_005504 BCAT1 branched chain Transferase, Aminotransferase, 2848 6816
    aminotransferase 1, Branched-chain amino acid
    cytosolic biosynthesis, Pyridoxal phosphate,
    Hypothetical protein
    NM_005505 SCARB1 scavenger receptor Transcription regulation, Nuclear 2849 6817
    class B, member 1 protein, Receptor, Transmembrane,
    Glycoprotein, Polymorphism,
    Alternative splicing
    NM_005507 CFL1 cofilin 1 (non- Nuclear protein, Actin-binding, 2850 6818
    muscle) Cytoskeleton, Phosphorylation
    NM_005510 DOM3Z dom-3 homolog Z Transferase, Serine/threonine- 2851 6819
    (C. elegans) protein kinase, ATP-binding,
    Manganese, Nuclear protein,
    Alternative splicing
    NM_005512 GARP glycoprotein A Glycoprotein, Leucine-rich repeat, 2852 6820
    repetitions Repeat, Transmembrane, Signal
    predominant
    NM_005514 HLA-B major Glycoprotein, MHC I, Signal, 2853 6821
    histocompatibility Transmembrane, Polymorphism, 3D-
    complex, class I, B structure, Alternative splicing,
    Hypothetical protein, Sulfation
    NM_005516 HLA-E major Glycoprotein, Transmembrane, 2854 6822
    histocompatibility Hypothetical protein, MHC I, Signal,
    complex, class I, E Polymorphism, 3D-structure
    NM_005517 HMGN2 high-mobility group Hypothetical protein, Microtubule, 2855 6823
    nucleosomal binding GTP-binding, Multigene family,
    domain 2 Nuclear protein, DNA-binding,
    Polymorphism
    NM_005527 HSPA1L heat shock 70 kDa ATP-binding, Multigene family, 2856 6824
    protein 1-like Polymorphism
    NM_005534 IFNGR2 interferon gamma Receptor, Transmembrane, 2857 6825
    receptor 2 (interferon Glycoprotein, Signal, Repeat
    gamma transducer
    1)
    NM_005541 INPP5D inositol 2858 6826
    polyphosphate-5-
    phosphatase,
    145 kDa
    NM_005548 KARS lysyl-tRNA Aminoacyl-tRNA synthetase, Protein 2859 6827
    synthetase biosynthesis, Ligase, ATP-binding,
    Polymorphism
    NM_005564 LCN2 lipocalin 2 Glycoprotein, Lipocalin, Signal, 3D- 2860 6828
    (oncogene 24p3) structure, Pyrrolidone carboxylic acid
    NM_005565 LCP2 lymphocyte cytosolic SH2 domain, Phosphorylation 2861 6829
    protein 2 (SH2
    domain containing
    leukocyte protein of
    76 kDa)
    NM_005574 LMO2 LIM domain only 2 Proto-oncogene, Repeat, LIM 2862 6830
    (rhombotin-like 1) domain, Metal-binding, Zinc, Nuclear
    protein, Alternative splicing,
    Chromosomal translocation
    NM_005578 LPP LIM domain LIM domain, Metal-binding, Zinc 2863 6831
    containing preferred
    translocation partner
    in lipoma
    NM_005586 MDFI MyoD family inhibitor Differentiation 2864 6832
    NM_005590 MRE11A MRE11 meiotic DNA repair, Hydrolase, Nuclease, 2865 6833
    recombination 11 Endonuclease, Exonuclease,
    homolog A (S. cerevisiae) Nuclear protein, Manganese,
    Meiosis, Alternative splicing,
    Disease mutation, Polymorphism,
    Hypothetical protein
    NM_005598 NHLH1 nescient helix loop DNA-binding, Transcription 2866 6834
    helix 1 regulation, Differentiation
    NM_005601 NKG7 natural killer cell Transmembrane 2867 6835
    group 7 sequence
    NM_005605 PPP3CC protein phosphatase Hypothetical protein, Hydrolase, 2868 6836
    3 (formerly 2B), Iron, Manganese, Calmodulin-
    catalytic subunit, binding, Metal-binding, Zinc,
    gamma isoform Multigene family
    (calcineurin A
    gamma)
    NM_005607 PTK2 PTK2 protein Hypothetical protein, ATP-binding, 2869 6837
    tyrosine kinase 2 Transferase, Kinase, Tyrosine-
    protein kinase, Phosphorylation,
    Alternative splicing, 3D-structure
    NM_005608 PTPRCAP protein tyrosine Transmembrane, Phosphorylation 2870 6838
    phosphatase,
    receptor type, C-
    associated protein
    NM_005611 RBL2 retinoblastoma-like 2 ATP-binding, Kinase, 2871 6839
    (p130) Serine/threonine-protein kinase,
    Transferase, Transcription
    regulation, DNA-binding, Nuclear
    protein, Cell cycle, Phosphorylation,
    Anti-oncogene
    NM_005620 S100A11 S100 calcium Calcium-binding 2872 6840
    binding protein A11
    (calgizzarin)
    NM_005621 S100A12 S100 calcium Calcium-binding, Zinc, Metal- 2873 6841
    binding protein A12 binding, Antibiotic, Fungicide, 3D-
    (calgranulin C) structure
    NM_005623 CCL8 chemokine (C-C Cytokine, Chemotaxis, Signal, 2874 6842
    motif) ligand 8 Heparin-binding, Inflammatory
    response, Polymorphism,
    Pyrrolidone carboxylic acid, 3D-
    structure
    NM_005625 SDCBP syndecan binding Cytoskeleton, Membrane, 2875 6843
    protein (syntenin) Endoplasmic reticulum, Nuclear
    protein, Phosphorylation, Repeat,
    Polymorphism
    NM_005646 TARBP1 TAR (HIV) RNA 2876 6844
    binding protein 1
    NM_005647 TBL1X transducin (beta)-like Repeat, WD repeat 2877 6845
    1X-linked
    NM_005654 NR2F1 nuclear receptor Receptor, Transcription regulation, 2878 6846
    subfamily 2, group F, DNA-binding, Nuclear protein, Zinc-
    member 1 finger, Activator
    NM_005658 TRAF1 TNF receptor- Apoptosis, Coiled coil 2879 6847
    associated factor 1
    NM_005687 FRSB phenylalanyl-tRNA Aminoacyl-tRNA synthetase, Protein 2880 6848
    synthetase beta- biosynthesis, Ligase, ATP-binding
    subunit
    NM_005690 DNM1L dynamin 1-like Hypothetical protein 2881 6849
    NM_005697 SCAMP2 secretory carrier Transmembrane, Transport, Protein 2882 6850
    membrane protein 2 transport, Multigene family
    NM_005704 PTPRU protein tyrosine Glycoprotein, Hydrolase, Receptor, 2883 6851
    phosphatase, Repeat, Signal, Transmembrane,
    receptor type, U Immunoglobulin domain
    NM_005710 PQBP1 polyglutamine Nuclear protein 2884 6852
    binding protein 1
    NM_005713 COL4A3BP collagen, type IV, Transferase, Kinase, 2885 6853
    alpha 3 Serine/threonine-protein kinase,
    (Goodpasture Coiled coil, Alternative splicing
    antigen) binding
    protein
    NM_005716 RGS19IP1 regulator of G- 2886 6854
    protein signalling 19
    interacting protein 1
    NM_005717 ARPC5 actin related protein Cytoskeleton 2887 6855
    2/3 complex, subunit
    5, 16 kDa
    NM_005720 ARPC1B actin related protein Hypothetical protein, Repeat, WD 2888 6856
    2/3 complex, subunit repeat, Polymorphism
    1B, 41 kDa
    NM_005724 TSPAN-3 transmembrane 4 Glycoprotein, Transmembrane 2889 6857
    superfamily member 8
    NM_005725 TSPAN-2 tetraspan 2 Glycoprotein, Transmembrane 2890 6858
    NM_005730 OS4 CTD (carboxy- Hypothetical protein, Nuclear protein 2891 6859
    terminal domain,
    RNA polymerase II,
    polypeptide A) small
    phosphatase
    2
    NM_005731 ARPC2 actin related protein Cytoskeleton 2892 6860
    2/3 complex, subunit
    2, 34 kDa
    NM_005732 RAD50 RAD50 homolog (S. cerevisiae) 2893 6861
    NM_005733 KIF20A kinesin family Motor protein, Microtubule, ATP- 2894 6862
    member 20A binding, Coiled coil, Golgi stack,
    Protein transport, Transport
    NM_005736 ACTR1A ARP1 actin-related Structural protein, Cytoskeleton, 2895 6863
    protein 1 homolog A, Multigene family
    centractin alpha
    (yeast)
    NM_005737 ARL7 ADP-ribosylation GTP-binding, Multigene family, 2896 6864
    factor-like 7 Nuclear protein
    NM_005741 ZNF263 zinc finger protein Transcription regulation, Zinc-finger, 2897 6865
    263 Metal-binding, Nuclear protein, DNA-
    binding, Repeat, Repressor
    NM_005759 ABI-2 abl-interactor 2 Kinase, SH3 domain 2898 6866
    NM_005761 PLXNC1 plexin C1 2899 6867
    NM_005762 TRIM28 tripartite motif- Transcription regulation, Repressor, 2900 6868
    containing 28 Nuclear protein, Zinc-finger, Repeat,
    3D-structure
    NM_005770 SERF2 small EDRK-rich Hypothetical protein 2901 6869
    factor 2
    NM_005771 RDHL dehydrogenase/reductase Oxidoreductase 2902 6870
    (SDR family)
    member 9
    NM_005772 PLAA RNA terminal Repeat, WD repeat, Hypothetical 2903 6871
    phosphate cyclase- protein, Nuclear protein
    like 1
    NM_005773 ZNF256 zinc finger protein Transcription regulation, DNA- 2904 6872
    256 binding, Zinc-finger, Metal-binding,
    Nuclear protein, Repeat
    NM_005787 NOT56L asparagine-linked Hypothetical protein, Transferase, 2905 6873
    glycosylation 3 Glycosyltransferase,
    homolog (yeast, Transmembrane, Endoplasmic
    alpha-1,3- reticulum, Disease mutation
    mannosyltransferase)
    NM_005797 EVA1 epithelial V-like Cell adhesion, Immunoglobulin 2906 6874
    antigen 1 domain, Transmembrane,
    Glycoprotein, Signal
    NM_005803 FLOT1 flotillin 1 Membrane 2907 6875
    NM_005805 PSMD14 proteasome Proteasome 2908 6876
    (prosome,
    macropain) 26S
    subunit, non-
    ATPase, 14
    NM_005811 GDF11 growth differentiation Growth factor, Cytokine, 2909 6877
    factor 11 Glycoprotein, Signal
    NM_005826 HNRPR heterogeneous Nucleocapsid, Ribonucleoprotein, 2910 6878
    nuclear Nuclear protein, RNA-binding,
    ribonucleoprotein R Repeat
    NM_005833 RAB9P40 Rab9 effector p40 2911 6879
    NM_005834 TIMM17B translocase of inner Transport, Protein transport, 2912 6880
    mitochondrial Translocation, Mitochondrion, Inner
    membrane 17 membrane, Transmembrane
    homolog B (yeast)
    NM_005836 UK114 translational inhibitor Nuclear protein 2913 6881
    protein p14.5
    NM_005845 ABCC4 ATP-binding ATP-binding, Glycoprotein, 2914 6882
    cassette, sub-family Transmembrane, Transport, Repeat
    C (CFTR/MRP),
    member 4
    NM_005849 IGSF6 immunoglobulin Signal, Hypothetical protein 2915 6883
    superfamily, member 6
    NM_005855 RAMP1 receptor (calcitonin) Signal, Transmembrane, Transport, 2916 6884
    activity modifying Receptor
    protein
    1
    NM_005860 FSTL3 follistatin-like 3 Glycoprotein, Repeat, Signal, 2917 6885
    (secreted Chromosomal translocation, Proto-
    glycoprotein) oncogene
    NM_005862 STAG1 stromal antigen 1 Mitosis, Cell cycle, Chromosome 2918 6886
    partition, Nuclear protein,
    Phosphorylation
    NM_005863 NET1 neuroepithelial cell 2919 6887
    transforming gene 1
    NM_005865 PRSS16 protease, serine, 16 Hydrolase, Serine protease, Signal 2920 6888
    (thymus)
    NM_005866 SR-BP1 opioid receptor, Hypothetical protein, Receptor 2921 6889
    sigma 1
    NM_005873 RGS19 regulator of G- Signal transduction inhibitor, 2922 6890
    protein signalling 19 Membrane, Lipoprotein, Palmitate,
    Phosphorylation, Autophagy, 3D-
    structure
    NM_005874 LILRB2 leukocyte Receptor, Repeat, Signal, 2923 6891
    immunoglobulin-like Transmembrane, Immune response,
    receptor, subfamily Immunoglobulin domain,
    B (with TM and ITIM Phosphorylation, Glycoprotein,
    domains), member 2 Antigen, Multigene family,
    Alternative splicing, Polymorphism
    NM_005884 PAK4 p21(CDKN1A)- Hypothetical protein, ATP-binding, 2924 6892
    activated kinase 4 Transferase, Serine/threonine-
    protein kinase, Phosphorylation,
    Alternative splicing
    NM_005886 KATNB1 katanin p80 (WD Repeat, WD repeat 2925 6893
    repeat containing)
    subunit B 1
    NM_005888 SLC25A3 solute carrier family Mitochondrion, Inner membrane, 2926 6894
    25 (mitochondrial Repeat, Transit peptide,
    carrier; phosphate Transmembrane, Transport,
    carrier), member 3 Symport, Alternative splicing,
    Hypothetical protein
    NM_005891 ACAT2 acetyl-Coenzyme A Chaperone, ATP-binding, Multigene 2927 6895
    acetyltransferase 2 family, Transferase
    (acetoacetyl
    Coenzyme A
    thiolase)
    NM_005892 FMNL formin-like 1 Hypothetical protein 2928 6896
    NM_005898 M11S1 membrane GPI-anchor 2929 6897
    component,
    chromosome 11,
    surface marker 1
    NM_005900 MADH1 MAD, mothers Transcription regulation, 2930 6898
    against Phosphorylation, Multigene family,
    decapentaplegic 3D-structure
    homolog 1
    (Drosophila)
    NM_005902 MADH3 MAD, mothers Transcription regulation, 2931 6899
    against Phosphorylation, Multigene family,
    decapentaplegic 3D-structure
    homolog 3
    (Drosophila)
    NM_005917 MDH1 malate Oxidoreductase, Tricarboxylic acid 2932 6900
    dehydrogenase 1, cycle, NAD
    NAD (soluble)
    NM_005931 MICB MHC class I Glycoprotein, Transmembrane, MHC 2933 6901
    polypeptide-related
    sequence B
    NM_005932 MIPEP mitochondrial Hydrolase, Metalloprotease, Zinc, 2934 6902
    intermediate Transit peptide, Mitochondrion,
    peptidase Magnesium, Manganese, Calcium,
    Cobalt, Iron
    NM_005935 MLLT2 myeloid/lymphoid or Alternative splicing, Chromosomal 2935 6903
    mixed-lineage translocation, Proto-oncogene, DNA-
    leukemia (trithorax binding, Bromodomain, Nuclear
    homolog, protein, Zinc-finger, Metal-binding,
    Drosophila); Transcription regulation, Repeat,
    translocated to, 2 Hypothetical protein,
    Serine/threonine-protein kinase,
    Transferase, ATP-binding, Tran
    NM_005950 MT1G metallothionein 1G Metal-binding, Metal-thiolate cluster, 2936 6904
    Zinc, Copper, Cadmium, Acetylation
    NM_005952 MT1X metallothionein 1X Hypothetical protein, Metal-binding, 2937 6905
    Metal-thiolate cluster, Zinc, Copper,
    Cadmium, Acetylation
    NM_005953 MT2A metallothionein 2A Metal-binding, Metal-thiolate cluster, 2938 6906
    Zinc, Acetylation, 3D-structure
    NM_005954 MT3 metallothionein 3 Metal-binding, Metal-thiolate cluster, 2939 6907
    (growth inhibitory Zinc, Copper, Acetylation
    factor (neurotrophic))
    NM_005955 MTF1 metal-regulatory Hypothetical protein, Metal-binding, 2940 6908
    transcription factor 1 Zinc, Zinc-finger
    NM_005965 MYLK myosin, light Immunoglobulin domain, Kinase, 2941 6909
    polypeptide kinase ATP-binding, Repeat,
    Serine/threonine-protein kinase,
    Transferase, Calmodulin-binding,
    Phosphorylation, Alternative
    initiation, Alternative splicing
    NM_005969 NAP1L4 nucleosome Nuclear protein 2942 6910
    assembly protein 1-
    like 4
    NM_005975 PTK6 PTK6 protein Transferase, Tyrosine-protein 2943 6911
    tyrosine kinase 6 kinase, ATP-binding, SH2 domain,
    SH3 domain, Phosphorylation
    NM_005979 S100A13 S100 calcium Calcium-binding 2944 6912
    binding protein A13
    NM_005980 S100P S100 calcium Calcium-binding, Placenta, 3D- 2945 6913
    binding protein P structure
    NM_005988 SPRR2A small proline-rich Keratinocyte, Repeat, Multigene 2946 6914
    protein 2A family
    NM_005990 STK10 serine/threonine Kinase, Transferase, 2947 6915
    kinase 10 Serine/threonine-protein kinase,
    ATP-binding, Phosphorylation,
    Coiled coil
    NM_005998 CCT3 chaperonin Chaperone, ATP-binding, Multigene 2948 6916
    containing TCP1, family, Hypothetical protein
    subunit 3 (gamma)
    NM_006002 UCHL3 ubiquitin carboxyl- Ubl conjugation pathway, Hydrolase, 2949 6917
    terminal esterase L3 Thiol protease, Multigene family, 3D-
    (ubiquitin structure
    thiolesterase)
    NM_006018 HM74 putative chemokine G-protein coupled receptor, 2950 6918
    receptor Transmembrane
    NM_006019 TCIRG1 T-cell, immune Hydrogen ion transport, 2951 6919
    regulator 1, ATPase, Transmembrane, Glycoprotein,
    H+ transporting, Alternative splicing, Hypothetical
    lysosomal V0 protein protein
    a isoform 3
    NM_006022 TSC22 transforming growth Hypothetical protein, Transcription 2952 6920
    factor beta- regulation, Repressor, Nuclear
    stimulated protein protein
    TSC-22
    NM_006027 EXO1 exonuclease 1 Exonuclease, Hypothetical protein 2953 6921
    NM_006029 PNMA1 paraneoplastic Antigen, Tumor antigen, Nuclear 2954 6922
    antigen MA1 protein
    NM_006031 PCNT2 pericentrin 2 Coiled coil, Hypothetical protein 2955 6923
    (kendrin)
    NM_006034 TP53I11 tumor protein p53 Hypothetical protein 2956 6924
    inducible protein 11
    NM_006053 TCIRG1 T-cell, immune Hydrogen ion transport, 2957 6925
    regulator 1, ATPase, Transmembrane, Glycoprotein,
    H+ transporting, Alternative splicing, Hypothetical
    lysosomal V0 protein protein
    a isoform 3
    NM_006054 RTN3 reticulon 3 Hypothetical protein, 2958 6926
    Transmembrane, Endoplasmic
    reticulum
    NM_006055 LANCL1 LanC lantibiotic Transmembrane 2959 6927
    synthetase
    component C-like 1
    (bacterial)
    NM_006060 ZNFN1A1 zinc finger protein, Transcription regulation, Activator, 2960 6928
    subfamily 1A, 1 Zinc-finger, Metal-binding, DNA-
    (lkaros) binding, Nuclear protein, Repeat,
    Alternative splicing
    NM_006061 SGP28 cysteine-rich Glycoprotein, Signal, Multigene 2961 6929
    secretory protein 3 family, Polymorphism
    NM_006069 MRVI1 murine retrovirus 2962 6930
    integration site 1
    homolog
    NM_006070 TFG TRK-fused gene Hypothetical protein, Ligase, GMP 2963 6931
    biosynthesis, Purine biosynthesis,
    ATP-binding, Glutamine
    amidotransferase
    NM_006079 CITED2 Cbp/p300-interacting Transcription regulation, Nuclear 2964 6932
    transactivator, with protein, Alternative splicing
    Glu/Asp-rich
    carboxy-terminal
    domain, 2
    NM_006088 TUBB2 tubulin, beta, 2 Microtubule, GTP-binding, Multigene 2965 6933
    family, Hypothetical protein
    NM_006093 PRG3 proteoglycan 3 2966 6934
    NM_006097 MYL9 myosin, light Myosin, Calcium-binding, Muscle 2967 6935
    polypeptide 9, protein, Phosphorylation,
    regulatory Acetylation, Multigene family
    NM_006103 WFDC2 WAP four-disulfide Serine protease inhibitor, Repeat, 2968 6936
    core domain 2 Signal, Glycoprotein, Alternative
    splicing
    NM_006107 LUC7A acid-inducible Phosphorylation, Hypothetical 2969 6937
    phosphoprotein protein
    NM_006109 SKB1 SKB1 homolog (S. pombe) Transferase, Methyltransferase, 2970 6938
    Alternative splicing
    NM_006111 ACAA2 acetyl-Coenzyme A Acyltransferase, Transferase, Fatty 2971 6939
    acyltransferase 2 acid metabolism, Mitochondrion,
    (mitochondrial 3- Transit peptide
    oxoacyl-Coenzyme
    A thiolase)
    NM_006113 VAV3 vav 3 oncogene SH3 domain, Phorbol-ester binding, 2972 6940
    Zinc, SH2 domain, Repeat, Guanine-
    nucleotide releasing factor,
    Alternative splicing
    NM_006115 PRAME preferentially Antigen 2973 6941
    expressed antigen in
    melanoma
    NM_006117 PECI peroxisomal D3,D2- Isomerase, Hypothetical protein, 2974 6942
    enoyl-CoA Peroxisome
    isomerase
    NM_006135 CAPZA1 capping protein Actin-binding, Multigene family, 3D- 2975 6943
    (actin filament) structure, Actin capping
    muscle Z-line, alpha 1
    NM_006138 MS4A3 membrane-spanning Receptor, Transmembrane, 2976 6944
    4-domains, Alternative splicing, Multigene family
    subfamily A,
    member 3
    (hematopoietic cell-
    specific)
    NM_006139 CD28 CD28 antigen (Tp44) Immunoglobulin domain, T-cell, 2977 6945
    Glycoprotein, Signal,
    Transmembrane, Alternative splicing
    NM_006140 CSF2RA colony stimulating Receptor, Transmembrane, 2978 6946
    factor 2 receptor, Glycoprotein, Signal, Alternative
    alpha, low-affinity splicing
    (granulocyte-
    macrophage)
    NM_006142 SFN stratifin Multigene family 2979 6947
    NM_006144 GZMA granzyme A Hydrolase, Serine protease, 2980 6948
    (granzyme 1, Zymogen, Signal, T-cell, Cytolysis,
    cytotoxic T- Apoptosis, 3D-structure
    lymphocyte-
    associated serine
    esterase 3)
    NM_006145 DNAJB1 DnaJ (Hsp40) Heat shock, Chaperone, 3D- 2981 6949
    homolog, subfamily structure
    B, member 1
    NM_006147 IRF6 interferon regulatory Transcription regulation, DNA- 2982 6950
    factor 6 binding, Nuclear protein,
    Polymorphism, Disease mutation
    NM_006148 LASP1 LIM and SH3 protein 1 LIM domain, Metal-binding, Zinc, 2983 6951
    SH3 domain
    NM_006159 NELL2 NEL-like 2 (chicken) EGF-like domain, Glycoprotein, 2984 6952
    Repeat, Signal
    NM_006161 NEUROG1 neurogenin 1 DNA-binding, Nuclear protein, 2985 6953
    Transcription regulation, Activator,
    Neurogenesis, Developmental
    protein, Differentiation
    NM_006176 NRGN neurogranin (protein Calmodulin-binding, 2986 6954
    kinase C substrate, Phosphorylation, Neurone
    RC3)
    NM_006185 NUMA1 nuclear mitotic Immunoglobulin domain, 2987 6955
    apparatus protein 1 Glycoprotein, Signal, Alternative
    splicing, Hypothetical protein
    NM_006196 PCBP1 poly(rC) binding Nuclear protein, RNA-binding, 2988 6956
    protein 1 Ribonucleoprotein, DNA-binding,
    Phosphorylation, Repeat
    NM_006202 PDE4A phosphodiesterase Hydrolase, cAMP, Alternative 2989 6957
    4A, cAMP-specific splicing, Multigene family
    (phosphodiesterase
    E2 dunce homolog,
    Drosophila)
    NM_006205 PDE6H phosphodiesterase Hydrolase, cGMP, Vision 2990 6958
    6H, cGMP-specific,
    cone, gamma
    NM_006214 PHYH phytanoyl-CoA Oxidoreductase, Peroxisome, 2991 6959
    hydroxylase Vitamin C, Iron, Transit peptide,
    (Refsum disease) Disease mutation, Deafness,
    Retinitis pigmentosa, Hydrolase,
    cGMP, Vision, Prenylation,
    Lipoprotein, Membrane, Hypothetical
    protein, Collagen
    NM_006224 PITPN phosphotidylinositol Lipid-binding, Transport 2992 6960
    transfer protein
    NM_006225 PLCD1 phospholipase C, Hydrolase, Lipid degradation, 2993 6961
    delta 1 Transducer, Calcium-binding,
    Repeat
    NM_006238 PPARD peroxisome Receptor, Transcription regulation, 2994 6962
    proliferative Activator, DNA-binding, Nuclear
    activated receptor, protein, Zinc-finger, Multigene family,
    delta 3D-structure, Metal-binding
    NM_006242 PPP1R3D protein phosphatase Hydrolase, Glycogen metabolism 2995 6963
    1, regulatory subunit
    3D
    NM_006243 PPP2R5A protein phosphatase Phosphorylation, Multigene family 2996 6964
    2, regulatory subunit
    B (B56), alpha
    isoform
    NM_006244 PPP2R5B protein phosphatase Phosphorylation, Alternative splicing, 2997 6965
    2, regulatory subunit Multigene family
    B (B56), beta
    isoform
    NM_006254 PRKCD protein kinase C, ATP-binding, Transferase, 2998 6966
    delta Serine/threonine-protein kinase,
    Phorbol-ester binding, Zinc, Repeat,
    Polymorphism, Phosphorylation,
    Membrane
    NM_006272 S100B S100 calcium Calcium-binding, Zinc, Metal- 2999 6967
    binding protein, beta binding, 3D-structure
    (neural)
    NM_006284 TAF10 TAF10 RNA Transcription regulation, Nuclear 3000 6968
    polymerase II, TATA protein, Polymorphism
    box binding protein
    (TBP)-associated
    factor, 30 kDa
    NM_006287 TFPI tissue factor Serine protease inhibitor, 3001 6969
    pathway inhibitor Glycoprotein, Repeat, Blood
    (lipoprotein- coagulation, Signal, Alternative
    associated splicing, 3D-structure, Polymorphism
    coagulation inhibitor)
    NM_006289 TLN1 talin 1 Hypothetical protein, Structural 3002 6970
    protein, Cytoskeleton
    NM_006290 TNFAIP3 tumor necrosis Apoptosis, DNA-binding, Zinc-finger, 3003 6971
    factor, alpha-induced Repeat, Hypothetical protein
    protein
    3
    NM_006291 TNFAIP2 tumor necrosis Angiogenesis 3004 6972
    factor, alpha-induced
    protein 2
    NM_006304 DSS1 split hand/foot Polymorphism, 3D-structure 3005 6973
    malformation
    (ectrodactyly) type 1
    NM_006310 NPEPPS aminopeptidase Hydrolase, Metalloprotease, 3006 6974
    puromycin sensitive Aminopeptidase, Zinc, Nuclear
    protein
    NM_006314 CNK1 connector enhancer Hypothetical protein, Kinase 3007 6975
    of KSR-like
    (Drosophila kinase
    suppressor of ras)
    NM_006317 BASP1 brain abundant, Membrane, Myristate, Neurone, 3008 6976
    membrane attached Lipoprotein
    signal protein
    1
    NM_006319 CDIPT CDP-diacylglycerol-- Transferase, Phospholipid 3009 6977
    inositol 3- biosynthesis, Transmembrane,
    phosphatidyltransferase Magnesium, Manganese
    (phosphatidylinositol
    synthase)
    NM_006321 ARIH2 ariadne homolog 2 Ubl conjugation pathway, Nuclear 3010 6978
    (Drosophila) protein, Coiled coil, Zinc-finger,
    Repeat
    NM_006323 SEC24B SEC24 related gene Transport, Protein transport, Golgi 3011 6979
    family, member B (S. cerevisiae) stack, Endoplasmic reticulum,
    Multigene family
    NM_006324 CFDP1 craniofacial 3012 6980
    development protein 1
    NM_006327 TIMM23 translocase of inner Transport, Protein transport, 3013 6981
    mitochondrial Translocation, Mitochondrion, Inner
    membrane
    23 membrane, Outer membrane,
    homolog (yeast) Transmembrane
    NM_006342 TACC3 transforming, acidic Coiled coil 3014 6982
    coiled-coil containing
    protein
    3
    NM_006344 HML2 C-type (calcium Lectin 3015 6983
    dependent,
    carbohydrate-
    recognition domain)
    lectin, superfamily
    member 13
    (macrophage-
    derived)
    NM_006345 C4orf1 solute carrier family Hypothetical protein 3016 6984
    30 (zinc transporter),
    member 9
    NM_006346 PIBF1 progesterone- 3017 6985
    induced blocking
    factor
    1
    NM_006351 TIMM44 translocase of inner Mitochondrion, Inner membrane, 3018 6986
    mitochondrial Transport, Protein transport,
    membrane 44 Translocation, Transit peptide, ATP-
    homolog (yeast) binding, Receptor
    NM_006353 HMGN4 high mobility group Nuclear protein, DNA-binding 3019 6987
    nucleosomal binding
    domain
    4
    NM_006355 TRIM38 tripartite motif- Zinc-finger, Polymorphism 3020 6988
    containing 38
    NM_006360 GA17 dendritic cell protein Hypothetical protein 3021 6989
    NM_006362 NXF1 nuclear RNA export Transport, mRNA transport, Nuclear 3022 6990
    factor 1 protein, RNA-binding, Repeat,
    Leucine-rich repeat, Multigene
    family, 3D-structure
    NM_006367 CAP CAP, adenylate Membrane, Multigene family 3023 6991
    cyclase-associated
    protein 1 (yeast)
    NM_006374 STK25 serine/threonine Hypothetical protein, ATP-binding, 3024 6992
    kinase 25 (STE20 Transferase, Serine/threonine-
    homolog, yeast) protein kinase, Phosphorylation
    NM_006377 UNC13 unc-13 homolog B Phorbol-ester binding 3025 6993
    (C. elegans)
    NM_006383 KIP2 DNA-dependent Calcium-binding, Repeat 3026 6994
    protein kinase
    catalytic subunit-
    interacting protein 2
    NM_006386 DDX17 DEAD (Asp-Glu-Ala- ATP-binding, RNA-binding, Helicase, 3027 6995
    Asp) box polypeptide Nuclear protein
    17
    NM_006387 CHERP calcium homeostasis 3028 6996
    endoplasmic
    reticulum protein
    NM_006389 HYOU1 hypoxia up-regulated 1 ATP-binding, Chaperone, 3029 6997
    Endoplasmic reticulum, Signal,
    Glycoprotein
    NM_006395 GSA7 APG7 autophagy 7- Hypothetical protein 3030 6998
    like (S. cerevisiae)
    NM_006399 BATF basic leucine zipper Transcription regulation, DNA- 3031 6999
    transcription factor, binding, Repressor, Phosphorylation,
    ATF-like Nuclear protein
    NM_006403 NEDD9 neural precursor cell Phosphorylation, SH3 domain, Cell 3032 7000
    expressed, adhesion, Growth regulation,
    developmentally Cytoskeleton, Mitosis, Nuclear
    down-regulated 9 protein
    NM_006404 PROCR protein C receptor, Blood coagulation, Receptor, Signal, 3033 7001
    endothelial (EPCR) Transmembrane, Glycoprotein,
    Antigen, Polymorphism, 3D-structure
    NM_006405 TM9SF1 transmembrane 9 Hypothetical protein, Plasmid, 3034 7002
    superfamily member 1 Signal, Transmembrane,
    Glycoprotein
    NM_006406 PRDX4 peroxiredoxin 4 Antioxidant, Peroxidase, 3035 7003
    Oxidoreductase, Redox-active
    center
    NM_006421 BIG1 brefeldin A-inhibited Guanine-nucleotide releasing factor 3036 7004
    guanine nucleotide-
    exchange protein 1
    NM_006429 CCT7 chaperonin Chaperone, ATP-binding, Multigene 3037 7005
    containing TCP1, family
    subunit 7 (eta)
    NM_006430 CCT4 chaperonin Chaperone, ATP-binding, Multigene 3038 7006
    containing TCP1, family, Hypothetical protein
    subunit 4 (delta)
    NM_006431 CCT2 chaperonin ATP-binding, Chaperone, Multigene 3039 7007
    containing TCP1, family
    subunit 2 (beta)
    NM_006433 GNLY granulysin Antibiotic, Fungicide, Signal, T-cell, 3040 7008
    Alternative splicing, 3D-structure
    NM_006435 IFITM2 interferon induced Interferon induction, 3041 7009
    transmembrane Transmembrane, Polymorphism
    protein 2 (1-8D)
    NM_006441 MTHFS 5,10- Ligase, Folate-binding, Acetylation, 3042 7010
    methenyltetrahydrofolate Magnesium, Hypothetical protein
    synthetase (5-
    formyltetrahydrofolate
    cyclo-ligase)
    NM_006451 PAIP1 poly(A) binding Hypothetical protein 3043 7011
    protein interacting
    protein
    1
    NM_006452 PAICS phosphoribosylaminoimidazole Multifunctional enzyme, Purine 3044 7012
    carboxylase, biosynthesis, Ligase, Lyase,
    phosphoribosylaminoimidazole Decarboxylase
    succinocarboxamide
    synthetase
    NM_006455 SC65 synaptonemal Nuclear protein, Antigen 3045 7013
    complex protein
    SC65
    NM_006456 STHM sialyltransferase Transferase, Glycosyltransferase, 3046 7014
    Glycoprotein, Transmembrane,
    Signal-anchor, Golgi stack
    NM_006461 SPAG5 sperm associated Hypothetical protein 3047 7015
    antigen 5
    NM_006465 DRIL2 dead ringer 3048 7016
    (Drosophila)-like 2
    (bright and dead
    ringer)
    NM_006469 IVNS1ABP influenza virus NS1A Hypothetical protein 3049 7017
    binding protein
    NM_006471 MLC-B myosin regulatory Myosin, Calcium-binding, Muscle 3050 7018
    light chain MRCL3 protein, Phosphorylation,
    Acetylation, Multigene family
    NM_006472 TXNIP thioredoxin 3051 7019
    interacting protein
    NM_006477 RRP22 RAS-related on GTP-binding, Prenylation, 3052 7020
    chromosome 22 Lipoprotein
    NM_006480 RGS14 regulator of G- Repeat, Thiol protease inhibitor, 3053 7021
    protein signalling 14 Alternative splicing, Phosphorylation,
    Signal transduction inhibitor
    NM_006495 EVI2B ecotropic viral Proto-oncogene, Transmembrane, 3054 7022
    integration site 2B Glycoprotein, Signal
    NM_006542 SPHAR S-phase response 3055 7023
    (cyclin-related)
    NM_006545 NPR2L homologous to yeast Hypothetical protein 3056 7024
    nitrogen permease
    (candidate tumor
    suppressor)
    NM_006560 CUGBP1 CUG triplet repeat, Hypothetical protein, mRNA 3057 7025
    RNA binding protein 1 processing, RNA-binding, Repeat,
    Nuclear protein, Alternative splicing
    NM_006567 FARS1 phenylalanine-tRNA Aminoacyl-tRNA synthetase 3058 7026
    synthetase 1
    (mitochondrial)
    NM_006568 CGR19 cell growth regulator Metal-binding, Zinc, Zinc-finger 3059 7027
    with ring finger
    domain
    1
    NM_006575 MAP4K5 mitogen-activated ATP-binding, Kinase, Transferase, 3060 7028
    protein kinase Tyrosine-protein kinase,
    kinase kinase kinase 5 Serine/threonine-protein kinase
    NM_006578 GNB5 guanine nucleotide Repeat, WD repeat, Transducer, 3061 7029
    binding protein (G Alternative splicing, Multigene family,
    protein), beta 5 Hypothetical protein
    NM_006589 C1orf2 chromosome 1 open Hypothetical protein 3062 7030
    reading frame 2
    NM_006598 SLC12A7 solute carrier family Transport, Ion transport, Symport, 3063 7031
    12 Potassium, Potassium transport,
    (potassium/chloride Transmembrane, Alternative splicing
    transporters),
    member 7
    NM_006636 MTHFD2 methylene Multifunctional enzyme, One-carbon 3064 7032
    tetrahydrofolate metabolism, Oxidoreductase, NAD,
    dehydrogenase Hydrolase, Mitochondrion, Transit
    (NAD+ dependent), peptide, Magnesium
    methenyltetrahydrofolate
    cyclohydrolase
    NM_006638 RNASEP1 ribonuclease P1 Hydrolase, Nuclear protein, tRNA 3065 7033
    processing
    NM_006643 SDCCAG3 serologically defined Hypothetical protein 3066 7034
    colon cancer antigen 3
    NM_006644 HSPH1 heat shock ATP-binding, Heat shock, Multigene 3067 7035
    105 kDa/110 kDa family, Alternative splicing
    protein
    1
    NM_006646 WASF3 WAS protein family, Actin-binding, Coiled coil 3068 7036
    member 3
    NM_006650 CPLX2 complexin 2 Neurotransmitter transport 3069 7037
    NM_006660 CLPX ClpX caseinolytic Hypothetical protein, ATP-binding, 3070 7038
    protease X homolog Chaperone, Mitochondrion, Transit
    (E. coli) peptide, Zinc-finger
    NM_006667 PGRMC1 progesterone Receptor, Steroid-binding, 3071 7039
    receptor membrane Transmembrane, Microsome
    component
    1
    NM_006669 LILRB1 leukocyte Receptor, Repeat, Signal, 3072 7040
    immunoglobulin-like Transmembrane, Immune response,
    receptor, subfamily Immunoglobulin domain,
    B (with TM and ITIM Phosphorylation, Glycoprotein,
    domains), member 1 Antigen, Multigene family,
    Alternative splicing, Polymorphism,
    3D-structure
    NM_006676 USP20 ubiquitin specific Ubl conjugation pathway, Hydrolase, 3073 7041
    protease 20 Thiol protease, Multigene family
    NM_006680 ME3 malic enzyme 3, Oxidoreductase, NADP, 3074 7042
    NADP(+)- Mitochondrion, Transit peptide
    dependent,
    mitochondrial
    NM_006681 NMU neuromedin U Neuropeptide, Cleavage on pair of 3075 7043
    basic residues, Amidation, Signal
    NM_006682 FGL2 fibrinogen-like 2 T-cell, Glycoprotein, Signal, 3076 7044
    Polymorphism
    NM_006700 FLN29 FLN29 gene product 3077 7045
    NM_006704 SUGT1 SGT1, suppressor of Ubl conjugation pathway, Repeat, 3078 7046
    G2 allele of SKP1 TPR repeat
    (S. cerevisiae)
    NM_006705 GADD45G growth arrest and Differentiation, Apoptosis 3079 7047
    DNA-damage-
    inducible, gamma
    NM_006706 TCERG1 transcription 3080 7048
    elongation regulator
    1 (CA150)
    NM_006708 GLO1 glyoxalase I Lyase, Zinc, Polymorphism, 3D- 3081 7049
    structure
    NM_006710 COP9 COP9 signalosome 3082 7050
    subunit 8
    NM_006719 ABLIM1 actin binding LIM LIM domain, Metal-binding, Zinc, 3083 7051
    protein 1 Hypothetical protein
    NM_006721 ADK adenosine kinase Transferase, Kinase, Purine salvage, 3084 7052
    Magnesium, Alternative splicing, 3D-
    structure
    NM_006732 FOSB FBJ murine Nuclear protein, DNA-binding 3085 7053
    osteosarcoma viral
    oncogene homolog B
    NM_006747 SIPA1 signal-induced GTPase activation, Coiled coil, 3086 7054
    proliferation- Nuclear protein, Membrane
    associated gene 1
    NM_006748 SLA Src-like-adaptor SH2 domain, SH3 domain, 3087 7055
    Myristate, Phosphorylation,
    Lipoprotein
    NM_006750 SNTB2 syntrophin, beta 2 Actin-binding, Cytoskeleton, 3088 7056
    (dystrophin- Microtubule, Calcium-binding,
    associated protein Calmodulin-binding, Membrane,
    A1, 59 kDa, basic Phosphorylation, Repeat,
    component 2) Polymorphism, Multigene family,
    Alternative splicing
    NM_006755 TALDO1 transaldolase 1 Hypothetical protein, Pentose shunt, 3089 7057
    Transferase, Disease mutation, 3D-
    structure
    NM_006756 TCEA1 transcription Transcription regulation, Zinc-finger, 3090 7058
    elongation factor A DNA-binding, Nuclear protein,
    (SII), 1 Alternative splicing, 3D-structure
    NM_006760 UPK2 uroplakin 2 Endoplasmic reticulum, Signal, 3091 7059
    Transmembrane, Glycoprotein
    NM_006761 YWHAE tyrosine 3- Neurone, Acetylation, Multigene 3092 7060
    monooxygenase/tryptophan family
    5-
    monooxygenase
    activation protein,
    epsilon polypeptide
    NM_006762 LAPTM5 Lysosomal- Transmembrane, Lysosome 3093 7061
    associated
    multispanning
    membrane protein-5
    NM_006763 BTG2 BTG family, member 2 Signal 3094 7062
    NM_006770 MARCO macrophage Collagen, Transmembrane, 3095 7063
    receptor with Receptor, Glycoprotein, Signal-
    collagenous anchor
    structure
    NM_006783 GJB6 gap junction protein, Gap junction, Transmembrane, 3096 7064
    beta 6 (connexin 30) Deafness, Disease mutation
    NM_006784 WDR3 WD repeat domain 3 WD repeat, Repeat, Nuclear protein 3097 7065
    NM_006787 MAGED2 melanoma antigen, Antigen, Multigene family, 3098 7066
    family D, 2 Polymorphism, Alternative splicing
    NM_006795 EHD1 EH-domain Calcium-binding, ATP-binding, 3099 7067
    containing 1 Coiled coil
    NM_006801 KDELR1 KDEL (Lys-Asp-Glu- Endoplasmic reticulum, 3100 7068
    Leu) endoplasmic Transmembrane, Protein transport,
    reticulum protein Receptor, Hypothetical protein,
    retention receptor 1 Transport
    NM_006805 HNRPA0 heterogeneous Nuclear protein, RNA-binding, 3101 7069
    nuclear Ribonucleoprotein, Repeat,
    ribonucleoprotein A0 Methylation
    NM_006806 BTG3 BTG family, member 3 Alternative splicing 3102 7070
    NM_006810 PDIR for protein disulfide Isomerase, Redox-active center, 3103 7071
    isomerase-related Endoplasmic reticulum, Repeat,
    Signal
    NM_006812 OS-9 amplified in Hypothetical protein, Signal, 3104 7072
    osteosarcoma Alternative splicing, Polymorphism
    NM_006818 AF1Q ALL1-fused gene Proto-oncogene, Chromosomal 3105 7073
    from chromosome translocation
    1q
    NM_006823 PKIA protein kinase Protein kinase inhibitor, 3D-structure 3106 7074
    (cAMP-dependent,
    catalytic) inhibitor
    alpha
    NM_006824 EBNA1BP2 EBNA1 binding Ribosome biogenesis, Nuclear 3107 7075
    protein 2 protein, Coiled coil
    NM_006825 CKAP4 cytoskeleton- Hypothetical protein 3108 7076
    associated protein 4
    NM_006826 YWHAQ tyrosine 3- Transcription regulation, Repressor, 3109 7077
    monooxygenase/tryptophan Activator, Nuclear protein, Zinc-
    5- finger, Metal-binding, DNA-binding,
    monooxygenase Repeat, 3D-structure, Tight junction,
    activation protein, Immunoglobulin domain,
    theta polypeptide Glycoprotein, Transmembrane,
    Signal, Neurone, Phosphorylation,
    Multigene family
    NM_006827 TMP21 transmembrane Transport, Protein transport, 3110 7078
    trafficking protein Transmembrane, Signal,
    Glycoprotein, Golgi stack,
    Polymorphism
    NM_006838 METAP2 methionyl Hydrolase, Aminopeptidase, Cobalt, 3111 7079
    aminopeptidase 2 3D-structure, Hypothetical protein
    NM_006840 LILRB5 leukocyte Receptor, Repeat, Signal, 3112 7080
    immunoglobulin-like Transmembrane, Immune response,
    receptor, subfamily Immunoglobulin domain,
    B (with TM and ITIM Phosphorylation, Glycoprotein,
    domains), member 2 Antigen, Multigene family,
    Alternative splicing
    NM_006863 LILRA1 leukocyte Immune response, Receptor, 3113 7081
    immunoglobulin-like Repeat, Signal, Transmembrane,
    receptor, subfamily Immunoglobulin domain,
    B (with TM and ITIM Glycoprotein, Antigen, Alternative
    domains), member 1 splicing, Multigene family
    NM_006864 LILRB3 leukocyte Receptor, Repeat, Signal, 3114 7082
    immunoglobulin-like Transmembrane, Immune response,
    receptor, subfamily Immunoglobulin domain,
    B (with TM and ITIM Phosphorylation, Glycoprotein,
    domains), member 3 Antigen, Multigene family,
    Alternative splicing, Polymorphism
    NM_006865 LILRA3 leukocyte Receptor, Repeat, Signal, Immune 3115 7083
    immunoglobulin-like response, Immunoglobulin domain,
    receptor, subfamily Glycoprotein, Antigen, Multigene
    A (without TM family, Polymorphism
    domain), member 3
    NM_006866 LILRA2 leukocyte Immune response, Receptor, 3116 7084
    immunoglobulin-like Repeat, Signal, Transmembrane,
    receptor, subfamily Immunoglobulin domain,
    B (with TM and ITIM Glycoprotein, Antigen, Alternative
    domains), member 1 splicing, Polymorphism, Multigene
    family
    NM_006868 RAB31 RAB31, member GTP-binding, Lipoprotein, 3117 7085
    RAS oncogene Prenylation
    family
    NM_006869 CENTA1 centaurin, alpha 1 3118 7086
    NM_006876 B3GNT6 UDP- Transferase, Glycosyltransferase, 3119 7087
    GlcNAc:betaGal Transmembrane, Signal-anchor,
    beta-1,3-N- Glycoprotein, Golgi stack
    acetylglucosaminyltransferase
    6
    NM_006890 CEACAM7 carcinoembryonic Immunoglobulin domain, Antigen, 3120 7088
    antigen-related cell Membrane, Signal, Glycoprotein,
    adhesion molecule 7 Lipoprotein, GPI-anchor, Repeat,
    Alternative splicing
    NM_006892 DNMT3B DNA (cytosine-5-)- Transferase, Methyltransferase, 3121 7089
    methyltransferase 3 Zinc-finger, Zinc, Metal-binding,
    beta Nuclear protein, Ubl conjugation,
    Alternative splicing, Disease
    mutation
    NM_006913 RNF5 ring finger protein 5 Hypothetical protein 3122 7090
    NM_006923 SDF2 stromal cell-derived Signal, Repeat 3123 7091
    factor 2
    NM_006930 SKP1A S-phase kinase- Ubl conjugation pathway, Alternative 3124 7092
    associated protein splicing, 3D-structure
    1A (p19A)
    NM_006931 SLC2A3 solute carrier family Sugar transport, Transmembrane, 3125 7093
    2 (facilitated glucose Transport, Glycoprotein, Multigene
    transporter), family
    member
    3
    NM_006932 SMTN smoothelin Structural protein, Alternative 3126 7094
    splicing
    NM_006936 SMT3H1 SMT3 suppressor of Ubl conjugation pathway 3127 7095
    mif two 3 homolog 1
    (yeast)
    NM_006938 SNRPD1 small nuclear Nuclear protein, Ribonucleoprotein, 3128 7096
    ribonucleoprotein D1 mRNA splicing, mRNA processing,
    polypeptide 16 kDa Systemic lupus erythematosus,
    Repeat, Methylation, 3D-structure
    NM_006941 SOX10 SRY (sex Transcription regulation, DNA- 3129 7097
    determining region binding, Nuclear protein, Disease
    Y)-box 10 mutation, Hirschsprung disease,
    Deafness
    NM_006945 SPRR2B small proline-rich Keratinocyte, Repeat, Multigene 3130 7098
    protein 2B family
    NM_006947 SRP72 signal recognition ATP-binding, Kinase, Transferase, 3131 7099
    particle 72 kDa Signal recognition particle,
    Ribonucleoprotein
    NM_006987 RPH3AL rabphilin 3A-like Hypothetical protein 3132 7100
    (without C2
    domains)
    NM_006993 NPM3 nucleophosmin/nucleoplasmin, 3 Nuclear protein, Chaperone, 3133 7101
    Phosphorylation
    NM_007000 UPK1A uroplakin 1A Hypothetical protein, 3134 7102
    Transmembrane, Glycoprotein
    NM_007007 CPSF6 cleavage and 3135 7103
    polyadenylation
    specific factor 6,
    68 kDa
    NM_007008 RTN4 reticulon 4 Endoplasmic reticulum, Alternative 3136 7104
    splicing, Transmembrane,
    Hypothetical protein
    NM_007014 WWP2 Nedd-4-like Ubl conjugation pathway, Ligase, 3137 7105
    ubiquitin-protein Repeat
    ligase
    NM_007022 101F6 putative tumor 3138 7106
    suppressor 101F6
    NM_007024 PL6 placental protein 6 Transmembrane 3139 7107
    NM_007032 HRIHFB2122 Tara-like protein Hypothetical protein, Cytoskeleton, 3140 7108
    Actin-binding, Coiled coil, Nuclear
    protein
    NM_007033 RER1 RER1 homolog (S. cerevisiae) Transmembrane, Golgi stack 3141 7109
    NM_007034 DNAJB4 DnaJ (Hsp40) Chaperone, Heat shock 3142 7110
    homolog, subfamily
    B, member 4
    NM_007043 HRB2 HIV-1 rev binding 3143 7111
    protein 2
    NM_007054 KIF3A kinesin family Motor protein, Microtubule, ATP- 3144 7112
    member 3A binding, Coiled coil, Neurone
    NM_007056 SWAP2 splicing factor, mRNA processing, mRNA splicing, 3145 7113
    arginine/serine-rich Nuclear protein, Alternative splicing,
    16 (suppressor-of- Polymorphism
    white-apricot
    homolog,
    Drosophila)
    NM_007059 KPTN kaptin (actin binding 3146 7114
    protein)
    NM_007062 PWP1 nuclear Repeat, WD repeat, Nuclear protein, 3147 7115
    phosphoprotein Phosphorylation
    similar to S. cerevisiae
    PWP1
    NM_007063 TBC1D8 TBC1 domain family, GTPase activation 3148 7116
    member 8 (with
    GRAM domain)
    NM_007065 CDC37 CDC37 cell division Chaperone 3149 7117
    cycle 37 homolog (S. cerevisiae)
    NM_007070 FAP48 glomulin, FKBP Coiled coil, Phosphorylation, 3150 7118
    associated protein Alternative splicing, Disease
    mutation, Polymorphism
    NM_007074 CORO1A coronin, actin Actin-binding, Repeat, WD repeat, 3151 7119
    binding protein, 1A Coiled coil, Polymorphism
    NM_007077 AP4S1 adaptor-related Coated pits, Endocytosis 3152 7120
    protein complex 4,
    sigma 1 subunit
    NM_007098 CLTCL1 clathrin, heavy Coated pits, Alternative splicing 3153 7121
    polypeptide-like 1
    NM_007099 ACP1 acid phosphatase 1, Hydrolase, Acetylation, Alternative 3154 7122
    soluble splicing, Polymorphism, 3D-structure
    NM_007108 TCEB2 transcription Transcription regulation, Ubl 3155 7123
    elongation factor B conjugation pathway, Nuclear
    (SIII), polypeptide 2 protein, 3D-structure
    (18 kDa, elongin B)
    NM_007115 TNFAIP6 tumor necrosis Cell adhesion, Signal, Glycoprotein, 3156 7124
    factor, alpha-induced Polymorphism, 3D-structure
    protein
    6
    NM_007145 ZNF146 zinc finger protein Zinc-finger, DNA-binding, Metal- 3157 7125
    146 binding, Nuclear protein, Repeat
    NM_007152 ZNF195 zinc finger protein Zinc-finger, Metal-binding, DNA- 3158 7126
    195 binding, Nuclear protein, Alternative
    splicing
    NM_007161 LST1 leukocyte specific Signal, Immune response, Cell 3159 7127
    transcript 1 shape, Transmembrane, Alternative
    splicing, Receptor
    NM_007169 PEMT phosphatidylethanol Phospholipid biosynthesis, 3160 7128
    amine N- Transferase, Methyltransferase,
    methyltransferase Transmembrane, Mitochondrion,
    Endoplasmic reticulum,
    Polymorphism
    NM_007172 NUP50 nucleoporin 50 kDa Hypothetical protein, Nuclear 3161 7129
    protein, Transport, Protein transport,
    Repeat, Porin
    NM_007178 UNRIP unr-interacting Hypothetical protein, Repeat, WD 3162 7130
    protein repeat
    NM_007186 CEP2 centrosomal protein 2 Cell cycle, Coiled coil, 3163 7131
    Phosphorylation, Alternative splicing,
    Polymorphism
    NM_007205 TREX2 three prime repair Hypothetical protein, Proteasome, 3164 7132
    exonuclease 2 Exonuclease
    NM_007208 MRPL3 mitochondrial Ribosomal protein, Mitochondrion 3165 7133
    ribosomal protein L3
    NM_007212 RNF2 ring finger protein 2 Metal-binding, Zinc, Zinc-finger 3166 7134
    NM_007213 JM4 JM4 protein 3167 7135
    NM_007219 RNF24 ring finger protein 24 Zinc-finger 3168 7136
    NM_007222 ZHX1 zinc-fingers and Homeobox, Metal-binding, Nuclear 3169 7137
    homeoboxes 1 protein, Zinc, Zinc-finger
    NM_007238 PXMP4 peroxisomal Peroxisome, Transmembrane, 3170 7138
    membrane protein 4, Glycoprotein, Polymorphism
    24 kDa
    NM_007240 DUSP12 dual specificity Hydrolase, Zinc, Metal-binding 3171 7139
    phosphatase 12
    NM_007248 TREX1 three prime repair Hypothetical protein, Exonuclease 3172 7140
    exonuclease 1
    NM_007255 B4GALT7 xylosylprotein beta Glycosyltransferase, Transferase, 3173 7141
    1,4- Glycoprotein, Transmembrane,
    galactosyltransferase, Signal-anchor, Golgi stack,
    polypeptide 7 Multigene family, Disease mutation,
    (galactosyltransferase Ehlers-Danlos syndrome
    I)
    NM_007274 BACH brain acyl-CoA Hydrolase, Serine esterase, Repeat, 3174 7142
    hydrolase Alternative splicing
    NM_007278 GABARAP GABA(A) receptor- Receptor 3175 7143
    associated protein
    NM_007284 PTK9L protein tyrosine Hypothetical protein, Kinase 3176 7144
    kinase 9-like (A6-
    related protein)
    NM_007311 BZRP benzodiazapine Mitochondrion, Receptor, 3177 7145
    receptor (peripheral) Transmembrane, Polymorphism
    NM_007317 KIF22 kinesin family DNA-binding, Motor protein, 3178 7146
    member 22 Microtubule, ATP-binding, Coiled
    coil, Nuclear protein
    NM_007318 PSEN1 presenilin 1 Transmembrane, Phosphorylation, 3179 7147
    (Alzheimer disease Endoplasmic reticulum, Golgi stack,
    3) Alzheimer's disease, Disease
    mutation, Polymorphism, Alternative
    splicing
    NM_007320 RANBP3 RAN binding protein 3 Hypothetical protein 3180 7148
    NM_007334 KLRD1 killer cell lectin-like Antigen, Receptor, Glycoprotein, 3181 7149
    receptor subfamily Transmembrane, Signal-anchor,
    D, member 1 Lectin, Alternative splicing, 3D-
    structure
    NM_007346 OGFR opioid growth factor Receptor, Growth regulation, 3182 7150
    receptor Repeat, Alternative splicing
    NM_007360 D12S2489E killer cell lectin-like Receptor, Transmembrane, 3183 7151
    receptor subfamily Multigene family, Signal-anchor,
    K, member 1 Lectin, Glycoprotein, Polymorphism,
    3D-structure
    NM_007375 TARDBP TAR DNA binding DNA-binding, RNA-binding, Nuclear 3184 7152
    protein protein, Transcription regulation,
    Repressor, mRNA processing,
    mRNA splicing, Repeat
    NM_009588 LTB lymphotoxin beta Cytokine, Transmembrane, 3185 7153
    (TNF superfamily, Glycoprotein, Signal-anchor,
    member 3) Alternative splicing, Polymorphism
    NM_012062 DNM1L dynamin 1-like Hypothetical protein 3186 7154
    NM_012064 MIP major intrinsic Gap junction, Transport, 3187 7155
    protein of lens fiber Transmembrane, Phosphorylation,
    Eye lens protein
    NM_012079 DGAT1 diacylglycerol O- Transferase, Acyltransferase, 3188 7156
    acyltransferase Transmembrane, Endoplasmic
    homolog 1 (mouse) reticulum, Hypothetical protein
    NM_012084 GLUD2 glutamate Hypothetical protein 3189 7157
    dehydrogenase 2
    NM_012086 GTF3C3 general transcription Hypothetical protein 3190 7158
    factor IIIC,
    polypeptide 3,
    102 kDa
    NM_012089 ABCB10 ATP-binding ATP-binding, Transmembrane, 3191 7159
    cassette, sub-family Transport, Mitochondrion, Inner
    B (MDR/TAP), membrane, Transit peptide,
    member 10 Polymorphism
    NM_012094 PRDX5 peroxiredoxin 5 Antioxidant, Peroxisome, 3192 7160
    Mitochondrion, Transit peptide,
    Alternative initiation, Polymorphism,
    3D-structure
    NM_012100 DNPEP aspartyl Hydrolase, Aminopeptidase, 3193 7161
    aminopeptidase Metalloprotease, Zinc, Hypothetical
    protein
    NM_012108 BRDG1 BCR downstream 3194 7162
    signaling 1
    NM_012114 CASP14 caspase 14, Hydrolase, Thiol protease, 3195 7163
    apoptosis-related Apoptosis, Zymogen
    cysteine protease
    NM_012124 CHORDC1 cysteine and 3196 7164
    histidine-rich domain
    (CHORD)-
    containing, zinc
    binding protein
    1
    NM_012130 CLDN14 claudin 14 Tight junction, Transmembrane, 3197 7165
    Polymorphism, Disease mutation,
    Deafness
    NM_012142 CCNDBP1 cyclin D-type Cyclin, Hypothetical protein 3198 7166
    binding-protein 1
    NM_012143 TFIP11 tuftelin interacting Biomineralization, Nuclear protein, 3199 7167
    protein 11 Alternative splicing
    NM_012151 F8A coagulation factor Hypothetical protein 3200 7168
    VIII-associated
    (intronic transcript)
    NM_012168 FBXO2 F-box only protein 2 Ubl conjugation pathway 3201 7169
    NM_012185 FOXE2 forkhead box E2 DNA-binding, Nuclear protein, 3202 7170
    Transcription regulation
    NM_012198 GCA grancalcin, EF-hand Calcium-binding, Repeat, 3D- 3203 7171
    calcium binding structure
    protein
    NM_012203 GRHPR glyoxylate Hypothetical protein, 3204 7172
    reductase/hydroxypyruvate Oxidoreductase, Pyruvate
    reductase
    NM_012214 MGAT4A mannosyl (alpha- Glycosyltransferase, Transferase 3205 7173
    1,3-)-glycoprotein
    beta-1,4-N-
    acetylglucosaminyltransferase,
    isoenzyme A
    NM_012218 ILF3 interleukin enhancer Hypothetical protein, Transcription 3206 7174
    binding factor 3, regulation, DNA-binding, RNA-
    90 kDa binding, Nuclear protein, Repeat,
    Phosphorylation, Methylation,
    Alternative splicing
    NM_012228 PILB pilin-like transcription Hypothetical protein 3207 7175
    factor
    NM_012229 NT5C2 5′-nucleotidase, Hydrolase, Allosteric enzyme 3208 7176
    cytosolic II
    NM_012236 SCMH1 sex comb on midleg 3209 7177
    homolog 1
    (Drosophila)
    NM_012244 SLC7A8 solute carrier family Hypothetical protein, Transport, 3210 7178
    7 (cationic amino Amino-acid transport,
    acid transporter, y+ Transmembrane
    system), member 8
    NM_012250 RRAS2 related RAS viral (r- GTP-binding, Prenylation, 3211 7179
    ras) oncogene Lipoprotein, Proto-oncogene,
    homolog 2 Disease mutation
    NM_012255 XRN2
    5′-3′ mRNA processing, Hydrolase, 3212 7180
    exoribonuclease 2 Nuclease, Exonuclease, Nuclear
    protein, RNA-binding, Zinc-finger
    NM_012258 HEY1 hairy/enhancer-of- Hypothetical protein, Transcription 3213 7181
    split related with regulation, DNA-binding, Nuclear
    YRPW motif
    1 protein
    NM_012262 HS2ST1 heparan sulfate 2-O- Hypothetical protein, Transferase 3214 7182
    sulfotransferase 1
    NM_012282 KCNE1L potassium voltage- Transmembrane, Glycoprotein, 3215 7183
    gated channel, lsk- Alport syndrome, Deafness,
    related family, Elliptocytosis
    member 1-like
    NM_012286 MORF4L2 mortality factor 4 like 2 Growth regulation, Nuclear protein 3216 7184
    NM_012290 TLK1 tousled-like kinase 1 ATP-binding, Kinase, 3217 7185
    Serine/threonine-protein kinase,
    Transferase, Chromatin regulator,
    Cell cycle, DNA damage, Nuclear
    protein, Coiled coil, Phosphorylation,
    Alternative splicing
    NM_012295 CABIN1 calcineurin binding Hypothetical protein, 3218 7186
    protein 1 Phosphorylation, Repeat, TPR
    repeat
    NM_012329 MMD monocyte to Transmembrane 3219 7187
    macrophage
    differentiation-
    associated
    NM_012331 MSRA methionine sulfoxide Oxidoreductase 3220 7188
    reductase A
    NM_012341 CRFG GTP binding protein 4 GTP-binding, Nuclear protein 3221 7189
    NM_012342 NMA putative Transmembrane, Signal, 3222 7190
    transmembrane Glycoprotein
    protein
    NM_012343 NNT nicotinamide Oxidoreductase, NAD, NADP, 3223 7191
    nucleotide Transmembrane, Mitochondrion,
    transhydrogenase Transit peptide, 3D-structure,
    Hypothetical protein
    NM_012347 FBXO9 F-box only protein 9 Hypothetical protein, Ubl conjugation 3224 7192
    pathway, TPR repeat
    NM_012383 OSTF1 osteoclast Hypothetical protein, ANK repeat, 3225 7193
    stimulating factor 1 Repeat, SH3 domain
    NM_012384 GMEB2 glucocorticoid Trans-acting factor, Nuclear protein, 3226 7194
    modulatory element DNA-binding, Coiled coil
    binding protein
    2
    NM_012387 PADI4 peptidyl arginine Hydrolase, Calcium-binding, 3227 7195
    deiminase, type IV Multigene family
    NM_012390 PROL5 proline rich 5 Saliva 3228 7196
    (salivary)
    NM_012392 PEF PEF protein with a Calcium-binding 3229 7197
    long N-terminal
    hydrophobic domain
    (peflin)
    NM_012400 PLA2G2D phospholipase A2, Hydrolase, Lipid degradation, Signal, 3230 7198
    group IID Calcium, Polymorphism
    NM_012403 ANP32C acidic (leucine-rich) 3231 7199
    nuclear
    phosphoprotein 32
    family, member C
    NM_012413 QPCT glutaminyl-peptide Transferase, Acyltransferase, Signal, 3232 7200
    cyclotransferase Polymorphism
    (glutaminyl cyclase)
    NM_012434 SLC17A5 solute carrier family Transmembrane, Hypothetical 3233 7201
    17 (anion/sugar protein, Sugar transport
    transporter),
    member 5
    NM_012445 SPON2 spondin 2, Hypothetical protein, Matrix protein 3234 7202
    extracellular matrix
    protein
    NM_012446 SSBP2 single-stranded DNA DNA-binding, Nuclear protein 3235 7203
    binding protein 2
    NM_012455 TIC SEC7 homolog 3236 7204
    NM_012460 TIMM9 translocase of inner Transport, Protein transport, 3237 7205
    mitochondrial Translocation, Mitochondrion, Inner
    membrane 9 membrane, Hypothetical protein
    homolog (yeast)
    NM_012463 ATP6V0A2 ATPase, H+ Hydrogen ion transport, 3238 7206
    transporting, Transmembrane, Glycoprotein,
    lysosomal V0 Hypothetical protein
    subunit a isoform 2
    NM_012483 GNLY granulysin Antibiotic, Fungicide, Signal, T-cell, 3239 7207
    Alternative splicing, 3D-structure
    NM_012484 HMMR hyaluronan- Hyaluronic acid, Alternative splicing, 3240 7208
    mediated motility Repeat, Glycoprotein, Antigen
    receptor (RHAMM)
    NM_012485 HMMR hyaluronan- Hyaluronic acid, Alternative splicing, 3241 7209
    mediated motility Repeat, Glycoprotein, Antigen
    receptor (RHAMM)
    NM_013229 APAF1 apoptotic protease Apoptosis, ATP-binding, Repeat, 3242 7210
    activating factor WD repeat, Alternative splicing, 3D-
    structure
    NM_013235 RNASE3L nuclear RNase III Ribosome biogenesis, Hydrolase, 3243 7211
    Drosha Nuclease, Endonuclease, Repeat,
    RNA-binding, Nuclear protein,
    Alternative splicing
    NM_013236 E46L like mouse brain Hypothetical protein 3244 7212
    protein E46
    NM_013242 GTL3 likely ortholog of 3245 7213
    mouse gene trap
    locus
    3
    NM_013248 NXT1 NTF2-like export Transport, Protein transport, Nuclear 3246 7214
    factor 1 protein, 3D-structure
    NM_013252 CLECSF5 C-type (calcium Transmembrane, Lectin 3247 7215
    dependent,
    carbohydrate-
    recognition domain)
    lectin, superfamily
    member
    5
    NM_013258 ASC apoptosis- Apoptosis, Anti-oncogene, 3248 7216
    associated speck- Alternative splicing
    like protein
    containing a CARD
    NM_013259 NP25 neuronal protein 3249 7217
    NM_013272 SLC21A11 solute carrier organic Transmembrane, Transport, Ion 3250 7218
    anion transporter transport, Glycoprotein
    family, member 3A1
    NM_013285 HUMAUANTIG nucleolar GTPase GTP-binding, Nuclear protein 3251 7219
    NM_013286 KIAA0800 chromosome 3p21.1 Hypothetical protein 3252 7220
    gene sequence
    NM_013289 KIR3DL1 killer cell Receptor, Immunoglobulin domain, 3253 7221
    immunoglobulin-like Glycoprotein, Signal,
    receptor, three Transmembrane, Repeat, Multigene
    domains, long family, Polymorphism, 3D-structure,
    cytoplasmic tail, 1 Alternative splicing
    NM_013296 MCLC LGN protein Hypothetical protein, Repeat, TPR 3254 7222
    repeat, Phosphorylation
    NM_013300 HSU79274 protein predicted by Hypothetical protein 3255 7223
    clone 23733
    NM_013301 HSU79303 protein predicted by Hypothetical protein 3256 7224
    clone 23882
    NM_013312 HOOK2 hook homolog 2 Hypothetical protein 3257 7225
    (Drosophila)
    NM_013319 TERE1 transitional epithelia 3258 7226
    response protein
    NM_013323 SNX11 sorting nexin 11 Transport, Protein transport 3259 7227
    NM_013328 P5CR2 pyrroline 5- Hypothetical protein 3260 7228
    carboxylate
    reductase isoform
    NM_013330 NME7 non-metastatic cells Transferase, Kinase, ATP-binding, 3261 7229
    7, protein expressed Sodium/potassium transport,
    in (nucleoside- Transmembrane, Glycoprotein,
    diphosphate kinase) Multigene family, Signal-anchor,
    Alternative splicing
    NM_013341 PTD004 hypothetical protein GTP-binding, Alternative splicing 3262 7230
    PTD004
    NM_013351 TBX21 T-box 21 Transcription regulation, DNA- 3263 7231
    binding, Nuclear protein, Activator
    NM_013354 CNOT7 CCR4-NOT Transcription regulation, Repressor, 3264 7232
    transcription Nuclear protein, Hypothetical protein
    complex, subunit 7
    NM_013363 PCOLCE2 procollagen C- Collagen 3265 7233
    endopeptidase
    enhancer
    2
    NM_013364 PNMA3 paraneoplastic Hypothetical protein 3266 7234
    antigen MA3
    NM_013368 RBT1 RPA-binding trans- Hypothetical protein 3267 7235
    activator
    NM_013382 POMT2 protein-O- Transferase, Glycosyltransferase, 3268 7236
    mannosyltransferase 2 Endoplasmic reticulum,
    Transmembrane, Glycoprotein,
    Repeat, Alternative splicing
    NM_013383 TCFL4 transcription factor- Transcription regulation, Repressor, 3269 7237
    like 4 Nuclear protein, DNA-binding,
    Alternative splicing, Receptor
    NM_013392 NRBP nuclear receptor Hypothetical protein, ATP-binding, 3270 7238
    binding protein Transferase, Nuclear protein,
    Receptor
    NM_013395 AD013 Homo sapiens Hypothetical protein, 3271 7239
    proteinx0008 Transmembrane
    (AD013) mRNA,
    complete cds.
    NM_013403 STRN4 striatin, calmodulin Calmodulin-binding, Repeat, WD 3272 7240
    binding protein 4 repeat, Coiled coil
    NM_013412 RABL2A RAB, member of Hypothetical protein, GTP-binding, 3273 7241
    RAS oncogene Alternative splicing
    family-like 2A
    NM_013416 NCF4 neutrophil cytosolic SH3 domain, Alternative splicing, 3274 7242
    factor 4, 40 kDa 3D-structure
    NM_013421 GGT1 gamma- Glutathione biosynthesis, 3275 7243
    glutamyltransferase 1 Transferase, Acyltransferase,
    Signal-anchor, Transmembrane,
    Zymogen, Glycoprotein, Sialic acid,
    Alternative splicing, Alternative
    promoter usage
    NM_013430 GGT1 gamma- Glutathione biosynthesis, 3276 7244
    glutamyltransferase 1 Transferase, Acyltransferase,
    Signal-anchor, Transmembrane,
    Zymogen, Glycoprotein, Sialic acid,
    Alternative splicing, Alternative
    promoter usage
    NM_013439 PILR(ALPHA) paired Receptor 3277 7245
    immunoglobin-like
    type
    2 receptor
    alpha
    NM_013440 PILR(BETA) paired Meiosis, Cell cycle, Chromosome 3278 7246
    immunoglobin-like partition, Nuclear protein, Alternative
    type
    2 receptor beta splicing, Hypothetical protein,
    Receptor
    NM_013444 UBQLN2 ubiquilin 2 Hypothetical protein 3279 7247
    NM_013448 BAZ1A bromodomain Transcription regulation, 3280 7248
    adjacent to zinc Bromodomain, Zinc-finger, Coiled
    finger domain, 1A coil, Nuclear protein, Alternative
    splicing
    NM_013940 OR10H1 olfactory receptor, 3281 7249
    family 10, subfamily
    H, member 1
    NM_013943 CLIC4 chloride intracellular Hypothetical protein, Ionic channel, 3282 7250
    channel 4 Ion transport, Chloride channel,
    Voltage-gated channel
    NM_013951 PAX8 paired box gene 8 DNA-binding, Developmental 3283 7251
    protein, Nuclear protein, Paired box,
    Transcription, Transcription
    regulation, Differentiation, Alternative
    splicing, Disease mutation,
    Polymorphism
    NM_013956 NRG1 neuregulin 1 EGF-like domain, Growth factor, 3284 7252
    Transmembrane, Multigene family,
    Alternative splicing, Immunoglobulin
    domain, Glycoprotein,
    Polymorphism, 3D-structure,
    Chromosomal translocation
    NM_013974 DDAH2 dimethylarginine Hydrolase 3285 7253
    dimethylaminohydrolase 2
    NM_013975 LIG3 ligase III, DNA, ATP- DNA repair, DNA replication, DNA 3286 7254
    dependent recombination, Cell division, Ligase,
    ATP-binding, Zinc-finger, Nuclear
    protein, Alternative splicing, 3D-
    structure, Hypothetical protein
    NM_013979 BNIP1 BCL2/adenovirus Apoptosis, Alternative splicing, 3287 7255
    E1B 19 kDa Transmembrane
    interacting protein
    1
    NM_013992 PAX8 paired box gene 8 DNA-binding, Developmental 3288 7256
    protein, Nuclear protein, Paired box,
    Transcription, Transcription
    regulation, Differentiation, Alternative
    splicing, Disease mutation,
    Polymorphism
    NM_013995 LAMP2 lysosomal- Transmembrane, Glycoprotein, 3289 7257
    associated Lysosome, Signal, Alternative
    membrane protein
    2 splicing, Polymorphism
    NM_014000 VCL vinculin Cell adhesion, Actin-binding, 3290 7258
    Cytoskeleton, Structural protein,
    Phosphorylation, Repeat, Alternative
    splicing, Lipoprotein
    NM_014011 SOCS5 suppressor of SH2 domain, Growth regulation, 3291 7259
    cytokine signaling 5 Signal transduction inhibitor
    NM_014018 MRPS28 mitochondrial Ribosomal protein, Mitochondrion 3292 7260
    ribosomal protein
    S28
    NM_014029 RAC2 ras-related C3 GTP-binding, Prenylation, 3293 7261
    botulinum toxin Lipoprotein, 3D-structure
    substrate 2 (rho
    family, small GTP
    binding protein
    Rac2)
    NM_014030 GIT1 G protein-coupled Hypothetical protein, GTPase 3294 7262
    receptor kinase- activation, Repeat, ANK repeat,
    interactor 1 Zinc-finger
    NM_014038 BZW2 basic leucine zipper Hypothetical protein 3295 7263
    and W2 domains 2
    NM_014042 DKFZP564M082 DKFZP564M082 Hypothetical protein 3296 7264
    protein
    NM_014050 MRPL42 mitochondrial Ribosomal protein, Mitochondrion 3297 7265
    ribosomal protein
    L42
    NM_014051 PTD011 transmembrane Transmembrane 3298 7266
    protein 14A
    NM_014052 GW128 GW128 protein 3299 7267
    NM_014055 CDV-1 carnitine deficiency- Hypothetical protein 3300 7268
    associated gene
    expressed in
    ventricle 1
    NM_014056 HIG1 likely ortholog of Hypothetical protein 3301 7269
    mouse hypoxia
    induced gene 1
    NM_014060 MCT-1 malignant T cell 3302 7270
    amplified sequence 1
    NM_014061 MAGEH1 APR-1 protein Antigen 3303 7271
    NM_014062 ART-4 likely ortholog of Hypothetical protein 3304 7272
    mouse nin one
    binding protein
    NM_014063 HIP-55 src homology 3 Hypothetical protein, SH3 domain 3305 7273
    domain-containing
    protein HIP-55
    NM_014078 MRPL13 mitochondrial Ribosomal protein, Mitochondrion 3306 7274
    ribosomal protein
    L13
    NM_014080 DUOX2 dual oxidase 2 Peroxidase 3307 7275
    NM_014147 CAPRI HSPC047 protein GTPase activation, Repeat 3308 7276
    NM_014165 C6orf66 chromosome 6 open 3309 7277
    reading frame 66
    NM_014170 HSPC135 HSPC135 protein Hypothetical protein 3310 7278
    NM_014175 MRPL15 mitochondrial Hypothetical protein 3311 7279
    ribosomal protein
    L15
    NM_014177 HSPC154 HSPC154 protein 3312 7280
    NM_014180 MRPL22 mitochondrial Hypothetical protein, Ribosomal 3313 7281
    ribosomal protein protein
    L22
    NM_014182 ORMDL2 ORM1-like 2 (S. cerevisiae) Hypothetical protein, Nuclear 3314 7282
    protein, DNA-binding, Transcription,
    Transcription regulation, Translation
    regulation, Receptor
    NM_014184 HSPC163 HSPC163 protein Hypothetical protein, 3315 7283
    Transmembrane
    NM_014204 BOK Homo sapiens Bcl-2 3316 7284
    related ovarian killer
    (BOK) mRNA,
    complete cds.
    NM_014207 CD5 CD5 antigen (p56-62) Signal, Transmembrane, 3317 7285
    Glycoprotein, T-cell, Repeat
    NM_014214 IMPA2 inositol(myo)-1(or 4)- Hydrolase 3318 7286
    monophosphatase 2
    NM_014216 ITPK1 inositol 1,3,4- Kinase, Hypothetical protein 3319 7287
    triphosphate 5/6
    kinase
    NM_014221 MTCP1 mature T-cell Proto-oncogene, Mitochondrion, 3320 7288
    proliferation 1 Alternative splicing, Chromosomal
    translocation, 3D-structure
    NM_014223 NFYC nuclear transcription Transcription regulation, DNA- 3321 7289
    factor Y, gamma binding, Activator, Nuclear protein,
    Alternative splicing, 3D-structure
    NM_014225 PPP2R1A protein phosphatase Hypothetical protein, Multigene 3322 7290
    2 (formerly 2A), family, Acetylation, Repeat,
    regulatory subunit A Polymorphism, 3D-structure
    (PR 65), alpha
    isoform
    NM_014231 VAMP1 vesicle-associated Mitochondrion, Synapse, 3323 7291
    membrane protein 1 Synaptosome, Transmembrane,
    (synaptobrevin 1) Coiled coil, Alternative splicing,
    Multigene family
    NM_014232 VAMP2 vesicle-associated Hypothetical protein, Synapse, 3324 7292
    membrane protein 2 Synaptosome, Transmembrane,
    (synaptobrevin 2) Coiled coil, Acetylation, Multigene
    family, 3D-structure
    NM_014239 EIF2B2 eukaryotic Initiation factor, Protein biosynthesis, 3325 7293
    translation initiation Disease mutation
    factor 2B, subunit 2
    beta, 39 kDa
    NM_014241 PTPLA protein tyrosine ATP-binding, Chaperone 3326 7294
    phosphatase-like
    (proline instead of
    catalytic arginine),
    member a
    NM_014242 ZNF237 zinc finger protein 3327 7295
    237
    NM_014245 RNF7 ring finger protein 7 Ubl conjugation pathway, Zinc, Zinc- 3328 7296
    finger, Metal-binding,
    Phosphorylation, Alternative splicing
    NM_014252 SLC25A15 solute carrier family Mitochondrion, Inner membrane, 3329 7297
    25 (mitochondrial Repeat, Transmembrane, Transport,
    carrier; ornithine Disease mutation, Polymorphism
    transporter) member
    15
    NM_014253 ODZ1 odz, odd Oz/ten-m EGF-like domain 3330 7298
    homolog
    1(Drosophila)
    NM_014254 TMEM5 transmembrane Transmembrane 3331 7299
    protein 5
    NM_014268 MAPRE2 microtubule- T-cell 3332 7300
    associated protein,
    RP/EB family,
    member 2
    NM_014280 DNAJC8 DnaJ (Hsp40) Chaperone 3333 7301
    homolog, subfamily
    C, member 8
    NM_014292 CBX6 chromobox homolog 6 Chromatin regulator, Nuclear 3334 7302
    protein, Transcription regulation,
    Repressor
    NM_014297 YF13H12 ethylmalonic 3335 7303
    encephalopathy 1
    NM_014306 HSPC117 hypothetical protein Hypothetical protein 3336 7304
    HSPC117
    NM_014313 SMP1 small membrane Transmembrane, Polymorphism 3337 7305
    protein 1
    NM_014326 DAPK2 death-associated Transferase, Serine/threonine- 3338 7306
    protein kinase 2 protein kinase, Calmodulin-binding,
    Phosphorylation, ATP-binding,
    Apoptosis
    NM_014330 PPP1R15A protein phosphatase Hypothetical protein 3339 7307
    1, regulatory
    (inhibitor) subunit
    15A
    NM_014335 CRI1 CREBBP/EP300 Hypothetical protein 3340 7308
    inhibitory protein 1
    NM_014339 IL17R interleukin 17 Receptor, Transmembrane, Signal, 3341 7309
    receptor Glycoprotein
    NM_014341 MTCH1 mitochondrial carrier 3342 7310
    homolog 1 (C. elegans)
    NM_014343 CLDN15 claudin 15 Tight junction, Transmembrane 3343 7311
    NM_014350 GG2-1 TNF-induced protein 3344 7312
    NM_014357 XP5 small proline rich-like 3345 7313
    (epidermal
    differentiation
    complex) 1B
    NM_014359 OPTC opticin Glycoprotein, Extracellular matrix, 3346 7314
    Signal, Repeat, Leucine-rich repeat,
    Sulfation
    NM_014362 HIBCH 3-hydroxyisobutyryl- Hydrolase 3347 7315
    Coenzyme A
    hydrolase
    NM_014366 E2IG3 nucleostemin Hypothetical protein 3348 7316
    NM_014373 GPCR1 G protein-coupled Receptor 3349 7317
    receptor 160
    NM_014381 MLH3 mutL homolog 3 (E. coli) DNA repair, Nuclear protein, 3350 7318
    Polymorphism, Alternative splicing,
    Hereditary nonpolyposis colorectal
    cancer, Disease mutation,
    Hypothetical protein
    NM_014399 NET-6 transmembrane 4 Glycoprotein, Transmembrane 3351 7319
    superfamily member
    13
    NM_014403 SIAT7D sialyltransferase 7D Transferase, Glycosyltransferase, 3352 7320
    ((alpha-N- Glycoprotein, Transmembrane,
    acetylneuraminyl- Signal-anchor, Golgi stack
    2,3-beta-galactosyl-
    1,3)-N-acetyl
    galactosaminide
    alpha-2,6-
    sialyltransferase)
    NM_014413 HRI heme-regulated Transferase, Kinase, 3353 7321
    initiation factor 2- Serine/threonine-protein kinase,
    alpha kinase Protein synthesis inhibitor, ATP-
    binding, Repeat, Phosphorylation,
    Alternative splicing, Polymorphism,
    Protein biosynthesis
    NM_014425 INVS inversin ANK repeat, Repeat 3354 7322
    NM_014426 SNX5 sorting nexin 5 Transport, Protein transport, 3355 7323
    Hypothetical protein
    NM_014430 CIDEB cell death-inducing Apoptosis, 3D-structure, RNA- 3356 7324
    DFFA-like effector b binding, Repeat, G-protein coupled
    receptor, Transmembrane,
    Glycoprotein
    NM_014434 NR1 NADPH-dependent 3357 7325
    FMN and FAD
    containing
    oxidoreductase
    NM_014437 SLC39A1 solute carrier family Transport, Zinc transport, 3358 7326
    39 (zinc transporter), Transmembrane
    member 1
    NM_014446 MIBP integrin beta 1 3359 7327
    binding protein 3
    NM_014450 SIT SHP2-interacting Signal 3360 7328
    transmembrane
    adaptor protein
    NM_014453 BC-2 putative breast 3361 7329
    adenocarcinoma
    marker (32 kD)
    NM_014465 SULT1B1 sulfotransferase Hypothetical protein, Transferase 3362 7330
    family, cytosolic, 1B,
    member 1
    NM_014473 HSA9761 putative rRNA processing, Transferase, 3363 7331
    dimethyladenosine Methyltransferase
    transferase
    NM_014481 APEX2 APEX nuclease Endonuclease 3364 7332
    (apurinic/apyrimidinic
    endonuclease) 2
    NM_014499 P2RY10 purinergic receptor Receptor, Transmembrane 3365 7333
    P2Y, G-protein
    coupled, 10
    NM_014503 DRIM down-regulated in 3366 7334
    metastasis
    NM_014517 UBP1 upstream binding Hypothetical protein 3367 7335
    protein 1 (LBP-1a)
    NM_014520 MYBBP1A MYB binding protein Hypothetical protein 3368 7336
    (P160) 1a
    NM_014575 SCHIP1 schwannomin Hypothetical protein 3369 7337
    interacting protein 1
    NM_014593 CGBP CpG binding protein Hypothetical protein, Transcription 3370 7338
    regulation, Activator, DNA-binding,
    Zinc-finger, Metal-binding, Coiled
    coil, Nuclear protein
    NM_014624 S100A6 S100 calcium Mitogen, Cell cycle, Calcium-binding, 3371 7339
    binding protein A6 Polymorphism, 3D-structure
    (calcyclin)
    NM_014630 KIAA0211 KIAA0211 gene Hypothetical protein, Transcription 3372 7340
    product regulation, DNA-binding, Zinc-finger,
    Metal-binding, Nuclear protein,
    Repeat
    NM_014638 KIAA0450 KIAA0450 gene Hypothetical protein 3373 7341
    product
    NM_014639 KIAA0372 KIAA0372 Hypothetical protein 3374 7342
    NM_014659 KIAA0377 KIAA0377 gene Hypothetical protein 3375 7343
    product
    NM_014671 KIAA0010 ubiquitin-protein Hypothetical protein, Ligase 3376 7344
    isopeptide ligase
    (E3)
    NM_014675 KIAA0445 ciliary rootlet coiled- Hypothetical protein 3377 7345
    coil, rootletin
    NM_014678 KIAA0685 KIAA0685 Hypothetical protein 3378 7346
    NM_014684 KIAA0373 KIAA0373 gene Hypothetical protein, Coiled coil 3379 7347
    product
    NM_014685 HERPUD1 homocysteine- Hypothetical protein, Unfolded 3380 7348
    inducible, protein response, Endoplasmic
    endoplasmic reticulum, Transmembrane,
    reticulum stress- Alternative splicing
    inducible, ubiquitin-
    like domain member 1
    NM_014688 RNTRE USP6 N-terminal like Hypothetical protein 3381 7349
    NM_014698 KIAA0792 KIAA0792 gene Hypothetical protein 3382 7350
    product
    NM_014699 KIAA0296 KIAA0296 gene Hypothetical protein, Transcription 3383 7351
    product regulation, DNA-binding, Zinc-finger,
    Metal-binding, Nuclear protein,
    Repeat
    NM_014707 HDAC9 histone deacetylase 9 Hydrolase, Nuclear protein, 3384 7352
    Chromatin regulator, Transcription
    regulation, Repressor, Alternative
    splicing, Hypothetical protein
    NM_014710 KIAA0443 G protein-coupled Hypothetical protein 3385 7353
    receptor-associated
    sorting protein
    NM_014716 CENTB1 centaurin, beta 1 GTPase activation, Repeat, ANK 3386 7354
    repeat, Zinc-finger
    NM_014718 CLSTN3 calsyntenin 3 Cell adhesion, Glycoprotein, 3387 7355
    Transmembrane, Calcium-binding,
    Repeat, Signal
    NM_014724 ZNF305 zinc finger protein Transcription regulation, DNA- 3388 7356
    305 binding, Zinc-finger, Metal-binding,
    Nuclear protein, Repeat
    NM_014727 WBP7 myeloid/lymphoid or DNA-binding, Bromodomain, 3389 7357
    mixed-lineage Nuclear protein, Zinc-finger, Metal-
    leukemia 4 binding, Transcription regulation,
    Alternative splicing, Repeat
    NM_014729 TOX thymus high mobility Hypothetical protein 3390 7358
    group box protein
    TOX
    NM_014732 KIAA0513 KIAA0513 gene Hypothetical protein 3391 7359
    product
    NM_014735 KIAA0215 PHD finger protein Zinc-finger 3392 7360
    16
    NM_014737 RASSF2 Ras association Hypothetical protein 3393 7361
    (RaIGDS/AF-6)
    domain family 2
    NM_014739 BTF Bcl-2-associated Hypothetical protein 3394 7362
    transcription factor
    NM_014740 KIAA0111 DEAD (Asp-Glu-Ala- ATP-binding, RNA-binding, DNA- 3395 7363
    Asp) box polypeptide binding, Helicase, Nuclear protein,
    48 rRNA processing
    NM_014750 DLG7 discs, large homolog Hypothetical protein 3396 7364
    7 (Drosophila)
    NM_014751 MTSS1 metastasis Cytoskeleton, Actin-binding, Coiled 3397 7365
    suppressor 1 coil, Anti-oncogene, Alternative
    splicing
    NM_014753 KIAA0187 BMS1-like, ribosome Ribosome biogenesis, Nuclear 3398 7366
    assembly protein protein, ATP-binding
    (yeast)
    NM_014763 MRPL19 mitochondrial Ribosomal protein, Mitochondrion, 3399 7367
    ribosomal protein Transit peptide
    L19
    NM_014764 DAZAP2 DAZ associated Hypothetical protein 3400 7368
    protein 2
    NM_014765 TOMM20- translocase of outer Transport, Protein transport, Outer 3401 7369
    PENDING mitochondrial membrane, Mitochondrion,
    membrane 20 Transmembrane
    homolog (yeast)
    NM_014767 SPOCK2 sparc/osteonectin, Extracellular matrix, Proteoglycan, 3402 7370
    cwcv and kazal-like Heparan sulfate, Glycoprotein,
    domains Calcium-binding, Signal
    proteoglycan
    (testican) 2
    NM_014776 GIT2 G protein-coupled GTPase activation, Repeat, ANK 3403 7371
    receptor kinase- repeat, Zinc-finger, Alternative
    interactor
    2 splicing, Hypothetical protein
    NM_014792 KIAA0125 KIAA0125 Hypothetical protein 3404 7372
    NM_014807 KIAA0285 KIAA0285 gene Hypothetical protein 3405 7373
    product
    NM_014808 FARP2 FERM, RhoGEF and Hypothetical protein 3406 7374
    pleckstrin domain
    protein
    2
    NM_014815 TRAP100 thyroid hormone Transcription regulation, Zinc-finger, 3407 7375
    receptor-associated Repeat, ATP-binding, Nuclear
    protein (100 kDa) protein
    NM_014820 TOMM70A translocase of outer Mitochondrion, Outer membrane, 3408 7376
    mitochondrial Transmembrane, Repeat, TPR
    membrane
    70 repeat
    homolog A (yeast)
    NM_014830 KIAA0352 KIAA0352 gene Hypothetical protein, Transcription 3409 7377
    product regulation, DNA-binding, Zinc-finger,
    Metal-binding, Nuclear protein,
    Repeat
    NM_014835 OSBPL2 oxysterol binding Lipid transport, Transport, 3410 7378
    protein-like 2 Alternative splicing
    NM_014838 ZBED4 zinc finger, BED Repeat, Zinc-finger 3411 7379
    domain containing 4
    NM_014844 KIAA0329 KIAA0329 Hypothetical protein 3412 7380
    NM_014846 KIAA0196 KIAA0196 gene Hypothetical protein 3413 7381
    product
    NM_014861 KIAA0703 KIAA0703 gene Hydrolase, Calcium transport, 3414 7382
    product Transmembrane, Phosphorylation,
    ATP-binding, Metal-binding,
    Magnesium, Calcium-binding,
    Multigene family
    NM_014863 GALNAC4S- B cell RAG Hypothetical protein, Transferase 3415 7383
    6ST associated protein
    NM_014865 CNAP1 chromosome DNA condensation, Mitosis, Cell 3416 7384
    condensation-related cycle, Nuclear protein,
    SMC-associated Phosphorylation
    protein
    1
    NM_014869 KIAA0763 KIAA0763 gene Hypothetical protein 3417 7385
    product
    NM_014872 KIAA0354 zinc finger and BTB Hypothetical protein, Metal-binding, 3418 7386
    domain containing 5 Zinc, Zinc-finger
    NM_014873 KIAA0205 KIAA0205 gene Hypothetical protein, Phospholipid 3419 7387
    product biosynthesis, Transferase,
    Acyltransferase, Transmembrane
    NM_014874 MFN2 mitofusin 2 Hypothetical protein 3420 7388
    NM_014878 KIAA0020 minor Hypothetical protein, RNA-binding, 3421 7389
    histocompatibility Repeat, Nuclear protein
    antigen HA-8
    NM_014882 KIAA0053 KIAA0053 gene Hypothetical protein 3422 7390
    product
    NM_014886 YR-29 TGF beta-inducible Nuclear protein 3423 7391
    nuclear protein 1
    NM_014888 FAM3C family with sequence Signal 3424 7392
    similarity 3, member C
    NM_014889 PITRM1 pitrilysin Metalloprotease, Protease, 3425 7393
    metalloproteinase 1 Hypothetical protein
    NM_014897 KIAA0924 KIAA0924 protein Hypothetical protein, Metal-binding, 3426 7394
    Nuclear protein, Zinc, Zinc-finger
    NM_014899 RHOBTB3 Rho-related BTB Repeat 3427 7395
    domain containing 3
    NM_014902 KIAA0964 disks large- Membrane, Alternative splicing 3428 7396
    associated protein 4
    NM_014907 KIAA0967 KIAA0967 protein Hypothetical protein 3429 7397
    NM_014913 KIAA0863 KIAA0863 protein Hypothetical protein, Metal-binding, 3430 7398
    Zinc, Zinc-finger
    NM_014915 KIAA1074 KIAA1074 protein ANK repeat, Repeat, Hypothetical 3431 7399
    protein
    NM_014929 KIAA0971 KIAA0971 protein Hypothetical protein 3432 7400
    NM_014931 KIAA1115 KIAA1115 protein Hypothetical protein 3433 7401
    NM_014937 SAC2 inositol Hypothetical protein 3434 7402
    polyphosphate-5-
    phosphatase F
    NM_014940 KIAA0872 HSV-1 stimulation- Hypothetical protein 3435 7403
    related gene 1
    NM_014944 CLSTN1 calsyntenin 1 Cell adhesion, Glycoprotein, 3436 7404
    Transmembrane, Calcium-binding,
    Repeat, Signal
    NM_014947 KIAA1041 KIAA1041 protein Hypothetical protein, Transcription 3437 7405
    regulation, DNA-binding, Nuclear
    protein
    NM_014949 KIAA0907 KIAA0907 protein Hypothetical protein 3438 7406
    NM_014953 DIS3 mitotic control Exosome, Hydrolase, Nuclease, 3439 7407
    protein dis3 homolog Exonuclease, rRNA processing,
    Nuclear protein, RNA-binding,
    Hypothetical protein
    NM_014965 KIAA1042 OGT(O-Glc-NAc Glycoprotein, Coiled coil, 3440 7408
    transferase)- Hypothetical protein
    interacting protein
    106 KDa
    NM_014966 DDX30 DEAH (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 3441 7409
    His) box polypeptide Hypothetical protein
    30
    NM_014967 KIAA1018 KIAA1018 protein Hypothetical protein 3442 7410
    NM_014977 ACINUS apoptotic chromatin Apoptosis, Nuclear protein, 3443 7411
    condensation Alternative splicing
    inducer in the
    nucleus
    NM_015057 KIAA0916 protein associated Hypothetical protein 3444 7412
    with Myc
    NM_015156 RCOR REST corepressor DNA-binding, Nuclear protein, 3445 7413
    Hypothetical protein
    NM_015239 AGTPBP1 ATP/GTP binding Hypothetical protein 3446 7414
    protein 1
    NM_015310 EFA6R ADP-ribosylation Hypothetical protein, Guanine- 3447 7415
    factor guanine nucleotide releasing factor
    nucleotide factor
    6
    NM_015361 R3HDM R3H domain (binds Hypothetical protein 3448 7416
    single-stranded
    nucleic acids)
    containing
    NM_015368 PANX1 pannexin 1 Gap junction, Transmembrane, 3449 7417
    Polymorphism
    NM_015379 BRI3 brain protein I3 Transmembrane 3450 7418
    NM_015383 DJ328E19.C1.1 hypothetical protein Hypothetical protein 3451 7419
    DJ328E19.C1.1
    NM_015392 NPDC1 neural proliferation, Hypothetical protein, Signal, 3452 7420
    differentiation and Transmembrane
    control, 1
    NM_015400 DKFZP586N0721 DKFZP586N0721 Hypothetical protein 3453 7421
    protein
    NM_015420 DKFZP564O0463 DKFZP564O0463 Repeat, WD repeat, Mitochondrion, 3454 7422
    protein Inner membrane, Transmembrane,
    Transport, Hypothetical protein
    NM_015462 DKFZP586L0724 DKFZP586L0724 Hypothetical protein 3455 7423
    protein
    NM_015492 DKFZP434H132 DKFZP434H132 Hypothetical protein 3456 7424
    protein
    NM_015515 KRT23 keratin 23 (histone Hypothetical protein, Intermediate 3457 7425
    deacetylase filament, Coiled coil, Keratin
    inducible)
    NM_015524 C6orf4 chromosome 6 open Alternative splicing 3458 7426
    reading frame 4
    NM_015527 DKFZP434P1750 DKFZP434P1750 Hypothetical protein 3459 7427
    protein
    NM_015530 GORASP2 golgi reassembly Hypothetical protein 3460 7428
    stacking protein 2,
    55 kDa
    NM_015556 KIAA0440 signal-induced Hypothetical protein 3461 7429
    proliferation-
    associated 1 like 1
    NM_015599 PGM3 phosphoglucomutase 3 Hypothetical protein, Isomerase, 3462 7430
    Phosphorylation, Polymorphism
    NM_015610 DKFZP434J154 DKFZP434J154 Repeat, WD repeat, Hypothetical 3463 7431
    protein protein
    NM_015629 PRPF31 TCF3 (E2A) fusion Hypothetical protein 3464 7432
    partner (in childhood
    Leukemia)
    NM_015640 PAI-RBP1 PAI-1 mRNA-binding Hypothetical protein 3465 7433
    protein
    NM_015644 ARPC4 actin related protein Cytoskeleton, Hypothetical protein, 3466 7434
    2/3 complex, subunit Ligase
    4, 20 kDa
    NM_015654 DKFZP564C103 DKFZP564C103 Hypothetical protein 3467 7435
    protein
    NM_015684 ATP5S ATP synthase, H+ Hydrogen ion transport, CF(0), 3468 7436
    transporting, Mitochondrion, Transit peptide,
    mitochondrial F0 Hypothetical protein
    complex, subunit s
    (factor B)
    NM_015696 CL683 glutathione Hypothetical protein, 3469 7437
    peroxidase 6 Oxidoreductase, Peroxidase, Signal
    NM_015699 DJ159A19.3 hypothetical protein Hypothetical protein 3470 7438
    DJ159A19.3
    NM_015711 GLTSCR1 glioma tumor 3471 7439
    suppressor
    candidate region
    gene
    1
    NM_015722 CALCYON calcyon protein Transmembrane, Glycoprotein 3472 7440
    NM_015836 WARS2 tryptophanyl tRNA Aminoacyl-tRNA synthetase, Protein 3473 7441
    synthetase 2 biosynthesis, Ligase, ATP-binding,
    (mitochondrial) Mitochondrion, Transit peptide
    NM_015838 FCN2 ficolin Lectin, Collagen, Repeat, 3474 7442
    (collagen/fibrinogen Glycoprotein, Signal, Multigene
    domain containing family
    lectin) 2 (hucolin)
    NM_015839 FCN2 ficolin Lectin, Collagen, Repeat, 3475 7443
    (collagen/fibrinogen Glycoprotein, Signal, Multigene
    domain containing family
    lectin) 2 (hucolin)
    NM_015853 LOC51035 ORF Hypothetical protein 3476 7444
    NM_015855 WIT-1 Wilms tumor Polymorphism 3477 7445
    associated protein
    NM_015868 KIR2DL3 killer cell Receptor, Immunoglobulin domain, 3478 7446
    immunoglobulin-like Glycoprotein, Signal,
    receptor, two Transmembrane, Repeat, Multigene
    domains, long family, Polymorphism, 3D-structure,
    cytoplasmic tail, 3 Alternative splicing
    NM_015872 ZFP67 zinc finger protein 67 Metal-binding, Zinc, Zinc-finger 3479 7447
    homolog (mouse)
    NM_015905 TIF1 transcriptional Elongation factor, Protein 3480 7448
    intermediary factor 1 biosynthesis, GTP-binding,
    Methylation, Multigene family,
    Transcription regulation, Repressor,
    DNA-binding, Bromodomain, Zinc-
    finger, Alternative splicing, Nuclear
    protein, Coiled coil, Repeat
    NM_015907 LAP3 leucine Hydrolase, Aminopeptidase, 3481 7449
    aminopeptidase 3 Acetylation, Zinc, Magnesium,
    Manganese
    NM_015908 ARS2 arsenate resistance Hypothetical protein, Alternative 3482 7450
    protein ARS2 splicing
    NM_015932 C13orf12 chromosome 13 Hypothetical protein 3483 7451
    open reading frame
    12
    NM_015942 LOC51001 CGI-12 protein Hypothetical protein 3484 7452
    NM_015945 OVCOV1 solute carrier family Hypothetical protein 3485 7453
    35, member C2
    NM_015956 MRPL4 mitochondrial Ribosomal protein 3486 7454
    ribosomal protein L4
    NM_015958 LOC51611 CGI-30 protein Transferase, Methyltransferase, 3487 7455
    Alternative splicing, Hypothetical
    protein
    NM_015959 LOC51075 thioredoxin-related Hypothetical protein 3488 7456
    transmembrane
    protein
    2
    NM_015963 LOC51078 THAP domain Zinc-finger, DNA-binding 3489 7457
    containing 4
    NM_015967 PTPN22 protein tyrosine Hydrolase, Alternative splicing, 3490 7458
    phosphatase, non- Hypothetical protein
    receptor type 22
    (lymphoid)
    NM_015971 MRPS7 mitochondrial Ribosomal protein 3491 7459
    ribosomal protein S7
    NM_015984 UCHL5 ubiquitin carboxyl- Hypothetical protein, Ubl conjugation 3492 7460
    terminal hydrolase pathway, Hydrolase, Thiol protease,
    L5 Proteasome, Alternative splicing,
    Polymorphism
    NM_015999 LOC51094 adiponectin receptor 1 Fatty acid metabolism, Lipid 3493 7461
    metabolism, Receptor,
    Transmembrane
    NM_016006 CGI-58 abhydrolase domain Hypothetical protein 3494 7462
    containing 5
    NM_016017 UCHL5 ubiquitin carboxyl- Hypothetical protein, Hydrolase, Ubl 3495 7463
    terminal hydrolase conjugation pathway, Thiol protease,
    L5 Proteasome, Alternative splicing,
    Polymorphism
    NM_016022 LOC51107 likely ortholog of C. elegans Transmembrane, Golgi stack, 3496 7464
    anterior Endoplasmic reticulum, Alternative
    pharynx defective 1A splicing
    NM_016026 RDH11 retinol Oxidoreductase, NADP, Signal- 3497 7465
    dehydrogenase 11 anchor, Transmembrane,
    (all-trans and 9-cis) Endoplasmic reticulum, Alternative
    splicing
    NM_016039 LOC51637 chromosome 14 Hypothetical protein 3498 7466
    open reading frame
    166
    NM_016045 C20orf45 chromosome 20 3499 7467
    open reading frame
    45
    NM_016052 LOC51018 CGI-115 protein 3500 7468
    NM_016055 MRPL48 mitochondrial Ribosomal protein, Mitochondrion 3501 7469
    ribosomal protein
    L48
    NM_016056 LOC51643 CGI-119 protein Transmembrane, Polymorphism 3502 7470
    NM_016058 LOC51002 CGI-121 protein 3503 7471
    NM_016064 PILB methionine sulfoxide Hypothetical protein 3504 7472
    reductase B
    NM_016072 LOC51026 CGI-141 protein Hypothetical protein, 3505 7473
    Transmembrane
    NM_016075 C13orf9 chromosome 13 Hypothetical protein 3506 7474
    open reading frame 9
    NM_016082 CDK5RAP1 CDK5 regulatory Alternative splicing 3507 7475
    subunit associated
    protein 1
    NM_016093 RPL26L1 ribosomal protein Ribosomal protein 3508 7476
    L26-like 1
    NM_016096 LOC51123 HSPC038 protein Metal-binding, Zinc, Zinc-finger 3509 7477
    NM_016101 HSPC031 comparative gene Hypothetical protein 3510 7478
    identification
    transcript 37
    NM_016120 RNF12 ring finger protein 12 Hypothetical protein, Metal-binding, 3511 7479
    Zinc, Zinc-finger, Transcription
    regulation
    NM_016122 LOC51134 NY-REN-58 antigen 3512 7480
    NM_016126 LOC51668 HSPCO34 protein 3513 7481
    NM_016127 MGC8721 hypothetical protein Hypothetical protein 3514 7482
    MGC8721
    NM_016129 COPS4 COP9 constitutive Hypothetical protein 3515 7483
    photomorphogenic
    homolog subunit 4
    (Arabidopsis)
    NM_016143 NSFL1C NSFL1 (p97) Hypothetical protein 3516 7484
    cofactor (p47)
    NM_016167 RANBP9 retinoic acid Hypothetical protein 3517 7485
    repressible protein
    NM_016175 SQSTM1 truncated calcium Hypothetical protein 3518 7486
    binding protein
    NM_016183 C1orf33 chromosome 1 open Hypothetical protein, Ribosomal 3519 7487
    reading frame 33 protein
    NM_016184 CLECSF6 C-type (calcium Receptor, Lectin 3520 7488
    dependent,
    carbohydrate-
    recognition domain)
    lectin, superfamily
    member
    6
    NM_016187 BIN2 bridging integrator 2 Hypothetical protein 3521 7489
    NM_016194 GNB5 guanine nucleotide Repeat, WD repeat, Transducer, 3522 7490
    binding protein (G Alternative splicing, Multigene family,
    protein), beta 5 Hypothetical protein
    NM_016199 LSM7 LSM7 homolog, U6 Nuclear protein, Ribonucleoprotein, 3523 7491
    small nuclear RNA mRNA splicing, mRNA processing,
    associated (S. cerevisiae) RNA-binding
    NM_016202 LOC51157 LDL induced EC Metal-binding, Zinc, Zinc-finger 3524 7492
    protein
    NM_016207 CPSF3 cleavage and mRNA processing, Nuclear protein, 3525 7493
    polyadenylation RNA-binding
    specific factor 3,
    73 kDa
    NM_016208 VPS28 vacuolar protein Transport, Protein transport 3526 7494
    sorting 28 (yeast)
    NM_016214 COL18A1 collagen, type XVIII, Collagen, Extracellular matrix, 3527 7495
    alpha 1 Connective tissue, Repeat,
    Hydroxylation, Cell adhesion,
    Glycoprotein, Signal, Alternative
    splicing, Polymorphism, 3D-structure
    NM_016221 DCTN4 dynactin 4 (p62) Hypothetical protein 3528 7496
    NM_016229 LOC51700 cytochrome b5 Hypothetical protein 3529 7497
    reductase b5R.2
    NM_016237 ANAPC5 anaphase promoting Ubl conjugation pathway, Cell cycle, 3530 7498
    complex subunit 5 Cell division, Mitosis, Repeat, TPR
    repeat, Alternative splicing
    NM_016258 HGRG8 high-glucose- 3531 7499
    regulated protein 8
    NM_016271 RNF138 ring finger protein Hypothetical protein, Metal-binding, 3532 7500
    138 Zinc, Zinc-finger
    NM_016274 CKIP-1 CK2 interacting Hypothetical protein 3533 7501
    protein 1; HQ0024c
    protein
    NM_016283 TAF9 TAF9 RNA ATP-binding, Transcription 3534 7502
    polymerase II, TATA regulation, Nuclear protein,
    box binding protein Polymorphism, Hypothetical protein,
    (TBP)-associated Cell cycle
    factor, 32 kDa
    NM_016293 BIN2 bridging integrator 2 Hypothetical protein 3535 7503
    NM_016299 HSP70-4 likely ortholog of ATP-binding 3536 7504
    mouse heat shock
    protein, 70 kDa 4
    NM_016304 C15orf15 chromosome 15 Ribosomal protein 3537 7505
    open reading frame
    15
    NM_016306 DNAJB11 DnaJ (Hsp40) Chaperone, Endoplasmic reticulum, 3538 7506
    homolog, subfamily Signal, Polymorphism
    B, member 11
    NM_016309 LCMT1 leucine carboxyl Hypothetical protein, 3539 7507
    methyltransferase 1 Methyltransferase, Transferase
    NM_016312 WBP11 WW domain binding Hypothetical protein 3540 7508
    protein 11
    NM_016316 REV1L REV1-like (yeast) Transferase, Integrin, Hypothetical 3541 7509
    protein
    NM_016326 CKLF chemokine-like Chemotaxis, Cytokine, 3542 7510
    factor Transmembrane, Alternative splicing
    NM_016327 UPB1 ureidopropionase, Hydrolase, Allosteric enzyme, Zinc 3543 7511
    beta
    NM_016331 LOC51193 zinc finger protein Metal-binding, Zinc, Zinc-finger 3544 7512
    ANC_2H01
    NM_016332 SEPX1 selenoprotein X, 1 Oxidoreductase, Metal-binding, Zinc, 3545 7513
    Selenium, Selenocysteine
    NM_016333 SRRM2 serine/arginine Hypothetical protein 3546 7514
    repetitive matrix 2
    NM_016334 SH120 putative G-protein Receptor 3547 7515
    coupled receptor
    NM_016354 SLC21A12 solute carrier organic Transmembrane, Transport, Ion 3548 7516
    anion transporter transport, Glycoprotein, Alternative
    family, member 4A1 splicing
    NM_016355 LOC51202 DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 3549 7517
    Asp) box polypeptide Hypothetical protein
    47
    NM_016362 GHRL ghrelin precursor Hormone, Cleavage on pair of basic 3550 7518
    residues, Signal, Lipoprotein,
    Alternative splicing
    NM_016364 DUSP13 dual specificity Hydrolase 3551 7519
    phosphatase 13
    NM_016373 WWOX WW domain Oxidoreductase 3552 7520
    containing
    oxidoreductase
    NM_016377 AKAP7 A kinase (PRKA) Membrane, Myristate, Palmitate, 3553 7521
    anchor protein 7 Lipoprotein, Alternative splicing
    NM_016381 TREX1 three prime repair Exonuclease, Hypothetical protein 3554 7522
    exonuclease 1
    NM_016385 CYLD cylindromatosis Hypothetical protein 3555 7523
    (turban tumor
    syndrome)
    NM_016387 HSPC060 hypothetical protein 3556 7524
    HSPC060
    NM_016391 HSPC111 hypothetical protein Hypothetical protein, Nuclear protein 3557 7525
    HSPC111
    NM_016397 TH1L TH1-like Transcription regulation, Repressor, 3558 7526
    (Drosophila) Nuclear protein, Alternative splicing,
    Alternative initiation
    NM_016399 HSPC132 hypothetical protein Hypothetical protein 3559 7527
    HSPC132
    NM_016403 HSPC148 hypothetical protein Hypothetical protein 3560 7528
    HSPC148
    NM_016407 C20orf43 chromosome 20 Alternative splicing 3561 7529
    open reading frame
    43
    NM_016418 NF2 neurofibromin 2 Structural protein, Cytoskeleton, 3562 7530
    (bilateral acoustic Anti-oncogene, Disease mutation,
    neuroma) Alternative splicing, Deafness, 3D-
    structure
    NM_016424 LUC7A cisplatin resistance- Phosphorylation, Hypothetical 3563 7531
    associated protein
    overexpressed
    protein
    NM_016431 MAPK8IP2 mitogen-activated SH3 domain, Alternative splicing 3564 7532
    protein kinase 8
    interacting protein 2
    NM_016441 CRIM1 cysteine-rich motor Signal 3565 7533
    neuron 1
    NM_016463 HSPC195 hypothetical protein Hypothetical protein 3566 7534
    HSPC195
    NM_016465 LOC51238 blocked early in Hypothetical protein 3567 7535
    transport 1 homolog
    (S. cerevisiae) like
    NM_016468 C14orf112 chromosome 14 Hypothetical protein 3568 7536
    open reading frame
    112
    NM_016477 FOXP1 forkhead box P1 Hypothetical protein, Transcription 3569 7537
    regulation, DNA-binding, Zinc-finger,
    Metal-binding, Nuclear protein,
    Alternative splicing
    NM_016479 SCOTIN scotin Hypothetical protein 3570 7538
    NM_016501 FLJ10597 hypothetical protein Hypothetical protein 3571 7539
    FLJ10597
    NM_016503 MRPL30 mitochondrial Hypothetical protein 3572 7540
    ribosomal protein
    L30
    NM_016507 CRK7 CDC2-related Transferase, Serine/threonine- 3573 7541
    protein kinase 7 protein kinase, ATP-binding, Nuclear
    protein
    NM_016524 LOC51760 B/K protein Hypothetical protein 3574 7542
    NM_016533 NINJ2 ninjurin 2 Cell adhesion, Transmembrane 3575 7543
    NM_016538 SIRT7 sirtuin (silent mating Hydrolase, NAD, Metal-binding, 3576 7544
    type information Zinc, Alternative splicing
    regulation
    2
    homolog) 7 (S. cerevisiae)
    NM_016565 E2IG2 E2IG2 protein 3577 7545
    NM_016567 BCCIP BRCA2 and Helicase, Hypothetical protein 3578 7546
    CDKN1A interacting
    protein
    NM_016572 USP21 ubiquitin specific Hypothetical protein, Ubl conjugation 3579 7547
    protease 21 pathway, Hydrolase, Thiol protease,
    Multigene family
    NM_016573 LOC51291 Gem-interacting 3580 7548
    protein
    NM_016574 DRD2 dopamine receptor G-protein coupled receptor, 3581 7549
    D2 Transmembrane, Glycoprotein,
    Multigene family, Alternative splicing,
    Disease mutation, Polymorphism,
    3D-structure
    NM_016582 FLJ20539 solute carrier family Hypothetical protein 3582 7550
    15, member 3
    NM_016594 FKBP11 FK506 binding Isomerase, Rotamase, Signal 3583 7551
    protein 11, 19 kDa
    NM_016598 ZDHHC3 zinc finger, DHHC Transmembrane, Golgi stack, Zinc- 3584 7552
    domain containing 3 finger, Alternative splicing
    NM_016603 C5orf5 chromosome 5 open GTPase activation 3585 7553
    reading frame 5
    NM_016608 ALEX1 ALEX1 protein Hypothetical protein 3586 7554
    NM_016610 TLR8 toll-like receptor 8 Hypothetical protein, Receptor, 3587 7555
    Immune response, Inflammatory
    response, Signal, Transmembrane,
    Repeat, Leucine-rich repeat,
    Glycoprotein
    NM_016612 MSCP mitochondrial solute Hypothetical protein 3588 7556
    carrier protein
    NM_016616 TXNDC3 thioredoxin domain Redox-active center 3589 7557
    containing 3
    (spermatozoa)
    NM_016619 PLAC8 placenta-specific 8 3590 7558
    NM_016623 BM-009 hypothetical protein Hypothetical protein 3591 7559
    BM-009
    NM_016626 LOC51320 hypothetical protein Metal-binding, Zinc, Zinc-finger 3592 7560
    LOC51320
    NM_016630 ACP33 acid cluster protein Hypothetical protein 3593 7561
    33
    NM_016639 TNFRSF12A tumor necrosis factor Receptor, Angiogenesis, Apoptosis, 3594 7562
    receptor superfamily, Transmembrane, Signal, Alternative
    member 12A splicing
    NM_016640 MRPS30 mitochondrial Ribosomal protein, Mitochondrion 3595 7563
    ribosomal protein
    S30
    NM_016733 LIMK2 LIM domain kinase 2 Transferase, Serine/threonine- 3596 7564
    protein kinase, ATP-binding, Repeat,
    LIM domain, Metal-binding, Zinc,
    Kinase, Tyrosine-protein kinase,
    Hypothetical protein
    NM_016826 OGG1 8-oxoguanine DNA Hydrolase, Nuclease, Endonuclease, 3597 7565
    glycosylase Lyase, DNA repair, Glycosidase,
    Multifunctional enzyme, Nuclear
    protein, Mitochondrion, Alternative
    splicing, Polymorphism, 3D-
    structure, Transferase,
    Serine/threonine-protein kinase,
    Calmodulin-binding,
    Phosphorylation,
    NM_016827 OGG1 8-oxoguanine DNA Hydrolase, Nuclease, Endonuclease, 3598 7566
    glycosylase Lyase, DNA repair, Glycosidase,
    Multifunctional enzyme, Nuclear
    protein, Mitochondrion, Alternative
    splicing, Polymorphism, 3D-
    structure, Transferase,
    Serine/threonine-protein kinase,
    Calmodulin-binding,
    Phosphorylation,
    NM_016836 RBMS1 RNA binding motif, DNA-binding, DNA replication, RNA- 3599 7567
    single stranded binding, Nuclear protein,
    interacting protein 1 Phosphorylation
    NM_016839 RBMS1 RNA binding motif, DNA-binding, DNA replication, RNA- 3600 7568
    single stranded binding, Nuclear protein,
    interacting protein 1 Phosphorylation
    NM_016936 UBN1 ubinuclein 1 3601 7569
    NM_016951 CKLF chemokine-like Chemotaxis, Cytokine, 3602 7570
    factor Transmembrane, Alternative splicing
    NM_017409 HOXC10 homeo box C10 Homeobox, DNA-binding, 3603 7571
    Developmental protein, Nuclear
    protein, Transcription regulation
    NM_017414 USP18 ubiquitin specific Ubl conjugation pathway, Hydrolase, 3604 7572
    protease 18 Thiol protease, Multigene family
    NM_017415 KLHL3 kelch-like 3 Cytoskeleton, Actin-binding, Kelch 3605 7573
    (Drosophila) repeat, Repeat, Alternative splicing
    NM_017421 COQ3 coenzyme Q3 Transferase 3606 7574
    homolog,
    methyltransferase
    (yeast)
    NM_017424 CECR1 cat eye syndrome Hydrolase, Signal, Hypothetical 3607 7575
    chromosome region, protein
    candidate
    1
    NM_017426 NUP54 nucleoporin 54 kDa Hypothetical protein, Transport, 3608 7576
    Nuclear protein, Repeat,
    Glycoprotein, Alternative splicing
    NM_017451 BAIAP2 BAI1-associated Receptor, SH3 domain, Hypothetical 3609 7577
    protein 2 protein, ATP-binding, Transferase
    NM_017455 SDFR1 stromal cell derived Immunoglobulin domain, 3610 7578
    factor receptor 1 Hypothetical protein, Receptor
    NM_017456 PSCD1 pleckstrin homology, Guanine-nucleotide releasing factor, 3611 7579
    Sec7 and coiled-coil Coiled coil, Alternative splicing, 3D-
    domains 1(cytohesin structure
    1)
    NM_017491 WDR1 WD repeat domain 1 Repeat, WD repeat, Hypothetical 3612 7580
    protein, Actin-binding, Cytoskeleton,
    Alternative splicing, Polymorphism
    NM_017493 HSHIN1 HIV-1 induced 3613 7581
    protein HIN-1
    NM_017535 DKFZp566H0824 hypothetical protein Hypothetical protein 3614 7582
    DKFZp566H0824
    NM_017544 NRF NF-kappa B- Transcription regulation, Repressor, 3615 7583
    repressing factor DNA-binding, Nuclear protein
    NM_017546 C40 hypothetical protein Hypothetical protein 3616 7584
    C40
    NM_017555 EGLN2 egl nine homolog 2 Oxidoreductase, Dioxygenase, 3617 7585
    (C. elegans) Nuclear protein, Iron, Vitamin C
    NM_017567 NAGK N-acetylglucosamine Kinase, Transferase, ATP-binding, 3618 7586
    kinase Phosphorylation, Hypothetical
    protein
    NM_017571 LOC55580 hypothetical protein Hypothetical protein 3619 7587
    LOC55580
    NM_017572 MKNK2 MAP kinase- Hypothetical protein, ATP-binding, 3620 7588
    interacting Kinase, Serine/threonine-protein
    serine/threonine kinase, Transferase, Translation
    kinase
    2 regulation, Phosphorylation,
    Alternative splicing
    NM_017596 KIAA0449 KIAA0449 protein Hypothetical protein, Repeat, WD 3621 7589
    repeat
    NM_017622 FLJ20014 hypothetical protein Hypothetical protein 3622 7590
    FLJ20014
    NM_017631 FLJ20035 hypothetical protein Hypothetical protein 3623 7591
    FLJ20035
    NM_017633 C6orf37 chromosome 6 open Hypothetical protein 3624 7592
    reading frame 37
    NM_017646 IPT tRNA Hypothetical protein, Transferase 3625 7593
    isopentenyltransferase 1
    NM_017664 ANKRD10 ankyrin repeat Hypothetical protein, ANK repeat, 3626 7594
    domain 10 Repeat
    NM_017681 FLJ20130 hypothetical protein Hypothetical protein, Porin 3627 7595
    FLJ20130
    NM_017694 FLJ20160 FLJ20160 protein Hypothetical protein 3628 7596
    NM_017700 FLJ20184 hypothetical protein Hypothetical protein 3629 7597
    FLJ20184
    NM_017703 FBXL12 F-box and leucine- Ubl conjugation pathway, Repeat, 3630 7598
    rich repeat protein Leucine-rich repeat, Alternative
    12 splicing
    NM_017714 C20orf13 chromosome 20 Hydrolase 3631 7599
    open reading frame
    13
    NM_017730 FLJ20259 FLJ20259 protein Hypothetical protein 3632 7600
    NM_017735 FLJ20272 hypothetical protein Hypothetical protein 3633 7601
    FLJ20272
    NM_017737 FLJ20275 transducer of Cdc42- Hypothetical protein, SH3 domain 3634 7602
    dependent actin
    assembly
    1
    NM_017740 ZDHHC7 zinc finger, DHHC Transmembrane, Zinc-finger, 3635 7603
    domain containing 7 Alternative splicing
    NM_017742 FLJ20281 zinc finger, CCHC Hypothetical protein, Zinc-finger 3636 7604
    domain containing 2
    NM_017746 FLJ20287 hypothetical protein Hypothetical protein 3637 7605
    FLJ20287
    NM_017756 FLJ20306 hypothetical protein Hypothetical protein 3638 7606
    FLJ20306
    NM_017775 FLJ20343 hypothetical protein Hypothetical protein 3639 7607
    FLJ20343
    NM_017785 FLJ20364 hypothetical protein Hypothetical protein 3640 7608
    FLJ20364
    NM_017787 FLJ20154 chromosome 10 Hypothetical protein 3641 7609
    open reading frame
    26
    NM_017801 CKLFSF6 chemokine-like Chemotaxis, Cytokine, 3642 7610
    factor super family 6 Transmembrane
    NM_017803 FLJ20399 hypothetical protein Hypothetical protein 3643 7611
    FLJ20399
    NM_017812 FLJ20420 hypothetical protein Hypothetical protein 3644 7612
    FLJ20420
    NM_017814 FLJ20422 hypothetical protein Hypothetical protein 3645 7613
    FLJ20422
    NM_017816 LYAR hypothetical protein Hypothetical protein 3646 7614
    FLJ20425
    NM_017817 RAB20 RAB20, member GTP-binding, Lipoprotein, 3647 7615
    RAS oncogene Prenylation, Protein transport,
    family Polymorphism
    NM_017819 FLJ20432 hypothetical protein Hypothetical protein 3648 7616
    FLJ20432
    NM_017820 FLJ20433 hypothetical protein Hypothetical protein 3649 7617
    FLJ20433
    NM_017821 RHBDL2 rhomboid, veinlet- Hydrolase, Protease, Serine 3650 7618
    like 2 (Drosophila) protease, Transmembrane
    NM_017824 FLJ20445 hypothetical protein Hypothetical protein 3651 7619
    FLJ20445
    NM_017836 FLJ20473 hypothetical protein Hypothetical protein 3652 7620
    FLJ20473
    NM_017838 NOLA2 nucleolar protein 3653 7621
    family A, member 2
    (H/ACA small
    nucleolar RNPs)
    NM_017840 MRPL16 mitochondrial Ribosomal protein, Hypothetical 3654 7622
    ribosomal protein protein
    L16
    NM_017844 ANKMY1 ankyrin repeat and Hypothetical protein, ANK repeat, 3655 7623
    MYND domain Repeat, Zinc-finger, Alternative
    containing 1 splicing
    NM_017847 C1orf27 chromosome 1 open Hypothetical protein 3656 7624
    reading frame 27
    NM_017849 FLJ20507 hypothetical protein Hypothetical protein 3657 7625
    FLJ20507
    NM_017850 FLJ20508 hypothetical protein Hypothetical protein 3658 7626
    FLJ20508
    NM_017859 URKL1 uridine kinase-like 1 Transferase, Kinase, ATP-binding 3659 7627
    NM_017866 FLJ20533 hypothetical protein Hypothetical protein 3660 7628
    FLJ20533
    NM_017874 C20orf27 chromosome 20 Hypothetical protein 3661 7629
    open reading frame
    27
    NM_017885 FLJ20568 host cell factor C1 Hypothetical protein 3662 7630
    regulator 1 (XPO1
    dependant)
    NM_017895 DDX27 DEAD (Asp-Glu-Ala- Hydrolase, Helicase, ATP-binding, 3663 7631
    Asp) box polypeptide Nuclear protein, Alternative splicing
    27
    NM_017899 TSC hypothetical protein Calcium-binding, Hypothetical 3664 7632
    FLJ20607 protein
    NM_017900 FLJ20608 aurora-A kinase Hypothetical protein, Nuclear protein 3665 7633
    interacting protein
    NM_017906 FLJ20624 PAK1 interacting Hypothetical protein, Repeat, WD 3666 7634
    protein 1 repeat
    NM_017907 FLJ20625 hypothetical protein Hypothetical protein 3667 7635
    FLJ20625
    NM_017910 FLJ20628 hypothetical protein Hypothetical protein 3668 7636
    FLJ20628
    NM_017942 BTBD1 BTB (POZ) domain 3669 7637
    containing 1
    NM_017952 FLJ20758 FLJ20758 protein Hypothetical protein 3670 7638
    NM_017953 FLJ20729 hypothetical protein Hypothetical protein 3671 7639
    FLJ20729
    NM_017956 FLJ20772 hypothetical protein Hypothetical protein 3672 7640
    FLJ20772
    NM_017983 KIAA1001 hypothetical protein Hypothetical protein, Repeat, WD 3673 7641
    FLJ10055 repeat
    NM_018007 FBXO4 Homo sapiens cDNA Ubl conjugation pathway, 3674 7642
    FLJ10141 fis, clone Hypothetical protein
    HEMBA1003199.
    NM_018024 FLJ10204 hypothetical protein Hypothetical protein 3675 7643
    FLJ10204
    NM_018044 WBSCR20A Williams Beuren Nuclear protein, Transport, 3676 7644
    syndrome Transmembrane, Repeat,
    chromosome region Hypothetical protein
    20A
    NM_018045 FLJ10276 hypothetical protein Hypothetical protein 3677 7645
    FLJ10276
    NM_018050 FLJ10298 hypothetical protein Hypothetical protein 3678 7646
    FLJ10298
    NM_018051 FLJ10300 hypothetical protein Hypothetical protein, Repeat, WD 3679 7647
    FLJ10300 repeat
    NM_018053 FLJ10307 hypothetical protein Hypothetical protein 3680 7648
    FLJ10307
    NM_018056 FLJ10315 hypothetical protein Hypothetical protein 3681 7649
    FLJ10315
    NM_018059 FLJ10324 hypothetical protein Hypothetical protein 3682 7650
    FLJ10324
    NM_018067 FLJ10350 hypothetical protein Hypothetical protein 3683 7651
    FLJ10350
    NM_018075 FLJ10375 hypothetical protein Hypothetical protein 3684 7652
    FLJ10375
    NM_018087 FLJ10407 hypothetical protein Hypothetical protein 3685 7653
    FLJ10407
    NM_018089 FLJ10415 hypothetical protein Hypothetical protein, ANK repeat, 3686 7654
    FLJ10415 Repeat
    NM_018093 FLJ10439 hypothetical protein Hypothetical protein, Repeat, WD 3687 7655
    FLJ10439 repeat
    NM_018099 FLJ10462 hypothetical protein Hypothetical protein 3688 7656
    FLJ10462
    NM_018100 FLJ10466 EF-hand domain (C- Hypothetical protein 3689 7657
    terminal) containing 1
    NM_018113 LIMR lipocalin-interacting Hypothetical protein, Receptor 3690 7658
    membrane receptor
    NM_018119 SIN RNA polymerase III Transferase, DNA-directed RNA 3691 7659
    80 kDa subunit polymerase, Transcription, Nuclear
    RPC5 protein, Alternative splicing
    NM_018125 FLJ10521 hypothetical protein Hypothetical protein 3692 7660
    FLJ10521
    NM_018127 ELAC2 elaC homolog 2 (E. coli) Hypothetical protein 3693 7661
    NM_018128 SRR hypothetical protein Isomerase, Pyridoxal phosphate, 3694 7662
    FLJ10534 Hypothetical protein
    NM_018137 PRMT6 protein arginine N- Transferase, Methyltransferase, 3695 7663
    methyltransferase 6 Nuclear protein, Methylation
    NM_018140 FLJ10565 hypothetical protein Hypothetical protein 3696 7664
    FLJ10565
    NM_018142 FLJ10569 hypothetical protein Hypothetical protein 3697 7665
    FLJ10569
    NM_018147 FAIM Fas apoptotic Apoptosis, Alternative splicing 3698 7666
    inhibitory molecule
    NM_018158 SLC4A1AP solute carrier family Hypothetical protein, Transcription 3699 7667
    4 (anion exchanger), regulation, Nuclear protein, Antigen,
    member 1, adaptor Alternative splicing
    protein
    NM_018161 FLJ10631 NAD synthetase 1 Hypothetical protein 3700 7668
    NM_018169 FLJ10652 hypothetical protein Hypothetical protein 3701 7669
    FLJ10652
    NM_018170 FLJ10656 hypothetical protein Kinase, Hypothetical protein 3702 7670
    FLJ10656
    NM_018174 VCY2IP1 VCY2 interacting Hypothetical protein 3703 7671
    protein 1
    NM_018182 FLJ10700 hypothetical protein Hypothetical protein 3704 7672
    FLJ10700
    NM_018191 RCBTB1 regulator of Hypothetical protein 3705 7673
    chromosome
    condensation
    (RCC1) and BTB
    (POZ) domain
    containing protein
    1
    NM_018194 FLJ10724 melanoma antigen Hypothetical protein 3706 7674
    recognized by T
    cells
    2
    NM_018195 FLJ10726 hypothetical protein Hypothetical protein 3707 7675
    FLJ10726
    NM_018197 ZFP64 zinc finger protein 64 Transcription regulation, Zinc-finger, 3708 7676
    homolog (mouse) Metal-binding, Nuclear protein, DNA-
    binding, Repeat, Alternative splicing
    NM_018203 FLJ10748 hypothetical protein Hypothetical protein 3709 7677
    FLJ10748
    NM_018208 FLJ10761 putative Transferase, Kinase 3710 7678
    ethanolamine kinase
    NM_018209 ARFGAP1 ADP-ribosylation Transport, Protein transport, 3711 7679
    factor GTPase GTPase activation, Golgi stack,
    activating protein 1 Zinc-finger, Alternative splicing,
    Polymorphism
    NM_018217 C20orf31 chromosome 20 Hydrolase, Glycosidase, 3712 7680
    open reading frame Glycoprotein, Signal, Polymorphism
    31
    NM_018226 RNPEPL1 arginyl Aminopeptidase, Hydrolase, Zinc, 3713 7681
    aminopeptidase Metalloprotease
    (aminopeptidase B)-
    like 1
    NM_018235 FLJ10830 cytosolic nonspecific Hydrolase, Carboxypeptidase, 3714 7682
    dipeptidase (EC Metalloprotease, Hypothetical
    3.4.13.18) protein
    NM_018243 FLJ10849 hypothetical protein Hypothetical protein 3715 7683
    FLJ10849
    NM_018246 FLJ10853 hypothetical protein Hypothetical protein 3716 7684
    FLJ10853
    NM_018255 STATIP1 signal transducer Hypothetical protein, Repeat, WD 3717 7685
    and activator of repeat
    transcription
    3
    interacting protein 1
    NM_018256 WDR12 WD repeat domain Repeat, WD repeat, Polymorphism 3718 7686
    12
    NM_018257 C20orf36 chromosome 20 Transcription regulation, Zinc-finger, 3719 7687
    open reading frame DNA-binding, Nuclear protein,
    36 Repeat, Alternative splicing
    NM_018259 FLJ10890 hypothetical protein Hypothetical protein 3720 7688
    FLJ10890
    NM_018264 FLJ10900 hypothetical protein Hypothetical protein 3721 7689
    FLJ10900
    NM_018265 FLJ10901 hypothetical protein Hypothetical protein 3722 7690
    FLJ10901
    NM_018267 H2AFJ H2A histone family, Hypothetical protein 3723 7691
    member J
    NM_018275 FLJ10925 hypothetical protein Hypothetical protein 3724 7692
    FLJ10925
    NM_018306 FLJ11036 hypothetical protein Hypothetical protein 3725 7693
    FLJ11036
    NM_018317 FLJ11082 hypothetical protein Hypothetical protein 3726 7694
    FLJ11082
    NM_018319 TDP1 tyrosyl-DNA Hypothetical protein, Hydrolase, 3727 7695
    phosphodiesterase 1 DNA repair, Repeat, Nuclear protein,
    3D-structure, Disease mutation
    NM_018321 RAD1 BRIX Hypothetical protein, Ribosome 3728 7696
    biogenesis, Nuclear protein, Cell
    cycle, Exonuclease
    NM_018322 C6orf64 chromosome 6 open Hypothetical protein, Dynein 3729 7697
    reading frame 64
    NM_018324 FLJ11106 hypothetical protein Hypothetical protein 3730 7698
    FLJ11106
    NM_018326 HIMAP4 immunity associated GTP-binding, Coiled coil, 3731 7699
    protein 4 Polymorphism
    NM_018332 DDX19 hypothetical protein ATP-binding, Helicase, Hydrolase, 3732 7700
    FLJ11126 RNA-binding, Nuclear protein,
    Hypothetical protein
    NM_018333 FLJ20666 hypothetical protein Hypothetical protein 3733 7701
    FLJ20666
    NM_018358 FLJ11198 ATP-binding Hypothetical protein, ATP-binding 3734 7702
    cassette, sub-family
    F (GCN20), member 3
    NM_018359 FLJ11200 hypothetical protein Hypothetical protein 3735 7703
    FLJ11200
    NM_018361 FLJ11210 acid acyltransferase- Phospholipid biosynthesis, 3736 7704
    epsilon Transferase, Acyltransferase,
    Transmembrane
    NM_018371 ChGn chondroitin beta1,4 Transferase, Hypothetical protein 3737 7705
    N-
    acetylgalactosaminyl
    transferase
    NM_018373 SYNJ2BP synaptojanin 2 Mitochondrion, Outer membrane, 3738 7706
    binding protein Transmembrane
    NM_018379 FLJ11280 hypothetical protein Hypothetical protein 3739 7707
    FLJ11280
    NM_018386 FLJ11305 hypothetical protein Hypothetical protein 3740 7708
    FLJ11305
    NM_018387 STRBP spermatid Hypothetical protein 3741 7709
    perinuclear RNA
    binding protein
    NM_018391 FLJ23277 ubiquitin specific Hypothetical protein, Protease 3742 7710
    protease 31
    NM_018394 FLJ11342 hypothetical protein Hypothetical protein 3743 7711
    FLJ11342
    NM_018399 VNN3 vanin 3 Hydrolase, Signal, Glycoprotein, 3744 7712
    GPI-anchor, Lipoprotein
    NM_018403 HSA275986 transcription factor Hypothetical protein 3745 7713
    SMIF
    NM_018404 CENTA2 centaurin, alpha 2 GTPase activation, Repeat, Zinc- 3746 7714
    finger
    NM_018407 LAPTM4B lysosomal 3747 7715
    associated protein
    transmembrane
    4
    beta
    NM_018421 TBC1D2 TBC1 domain family, Hypothetical protein, GTPase 3748 7716
    member 2 activation, Antigen
    NM_018422 DKFZp761K1423 hypothetical protein Hypothetical protein 3749 7717
    DKFZp761K1423
    NM_018423 DKFZp761p1010 protein kinase ATP-binding, Kinase, Receptor, 3750 7718
    STYK1 Transferase, Tyrosine-protein
    kinase, Hypothetical protein
    NM_018441 PECR peroxisomal trans 2- Oxidoreductase 3751 7719
    enoyl CoA reductase
    NM_018443 ZNF302 zinc finger protein Hypothetical protein, Metal-binding, 3752 7720
    302 Zinc, Zinc-finger, Transcription
    regulation, DNA-binding, Nuclear
    protein, Repeat, Alternative splicing
    NM_018449 UBAP2 ubiquitin associated Hypothetical protein 3753 7721
    protein 2
    NM_018452 C6orf35 chromosome 6 open Hypothetical protein 3754 7722
    reading frame 35
    NM_018457 DKFZP564J157 DKFZp564J157 Hypothetical protein 3755 7723
    protein
    NM_018465 MDS030 chromosome 9 open Hypothetical protein 3756 7724
    reading frame 46
    NM_018472 HT011 uncharacterized Hypothetical protein 3757 7725
    hypothalamus
    protein HT011
    NM_018480 HT007 uncharacterized Hypothetical protein 3758 7726
    hypothalamus
    protein HT007
    NM_018485 GPR77 G protein-coupled G-protein coupled receptor, 3759 7727
    receptor 77 Transmembrane, Glycoprotein
    NM_018486 HDAC8 histone deacetylase 8 Hydrolase, Nuclear protein, 3760 7728
    Chromatin regulator, Transcription
    regulation, Repressor, Alternative
    splicing
    NM_018491 LOC55871 COBW-like protein Hypothetical protein 3761 7729
    NM_018515 PRO2176 EST, Highly similar 3762 7730
    to hypothetical
    protein PRO2176
    [Homo sapiens]
    [H. sapiens]
    NM_018520 PRO2268 hypothetical protein 3763 7731
    PRO2268
    NM_018533 RAB7 Homo sapiens cDNA GTP-binding, Lipoprotein, 3764 7732
    FLJ20819 fis, clone Prenylation, Protein transport,
    ADSE00511. Hypothetical protein
    NM_018556 SIRPB2 signal-regulatory Repeat, Signal, Transmembrane, 3765 7733
    protein beta 2 Immunoglobulin domain,
    Glycoprotein, Alternative splicing
    NM_018569 PRO0971 hypothetical protein Hypothetical protein 3766 7734
    PRO0971
    NM_018572 PRO1051 E2F transcription 3767 7735
    factor 3
    NM_018590 PRO0082 chondroitin sulfate Hypothetical protein, Transferase 3768 7736
    GalNAcT-2
    NM_018594 PRO0823 FYN binding protein SH3 domain, Phosphorylation, 3769 7737
    (FYB-120/130) Nuclear protein, Coiled coil,
    Alternative splicing
    NM_018615 PRO2032 Homo sapiens 3770 7738
    hypothetical protein
    PRO2032
    (PRO2032), mRNA.
    NM_018638 EKI1 ethanolamine kinase Transferase, Kinase 3771 7739
    NM_018643 TREM1 triggering receptor Receptor 3772 7740
    expressed on
    myeloid cells 1
    NM_018648 NOLA3 nucleolar protein 3773 7741
    family A, member 3
    (H/ACA small
    nucleolar RNPs)
    NM_018676 THSD1 thrombospondin, Signal 3774 7742
    type I, domain 1
    NM_018687 LOC55908 hepatocellular 3775 7743
    carcinoma-
    associated gene
    TD26
    NM_018688 BIN3 bridging integrator 3 Septation, Cytoskeleton, Coiled coil, 3776 7744
    Hypothetical protein
    NM_018690 APOB48R apolipoprotein B48 Hypothetical protein, Lipoprotein, 3777 7745
    receptor Receptor
    NM_018699 PRDM5 PR domain Transcription regulation, DNA- 3778 7746
    containing 5 binding, Zinc-finger, Metal-binding,
    Nuclear protein, Repeat
    NM_018728 MYO5C myosin VC Myosin, Repeat, ATP-binding, 3779 7747
    Calmodulin-binding, Actin-binding,
    Coiled coil, Polymorphism
    NM_018834 MATR3 matrin 3 Nuclear protein, RNA-binding, 3780 7748
    Repeat, Zinc-finger
    NM_018839 NSFL1C NSFL1 (p97) Hypothetical protein 3781 7749
    cofactor (p47)
    NM_018840 C20orf24 chromosome 20 Alternative splicing, Membrane, SH2 3782 7750
    open reading frame domain, SH3 domain, Myristate,
    24 Phosphorylation, Alternative
    initiation, Lipoprotein
    NM_018939 PCDHB6 protocadherin beta 6 Calcium-binding, Cell adhesion, 3783 7751
    Glycoprotein, Signal, Repeat,
    Transmembrane, Multigene family
    NM_018959 DAZAP1 DAZ associated Hypothetical protein 3784 7752
    protein 1
    NM_018961 UBASH3A ubiquitin associated Nuclear protein, SH3 domain, 3785 7753
    and SH3 domain Alternative splicing
    containing, A
    NM_018983 NOLA1 nucleolar protein 3786 7754
    family A, member 1
    (H/ACA small
    nucleolar RNPs)
    NM_018996 FLJ20015 KIAA1582 protein Hypothetical protein 3787 7755
    NM_019002 ETAA16 ETAA16 protein 3788 7756
    NM_019009 TOLLIP toll interacting Hypothetical protein, Immune 3789 7757
    protein response, Inflammatory response
    NM_019012 PEPP2 phosphoinositol 3- Hypothetical protein 3790 7758
    phosphate-binding
    protein-2
    NM_019018 FLJ11127 hypothetical protein Hypothetical protein 3791 7759
    FLJ11127
    NM_019042 FLJ20485 hypothetical protein Hypothetical protein, tRNA 3792 7760
    FLJ20485 processing, Lyase
    NM_019057 FLJ10404 hypothetical protein Hypothetical protein 3793 7761
    FLJ10404
    NM_019063 EML4 echinoderm Microtubule, Repeat, WD repeat, 3794 7762
    microtubule Hypothetical protein
    associated protein
    like 4
    NM_019067 FLJ10613 hypothetical protein Hypothetical protein 3795 7763
    FLJ10613
    NM_019084 FLJ10895 hypothetical protein Hypothetical protein 3796 7764
    FLJ10895
    NM_019096 GTPBP2 GTP binding protein 2 GTP-binding, Protein biosynthesis, 3797 7765
    Hypothetical protein
    NM_019112 ABCA7 ATP-binding ATP-binding, Hypothetical protein 3798 7766
    cassette, sub-family
    A (ABC1), member 7
    NM_019554 S100A4 S100 calcium Calcium-binding, 3D-structure 3799 7767
    binding protein A4
    (calcium protein,
    calvasculin,
    metastasin, murine
    placental homolog)
    NM_019604 CRTAM class-I MHC- 3800 7768
    restricted T cell
    associated molecule
    NM_019848 P3 solute carrier family Transmembrane, Transport, 3801 7769
    10 (sodium/bile acid Symport
    cotransporter
    family), member 3
    NM_019892 PPI5PIV inositol 3802 7770
    polyphosphate-5-
    phosphatase, 72 kDa
    NM_019896 POLE4 polymerase (DNA- DNA-directed DNA polymerase, 3803 7771
    directed), epsilon 4 DNA-binding, Nuclear protein
    (p12 subunit)
    NM_020038 ABCC3 ATP-binding ATP-binding, Glycoprotein, 3804 7772
    cassette, sub-family Transmembrane, Transport, Repeat,
    C (CFTR/MRP), Alternative splicing
    member
    3
    NM_020123 SMBP SM-11044 binding Hypothetical protein, Signal, 3805 7773
    protein Transmembrane
    NM_020133 LPAAT- 1-acylglycerol-3- Phospholipid biosynthesis, 3806 7774
    delta phosphate O- Transferase, Acyltransferase,
    acyltransferase 4 Transmembrane
    (lysophosphatidic
    acid acyltransferase,
    delta)
    NM_020134 DPYSL5 dihydropyrimidinase- Hypothetical protein 3807 7775
    like 5
    NM_020135 WHIP Werner helicase ATP-binding, Helicase, Hypothetical 3808 7776
    interacting protein 1 protein
    NM_020139 LOC56898 dehydrogenase/reductase Oxidoreductase, Hypothetical protein 3809 7777
    (SDR family)
    member 6
    NM_020143 LOC56902 putatative 28 kDa Hypothetical protein 3810 7778
    protein
    NM_020149 MEIS2 Meis1, myeloid Hypothetical protein, Homeobox, 3811 7779
    ecotropic viral DNA-binding, Nuclear protein,
    integration site 1 Alternative splicing
    homolog 2 (mouse)
    NM_020152 C21orf7 chromosome 21 Alternative splicing, Hypothetical 3812 7780
    open reading frame 7 protein
    NM_020158 RRP46 exosome component Exosome, Hydrolase, Nuclease, 3813 7781
    Rrp46 Exonuclease, rRNA processing,
    Nuclear protein, RNA-binding,
    Antigen
    NM_020166 MCCC1 methylcrotonoyl- Mitochondrion, Ligase, Biotin, ATP- 3814 7782
    Coenzyme A binding, Transit peptide, Disease
    carboxylase
    1 mutation, Polymorphism
    (alpha)
    NM_020179 FN5 FN5 protein 3815 7783
    NM_020184 CNNM4 cyclin M4 Hypothetical protein 3816 7784
    NM_020188 DC13 DC13 protein 3817 7785
    NM_020193 C11ORF30 chromosome 11 Hypothetical protein 3818 7786
    open reading frame
    30
    NM_020198 GK001 GK001 protein Hypothetical protein 3819 7787
    NM_020200 HHGP phosphoribosyl Transferase 3820 7788
    transferase domain
    containing 1
    NM_020201 NT5M 5′,3′-nucleotidase, Nucleotide metabolism, Hydrolase, 3821 7789
    mitochondrial Mitochondrion, Nucleotide-binding,
    Magnesium, Transit peptide, 3D-
    structure
    NM_020216 RNPEP arginyl Aminopeptidase, Hydrolase, Zinc, 3822 7790
    aminopeptidase Metalloprotease
    (aminopeptidase B)
    NM_020229 PRDM11 PR domain Hypothetical protein 3823 7791
    containing 11
    NM_020231 MDS010 x 010 protein Hypothetical protein 3824 7792
    NM_020234 MDS009 x 009 protein Hypothetical protein 3825 7793
    NM_020236 MRPL1 mitochondrial Hypothetical protein, Ribosomal 3826 7794
    ribosomal protein L1 protein
    NM_020239 SPEC1 small protein effector Hypothetical protein 3827 7795
    1 of Cdc42
    NM_020243 TOMM22 translocase of outer Receptor, Translocation, Transport, 3828 7796
    mitochondrial Protein transport, Outer membrane,
    membrane 22 Mitochondrion, Transmembrane
    homolog (yeast)
    NM_020313 LOC57019 hypothetical protein Hypothetical protein 3829 7797
    LOC57019
    NM_020314 MGC16824 esophageal cancer Hypothetical protein 3830 7798
    associated protein
    NM_020322 ACCN3 amiloride-sensitive Ionic channel 3831 7799
    cation channel 3
    NM_020344 SLC24A2 solute carrier family Vision, Transport, Antiport, Symport, 3832 7800
    24 Calcium transport, Potassium
    (sodium/potassium/calcium transport, Sodium transport,
    exchanger), Transmembrane, Glycoprotein,
    member 2 Signal, Repeat, Alternative splicing
    NM_020347 LZTFL1 leucine zipper 3833 7801
    transcription factor-
    like 1
    NM_020350 AGTRAP angiotensin II Receptor 3834 7802
    receptor-associated
    protein
    NM_020357 PCNP PEST-containing Nuclear protein 3835 7803
    nuclear protein
    NM_020360 PLSCR3 phospholipid Hypothetical protein, 3836 7804
    scramblase 3 Transmembrane, Lipoprotein,
    Calcium-binding, SH3-binding,
    Repeat, Phosphorylation, Palmitate,
    Polymorphism
    NM_020365 EIF2B3 eukaryotic Initiation factor, Protein biosynthesis, 3837 7805
    translation initiation Alternative splicing, Disease
    factor 2B, subunit 3 mutation, Hypothetical protein
    gamma, 58 kDa
    NM_020366 RPGRIP1 retinitis pigmentosa 3838 7806
    GTPase regulator
    interacting protein
    1
    NM_020370 GPR84 G protein-coupled Receptor 3839 7807
    receptor 84
    NM_020371 AVEN apoptosis, caspase Apoptosis 3840 7808
    activation inhibitor
    NM_020385 XPMC2H XPMC2 prevents Hypothetical protein 3841 7809
    mitotic catastrophe 2
    homolog (Xenopus
    laevis)
    NM_020390 EIF5A2 eukaryotic Initiation factor, Hypothetical protein 3842 7810
    translation initiation
    factor 5A2
    NM_020394 LOC57116 zinc finger protein Metal-binding, Zinc, Zinc-finger 3843 7811
    SBZF3
    NM_020399 PIST golgi associated Hypothetical protein 3844 7812
    PDZ and coiled-coil
    motif containing
    NM_020401 NUP107 nuclear pore Nuclear protein, Transport 3845 7813
    complex protein
    NM_020406 PRV1 polycythemia rubra Signal, Receptor 3846 7814
    vera 1
    NM_020408 CGI-203 chromosome 6 open Hypothetical protein 3847 7815
    reading frame 149
    NM_020410 CGI-152 cation-transporting Hydrolase, Transmembrane, 3848 7816
    ATPase Phosphorylation, Magnesium, ATP-
    binding, Alternative splicing,
    Hypothetical protein
    NM_020414 DDX24 DEAD (Asp-Glu-Ala- Hydrolase, Helicase, ATP-binding, 3849 7817
    Asp) box polypeptide RNA-binding
    24
    NM_020415 RETN resistin Hormone, Signal, Diabetes mellitus, 3850 7818
    Obesity
    NM_020466 DJ122O8.2 hypothetical protein Hypothetical protein 3851 7819
    dJ122O8.2
    NM_020469 ABO ABO blood group Transferase, Glycosyltransferase, 3852 7820
    (transferase A, alpha Blood group antigen, Golgi stack,
    1-3-N- Metal-binding, Manganese, Signal-
    acetylgalactosaminyl anchor, Transmembrane,
    transferase; Glycoprotein, Polymorphism, 3D-
    transferase B, alpha structure
    1-3-
    galactosyltransferase)
    NM_020480 ANK1 ankyrin 1, ANK repeat, Repeat, Cytoskeleton, 3853 7821
    erythrocytic Alternative splicing, Phosphorylation,
    Lipoprotein, Disease mutation,
    Elliptocytosis, Polymorphism
    NM_020484 AF011757 Homo sapiens 3854 7822
    RAGE binding
    protein (AF011757),
    mRNA.
    NM_020530 OSM oncostatin M Growth regulation, Cytokine, 3855 7823
    Glycoprotein, Signal, 3D-structure
    NM_020533 MCOLN1 mucolipin 1 Hypothetical protein, Ionic channel, 3856 7824
    Transmembrane
    NM_020548 DBI diazepam binding Transport, Lipid-binding, Acetylation, 3857 7825
    inhibitor (GABA Alternative splicing
    receptor modulator,
    acyl-Coenzyme A
    binding protein)
    NM_020632 ATP6V0A4 ATPase, H+ Hydrogen ion transport, 3858 7826
    transporting, Transmembrane, Glycoprotein,
    lysosomal V0 Disease mutation, Hypothetical
    subunit a isoform 4 protein
    NM_020639 ANKRD3 ankyrin repeat ANK repeat, Repeat, Hypothetical 3859 7827
    domain 3 protein, ATP-binding, Kinase,
    Serine/threonine-protein kinase,
    Transferase, Alternative splicing
    NM_020648 TWSG1 twisted gastrulation Hypothetical protein, Signal 3860 7828
    homolog 1
    (Drosophila)
    NM_020652 ZNF286 zinc finger protein Transcription regulation, Zinc-finger, 3861 7829
    286 Metal-binding, Nuclear protein, DNA-
    binding, Repeat
    NM_020659 TTYH1 tweety homolog 1 3862 7830
    (Drosophila)
    NM_020664 DECR2 2,4-dienoyl CoA Hypothetical protein, Oxidoreductase 3863 7831
    reductase 2,
    peroxisomal
    NM_020686 NPD009 4-aminobutyrate 3864 7832
    aminotransferase
    NM_020905 RDH14 retinol Oxidoreductase, NADP 3865 7833
    dehydrogenase 14
    (all-trans and 9-cis)
    NM_020980 AQP9 aquaporin 9 Transport, Repeat, Transmembrane 3866 7834
    NM_020983 ADCY6 adenylate cyclase 6 Lyase, cAMP biosynthesis, 3867 7835
    Transmembrane, Glycoprotein,
    Repeat, Metal-binding, Magnesium,
    Alternative splicing
    NM_020995 HPR haptoglobin-related Hydrolase, Protease, Serine 3868 7836
    protein protease
    NM_020999 NEUROG3 neurogenin 3 3869 7837
    NM_021018 HIST1H3F histone 1, H3f Nuclear protein, Chromosomal 3870 7838
    protein, DNA-binding, Nucleosome
    core, Multigene family, Acetylation,
    Methylation
    NM_021019 MYL6 myosin, light Myosin, Muscle protein, Acetylation, 3871 7839
    polypeptide 6, alkali, Alternative splicing, Multigene family
    smooth muscle and
    non-muscle
    NM_021025 TLX3 T-cell leukemia, Homeobox, DNA-binding, Nuclear 3872 7840
    homeobox 3 protein, Developmental protein
    NM_021031 CYCL Homo sapiens Hypothetical protein 3873 7841
    cytochrome c-like
    antigen (CYCL),
    mRNA
    NM_021039 S100A14 S100 calcium Transcription regulation, DNA- 3874 7842
    binding protein A14 binding, Nuclear protein,
    (calgizzarin) Hypothetical protein, Calcium-
    binding
    NM_021074 NDUFV2 NADH Oxidoreductase, NAD, Ubiquinone, 3875 7843
    dehydrogenase Mitochondrion, Transit peptide,
    (ubiquinone) Metal-binding, Iron-sulfur, Iron, 2Fe—2S,
    flavoprotein 2, Polymorphism
    24 kDa
    NM_021075 NDUFV3 NADH Hypothetical protein 3876 7844
    dehydrogenase
    (ubiquinone)
    flavoprotein 3,
    10 kDa
    NM_021078 GCN5L2 GCN5 general Transcription regulation, 3877 7845
    control of amino-acid Transferase, Nuclear protein,
    synthesis 5-like 2 Bromodomain, Alternative splicing,
    (yeast) 3D-structure
    NM_021079 NMT1 N- Acyltransferase, Transferase, 3878 7846
    myristoyltransferase 1 Alternative splicing
    NM_021090 MTMR3 myotubularin related Hydrolase, Zinc-finger, Alternative 3879 7847
    protein 3 splicing
    NM_021103 TMSB10 thymosin, beta 10 Actin-binding, Cytoskeleton, 3880 7848
    Acetylation
    NM_021106 RGS3 regulator of G- Hypothetical protein, Signal 3881 7849
    protein signalling 3 transduction inhibitor, Alternative
    splicing, Phosphorylation
    NM_021131 PPP2R4 protein phosphatase Alternative splicing 3882 7850
    2A, regulatory
    subunit B′ (PR 53)
    NM_021173 POLD4 polymerase (DNA- DNA-directed DNA polymerase, 3883 7851
    directed), delta 4 DNA replication, Nuclear protein
    NM_021178 HEI10 chromosome 14 Ubl conjugation pathway, Ligase, 3884 7852
    open reading frame Nuclear protein, Metal-binding, Zinc,
    18 Coiled coil, Zinc-finger,
    Phosphorylation, Ubl conjugation
    NM_021197 WFDC1 WAP four-disulfide Serine protease inhibitor, Signal 3885 7853
    core domain 1
    NM_021198 NLI-IF CTD (carboxy- Hypothetical protein, Nuclear protein 3886 7854
    terminal domain,
    RNA polymerase II,
    polypeptide A) small
    phosphatase
    1
    NM_021199 SQRDL sulfide quinone Oxidoreductase, Flavoprotein, FAD, 3887 7855
    reductase-like NADP, Mitochondrion, Transit
    (yeast) peptide, Polymorphism
    NM_021212 ZF HCF-binding DNA-binding, Nuclear protein 3888 7856
    transcription factor
    Zhangfei
    NM_021238 TERA TERA protein Hypothetical protein 3889 7857
    NM_021242 STRAIT11499 MID1 interacting Hypothetical protein 3890 7858
    G12-like protein
    NM_021251 CAPN10 calpain 10 Hydrolase, Thiol protease, Repeat, 3891 7859
    Alternative splicing, Polymorphism,
    Diabetes mellitus
    NM_021259 TMEM8 transmembrane Cell adhesion, Signal, 3892 7860
    protein 8 (five Transmembrane, EGF-like domain,
    membrane-spanning Glycoprotein
    domains)
    S73288 small small proline-rich 3893 7861
    proline-rich protein 1A
    protein
    SPRK
    S74639 IGHM Clone I50 Immunoglobulin domain, 3894 7862
    immunoglobulin Immunoglobulin C region,
    heavy chain variable Glycoprotein, Repeat, Pyrrolidone
    region mRNA, partial carboxylic acid, Polymorphism,
    cds Membrane, Hypothetical protein,
    Receptor, T-cell, Signal
    S77356 ATP5O ATP synthase, H+ Hydrolase, ATP synthesis, CF(1), 3895 7863
    transporting, Hydrogen ion transport,
    mitochondrial F1 Mitochondrion, Transit peptide,
    complex, O subunit Polymorphism
    (oligomycin
    sensitivity conferring
    protein)
    S80864 cytochrome cytochrome c-like Hypothetical protein 3896 7864
    c-like antigen
    polypeptide
    S90469 POR P450 (cytochrome) Oxidoreductase, Flavoprotein, FMN, 3897 7865
    oxidoreductase FAD, NADP, Endoplasmic reticulum,
    Membrane, Acetylation,
    Polymorphism, 3D-structure
    U00946 KIAA0344 protein kinase, lysine Hypothetical protein, ATP-binding, 3898 7866
    deficient 1 Kinase, Serine/threonine-protein
    kinase, Transferase
    U01147 ABR active BCR-related Guanine-nucleotide releasing factor, 3899 7867
    gene Alternative splicing
    U02032 RPL23A ribosomal protein Ribosomal protein, rRNA-binding 3900 7868
    L23a
    U09196 POLD4 polymerase (DNA- DNA-directed DNA polymerase, 3901 7869
    directed), delta 4 DNA replication, Nuclear protein
    U14383 MUC8 Human mucin 3902 7870
    (MUC8) mRNA,
    partial cds.
    U20180 IREB2 iron-responsive Iron-sulfur, 4Fe—4S, RNA-binding, 3903 7871
    element binding Hypothetical protein
    protein
    2
    U25750 hypothetical protein Hypothetical protein 3904 7872
    MGC20235
    U36759 PTCRA pre T-cell antigen 3905 7873
    receptor alpha
    U37689 POLR2H polymerase (RNA) II Transferase, DNA-directed RNA 3906 7874
    (DNA directed) polymerase, Transcription, Nuclear
    polypeptide H protein
    U41387 DDX21 DEAD (Asp-Glu-Ala- Helicase, RNA-binding, ATP-binding, 3907 7875
    Asp) box polypeptide Nuclear protein, Antigen, Repeat
    21
    U43431 TOP3A topoisomerase Isomerase, Topoisomerase, DNA- 3908 7876
    (DNA) III alpha binding, Repeat, Zinc-finger,
    Alternative splicing, Polymorphism
    U43604 Human unidentified 3909 7877
    mRNA, partial
    sequence.
    U56725 HSPA2 Human heat shock ATP-binding, Chaperone, Heat 3910 7878
    protein mRNA, shock, Multigene family
    complete cds.
    U58033 MTMR2 myotubularin related Hydrolase, Charcot-Marie-Tooth 3911 7879
    protein 2 disease
    U64205 MARK3 MAP/microtubule Transferase, Serine/threonine- 3912 7880
    affinity-regulating protein kinase, ATP-binding,
    kinase 3 Alternative splicing, Plasmid
    U66702 PTPRN2 protein tyrosine Hypothetical protein, Hydrolase, 3913 7881
    phosphatase, Receptor, Glycoprotein, Signal,
    receptor type, N Transmembrane, Diabetes mellitus,
    polypeptide 2 Alternative splicing
    U68382 MAN2B1 mannosidase, alpha, Glycosidase, Hydrolase, 3914 7882
    class 2B, member 1 Glycoprotein, Lysosome, Zymogen,
    Signal, Disease mutation,
    Polymorphism
    U68494 solute carrier family 3915 7883
    30 (zinc transporter),
    member 1
    U69127 FUBP3 far upstream Transcription regulation, Transacting 3916 7884
    element (FUSE) factor, Nuclear protein, DNA-
    binding protein 3 binding, Repeat, Alternative splicing
    U69645 ZNF32 zinc finger protein 32 Hypothetical protein, Metal-binding, 3917 7885
    (KOX 30) Zinc, Zinc-finger, Transcription
    regulation, DNA-binding, Nuclear
    protein, Repeat
    U72882 IFI35 interferon-induced Interferon induction, Alternative 3918 7886
    protein 35 splicing
    U79246 DIS3 FLJ22624 protein Hypothetical protein 3919 7887
    U79260 MGC5149 fatso Hypothetical protein 3920 7888
    U79277 tyrosine 3- Neurone, Phosphorylation, 3921 7889
    monooxygenase/tryptophan Acetylation, Multigene family, 3D-
    5- structure
    monooxygenase
    activation protein,
    zeta polypeptide
    U79280 PIPPIN RNA-binding protein Hypothetical protein, mRNA 3922 7890
    pippin processing, RNA-binding, Nuclear
    protein
    U79282 hypothetical protein Hypothetical protein 3923 7891
    LOC137886
    U79290 Human clone 23908 3924 7892
    mRNA sequence
    U79298 MGC39325 hypothetical protein Hypothetical protein 3925 7893
    MGC39325
    U79458 WBP2 Human WW domain Hypothetical protein 3926 7894
    binding protein-2
    mRNA, complete
    cds.
    U80628 TK2 thymidine kinase 2, Kinase, Transferase, DNA synthesis, 3927 7895
    mitochondrial ATP-binding, Mitochondrion, Transit
    peptide, Alternative splicing
    U82277 LILRA2 leukocyte Immune response, Receptor, 3928 7896
    immunoglobulin-like Repeat, Signal, Transmembrane,
    receptor, subfamily Immunoglobulin domain,
    B (with TM and ITIM Glycoprotein, Antigen, Alternative
    domains), member 1 splicing, Polymorphism, Multigene
    family, Phosphorylation, 3D-structure
    U83115 AIM1 absent in melanoma 1 Repeat, Lectin 3929 7897
    U90878 PDLIM1 PDZ and LIM Cytoskeleton, LIM domain, Metal- 3930 7898
    domain 1 (elfin) binding, Zinc
    U90909 MISS chromosome 14 Hypothetical protein 3931 7899
    open reading frame
    32
    U90911 WIRE WIRE protein 3932 7900
    U90916 sortilin-related Endocytosis, Receptor, 3933 7901
    receptor, L(DLR Transmembrane, EGF-like domain,
    class) A repeats- Repeat, Glycoprotein, LDL, Lipid
    containing transport, Cholesterol metabolism,
    Signal
    W61000_RC NORE1 Ras association Hypothetical protein 3934 7902
    (RaIGDS/AF-6)
    domain family 5
    X00437 IGHM Human mRNA for T- Immunoglobulin domain, 3935 7903
    cell specific protein. Immunoglobulin C region,
    Glycoprotein, Repeat, Pyrrolidone
    carboxylic acid, Polymorphism,
    Membrane, Hypothetical protein,
    Receptor, T-cell, Signal
    X04201 TPM3 tropomyosin 3 Hypothetical protein, Muscle protein, 3936 7904
    Cytoskeleton, Actin-binding, Coiled
    coil, Alternative splicing, Multigene
    family, Disease mutation
    X04526 GNB1 Human liver mRNA Transducer, Repeat, WD repeat, 3937 7905
    for beta-subunit Multigene family, 3D-structure
    signal transducing
    proteins Gs/Gi (beta-
    G).
    X07618 CYP2D6 cytochrome P450, Heme, Monooxygenase, 3938 7906
    family 2, subfamily Oxidoreductase, Electron transport,
    D, polypeptide 6 Membrane, Microsome,
    Endoplasmic reticulum,
    Polymorphism
    X13956 MGC10471 hypothetical protein 3939 7907
    MGC10471
    X15183 HSPCA heat shock 90 kDa Heat shock, Chaperone, ATP- 3940 7908
    protein 1, alpha binding, Phosphorylation, 3D-
    structure, Hypothetical protein,
    Plasmid
    X51630 WT1 Wilms tumor 1 Zinc-finger, Metal-binding, DNA- 3941 7909
    binding, Repeat, Nuclear protein,
    Transcription regulation, Alternative
    splicing, Anti-oncogene, Disease
    mutation, Chromosomal
    translocation, 3D-structure
    X52015 IL1RN interleukin 1 receptor Glycoprotein, Signal, Alternative 3942 7910
    antagonist splicing, 3D-structure
    X52882 TCP1 t-complex 1 Chaperone, ATP-binding, Multigene 3943 7911
    family
    X56789 TTS-2.2 transport-secretion Hypothetical protein 3944 7912
    protein 2.2
    X57352 IFITM3 interferon induced Interferon induction, 3945 7913
    transmembrane Transmembrane
    protein 3 (1-8U)
    X58536 HLA-C major Glycoprotein, Signal, 3946 7914
    histocompatibility Transmembrane, Hypothetical
    complex, class I, C protein, MHC, MHC I,
    Polymorphism, 3D-structure,
    Alternative splicing
    X58794 AZU1 azurocidin 1 Serine protease homolog, 3947 7915
    (cationic Glycoprotein, Chemotaxis, Antibiotic,
    antimicrobial protein Heparin-binding, Signal, 3D-
    37) structure
    X59417 PSMA6 proteasome Proteasome, Hydrolase, Protease, 3948 7916
    (prosome, Threonine protease
    macropain) subunit,
    alpha type, 6
    X61079 IGHM T cell receptor Immunoglobulin domain, 3949 7917
    alpha-chain (TCR Immunoglobulin C region,
    Valpha20Jalpha9.14) Glycoprotein, Repeat, Pyrrolidone
    mRNA, partial cds. carboxylic acid, Polymorphism,
    Membrane, Hypothetical protein,
    Receptor, T-cell, Signal
    X62535 DGKA diacylglycerol Hypothetical protein, Kinase, 3950 7918
    kinase, alpha 80 kDa Transferase, Calcium-binding,
    Phorbol-ester binding, Repeat,
    Multigene family
    X63417 IRLB c-myc promoter- DNA-binding, Hypothetical protein 3951 7919
    binding protein
    X69115 ZNF37A zinc finger protein Hypothetical protein, Metal-binding, 3952 7920
    37a (KOX 21) Nuclear protein, Zinc, Zinc-finger,
    Transcription regulation, DNA-
    binding, Repeat
    X71490 ATP6V0D1 H. sapiens mRNA for Hydrolase, ATP synthesis, Hydrogen 3953 7921
    vacuolar proton ion transport
    ATPase, subunit D.
    X78817 ARHGAP4 Rho GTPase GTPase activation, SH3 domain, 3954 7922
    activating protein 4 Coiled coil
    X87949 HSPA5 heat shock 70 kDa ATP-binding, Endoplasmic reticulum, 3955 7923
    protein 5 (glucose- Signal
    regulated protein,
    78 kDa)
    X89214 hpr H. sapiens mRNA for Hydrolase, Protease, Serine 3956 7924
    haptoglobin related protease
    protein.
    X94232 MAPRE2 microtubule- T-cell 3957 7925
    associated protein,
    RP/EB family,
    member 2
    X98258 MPHOSPH9 M-phase Phosphorylation, Golgi stack, 3958 7926
    phosphoprotein 9 Membrane, Coiled coil
    X98261 ZWINTAS ZW10 interactor Phosphorylation, Nuclear protein, 3959 7927
    Coiled coil
    X98411 MYO1F myosin IF Myosin, ATP-binding, Actin-binding, 3960 7928
    Calmodulin-binding, SH3 domain,
    Multigene family
    Y00433 GPX1 glutathione Oxidoreductase, Peroxidase, 3961 7929
    peroxidase 1 Selenium, Selenocysteine,
    Erythrocyte, Polymorphism,
    Hypothetical protein
    Y00816 CR1 complement Complement pathway, Glycoprotein, 3962 7930
    component (3b/4b) Transmembrane, Repeat, Signal,
    receptor 1, including Receptor, Sushi, Blood group
    Knops blood group antigen, Polymorphism, Pyrrolidone
    system carboxylic acid, 3D-structure
    Y14442 OR1F1 olfactory receptor, G-protein coupled receptor, 3963 7931
    family 1, subfamily Transmembrane, Glycoprotein,
    F, member 1 Multigene family, Olfaction
    Y18490 LST1 leukocyte specific Immune response, Cell shape, 3964 7932
    transcript 1 Transmembrane, Alternative splicing
    Z15114 PRKCG protein kinase C, Transferase, Serine/threonine- 3965 7933
    gamma protein kinase, ATP-binding,
    Calcium-binding, Metal-binding,
    Zinc, Repeat, Phorbol-ester binding,
    Phosphorylation, Polymorphism
    Z34893 IGHM Clone P2-114 anti- Immunoglobulin domain, 3966 7934
    oxidized LDL Immunoglobulin C region,
    immunoglobulin Glycoprotein, Repeat, Pyrrolidone
    heavy chain Fab carboxylic acid, Polymorphism,
    mRNA, partial cds Membrane, Hypothetical protein,
    Receptor, T-cell, Signal
    Z48314 MUC5AC mucin 5, subtypes A Repeat, Glycoprotein, Signal, 3967 7935
    and C, Polymorphism, Hypothetical protein
    tracheobronchial/gastric
    Z49105 SSX2 synovial sarcoma, X Chromosomal translocation, Proto- 3968 7936
    breakpoint 2 oncogene, Multigene family,
    Transcription regulation
    • 7. REFERENCES CITED
  • All references cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual publication or patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety for all purposes.
  • Many modifications and variations of the present invention can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. The specific embodiments described herein are offered by way of example only, and the invention is to be limited only by the terms of the appended claims along with the full scope of equivalents to which such claims are entitled.

Claims (15)

What is claimed:
1. A computer-implemented method for determining the responsiveness of a chronic myeloid leukemia (CML) patient to imatinib mesylate (IM), comprising:
(a) classifying, on a computer, a marker profile comprising measurements of a plurality of gene products in a cell sample taken from said patient as an IM-sensitive profile or an IM-resistant profile, wherein said gene products are respectively products of at least five of the genes listed in Table 4;
(b) determining said patient as responsive to IM treatment if said marker profile is classified as an IM-sensitive profile, or determining said patient as resistant to IM treatment if said marker profile is classified as an IM-resistant profile; and
(c) outputting to a user, a user interface device, a monitor, a computer readable storage medium, a local computer, or a computer that is part of a network; or displaying; the determination resulting from step (b).
2. The method of claim 1, wherein the gene products are products consisting of 5, 10, 15, 20, 25, 30, 40, 60, 70, 80, 90, 100, 200, or 228 of the genes listed in Table 4.
3. The method of claim 1, further comprising obtaining said marker profile by a method comprising measuring said plurality of gene products in a cell sample taken from said patient.
4. The method of claim 3, wherein said cell sample is a sample from bone marrow or peripheral blood.
5. The method of claim 1, wherein said classifying is carried out by a method comprising using a progression classifier, wherein said progression classifier receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is an IM-sensitive profile or an IM-resistant profile.
6. The method of claim 1, wherein the gene products are selected from the group consisting of at least 5, 6, 7, or 8 of the genes selected from the group consisting of serine threonine kinases CTRL, MAP21K14, CLK3, MAP kinase MKNK2, tyrosine kinase oncogene FYN, TCF7, guanine nucleotide binding proteins GNAZ and GNG11, and MAF.
7. The method of claim 1, wherein each of said gene products is a gene transcript.
8. The method of claim 7, wherein measurement of each said gene transcript is obtained by a method comprising contacting a positionally-addressable microarray with nucleic acids from said cell sample or nucleic acids derived therefrom under hybridization conditions, and detecting the amount of hybridization that occurs, said microarray comprising one or more polynucleotide probes complementary to a hybridizable sequence of each said gene transcript.
9. The method of claim 7, wherein measurement of each said gene transcript is obtained by quantitative reverse transcriptase PCR (qRT-PCR).
10. The method of claim 1, wherein each of said plurality of gene products is a protein.
11. The method of claim 1, wherein said classifying is carried out using a progression classifier, wherein said progression classifier receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is a IM resistant profile or an IM responsive profile.
12. The method of claim 11, wherein said step of classifying is carried out by a method comprising (i) comparing said marker profile with an IM resistant template profile and/or an IM responsive template profile, wherein said IM resistant template profile and IM responsive template profile are obtained from a training population comprising IM resistant patients and IM responsive patients, respectively; and (ii) classifying said marker profile as an IM resistant profile if said marker profile has a high similarity to said IM resistant template profile and/or has a low similarity to said IM resistant template profile, or classifying said marker profile as an IM responsive profile if said marker profile has a high similarity to said IM responsive template profile and/or has a low similarity to said IM resistant template profile, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.
13. The method of claim 11, wherein said step of classifying is carried out by a method comprising (i) comparing said marker profile with said IM resistant template profile or said IM responsive template profile; and (ii) classifying said marker profile as an IM resistant profile if said marker profile has a high similarity to said IM resistant template profile or has a low similarity to said IM responsive template profile, or classifying said marker profile as an IM responsive profile if said marker profile has a high similarity to said IM responsive template profile or has a low similarity to said IM resistant template profile, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.
14. The method of claim 12, wherein said step of classifying is carried out by a method comprising (i) comparing said marker profile with said IM resistant template profile and said IM responsive template profile; and (ii) classifying said marker profile as an IM resistant profile if said marker profile has a higher similarity to said IM resistant template profile than to said IM responsive template profile, or classifying said marker profile as a IM responsive profile if said marker profile has a higher similarity to said IM responsive template profile than to said IM resistant template profile.
15. The method of claim 11, wherein said progression classifier is based on a classification method selected from the group consisting of an artificial neural network, a support vector machine, logic regression, linear or quadratic discriminant analysis, decision trees, principal component analysis, and nearest neighbor classifier analysis.
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