CDKN2A
Summary: This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. [provided by RefSeq, Sep 2012].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| cyclin dependent kinase inhibitor 2A | MIM:600160 | Ensembl:ENSG00000147889 | HGNC:HGNC:1787 | PA106 | 9p21.3 |
GO terms in CDKN2A
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| BP | IDA | GO:0000082 | G1/S transition of mitotic cell cycle |
| BP | IMP | GO:0001953 | negative regulation of cell-matrix adhesion |
| BP | IDA | GO:0007050 | cell cycle arrest |
| BP | IMP | GO:0007050 | cell cycle arrest |
| BP | IEP | GO:0007265 | Ras protein signal transduction |
| BP | IDA | GO:0008285 | negative regulation of cell proliferation |
| BP | IMP | GO:0008285 | negative regulation of cell proliferation |
| BP | IDA | GO:0030308 | negative regulation of cell growth |
| BP | TAS | GO:0031658 | negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle |
| BP | IDA | GO:0032088 | negative regulation of NF-kappaB transcription factor activity |
| BP | ISS | GO:0034393 | positive regulation of smooth muscle cell apoptotic process |
| BP | IMP | GO:0035986 | senescence-associated heterochromatin focus assembly |
| BP | IDA | GO:0042326 | negative regulation of phosphorylation |
| BP | IDA | GO:0045736 | negative regulation of cyclin-dependent protein serine/threonine kinase activity |
| BP | IMP | GO:0045892 | negative regulation of transcription, DNA-templated |
| BP | IMP | GO:0090398 | cellular senescence |
| BP | IMP | GO:0090399 | replicative senescence |
| BP | ISS | GO:2000111 | positive regulation of macrophage apoptotic process |
| BP | IMP | GO:2000774 | positive regulation of cellular senescence |
| CC | IBA | GO:0005634 | nucleus |
| CC | IDA | GO:0005634 | nucleus |
| CC | IDA | GO:0005737 | cytoplasm |
| CC | TAS | GO:0005829 | cytosol |
| CC | IDA | GO:0035985 | senescence-associated heterochromatin focus |
| MF | HDA | GO:0003723 | RNA binding |
| MF | IBA | GO:0004861 | cyclin-dependent protein serine/threonine kinase inhibitor activity |
| MF | IDA | GO:0004861 | cyclin-dependent protein serine/threonine kinase inhibitor activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IPI | GO:0019901 | protein kinase binding |
| MF | IDA | GO:0051059 | NF-kappaB binding |
Gene expression in normal tissue: CDKN2A
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in CDKN2A
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| biocarta | arfpathway | tumor suppressor arf inhibits ribosomal biogenesis |
| biocarta | cellcyclepathway | cyclins and cell cycle regulation |
| biocarta | ctcfpathway | ctcf: first multivalent nuclear factor |
| biocarta | g1pathway | cell cycle: g1/s check point |
| reactome | R-HSA-1640170 | Cell Cycle |
| reactome | R-HSA-212436 | Generic Transcription Pathway |
| reactome | R-HSA-2262752 | Cellular responses to stress |
| reactome | R-HSA-2559580 | Oxidative Stress Induced Senescence |
| reactome | R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) |
| reactome | R-HSA-2559583 | Cellular Senescence |
| reactome | R-HSA-2559585 | Oncogene Induced Senescence |
| reactome | R-HSA-2990846 | SUMOylation |
| reactome | R-HSA-3108214 | SUMOylation of DNA damage response and repair proteins |
| reactome | R-HSA-3108232 | SUMO E3 ligases SUMOylate target proteins |
| reactome | R-HSA-3232118 | SUMOylation of transcription factors |
| reactome | R-HSA-3700989 | Transcriptional Regulation by TP53 |
| reactome | R-HSA-392499 | Metabolism of proteins |
| reactome | R-HSA-453279 | Mitotic G1-G1/S phases |
| reactome | R-HSA-5633007 | Regulation of TP53 Activity |
| reactome | R-HSA-597592 | Post-translational protein modification |
| reactome | R-HSA-6804757 | Regulation of TP53 Degradation |
| reactome | R-HSA-6806003 | Regulation of TP53 Expression and Degradation |
| reactome | R-HSA-69231 | Cyclin D associated events in G1 |
| reactome | R-HSA-69236 | G1 Phase |
| reactome | R-HSA-69278 | Cell Cycle, Mitotic |
| reactome | R-HSA-69541 | Stabilization of p53 |
| reactome | R-HSA-69563 | p53-Dependent G1 DNA Damage Response |
| reactome | R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint |
| reactome | R-HSA-69615 | G1/S DNA Damage Checkpoints |
| reactome | R-HSA-69620 | Cell Cycle Checkpoints |
| reactome | R-HSA-73857 | RNA Polymerase II Transcription |
| reactome | R-HSA-74160 | Gene expression (Transcription) |
| reactome | R-HSA-8878159 | Transcriptional regulation by RUNX3 |
| reactome | R-HSA-8941858 | Regulation of RUNX3 expression and activity |
| reactome | R-HSA-8953897 | Cellular responses to external stimuli |
| wikipathways | WP1742 | TP53 Network |
| wikipathways | WP1772 | Apoptosis Modulation and Signaling |
| wikipathways | WP179 | Cell Cycle |
| wikipathways | WP2002 | miR-targeted genes in epithelium - TarBase |
| wikipathways | WP2004 | miR-targeted genes in lymphocytes - TarBase |
| wikipathways | WP2261 | Signaling Pathways in Glioblastoma |
| wikipathways | WP254 | Apoptosis |
| wikipathways | WP2828 | Bladder Cancer |
| wikipathways | WP2877 | Vitamin D Receptor Pathway |
| wikipathways | WP3308 | Oncogene Induced Senescence |
| wikipathways | WP3404 | Oxidative Stress Induced Senescence |
| wikipathways | WP3611 | Photodynamic therapy-induced AP-1 survival signaling. |
| wikipathways | WP3639 | Apoptotic Signaling Pathway |
| wikipathways | WP4107 | Transcriptional regulation by RUNX3 |
| wikipathways | WP4204 | Tumor suppressor activity of SMARCB1 |
| wikipathways | WP45 | G1 to S cell cycle control |
| wikipathways | WP615 | Senescence and Autophagy in Cancer |
| wikipathways | WP710 | DNA Damage Response (only ATM dependent) |
| pid | ap1_pathway | AP-1 transcription factor network |
| pid | ar_pathway | Coregulation of Androgen receptor activity |
| pid | betacatenin_nuc_pathway | Regulation of nuclear beta catenin signaling and target gene transcription |
| pid | cmyb_pathway | C-MYB transcription factor network |
| pid | deltanp63pathway | Validated transcriptional targets of deltaNp63 isoforms |
| pid | e2f_pathway | E2F transcription factor network |
| pid | foxm1pathway | FOXM1 transcription factor network |
| pid | fra_pathway | Validated transcriptional targets of AP1 family members Fra1 and Fra2 |
| pid | hif1apathway | Hypoxic and oxygen homeostasis regulation of HIF-1-alpha |
| pid | myc_pathway | C-MYC pathway |
| pid | p53regulationpathway | p53 pathway |
| pid | rb_1pathway | Regulation of retinoblastoma protein |
| pid | tap63pathway | Validated transcriptional targets of TAp63 isoforms |
| kegg | hsa04110 | Cell cycle - Homo sapiens (human) |
| kegg | hsa04115 | p53 signaling pathway - Homo sapiens (human) |
| kegg | hsa04218 | Cellular senescence - Homo sapiens (human) |
| kegg | hsa04934 | Cushing,s syndrome - Homo sapiens (human) |
| kegg | hsa05166 | HTLV-I infection - Homo sapiens (human) |
| kegg | hsa05200 | Pathways in cancer - Homo sapiens (human) |
| kegg | hsa05203 | Viral carcinogenesis - Homo sapiens (human) |
| kegg | hsa05206 | MicroRNAs in cancer - Homo sapiens (human) |
| kegg | hsa05212 | Pancreatic cancer - Homo sapiens (human) |
| kegg | hsa05214 | Glioma - Homo sapiens (human) |
| kegg | hsa05218 | Melanoma - Homo sapiens (human) |
| kegg | hsa05219 | Bladder cancer - Homo sapiens (human) |
| kegg | hsa05220 | Chronic myeloid leukemia - Homo sapiens (human) |
| kegg | hsa05223 | Non-small cell lung cancer - Homo sapiens (human) |
| kegg | hsa05225 | Hepatocellular carcinoma - Homo sapiens (human) |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD27 | WHI-P97 | 1 |
| iGMDRD50 | Cytarabine | 2 |
| iGMDRD123 | Isoevodiamine | 1 |
| iGMDRD1002 | rTRAIL | 1 |
| iGMDRD237 | ABT-751 | 1 |
| iGMDRD314 | Tanespimycin | 1 |
| iGMDRD352 | PD-0325901 | 1 |
| iGMDRD213 | SMR000068650 | 8 |
| iGMDRD137 | Indisulam | 6 |
| iGMDRD121 | GMX1778 | 5 |
| iGMDRD293 | Bleomycin | 2 |
| iGMDRD103 | SN-38 | 1 |
| iGMDRD5 | Tyrphostin AG 1478 | 1 |
| iGMDRD200 | STF62247 | 1 |
| iGMDRD367 | Ro 28-1675 | 2 |
| iGMDRD662 | JQ-1 | 2 |
| iGMDRD476 | WH-4-023 | 1 |
| iGMDRD409 | Saracatinib | 2 |
| iGMDRD76 | Simvastatin | 2 |
| iGMDRD654 | SL 0101-1 | 1 |
| iGMDRD470 | Trametinib | 1 |
| iGMDRD61 | Kinetin riboside | 4 |
| iGMDRD748 | PHA-665752 | 1 |
| iGMDRD639 | YK 4-279 | 1 |
| iGMDRD468 | AZ628 | 1 |
| iGMDRD226 | ML006 | 1 |
| iGMDRD493 | GSK269962A | 2 |
| iGMDRD260 | FQI-2 | 1 |
| iGMDRD568 | SCHEMBL15005512 | 1 |
| iGMDRD602 | Foretinib | 1 |
| iGMDRD516 | Z-LLNle-CHO | 1 |
| iGMDRD133 | Lapatinib | 2 |
| iGMDRD888 | Compound 44 | 6 |
| iGMDRD424 | Tamatinib | 6 |
| iGMDRD116 | CD437 | 2 |
| iGMDRD125 | BIRB-796 | 3 |
| iGMDRD32 | Metformin | 1 |
| iGMDRD307 | Manumycin A | 5 |
| iGMDRD148 | Pifithrin-mu | 4 |
| iGMDRD619 | BRD-K64610608 | 1 |
| iGMDRD792 | Cetuximab | 2 |
| iGMDRD317 | CCT 018159 | 1 |
| iGMDRD536 | PLX-4720 | 1 |
| iGMDRD57 | Chloropentafluorobenzene | 1 |
| iGMDRD434 | BMS-536924 | 3 |
| iGMDRD6 | AM-580 | 1 |
| iGMDRD481 | Dactolisib | 2 |
| iGMDRD1016 | THZ-2-49 | 1 |
| iGMDRD246 | NPC26 | 2 |
| iGMDRD886 | Compound 1541A | 2 |
| iGMDRD400 | A-443654 | 1 |
| iGMDRD695 | FR-180204 | 1 |
| iGMDRD967 | Panitumumab | 2 |
| iGMDRD354 | Midostaurin | 1 |
| iGMDRD462 | OSI-906 (Linsitinib) | 2 |
| iGMDRD494 | Neopeltolide | 1 |
| iGMDRD274 | Flavopiridol | 1 |
| iGMDRD282 | GNF-2 | 1 |
| iGMDRD378 | ZM-447439 | 2 |
| iGMDRD280 | CYTOCHALASIN B | 1 |
| iGMDRD297 | Austocystin D | 1 |
| iGMDRD776 | QL-XI-92 | 1 |
| iGMDRD253 | Vincaleukoblastine | 1 |
| iGMDRD446 | LY 2183240 | 2 |
| iGMDRD648 | ILORASERTIB | 2 |
| iGMDRD309 | 17AAG | 2 |
| iGMDRD869 | BRD55319 | 2 |
| iGMDRD440 | Nutlin-3A | 2 |
| iGMDRD736 | UNC1215 | 1 |
| iGMDRD134 | Sorafenib | 2 |
| iGMDRD291 | AC1NS4S0 | 1 |
| iGMDRD453 | GW2580 | 2 |
| iGMDRD185 | DMOG | 1 |
| iGMDRD532 | Olaparib | 1 |
| iGMDRD1036 | X17AAG | 1 |
| iGMDRD564 | GSK-650394 | 1 |
| iGMDRD370 | TPCA-1 | 1 |
| iGMDRD324 | CI-1040 | 2 |
| iGMDRD49 | Mitomycin | 1 |
| iGMDRD341 | Triacsin c | 5 |
| iGMDRD461 | VX-11e | 2 |
| iGMDRD705 | Nakiterpiosin | 1 |
| iGMDRD28 | Letrozole | 3 |
| iGMDRD251 | ML162 | 2 |
| iGMDRD173 | Epothilone B | 2 |
| iGMDRD402 | AKT Inhibitor VIII | 3 |
| iGMDRD658 | CHEMBL1673039 | 1 |
| iGMDRD286 | Nsc 632839 | 6 |
| iGMDRD366 | PI-103 | 7 |
| iGMDRD781 | Sirolimus | 1 |
| iGMDRD135 | Lenalidomide | 1 |
| iGMDRD151 | CHM-1 | 1 |
| iGMDRD394 | BX-795 | 1 |
| iGMDRD152 | 179324-69-7 | 2 |
| iGMDRD117 | Docetaxel | 1 |
| iGMDRD284 | Palbociclib | 14 |
| iGMDRD593 | CX-5461 | 3 |
| iGMDRD1019 | TL-2-105 | 1 |
| iGMDRD801 | 2,4-dideoxy-DC-45-A2 | 7 |
| iGMDRD513 | BML-259 | 2 |
| iGMDRD507 | GSK690693 | 1 |
| iGMDRD190 | Nilotinib | 1 |
| iGMDRD41 | Imatinib | 1 |
| iGMDRD399 | Selumetinib | 11 |
| iGMDRD188 | Piperlongumine | 2 |
| iGMDRD506 | Fedratinib | 5 |
| iGMDRD299 | ICL 670 | 2 |
| iGMDRD456 | Crizotinib | 3 |
| iGMDRD382 | CEP-701 | 1 |
| iGMDRD347 | Y-39983 | 3 |
| iGMDRD178 | MG-132 | 1 |
| iGMDRD351 | GW843682X | 2 |
| iGMDRD241 | Sunitinib | 1 |
| iGMDRD459 | RO-3306 | 1 |
| iGMDRD389 | SB525334 | 1 |
| iGMDRD68 | Paclitaxel | 2 |
| iGMDRD550 | CGP-082996 | 1 |
| iGMDRD300 | Tozasertib | 1 |
| iGMDRD894 | EGFR inhibitor | 1 |
| iGMDRD646 | PHA-793887 | 1 |
| iGMDRD353 | PD0325901 | 2 |
| iGMDRD414 | MST-312 | 5 |
| iGMDRD239 | Dasatinib | 1 |
| iGMDRD63 | Camptothecin | 2 |
| iGMDRD678 | Tubastatin A | 1 |
| iGMDRD136 | Nutlin-3 | 1 |
| iGMDRD1008 | SR-II-138A | 1 |
| iGMDRD387 | CHIR-99021 | 4 |
| iGMDRD673 | LSM-1215 | 1 |
| iGMDRD401 | Afatinib | 1 |
| iGMDRD608 | Refametinib | 2 |
| iGMDRD519 | GDC-0941 | 1 |
| iGMDRD193 | Fqi1 | 1 |
| iGMDRD782 | DC-45-A2 | 1 |
| iGMDRD870 | BRD63610 | 5 |
| iGMDRD318 | PAC-1 | 1 |
| iGMDRD491 | TAE-684 | 1 |
| iGMDRD669 | PDK1 inhibitor | 1 |
| iGMDRD255 | SB225002 | 3 |
| iGMDRD131 | Erlotinib | 2 |
| iGMDRD183 | CDK4/6 inhibitor | 18 |
| iGMDRD312 | Pelitinib | 1 |
| iGMDRD332 | A-770041 | 1 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in CDKN2A
CLASSFICATION
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