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CDKN2A (Cyclin-dependent kinase inhibitor 2A) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Skin cancer, Lung cancer, Bladder & urothelial cancer and 5 more.
Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein.
CIViC holds 59 clinical evidence items and 0 assertions across 27 variants, naming Palbociclib, Trametinib, Afatinib and Bevacizumab and others. Open Targets scores its association with cancer at 0.90 (direct and indirect evidence; datatypes genetic literature 0.61, affected pathway 0.90, literature 1.00, genetic association 0.90, somatic mutation 0.98, animal model 0.67). IntOGen calls it a driver in 70 cohorts (15 activating, 55 loss-of-function), covering Adenoid Cystic Carcinoma, Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Cholangiocarcinoma, Colon Adenocarcinoma, Colorectal Adenocarcinoma and others. In OnCo, 1 product record names it (UroVysion Bladder Cancer Kit).
In plain words · CDKN2A (Cyclin-dependent kinase inhibitor 2A) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Skin cancer, Lung cancer, Bladder & urothelial cancer and 5 more.
CDKN2A (Cyclin-dependent kinase inhibitor 2A) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Skin cancer, Lung cancer, Bladder & urothelial cancer and 5 more.
Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein.
No product in this corpus aims at CDKN2A yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
Lineage antigen shared with normal T-cells: HPA finds the gene group enriched in that blood lineage, and the 1 medicine aimed at it (UroVysion Bladder Cancer Kit) act on the wild-type protein, so the normal lineage is hit too. HPA CDKN2A: RNA tissue enhanced (choroid plexus 43 nTPM, pituitary gland 36 nTPM); blood lineage group enriched (B-cells 16 nTPM, T-cells 38 nTPM); high antibody staining in 3 normal tissues; highest cancer staining cervical cancer (9 of 12 high). Distribution: 9 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Biliary tract cancer (all types), Skin cancer (all types), Lung cancer (all types), Bladder & urothelial cancer, Head and neck squamous cell carcinoma, Lymphoma, Oesophageal cancer and more); Open Targets associates it with 19 specific cancer types at or above 0.5 (dysplastic nevus, familial atypical multiple mole melanoma syndrome, melanoma, cutaneous melanoma, melanoma and neural system tumor syndrome, familial melanoma and more). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas CDKN2A tissue; Human Protein Atlas CDKN2A pathology; Open Targets ENSG00000147889 associations
First described 1993. Earliest sequence paper UniProt cites for the protein: Serrano et al, Nature, 1993, "A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4". Source.
Sources: HGNC HGNC:1787 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P42771 (protein name, function text, keywords and locations (REST API)); CIViC gene CDKN2A (59 evidence items, 0 assertions, 27 variants; diseases: Head And Neck Squamous Cell Carcinoma, Lung Non-small Cell Carcinoma, Pancreatic Cancer, Melanoma, Cholangiocarcinoma and 20 more (GraphQL API, CC0)); Open Targets ENSG00000147889 (association with cancer (MONDO_0004992) 0.90; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.66, gastric cancer 0.58, oesophageal cancer 0.69, hepatocellular carcinoma 0.61, urinary bladder cancer 0.70, ovarian cancer 0.65 (GraphQL API, CC0)); IntOGen CDKN2A (driver in 70 cohorts (Act 15, LoF 55); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein. Location: Cytoplasm; Nucleus (UniProt). Locus 9p21.3 (HGNC).
RNA: tissue enhanced (choroid plexus 43 nTPM, pituitary gland 36 nTPM), detected in many normal tissues. Blood: group enriched (B-cells 16 nTPM, T-cells 38 nTPM).
Medium: Adrenal gland, Breast, Caudate, Cerebellum, Cervix, Duodenum, Endometrium, Epididymis.
RNA cancer enhanced: Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma 356 pTPM, Ovary Serous Cystadenocarcinoma 419 pTPM.
Medium only: lymphoma, prostate cancer, renal cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Pancreatic ductal adenocarcinoma | 37-48% | Mutation or deep deletion (with CDKN2B and MTAP co-deletion) | cBioPortal: mutation in 546 of 2,336, 23.4%, and deep deletion in 359, 15.4%, in pdac_msk_2024; mutation 35 of 179, 19.6%, and deep deletion 52 of 183, 28.4%, in paad_tcga_pan_can_atlas_2018; mutation 6 and deep deletion 40 of 109, 42.2%, in paad_utsw_2015; mutation 93 of 395, 23.5%, and deep deletion 19 in pancreas_msk_2024; mutation 71 of 383, 18.5%, in paad_qcmg_uq_2016 (no copy-number profile); 29 of 140, 20.7%, in paad_cptac_2021. CDKN2B was co-deleted in 333 of 2,336 (pdac_msk_2024) and 50 of 183 (TCGA); MTAP deep deletion in 40 of 183, 21.9% (TCGA) and 34 of 109, 31.2% (UTSW), 51 of 2,336 on the MSK panel. | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 26-41% | Deletion or mutation of CDKN2A, with RB1 loss | cBioPortal: CDKN2A deep deletion 128 of 487, 26.3%, plus mutation in 73 of 484, 15.1%, in lusc_tcga_pan_can_atlas_2018; deletion 47 of 178, 26.4%, plus mutation 31, 17.4%, in lusc_tcga_pub; mutation 17 of 108, 15.7%, in lusc_cptac_2021. RB1 is mutated in 31 of 484, 6.4%, with deep deletion in 16 of 487. The founding paper put CDKN2A and RB1 alteration together at 72% of tumours, counting epigenetic silencing and exon skipping as well as deletion and mutation (Cancer Genome Atlas Research Network 2012). | cBioPortal (TCGA) |
| Gallbladder cancer | 21% | Deletion or mutation | CDKN2A 21% (Giraldo 2022); CDKN2A/B 19% of 85 (Javle 2016); CDKN2A 9% of 376 Indian patients, significantly lower than Western and Asian cohorts (Suryavanshi 2025); cBioPortal gbc_mskcc_2022: CDKN2A deep deletion in 35 of 244, 14.3%, mutation in 26 of 244, 10.7%; CDKN2B deep deletion in 34 of 244, 13.9%. | doi.org |
| Non-small-cell lung cancer | 15-20% | Homozygous deletion and inactivating mutation | cBioPortal deep deletion: 358 of 2,422, 14.8%, in luad_mskcc_2023_met_organotropism; 86 of 511, 16.8%, in luad_tcga_pan_can_atlas_2018; 45 of 230, 19.6%, in luad_tcga_pub; 87 of 915, 9.5%, in lung_msk_2017, with mutation on top in 137, 25, 10 and 49 samples respectively. | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
For gallbladder cancer the points that matter are that HER2 can disappear under HER2-directed pressure, that SMAD4 co-mutation predicts a worse response, and that sequencing at progression, not just at diagnosis, may be needed to guide the next line.
HER2 is as frequent in India as in the West, so HER2 testing pays off in the highest-incidence population, while tumour-agnostic immunotherapy markers will rarely apply. The paper also shows plasma testing is feasible where tissue is scarce.
The reference Western cohort for gallbladder cancer frequencies, deposited on cBioPortal as gbc_mskcc_2022, where the per-gene sample counts on OnCo were read. It supports panel testing at diagnosis: one patient in three has a targetable finding.
The rulebook behind the CAPS cohorts and the UK EUROPAC programme; it is also the reason surveillance for carriers is not yet a routine NHS service, because the consortium itself asked for it to stay within research until benefit was shown.
The FUSCC cohort is the East Asian reference and the basis of the FUTURE subtype-guided umbrella trial; its LAR findings point to CDK4/6 and HER2-mutant strategies rather than PARP inhibitors for that subtype.
A germline result is not the whole story: without loss of the second allele the tumour may not be repair-deficient, which is why tumour sequencing and, in trials, HRD signatures are read alongside.
It fixed the working numbers for a comprehensive panel in pancreatic cancer: a hit worth acting on in about one patient in six, most of it in repair genes and the KRAS wild-type minority.
Family history misses most carriers, so the NCCN and ASCO guidelines moved to testing every patient; each carrier found is a family that can be offered surveillance and a patient who may be eligible for platinum and PARP inhibition.
Query for this target: (TITLE:"CDKN2A" OR ABSTRACT:"CDKN2A" OR TITLE:"cyclin dependent kinase inhibitor 2A" OR ABSTRACT:"cyclin dependent kinase inhibitor 2A" OR TITLE:"Cyclin-dependent kinase inhibitor 2A" OR ABSTRACT:"Cyclin-dependent kinase inhibitor 2A" OR TITLE:"CDK4I" OR ABSTRACT:"CDK4I" OR TITLE:"p16" OR ABSTRACT:"p16" OR TITLE:"INK4a" OR ABSTRACT:"INK4a") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CDKN2A, not a curated reading list.
Shares Pancreatic intraepithelial neoplasia (PanIN), the microscopic precursor of pancreatic cancer, A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns, Association of alterations in main driver genes with outcomes of patients with resected pancreatic ductal adenocarcinoma, Molecular and clinical determinants of targeted therapy treatment in biliary tract cancer.
Shares Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer, Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma, Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.
Shares Biliary cancer: utility of next-generation sequencing for clinical management, Genomic profiling of Indian gallbladder carcinoma: mutational insights in a high-incidence population, Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes, Integrated genomic characterization of pancreatic ductal adenocarcinoma.
Shares Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma, Familial pancreatic cancer and inherited risk (who qualifies for surveillance), Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium.
Shares Transformation: when a slow lymphoma turns into a fast one, Bladder cancer (KEGG map), The p53 network (guardian of the genome), The cell-cycle engine (cyclins & CDKs).
Shares Pancreatic intraepithelial neoplasia (PanIN), the microscopic precursor of pancreatic cancer, A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns, Association of alterations in main driver genes with outcomes of patients with resected pancreatic ductal adenocarcinoma, A combination of molecular markers and clinical features improve the classification of pancreatic cysts.
Shares Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia, A combination of molecular markers and clinical features improve the classification of pancreatic cysts, Integrated genomic characterization of pancreatic ductal adenocarcinoma, Oesophageal cancer.
Shares LymphGen and the genetic clusters of large B-cell lymphoma, Comprehensive genomic characterization of squamous cell lung cancers, Richter transformation of chronic lymphocytic leukaemia, Leukaemia (all types).