# CDKN2A

Source: https://onco.cc/targets/cdkn2a/  
OnCo record `cdkn2a` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: cyclin dependent kinase inhibitor 2A; Cyclin-dependent kinase inhibitor 2A; CDK4I; p16; INK4a; MTS1; CMM2; p19; p14; INK4; p16INK4a; p19Arf; p14ARF; P16-INK4A; CAI2; CDKN2
- Tags: cancer-genes-wave
- Symbol: CDKN2A
- Class: tumor-suppressor
- Biology: 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).
- Where found: Skin cancer: Open Targets association 0.80 with skin cancer (MONDO_0002898); IntOGen driver in 1 cohort (SKIN); Lung cancer: Open Targets association 0.75 with lung cancer (MONDO_0008903); Bladder & urothelial cancer: Open Targets association 0.70 with urinary bladder cancer (MONDO_0001187); CIViC evidence names this disease; Head and neck squamous cell carcinoma: Open Targets association 0.70 with head and neck squamous cell carcinoma (MONDO_0010150); CIViC evidence names this disease; Non-Hodgkin lymphoma: Open Targets association 0.69 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 1 cohort (MLYM); Oesophageal cancer: Open Targets association 0.69 with oesophageal cancer (MONDO_0007576); CIViC evidence names this disease; Pancreatic ductal adenocarcinoma: mutation or deep deletion (with cdkn2b and mtap co-deletion) 37-48%; Gallbladder cancer: deletion or mutation about 21%; Non-small-cell lung cancer: homozygous deletion and inactivating mutation 15-20%; Non-small-cell lung cancer: deletion or mutation of cdkn2a, with rb1 loss 26-41%

## Notes

- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 18 therapies; IntOGen calls it an activating (Act) driver in 15 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 55 cohorts; CIViC holds 59 clinical evidence items on its variants. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Oropharynx Cancer; Supratentorial Ependymoma, ZFTA Fusion-positive; Ganglioglioma; Low-Grade Glioma, NOS.
- Pancreatic ductal adenocarcinoma: lost by mutation or deep deletion in 37 to 48%, usually with CDKN2B and often MTAP (deep deletion in 22 to 31% of exome cohorts; cBioPortal). Loss of expression shortened overall survival (19.7 versus 24.6 months) after resection (Qian 2018), and germline CDKN2A carries the highest odds ratio of the six pancreatic risk genes (12.33; Hu 2018). MTAP co-deletion is the entry point for PRMT5-directed agents in trials.
- Lung cancer: deep deletion in 15 to 20% of adenocarcinomas and 26.3% of squamous tumours, with mutation on top (cBioPortal); counting methylation and exon skipping as well, CDKN2A and RB1 were altered in 72% of squamous cancers (Cancer Genome Atlas Research Network 2012). The deletion usually takes MTAP with it, which is the entry point for the PRMT5 inhibitors in trials.
- Lymphoma, TP53 loss, in mantle cell lymphoma and in Richter transformation: TP53 is the commonest route by which a lymphoma stops responding to chemotherapy, because chemotherapy kills largely by provoking a p53-dependent death. In mantle cell lymphoma it travels with blastoid morphology, a high Ki-67 and CDKN2A deletion. In Richter transformation it is one of two lesions that dominate the genetics, and the transformed clone is usually the same clone as the leukaemia rather than a second cancer. Frequency: In 183 younger mantle cell lymphoma patients from the Nordic MCL2 and MCL3 trials, TP53 mutation in 11% and TP53 deletion in 16%, with CDKN2A deletion in 20% and NOTCH1 mutation in 4%; only TP53 mutation kept its prognostic weight in multivariable analysis, with a hazard ratio of 6.2 for overall survival, a median overall survival of 1.8 years against 12.7 years for unmutated cases, and half the mutated group relapsing within a year (Eskelund 2017). In 86 cases of Richter syndrome, TP53 disruption in 47.1% and MYC abnormality in 26.2%; clonally unrelated transformations had both a longer median survival, 62.5 against 14.2 months, and less TP53 disruption, 23.1% against 60.0% (Rossi 2011). What it changes about treatment: In mantle cell lymphoma, yes in practice if not yet on any label: a TP53 mutation is the usual reason to abandon intensive cytarabine-based induction and autologous transplant and to go to a BTK inhibitor, a BCL-2 inhibitor or CAR-T instead. In Richter transformation it is the main prognostic variable, and establishing whether the large-cell clone is related to the leukaemic one changes the expected outcome more than any drug does.

## Sources

- HGNC HGNC:1787: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1787
- UniProt P42771: https://www.uniprot.org/uniprotkb/P42771/entry
- NCBI Gene 1029: https://www.ncbi.nlm.nih.gov/gene/1029
- Ensembl ENSG00000147889: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000147889
- Eskelund et al., Blood 2017: TP53 mutations in 183 younger mantle cell lymphoma patients from Nordic MCL2 and MCL3: https://doi.org/10.1182/blood-2017-04-779736
- Rossi et al., Blood 2011: the genetics of Richter syndrome in 86 pathologically proven cases: https://doi.org/10.1182/blood-2010-09-302174

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Richter transformation of chronic lymphocytic leukaemia](https://onco.cc/cancers/richter-transformation-cll/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)
- drugs: [UroVysion Bladder Cancer Kit](https://onco.cc/drugs/urovysion/)
- pathways: [Bladder cancer (KEGG map)](https://onco.cc/pathways/bladder-cancer-signalling/), [Cellular senescence](https://onco.cc/pathways/senescence/), [Chromosomal instability & aneuploidy](https://onco.cc/pathways/chromosomal-instability/), [Chronic myeloid leukaemia (KEGG map)](https://onco.cc/pathways/cml-signalling/), [Glioma (KEGG map)](https://onco.cc/pathways/glioma-signalling/), [Hepatocellular carcinoma (KEGG map)](https://onco.cc/pathways/hepatocellular-carcinoma-signalling/), [Melanoma (KEGG map)](https://onco.cc/pathways/melanoma-signalling/), [Non-small cell lung cancer (KEGG map)](https://onco.cc/pathways/nsclc-signalling/), [Pancreatic cancer (KEGG map)](https://onco.cc/pathways/pancreatic-cancer-signalling/), [The cell-cycle engine (cyclins & CDKs)](https://onco.cc/pathways/cell-cycle-engine-cdks/), [The p53 network (guardian of the genome)](https://onco.cc/pathways/p53-mdm2-axis/)
- terms: [CDKN2A/B homozygous deletion](https://onco.cc/terms/cdkn2a-homozygous-deletion/), [Checkpoint (two meanings)](https://onco.cc/terms/checkpoint/), [Familial pancreatic cancer and inherited risk (who qualifies for surveillance)](https://onco.cc/terms/familial-pancreatic-cancer/), [LymphGen and the genetic clusters of large B-cell lymphoma](https://onco.cc/terms/lymphoma-bio-lymphgen/), [Pancreatic intraepithelial neoplasia (PanIN), the microscopic precursor of pancreatic cancer](https://onco.cc/terms/panin/), [Transformation: when a slow lymphoma turns into a fast one](https://onco.cc/terms/lymphoma-bio-transformation/)
- key papers: [A combination of molecular markers and clinical features improve the classification of pancreatic cysts](https://onco.cc/key-papers/paper-springer-pancreatic-cyst-molecular-classification-gastroenterology-2015/), [A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns](https://onco.cc/key-papers/paper-notta-punctuated-evolution-pancreatic-nature-2016/), [Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer](https://onco.cc/key-papers/paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018/), [Association of alterations in main driver genes with outcomes of patients with resected pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-qian-driver-genes-outcomes-resected-pancreatic-jama-oncol-2018/), [Biliary cancer: utility of next-generation sequencing for clinical management](https://onco.cc/key-papers/paper-javle-biliary-ngs-cancer-2016/), [Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities](https://onco.cc/key-papers/paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015/), [Comprehensive genomic characterization of squamous cell lung cancers](https://onco.cc/key-papers/paper-tcga-lung-squamous-nature-2012/), [Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention](https://onco.cc/key-papers/paper-giraldo-gallbladder-msk-impact-ccr-2022/), [Core signaling pathways in human pancreatic cancers revealed by global genomic analyses](https://onco.cc/key-papers/paper-jones-pancreatic-core-pathways-science-2008/), [Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-shindo-germline-sporadic-pancreatic-jco-2017/), [Genomic analyses identify molecular subtypes of pancreatic cancer](https://onco.cc/key-papers/paper-bailey-molecular-subtypes-pancreatic-nature-2016/), [Genomic and transcriptomic landscape of triple-negative breast cancers: subtypes and treatment strategies](https://onco.cc/key-papers/paper-jiang-fuscc-tnbc-landscape-cancer-cell-2019/), [Genomic profiling of Indian gallbladder carcinoma: mutational insights in a high-incidence population](https://onco.cc/key-papers/paper-suryavanshi-indian-gallbladder-genomics-jco-go-2025/), [Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer](https://onco.cc/key-papers/paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019/), [Integrated genomic characterization of pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-tcga-pancreatic-integrated-characterisation-cancer-cell-2017/), [Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium](https://onco.cc/key-papers/paper-caps-consortium-surveillance-recommendations-gut-2020/), [Molecular and clinical determinants of targeted therapy treatment in biliary tract cancer](https://onco.cc/key-papers/paper-cowzer-biliary-targeted-therapy-determinants-ccr-2026/), [Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes](https://onco.cc/key-papers/paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018/), [Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes](https://onco.cc/key-papers/paper-biankin-pancreatic-exomes-axon-guidance-nature-2012/), [Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia](https://onco.cc/key-papers/paper-kanda-panin-1-somatic-mutations-gastroenterology-2012/), [Real-time targeted genome profile analysis of pancreatic ductal adenocarcinomas identifies genetic alterations that might be targeted with existing drugs or used as biomarkers](https://onco.cc/key-papers/paper-singhi-targeted-genome-profiling-3594-pdac-gastroenterology-2019/), [Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer](https://onco.cc/key-papers/paper-roberts-familial-pancreatic-whole-genome-cancer-discov-2016/), [Whole genomes redefine the mutational landscape of pancreatic cancer](https://onco.cc/key-papers/paper-waddell-whole-genomes-pancreatic-nature-2015/)

---
JSON: https://onco.cc/api/v1/entities/cdkn2a.json