CDKN1A
CDKN1A (Cyclin-dependent kinase inhibitor 1) 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 Bladder & urothelial cancer, Hepatocellular carcinoma, Colorectal cancer and 4 more.
Overview
Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest. Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Also involved in p53-independent DNA damage-induced G2 arrest mediated by CREB3L1 in astrocytes and osteoblasts.
CIViC holds 4 clinical evidence items and 0 assertions across 4 variants, naming Fluorouracil. Open Targets scores its association with cancer at 0.72 (direct and indirect evidence; datatypes affected pathway 0.76, literature 1.00, genetic association 0.62, somatic mutation 0.80, animal model 0.53). IntOGen calls it a driver in 9 cohorts (2 activating, 7 loss-of-function), covering Bladder Urothelial Carcinoma, Chromophobe Renal Cell Carcinoma, Hepatocellular Carcinoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · CDKN1A (Cyclin-dependent kinase inhibitor 1) 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 Bladder & urothelial cancer, Hepatocellular carcinoma, Colorectal cancer and 4 more.
- 1 · What it is
CDKN1A (Cyclin-dependent kinase inhibitor 1) 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 Bladder & urothelial cancer, Hepatocellular carcinoma, Colorectal cancer and 4 more.
- 2 · What goes wrong in cancer
Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest. Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage.
- 3 · How drugs use it
No product in this corpus aims at CDKN1A yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:1784 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P38936 (protein name, function text, keywords and locations (REST API)); CIViC gene CDKN1A (4 evidence items, 0 assertions, 4 variants; diseases: Retinoblastoma, Colorectal Cancer (GraphQL API, CC0)); Open Targets ENSG00000124762 (association with cancer (MONDO_0004992) 0.72; per-cancer scores at or above 0.5: urinary bladder cancer 0.64, breast cancer 0.51 (GraphQL API, CC0)); IntOGen CDKN1A (driver in 9 cohorts (Act 2, LoF 7); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest. Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Also involved in p53-independent DNA damage-induced G2 arrest mediated by CREB3L1 in astrocytes and osteoblasts. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localisation and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Location: Cytoplasm; Nucleus (UniProt). Locus 6p21.2 (HGNC).
- Bladder & urothelial cancer: Open Targets association 0.64 with urinary bladder cancer (MONDO_0001187); IntOGen driver in 5 cohorts (BLCA)
- Hepatocellular carcinoma: IntOGen driver in 3 cohorts (HCC)
- Colorectal cancer: CIViC evidence names this disease
- Renal cell carcinoma: IntOGen driver in 1 cohort (CHRCC)
- Breast cancer: Open Targets association 0.51 with breast cancer (MONDO_0007254)
- Retinoblastoma: CIViC evidence names this disease
Notes
top- 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 1 therapies; IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 7 cohorts; CIViC holds 4 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.
Latest papers
topQuery for this target: (TITLE:"CDKN1A" OR ABSTRACT:"CDKN1A" OR TITLE:"cyclin dependent kinase inhibitor 1A" OR ABSTRACT:"cyclin dependent kinase inhibitor 1A" OR TITLE:"Cyclin-dependent kinase inhibitor 1" OR ABSTRACT:"Cyclin-dependent kinase inhibitor 1" OR TITLE:"P21" OR ABSTRACT:"P21" OR TITLE:"CIP1" OR ABSTRACT:"CIP1" OR TITLE:"WAF1" OR ABSTRACT:"WAF1") 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 CDKN1A, not a curated reading list.
Similar pages
not linked directly; found by shared links- TargetATM
Shares The p53 network (guardian of the genome), p53 / RB / cell-cycle checkpoint, Bladder & urothelial cancer, Breast cancer (all types).
- TargetMDM4
Shares The p53 network (guardian of the genome), Breast cancer (all types), CIViC, Open Targets Platform.
- TargetVHL
Shares Chromophobe renal cell carcinoma, Renal cell carcinoma, Breast cancer (all types), CIViC.
- TargetGRM3
Shares Chromophobe renal cell carcinoma, Renal cell carcinoma, IntOGen.
- TargetCDKN2A
Shares Cellular senescence, The cell-cycle engine (cyclins & CDKs), Bladder & urothelial cancer, CIViC.
- TermHallmark: evading growth suppressors
Shares The p53 network (guardian of the genome), The cell-cycle engine (cyclins & CDKs), p53 / RB / cell-cycle checkpoint.
- InstitutionFox Chase Cancer Center
Shares Retinoblastoma, Renal cell carcinoma, Hepatocellular carcinoma.
- Key paperSherr and Roberts 1999: CDK inhibitors as regulators of the G1 phase
Shares The cell-cycle engine (cyclins & CDKs), p53 / RB / cell-cycle checkpoint.