{"entity":{"id":"chek2","kind":"target","name":"CHEK2","aka":["checkpoint kinase 2","Serine/threonine-protein kinase Chk2","CDS1","CHK2","HuCds1","PP1425","bA444G7","RAD53"],"tldr":"CHEK2 (Serine/threonine-protein kinase Chk2) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Breast cancer, Prostate cancer, Sarcomas and 5 more.","summary":"Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T].\n\nCIViC holds 9 clinical evidence items and 0 assertions across 6 variants, naming Olaparib, Enzalutamide and Talazoparib. Open Targets scores its association with cancer at 0.91 (direct and indirect evidence; datatypes genetic literature 0.86, clinical 0.19, affected pathway 0.76, literature 0.99, genetic association 0.95, somatic mutation 0.88). IntOGen calls it a driver in 1 cohort (1 activating, 0 loss-of-function), covering Invasive Breast Carcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:16627","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16627"},{"label":"UniProt O96017","url":"https://www.uniprot.org/uniprotkb/O96017/entry"},{"label":"NCBI Gene 11200","url":"https://www.ncbi.nlm.nih.gov/gene/11200"},{"label":"Ensembl ENSG00000183765","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000183765"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["breast-cancer","prostate","sarcoma","colorectal","ovarian","lung-cancer","thyroid","gastric"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"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: Open Targets known-drug datatype score 0.19; IntOGen calls it an activating (Act) driver in 1 cohort; CIViC holds 9 clinical evidence items on its variants; UniProt keyword \"DNA repair\". Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"CHEK2","role":["drug-target","oncogene-driver","biomarker","dna-repair"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:16627","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16627","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt O96017","url":"https://www.uniprot.org/uniprotkb/O96017/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CHEK2","url":"https://civicdb.org/features/8950","note":"9 evidence items, 0 assertions, 6 variants; diseases: Prostate Cancer, Cancer, Castration-resistant Prostate Carcinoma, Breast Cancer (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000183765","url":"https://platform.opentargets.org/target/ENSG00000183765/associations","note":"association with cancer (MONDO_0004992) 0.91; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.58, colorectal cancer 0.74, gastric cancer 0.63, prostate cancer 0.80, ovarian cancer 0.73, endometrial cancer 0.54 (GraphQL API, CC0)"},{"label":"IntOGen CHEK2","url":"https://www.intogen.org/search?gene=CHEK2","note":"driver in 1 cohort (Act 1, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance); what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA CHEK2: RNA low tissue specificity; high antibody staining in 21 normal tissues; highest cancer staining head and neck cancer (4 of 4 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Prostate cancer, Sarcomas (soft tissue, bone, GIST), Colorectal cancer, Ovarian cancer, Lung cancer (all types), Thyroid cancer and more); Open Targets associates it with 23 specific cancer types at or above 0.5 (breast cancer, breast carcinoma, hereditary breast carcinoma, bone osteosarcoma, Li-Fraumeni syndrome, prostate cancer and more). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt O96017","url":"https://www.uniprot.org/uniprotkb/O96017/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CHEK2","url":"https://civicdb.org/features/8950","note":"9 evidence items, 0 assertions, 6 variants; diseases: Prostate Cancer, Cancer, Castration-resistant Prostate Carcinoma, Breast Cancer (GraphQL API, CC0)"},{"label":"IntOGen CHEK2","url":"https://www.intogen.org/search?gene=CHEK2","note":"driver in 1 cohort (Act 1, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas CHEK2 tissue","url":"https://www.proteinatlas.org/ENSG00000183765-CHEK2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000183765 associations","url":"https://platform.opentargets.org/target/ENSG00000183765/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:16627","ensembl":"ENSG00000183765","uniprot":"O96017","entrez":"11200","firstDescribed":1998,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Matsuoka et al, Science, 1998, \"Linkage of ATM to cell cycle regulation by the Chk2 protein kinase\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9836640/","biology":"Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Location: Nucleus; Nucleus, PML body; Nucleus, nucleoplasm (UniProt). Locus 22q12.1 (HGNC).","whereFound":["Breast cancer: Open Targets association 0.87 with breast cancer (MONDO_0007254); CIViC evidence names this disease","Prostate cancer: Open Targets association 0.80 with prostate cancer (MONDO_0008315); CIViC evidence names this disease","Sarcomas: Open Targets association 0.75 with sarcoma (MONDO_0005089)","Colorectal cancer: Open Targets association 0.74 with colorectal cancer (MONDO_0005575)","Ovarian cancer: Open Targets association 0.73 with ovarian cancer (MONDO_0008170)","Lung cancer: Open Targets association 0.69 with lung cancer (MONDO_0008903)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/chek2/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"pathway":[{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"}],"paper":[{"id":"paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021","kind":"paper","name":"Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference","route":"/key-papers/paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021/"},{"id":"paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021","kind":"paper","name":"Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms","route":"/key-papers/paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021/"},{"id":"paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","kind":"paper","name":"Inherited DNA-repair gene mutations in men with metastatic prostate cancer","route":"/key-papers/paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016/"},{"id":"paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018","kind":"paper","name":"Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer","route":"/key-papers/paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018/"},{"id":"paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019","kind":"paper","name":"Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines","route":"/key-papers/paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019/"}],"biomarker":[{"id":"hrr-gene-mutation","kind":"biomarker","name":"Homologous recombination repair gene mutation in prostate cancer","route":"/biomarkers/hrr-gene-mutation/"}],"term":[{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"}]}}