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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.
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].
CIViC 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.
In plain words · 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.
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.
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.
No product in this corpus aims at CHEK2 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
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.)
Sources: UniProt O96017; CIViC gene CHEK2; IntOGen CHEK2; Human Protein Atlas CHEK2 tissue; Open Targets ENSG00000183765 associations
First described 1998. 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". Source.
Sources: HGNC HGNC:16627 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt O96017 (protein name, function text, keywords and locations (REST API)); CIViC gene CHEK2 (9 evidence items, 0 assertions, 6 variants; diseases: Prostate Cancer, Cancer, Castration-resistant Prostate Carcinoma, Breast Cancer (GraphQL API, CC0)); Open Targets ENSG00000183765 (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)); IntOGen CHEK2 (driver in 1 cohort (Act 1, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
RNA: low tissue specificity, detected in many normal tissues.
Medium: Caudate, Cerebral cortex, Cervix, Kidney, Lung, Lymph node, Salivary gland, Small intestine.
Medium only: 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.
It identifies a way that a good test produces a wrong answer, and it names the fix. Any plasma repair-gene result used to decide on a PARP inhibitor should be run with a paired blood control, or an older man may be treated for a marrow clone rather than for his prostate cancer.
It established plasma profiling as a routine alternative to tissue for the BRCA question in advanced prostate cancer, with a sensible rule attached: if plasma finds nothing actionable, go back to tissue. It also documents at scale both the extra resistance information plasma gives and the clonal haematopoiesis noise that comes with it.
It is the second half of the argument for unselected germline testing, and it widens the target beyond BRCA: two thirds of the actionable inherited findings in prostate cancer are in other genes, including the mismatch repair genes that open a checkpoint inhibitor route.
It links a line on a UK pathology report to a question about a family. Intraductal carcinoma is a reportable item in the current dataset, and its presence is a practical prompt to check that germline testing has actually been offered rather than assumed.
The evidence that made germline testing standard for every man with metastatic prostate cancer, whatever his family history. It changes his treatment, because PARP inhibitors and platinum work better in these tumours, and it changes his relatives' screening, because BRCA2 carries breast, ovarian and pancreatic risk as well.
Query for this target: (TITLE:"CHEK2" OR ABSTRACT:"CHEK2" OR TITLE:"checkpoint kinase 2" OR ABSTRACT:"checkpoint kinase 2" OR TITLE:"Serine/threonine-protein kinase Chk2" OR ABSTRACT:"Serine/threonine-protein kinase Chk2" OR TITLE:"CDS1" OR ABSTRACT:"CDS1" OR TITLE:"CHK2" OR ABSTRACT:"CHK2" OR TITLE:"HuCds1" OR ABSTRACT:"HuCds1") 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 CHEK2, not a curated reading list.
Shares Homologous recombination repair gene mutation in prostate cancer, CIViC, IntOGen, Gastric & gastro-oesophageal junction cancer.
Shares Homologous recombination repair gene mutation in prostate cancer, CIViC, Gastric & gastro-oesophageal junction cancer, Ovarian cancer.
Shares Inherited DNA-repair gene mutations in men with metastatic prostate cancer, Homologous recombination repair gene mutation in prostate cancer, CIViC, Gastric & gastro-oesophageal junction cancer.
Shares Thyroid cancer, CIViC, IntOGen, Gastric & gastro-oesophageal junction cancer.
Shares Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference, Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines, Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms.
Shares Double-strand break repair: HR versus end joining, IntOGen, Gastric & gastro-oesophageal junction cancer, Ovarian cancer.
Shares Thyroid cancer, CIViC, IntOGen, Lung cancer (all types).
Shares Thyroid cancer, Sarcomas (soft tissue, bone, GIST), CIViC, IntOGen.