CHEK2
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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.
External identifiers
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)
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).
- 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)
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: 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.
Latest papers
topQuery 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.
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