CHEK2
In databases:
● Ensembl (http://www.ensembl.org/index.html): ENSG00000183765
● UniProt (http://www.uniprot.org/): O96017
● OMIM (http://www.ncbi.nlm.nih.gov/omim): 604373
● GeneCards (http://www.genecards.org/): CHEK2
● HGNC (http://www.genenames.org/): 16627 or CHEK2
● EC enzyme number: EC 2.7.11.1
Gene locus:
22q12.1
Protein name:
CHK2 checkpoint homolog (S. pombe)
Protein Size:
543 amino acids; about 61 kDa
Function:
The CHEK2-encoded protein, Chk2, regulates cell cycle checkpoints and apoptosis, especially in response to DNA double-strand breaks. Activated Chk2 may phosphorylate various targets, among which p53, Cdc25a, PML and Brca1, ultimately leading to cell cycle arrest and DNA repair.
Cancer-related alterations:
Germline mutations: the northern european founder mutation "1100delC" is the most common found in breast cancer families. Other small deletions, stops, and missense mutations, such as Arg145Trp and Ile157Thr are rare in cancer families but not found in controls. The 1100delC mutation appears to increase the penetrance of mutations in certain other breast cancer genes, notably BRCA2.
Somatic mutations: missense mutations in the CHK2 FHA and kinase domains as well as frameshifts and nonsense mutations have been found at low frequencies in osteosarcoma and more rarely in carcinomas of the ovary, lung, and vulva.
References (open access) :
Pathology of hereditary breast cancer. van der Groep P, van der Wall E, van Diest PJ. Cell Oncol (Dordr). 2011 Apr;34(2):71-88.
Evaluating cancer epidemiologic risk factors using multiple primary malignancies. Kuligina E, Reiner A, Imyanitov EN, Begg CB. Epidemiology. 2010 May;21(3):366-72.
Are the so-called low penetrance breast cancer genes, ATM, BRIP1, PALB2 and CHEK2, high risk for women with strong family histories? Byrnes GB, Southey MC, Hopper JL. Breast Cancer Res. 2008;10(3):208.
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