CHEK2

About CHEK2

CHEK2 on chromosome 22q12.1 encodes checkpoint kinase 2, a serine threonine kinase activated by ATM in response to DNA double strand breaks. Once activated, CHK2 phosphorylates targets such as p53, BRCA1, and CDC25 phosphatases, halting the cell cycle to allow repair or triggering apoptosis. The c.1100delC founder variant, found at a frequency of around 1 percent in some Northern European populations, roughly doubles breast cancer risk, and other variants such as I157T confer smaller increases. CHEK2 variants are also associated with modestly increased risks of colorectal, prostate, kidney, and thyroid cancer. CHEK2 is included in multigene hereditary breast cancer panels and is considered a moderate penetrance gene. Unlike BRCA1 and BRCA2, the absolute cancer risk from CHEK2 variants is lower and more strongly influenced by family history and other genetic factors, including polygenic risk, so risk assessment is individualized and typically focuses on enhanced breast surveillance rather than risk reducing surgery. CHEK2 variants were originally reported in some families with features of Li Fraumeni syndrome, but CHEK2 is no longer regarded as a cause of that syndrome. The gene was identified as a human counterpart of the yeast checkpoint kinases Rad53 and Cds1.