Loss-of-function variants in CHEK2 confer increased risk of developing cancers. Most CHEK2 variants, however, have an unknown effect on the function of the Chk2 protein kinase. This study tested the functional impact of all possible variants in the CHEK2 coding region. The protein structure is shown with a heat map overlay showing the fraction of variants at each position that were damaging to function; red positions indicate that all amino acid changes were damaging, while blue positions indicate all changes were tolerated. Regions the least tolerant to changes (red) include the catalytic site in the kinase domain. See McCarthy-Leo et al. Download August’s cover page

Image Credit: Claire E. McCarthy-Leo