| Popis: |
Mutations of protein kinases are common and can cause cancer and other diseases. However, our understanding of the mutability in genes encoding kinases remains rudimentary. Given previously proposed factors associated with high mutation rates, we analyzed how many genes encoding druggable kinases match with (i) proximity to telomeres or (ii) high A+T content. We extracted genomic information using National Institute of Health Genome Data Viewer. Among 129 druggable human kinase genes studied, 106 genes satisfied either factors (i) or (ii), resulting in an 82% match. A similar 85% match rate was found in 73 genes encoding pro-inflammatory cytokines of multisystem inflammatory syndrome in children. As we further compared these two factors in 20 de novo mutations of mice exposed to space-like ionizing radiation, however, 10 of 20 murine genetic loci met (i) or (ii), leading to only a 50% match. When compared with the top selling approved drugs, the data suggest that matching rate analysis on factor-druggable genome is feasible to systematically prioritize the relative mutability of the novel druggable candidates. These two factors not only predict how mutations of the disease phenotype are attributed to genetic and/or environmental factors but also sort out druggable proteins by their relative mutability. |
