Structural bioinformatics enhances the interpretation of somatic mutations in KDM6A found in human cancers.

ABSTRACT: The histone demethylase KDM6A has recently elicited significant attention because its mutations are associated with a rare congenital disorder (Kabuki syndrome) and various types of human cancers. However, distinguishing KDM6A mutations that are deleterious to the enzyme and their underlying mechanisms of dysfunction remain to be fully understood. Here, we report the results from a multi-tiered approach evaluating the impact of 197 KDM6A somatic mutations using information derived from combining conventional genomics data with computational biophysics. This comprehensive approach incorporates multiple scores derived from alterations in protein sequence, structure, and molecular dynamics. Using this method, we classify the KDM6A mutations into 136 damaging variants (69.0%), 32 tolerated var

SUBMITTER: Chi YI 

PROVIDER: S-EPMC9111933 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature