Widespread macromolecular interaction perturbations in human genetic disorders.

ABSTRACT: How disease-associated mutations impair protein activities in the context of biological networks remains mostly undetermined. Although a few renowned alleles are well characterized, functional information is missing for over 100,000 disease-associated variants. Here we functionally profile several thousand missense mutations across a spectrum of Mendelian disorders using various interaction assays. The majority of disease-associated alleles exhibit wild-type chaperone binding profiles, suggesting they preserve protein folding or stability. While common variants from healthy individuals rarely affect interactions, two-thirds of disease-associated alleles perturb protein-protein interactions, with half corresponding to "edgetic" alleles affecting only a subset of interactions while leaving m

SUBMITTER: Sahni N 

PROVIDER: S-EPMC4441215 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature