Pathogenic missense protein variants affect different functional pathways and proteomic features than healthy population variants.

ABSTRACT: Missense variants are present amongst the healthy population, but some of them are causative of human diseases. A classification of variants associated with "healthy" or "diseased" states is therefore not always straightforward. A deeper understanding of the nature of missense variants in health and disease, the cellular processes they may affect, and the general molecular principles which underlie these differences is essential to offer mechanistic explanations of the true impact of pathogenic variants. Here, we have formalised a statistical framework which enables robust probabilistic quantification of variant enrichment across full-length proteins, their domains, and 3D structure-defined regions. Using this framework, we validate and extend previously reported trends of variant enrichme

SUBMITTER: Laddach A 

PROVIDER: S-EPMC8110273 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature