Missense mutations in intrinsically disordered protein regions link pathogenicity and phase separation.

ABSTRACT: The impact of missense genetic variations on protein function is often enigmatic, especially for mutations that map to intrinsically disordered regions (IDRs). Given the functional importance of phase separation of IDRs, it has been proposed that mutations that modulate phase separation might preferentially lead to disease. To examine this idea, we used the robust predictability of phase-separating (PS) IDRs and annotation of disease-associated proteins and mutations to map the correlation between disease and phase separation. Consistent with previous work linking phase separation to cancer and autism spectrum disorder, we find a higher prevalence of predicted phase separation behavior in disease-associated proteins than typical for human proteins. We map the prevalence of phase separation

SUBMITTER: Kipp OL 

PROVIDER: S-EPMC12597276 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature