Phase Separation as a Missing Mechanism for Interpretation of Disease Mutations.
Cell
; 183(7): 1742-1756, 2020 12 23.
Article
em En
| MEDLINE
| ID: mdl-33357399
ABSTRACT
It is unclear how disease mutations impact intrinsically disordered protein regions (IDRs), which lack a stable folded structure. These mutations, while prevalent in disease, are frequently neglected or annotated as variants of unknown significance. Biomolecular phase separation, a physical process often mediated by IDRs, has increasingly appreciated roles in cellular organization and regulation. We find that autism spectrum disorder (ASD)- and cancer-associated proteins are enriched for predicted phase separation propensities, suggesting that IDR mutations disrupt phase separation in key cellular processes. More generally, we hypothesize that combinations of small-effect IDR mutations perturb phase separation, potentially contributing to "missing heritability" in complex disease susceptibility.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article