Genetic variation associated with condensate dysregulation in disease. Academic Article uri icon

Overview

abstract

  • A multitude of cellular processes involve biomolecular condensates, which has led to the suggestion that diverse pathogenic mutations may dysregulate condensates. Although proof-of-concept studies have identified specific mutations that cause condensate dysregulation, the full scope of the pathological genetic variation that affects condensates is not yet known. Here, we comprehensively map pathogenic mutations to condensate-promoting protein features in putative condensate-forming proteins and find over 36,000 pathogenic mutations that plausibly contribute to condensate dysregulation in over 1,200 Mendelian diseases and 550 cancers. This resource captures mutations presently known to dysregulate condensates, and experimental tests confirm that additional pathological mutations do indeed affect condensate properties in cells. These findings suggest that condensate dysregulation may be a pervasive pathogenic mechanism underlying a broad spectrum of human diseases, provide a strategy to identify proteins and mutations involved in pathologically altered condensates, and serve as a foundation for mechanistic insights into disease and therapeutic hypotheses.

publication date

  • July 8, 2022

Research

keywords

  • Proteins

Identity

PubMed Central ID

  • PMC9339523

Scopus Document Identifier

  • 85134984294

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2022.06.010

PubMed ID

  • 35809564

Additional Document Info

volume

  • 57

issue

  • 14