Pathogenic variations illuminate functional constraints in intrinsically disordered proteins
Abstract
and uncovered localized "island-like" patterns of elevated pathogenicity within IDRs. Leveraging these signals, we developed a classifier to prioritize predicted ELM motifs (PEMs), revealing thousands of candidate functional sites linked to major disease classes, including neurological, cardiovascular, and cancer-associated genes. Case studies, including POLK and FOXP2, demonstrate how this approach connects genetic variation to molecular mechanisms. This framework provides a scalable strategy to interpret variants of uncertain significance and defines the functional constraints governing the disordered proteome.
Fields of Study & Subjects
Protein Structure and Dynamics
Enzyme Structure and Function
Evolution and Genetic Dynamics
Publication details
- Journal / source
- iScience
- Publisher
- Elsevier BV
- Volume
- 29
- Issue
- 4
- Pages
- 115215–115215
- Publication date
- 4 March 2026
- Language
- EN