NEDAMSS syndrome-related truncating and missense mutations are associated with aberrant liquid-liquid phase separation of IRF2BPL - PubMed
3 hours ago
- #IRF2BPL
- #NEDAMSS syndrome
- #liquid-liquid phase separation
- Truncating and missense mutations in IRF2BPL are linked to NEDAMSS syndrome and related neurodevelopmental disorders.
- The central portion of IRF2BPL contains low-complexity regions (LCR1-3) and a higher-complexity domain (HCD), with LCR1 driving liquid-liquid phase separation (LLPS).
- Disease-related mutations disrupt IRF2BPL LLPS, leading to aberrant cytoplasmic condensates and nuclear depletion of wild-type IRF2BPL.
- Aberrant LLPS triggers molecular disease mechanisms, including WNT1 upregulation and altered neuronal electrophysiology.
- The findings highlight LLPS disruption as a key pathogenic mechanism in NEDAMSS syndrome.