PACS ‐1 unlocked: How a single mutation disrupts intramolecular regulation to drive neurodevelopmental disease
Abstract
Rare monogenic disorders provide powerful insights into fundamental cell biology. PACS1 syndrome is a striking example of this: a neurodevelopmental disorder, caused almost exclusively by a single missense mutation in the PACS1 gene (c.607C>T), resulting in the Arg203Trp (R203W) amino-acid substitution. Despite the relative genetic simplicity, the exact molecular mechanism through which this mutation drives disease remains unknown. In their study published in this issue of The FEBS Journal, Krzysiak et al. provide a compelling mechanistic framework, demonstrating that the R203W substitution disrupts intramolecular regulation of PACS-1, thereby impairing a critical signalling hub.
Fields of Study & Subjects
Genomics and Rare Diseases
Hereditary Neurological Disorders
Protein Tyrosine Phosphatases
Publication details
- Journal / source
- FEBS Journal
- Publisher
- Wiley
- Volume
- 293
- Issue
- 19
- Pages
- 5700-5702
- Publication date
- 16 June 2026
- Language
- EN