A Novel <scp>YWHAG</scp> Variant <scp>L173S</scp> Causes Developmental and Epileptic Encephalopathy by Disrupting the Hydrophobic Internal Protein Structure

The functional domain involving the L173 residue of YWHAG remains unknown. Our findings suggest that the disruption of the stability of the highly conserved internal core of the YWHAG protein may be one mechanism leading to functional impairment, distinct from the previously proposed pathogenic models of dimer formation defects and/or impaired binding to phosphopeptide ligands. This may provide insights into the functional mechanisms of YWHAG and potential therapeutic strategies.