Isra Sadiya, Irina Nekrasova, Meirav Avital-Shacham, Naomi van Wijk, Keren Zohar, Nir Kalisman, Dina Shneidman-Duhovny, Ehud Banne, A. Nissenkorn, L. Blumkin, M. Linial, M. Kosloff
2026.1.1BBA Advances
tlooto Summary
GNAO1 E246K causes complex developmental delays and substantial motor difficulties and Proteomics revealed enhanced Gβγ binding and reduced RGS interactions.
Abstract
Highlights • GNAO1 E246K causes complex developmental delays and substantial motor difficulties.• Gαo E246K does not alter nucleotide binding or RGS-mediated GTP hydrolysis.• Proteomics revealed enhanced Gβγ binding and reduced RGS interactions.• No novel or increased interactions with GNAO1 downstream partners were observed.• E246K impairs Gβγ dissociation and dominantly suppresses wild-type Gαo signaling.
Citation format
SADIYA, Isra, et al. Deciphering a mechanistic basis for the pathological effect of the GNAO1 E246K variant in neurodevelopmental disorder. BBA Advances, 2026, 9: 100182.