Disrupted RGS coupling underlies a clinically distinct subset of GNAO1-related disorder

A subset of disease-linked Go (GNAO1-related disorder) variants impairs interactions with RGS proteins, despite lacking obvious biochemical defects.

• Why it matters: Some GNAO1-related cases show movement disorders, developmental delays, and/or epileptic seizures, yet a subset of Go mutations does not show clear biochemical abnormalities.
• What they did: The work combined structural modeling, protein-protein binding assays in vitro and in cells, and downstream ion channel electrophysiology to test effects on RGS coupling.
• The result: Patients with these RGS-interaction–impairing variants had comparatively mild symptoms, supporting RGS regulation as important for G protein signaling and human neurobiology.

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