P557: Functional analysis of GNAI1 variants and their impact on cellular signaling in neurodevelopmental disorders*

Genetics in Medicine Open 2026 Open access

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Authors: Khaled Berro, Esmat Fathi, Sebastian Rading, Christian Kubisch, Heather C. Mefford, Meliha Karsak
DOI: 10.1016/j.gimo.2026.104048
Cited by: 0

Abstract

GNAI1 (HGNC:4384) encodes Gαi1, the α-subunit of an inhibitory heterotrimeric (αβγ) G protein coupled to G protein-coupled receptors (GPCRs). Upon GPCR activation, Gαi1 bound to GTP (Gαi1–GTP) dissociates from Gβγ and inhibits adenylate cyclase, thereby lowering intracellular 3',5'-cyclic adenosine monophosphate (cAMP). Likely pathogenic or pathogenic GNAI1 variants cause a neurodevelopmental disorder (OMIM 619854) characterized by global developmental delay, intellectual disability, hypotonia, and epilepsy; however, the underlying signal transduction defects remain poorly defined.

Fields of Study & Subjects

Genetics and Neurodevelopmental Disorders Genomics and Rare Diseases Receptor Mechanisms and Signaling

Publication details

Journal / source
Genetics in Medicine Open
Volume
4
Pages
104048–104048
Publication date
1 January 2026
Language
EN