This report describes a potential model of GNAO1-related neurological disorders. Two diseases, developmental and epileptic encephalopathy 17 (MIM:615473; FBhh0001481) and neurodevelopmental disorder with involuntary movements(MIM:617493) are associated with this gene; both exhibit autosomal dominant inheritance. The GNAO1 gene encodes an alpha subunit of the heterotrimeric guanine nucleotide-binding proteins (G proteins), modulators of various transmembrane signaling systems. In Drosophila, Dmel\Gαo is the highest-scoring ortholog of GNAO1; an amorphic allele created by targeted recombination, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\Gαo.
A human disease model report has been created for this potential model because variants analogous to disease-implicated mutations have been introduced into the endogenous the Dmel\Gαo gene and humanized genes have been introduced at the endogenous Drosophila locus. However, most of these reagents have not been used to investigate disease-related phenotypes.
The wild-type human Hsap\GNAO1 gene has been introduced into flies in several contexts: as a UAS construct and as "humanized" genes at the endogenous Drosophila Gαo locus; for the latter, heterologous rescue (function complementation) has been demonstrated.
Variants analogous to disease-implicated mutations in the human GNAO1 gene have been introduced into Dmel\Gαo by homologous recombination; however, most have not yet been characterized. Variant(s) implicated in human disease introduced (as analogous mutation in fly gene): A221D in the fly Gαo gene (corresponds to A221D in the human GNAO1 gene); G45E in the fly Gαo gene (corresponds to G45E in the human GNAO1 gene); G203R in the fly Gαo gene (corresponds to G203R in the human GNAO1 gene); the last variant has been analyzed in the developmental and epileptic encephalopathy 17 fly model.
Knockdown of Dmel\Gαo in neural tissues, effected by RNAi, results in neuroanatomy- and memory-defective phenotypes. Multiple physical and genetic interactions have been described for Gαo; see below and in the Gαo gene report.
[updated Jan. 2021 by FlyBase; FBrf0222196]
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Heterotrimeric G proteins are membrane-bound GTPases that are linked to 7-TM receptors. Ligand binding causes a receptor conformational change, detaching the G protein and switching it 'on'. [Gene Cards, GNAO1; 2019.11.02]
The GNAO1 gene encodes an alpha subunit of the heterotrimeric guanine nucleotide-binding proteins (G proteins), a large family of signal-transducing molecules. [from MIM:139311]
One to one (1 human to 1 Drosophila); multiple related genes in both species.
High-scoring ortholog of human GNAO1; multiple related genes in both species (1 Drosophila to 1 human). Dmel\Gαo shares 82% identity and 90% similarity with the human gene.
