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FB2026_01
,
released March 12, 2026
This report describes developmental and epileptic encephalopathy 17, a subtype of developmental and epileptic encephalopathy that exhibits 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.
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. See the 'Disease-Implicated Variants' table below. 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). The variant G203R in the fly Gαo gene (corresponds to G203R in the human GNAO1 gene) has been analyzed in the context of a Drosophila model of DEE17. Flies heterozygous for the G203R variant exhibit significant motor dysfunction, a reduction in lifespan, and limited but significant age-related brain degeneration.
Knockdown of Dmel\Gαo in neural tissues, effected by RNAi, results in neuroanatomy- and memory-defective phenotypes.
[updated Apr. 2024 by FlyBase; FBrf0222196]
[DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 17; DEE17](https://omim.org/entry/615473)
[GUANINE NUCLEOTIDE-BINDING PROTEIN, ALPHA-ACTIVATING ACTIVITY POLYPEPTIDE O; GNAO1](https://omim.org/entry/139311)
Developmental and epileptic encephalopathy 17 (DEE17) is a severe neurologic disorder characterized by onset of intractable seizures in the first weeks or months of life. EEG often shows a burst-suppression pattern consistent with a clinical diagnosis of Ohtahara syndrome. Affected infants have very poor psychomotor development and may have brain abnormalities, such as cerebral atrophy or thin corpus callosum. Some patients may show involuntary movements (summary by Nakamura et al., 2013; pubmed:23993195). [from MIM:615473; 2022.11.02]
Developmental and epileptic encephalopathy 17 is caused by heterozygous mutation in the GNAO1 gene on chromosome 16q13. [from MIM:615473; 2022.11.02]
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; 2022.11.02]
The GNAO1 gene encodes an alpha subunit of the heterotrimeric guanine nucleotide-binding proteins (G proteins), a large family of signal-transducing molecules (Strathmann et al., 1990; pubmed:1697681). [from MIM:139311; 2022.11.02]
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).