GABRG3 encodes the gamma-3 subunit of GABAA receptors, heteropentameric ligand-gated chloride channels that mediate inhibitory GABAergic neurotransmission in the brain. The subunit assembles with four other subunits around a central pore; GABA binding at alpha-beta interfaces activates the channel to permit selective chloride influx down its electrochemical gradient, hyperpolarizing neurons. GABRG3 maps to chromosome 15-q13, clustered with GABRB3 and GABRA5, and exhibits imprinting with differential parental methylation 1 2. GABRG3 variants associate with multiple neurodevelopmental disorders. In autism spectrum disorder (ASD), the rs7180500 C allele confers risk in Chinese Han populations, with eQTL analysis linking it to cerebellar GABRG3 expression, while rare variants p.Val233Met and p.Pro365Ser show enrichment in autistic patients 3. The rs140679 T allele and rs208129 TT genotype demonstrate significant ASD associations in other populations 4 5. GABRG3 alterations—including sequence variants and methylation abnormalities—expand the clinico-molecular spectrum of Angelman syndrome in approximately 10% of undiagnosed cases 2. Additionally, GABRG3 variants associate with atypical absence seizures and developmental epileptic encephalopathies 6, and common variants influence sleep duration through gene-gene interactions within the GABRB3-GABRA5-GABRG3 cluster 7. GABRG3 represents a versatile susceptibility locus for neurological and neurodevelopmental conditions.