Gabra3, encoding the α3-subunit of the GABAA receptor, is a gene located on chromosome Xq28. GABAA receptors are ligand-gated ion channels that play a crucial role in inhibitory neurotransmission in the central nervous system, regulating neuronal excitability. Mutations in genes coding for GABAA receptor subunits have been associated with various epileptic disorders, suggesting the importance of Gabra3 in maintaining normal neural function [1].

Functional studies in Xenopus laevis oocytes with rare loss-of-function variants in Gabra3 identified in patients with epileptic seizures, encephalopathy, and dysmorphic features revealed a significant reduction of GABA-evoked anion currents for mutants compared to wild-type receptors. The degree of current reduction correlated partially with the phenotype, indicating that these loss-of-function variants increase the risk for a combination of epilepsy, intellectual disability/developmental delay, and dysmorphic features, presenting in some pedigrees with an X-linked inheritance pattern [1].

In conclusion, Gabra3 is essential for normal inhibitory neurotransmission via its role in the GABAA receptor. Studies with functional variants in model systems like Xenopus laevis oocytes have revealed its significance in epilepsy and related disorders. Understanding Gabra3 function provides insights into the molecular mechanisms underlying these neurological conditions, which may aid in developing novel therapeutic strategies.

References:

1. Niturad, Cristina Elena, Lev, Dorit, Kalscheuer, Vera M, Maljevic, Snezana, Leshinsky-Silver, Esther. . Rare GABRA3 variants are associated with epileptic seizures, encephalopathy and dysmorphic features. In Brain : a journal of neurology, 140, 2879-2894. doi:10.1093/brain/awx236. https://pubmed.ncbi.nlm.nih.gov/29053855/