[5] Due to alternative splicing, the gene codes for many protein isoforms, all being subunits in the GABAA receptor, a ligand-gated ion channel.

The encoded protein is one of at least 13 distinct subunits of a multisubunit chloride channel that serves as the receptor for gamma-aminobutyric acid, the major inhibitory neurotransmitter of the nervous system.

[14] De novo heterozygous missense mutations within a highly conserved region of the GABRB3 gene can decrease the peak current amplitudes of neurons or alter the kinetic properties of the channel.

[16][17] The study of the crystal structure of the human β3 homopentamer revealed unique qualities that are only observed in eukaryotic cysteine-loop receptors.

The distribution of expression of the GABAA receptor subunits (GABRB3 included) during development indicates that GABA may function as a neurotrophic factor, impacting neural differentiation, growth, and circuit organization.

The highest levels of Gabrb3 expression in the mature mouse brain occur in the Purkinje and granule cells of the cerebellum, the hippocampus, and the piriform cortex.

[11] Phosphorylation of the GABAA by cAMP-dependent protein kinase (PKA) has a regulatory effect dependent on the beta subunit involved.

[20] In mice, the knockout mutation of Gabrb3 causes severe neonatal mortality with the cleft palate phenotype present, the survivors experiencing hyperactivity, lack of coordination and suffering with epileptic seizures.

[12] These mice also exhibit changes to the vestibular system within the ear, resulting in poor swimming skills, difficulty in walking on grid floors, and are found to run in circles erratically.

Normal facial characteristics can be restored through the insertion of a Gabrb3 transgene into the mouse genome, making the Gabrb3 gene primarily responsible for cleft palate formation.

Duplications of the 15q11-13 region displayed in autistic patients are almost always of maternal origin (not paternal) and account for 1–2% of diagnosed autism disorder cases.

[13] This gene is also a candidate for autism because of the physiological response that benzodiazepine has on the GABA-A receptor, when used to treat seizures and anxiety disorders.

[13] These mice exhibit similar phenotypic symptoms such as non-selective attention, deficits in a variety of exploratory parameters, sociability, social novelty, nesting and lower rearing frequency as can be equated to characteristics found in patients diagnosed with autism spectrum disorder.