GABRA3

GABRA3 is a gene that encodes the alpha 3 subunit of the GABA_A receptor, a protein that plays a crucial role in the function of the central nervous system. The GABA_A receptor is a type of ligand-gated ion channel that responds to the neurotransmitter gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the mammalian brain.

Structure

The GABRA3 gene is located on the X chromosome (specifically, Xq28), and it spans approximately 16 kilobases. The encoded protein is composed of four transmembrane domains, with both the N- and C-termini located intracellularly. The alpha 3 subunit is one of several possible alpha subunits that can be incorporated into the GABA_A receptor, which is typically a pentamer composed of five subunits.

Function

The alpha 3 subunit of the GABA_A receptor contributes to the receptor's functional diversity. When GABA binds to the GABA_A receptor, the receptor undergoes a conformational change that allows chloride ions to flow into the neuron, resulting in hyperpolarization of the neuron and inhibition of neuronal firing. The specific subunit composition of the GABA_A receptor can influence the receptor's pharmacological and biophysical properties, including its sensitivity to GABA, its rate of desensitization, and its modulation by drugs such as benzodiazepines and barbiturates.

Clinical significance

Mutations in the GABRA3 gene have been associated with various neurological and psychiatric disorders, including epilepsy, autism, schizophrenia, and anxiety disorders. In particular, a mutation in GABRA3 has been identified in a family with X-linked juvenile myoclonic epilepsy. Additionally, variations in GABRA3 have been linked to differences in sensitivity to the effects of alcohol, suggesting a potential role in alcohol use disorder.

See also

• GABA_A receptor
• Gamma-aminobutyric acid
• X chromosome