GABA(A) receptors are the main inhibitory neurotransmitter receptors in the mammalian brain. They respond to a wide variety of drugs including benzodiazepines. The entire GABA receptor family contains 19 known genes.

GABA(A) receptors are mostly pentameric proteins composed of different subunits and each subunit has several subtypes. Half of each subunit consists of a hydrophilic extracellular N-terminal domain containing a Cys loop, followed by four transmembrane sequences (M1-M4). M2 lines the ion channel and between M3 and M4 there is a large intracellular loop involved in receptor modulation by phosphorylation. Five subunits form a complex and surround a central ion channel with all five M2 segments contributing to the channel¹.

The gene encoding the GABA(A) receptor subunit α-5 (also known as GABRA5) is mapped to chromosome 15q11-q13 (together with GABRB3 and GABRG3) and is contained within approximately 800 kb of the distal part of the imprinted Prader-Willi and Angleman syndrome region. The receptor is mostly expressed in the hippocampus and prefrontal cortex². GABAR5 is anchored to neuronal extra synaptic regions by the cytosolic protein radixin.

GABRA5 is implicated in the development of various social disorders. PET studies have shown reduced binding of a GABRA5 selective ligand in the amygdala and nucleus acumbens of people with Autism spectrum disorders (ASD). In addition, post-mortem analysis of brain tissue obtained from individuals with ASD shows reduced amounts of GABRA5 encoding DNA. Deletion of the GABRA5 gene in mice causes autism-like behavior³.