GABRA4

Chr 4

gamma-aminobutyric acid type A receptor subunit alpha4

NCBI Gene: 2557 ENSG00000109158 UniProt: P48169 OMIM: 137141

The GABRA4 protein forms the alpha-4 subunit of GABA-A receptors, heteropentameric chloride channels that mediate inhibitory neurotransmission in the brain, with alpha-4-containing receptors predominantly located extrasynaptically where they provide tonic inhibition. Mutations in GABRA4 have been associated with autism spectrum disorders, following autosomal dominant inheritance. The gene shows high constraint against loss-of-function variants (LOEUF 0.41), indicating that such variants are likely to be pathogenic when they occur.

OMIM ResearchSummary from RefSeq, UniProt

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. This gene encodes subunit alpha-4, which is involved in the etiology of autism and eventually increases autism risk through interaction with another subunit, gamma-aminobutyric acid receptor beta-1 (GABRB1). Alternatively spliced transcript variants encoding different isoforms have been found in this gene.[provided by RefSeq, Feb 2011]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.41

LOEUF

Multiple*

Mechanism· predicted