GABRA2

Chr 4MultiAD

gamma-aminobutyric acid type A receptor subunit alpha2

Also known as: DEE78, EIEE78

NCBI Gene: 2555 ENSG00000151834 UniProt: P47869 OMIM: 137140

The GABRA2 gene encodes the alpha-2 subunit of GABA-A receptors, which are ligand-gated chloride channels that mediate inhibitory neurotransmission in the brain. Pathogenic variants cause developmental and epileptic encephalopathy 78 through autosomal dominant inheritance, likely due to disrupted GABAergic inhibition. The gene shows extreme intolerance to loss-of-function variants (pLI 0.996, LOEUF 0.229), consistent with dominant negative or haploinsufficiency mechanisms.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Alcohol dependence, susceptibility to}MIM #103780

Multi

Developmental and epileptic encephalopathy 78MIM #618557

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

0.23

LOEUF· LoF intol.

Multiple*

Mechanism· predicted