GABRA1

Chr 5AD

gamma-aminobutyric acid type A receptor subunit alpha1

Also known as: DEE19, ECA4, EIEE19, EJM, EJM5

NCBI Gene: 2554 ENSG00000022355 UniProt: P14867 OMIM: 137160

The protein functions as the alpha-1 subunit of GABA-A receptors, heteropentameric ligand-gated chloride channels that mediate inhibitory neurotransmission in the brain. Mutations cause developmental and epileptic encephalopathy 19, childhood absence epilepsy, and juvenile myoclonic epilepsy through an autosomal dominant inheritance pattern. Disease mechanisms are variant-dependent, with mutations causing pathogenicity through either loss-of-function or dominant-negative effects.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a gamma-aminobutyric acid (GABA) receptor. 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. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene cause juvenile myoclonic epilepsy and childhood absence epilepsy type 4. Multiple transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Epilepsy, childhood absence, susceptibility to, 4}MIM #611136

{Epilepsy, juvenile myoclonic, susceptibility to, 5}MIM #611136

Developmental and epileptic encephalopathy 19MIM #615744

UniProtEpilepsy, idiopathic generalized 13

Clinical highlights

Gene-disease validity (ClinGen)

epilepsy · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Both loss of function and dominant negative mechanisms are described for this gene and which one applies is variant-dependent. Do not assume a null variant is — or isn't — the pathogenic class without checking the specific variant against curated evidence.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.37

LOEUF

LOF/DN*

Mechanism· annotated

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GeneReview available — GABRA1