GABRD

Chr 1AD

gamma-aminobutyric acid type A receptor subunit delta

Also known as: EIG10, EJM7, GABAARdelta, GEFSP5

NCBI Gene: 2563 ENSG00000187730 UniProt: O14764 OMIM: 137163

The protein encodes the delta subunit of GABA-A receptors, which are pentameric ligand-gated chloride channels that mediate inhibitory neurotransmission in the brain. Mutations cause autosomal dominant generalized epilepsy with febrile seizures plus, type 5 through a predicted gain-of-function mechanism. The gene is highly intolerant to loss-of-function variants, consistent with the gain-of-function pathogenic mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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. The GABA-A receptor is generally pentameric and there are five types of subunits: alpha, beta, gamma, delta, and rho. This gene encodes the delta subunit. Mutations in this gene have been associated with susceptibility to generalized epilepsy with febrile seizures, type 5. Alternatively spliced transcript variants have been described for this gene, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{?Generalized epilepsy with febrile seizures plus, type 5, susceptibility to}MIM #613060

UniProtEpilepsy, idiopathic generalized 10

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADModerateconsider for supplementary testing2 gene-disease associations curated in total

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.24

LOEUF· LoF intol.

GOF

Mechanism· G2P

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GeneReview available — GABRD