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GABRA4

Chr 4p12

gamma-aminobutyric acid type A receptor subunit alpha4

MANE:
ENST00000264318.4

Annotations refreshed 1 month ago.

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • DDG2P

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Disease associations (Open Targets)

  • epilepsy

    0.61
  • migraine disorder

    0.61
  • major depressive disorder

    0.61
  • insomnia

    0.61
  • panic disorder

    0.60
  • Agitation

    0.60
  • anxiety disorder

    0.60
  • Anxiety

    0.59
  • alcohol dependence

    0.59
  • Seizure

    0.59

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Gamma-aminobutyric acid receptor subunit alpha-4

Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:35355020). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:35355020). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:35355020). GABAARs containing alpha-4 are predominantly extrasynaptic, contributing to tonic inhibition in dentate granule cells and thalamic relay neurons (By similarity). Extrasynaptic alpha-4-containing GABAARs control levels of excitability and network activity (By similarity). GABAAR containing alpha-4-beta-3-delta subunits can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness (PubMed:35355020)

Curated MONDO disease pages that list GABRA4 among their top associated genes.

Data sources: HGNC (CC BY 4.0), AlphaFold (CC BY 4.0, Jumper et al. Nature 2021), Genomics England PanelApp (CC BY 4.0), ClinGen, Open Targets (CC0), UniProt.

Not for sole clinical decision-making. Always verify against primary sources.