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GABRB3

Chr 15q12

gamma-aminobutyric acid type A receptor subunit beta3

MANE:
ENST00000311550.10

Annotations refreshed 9 hours ago.

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • DDG2P

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
  • Early onset or syndromic epilepsy

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
  • Intellectual disability

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
  • Fetal anomalies

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Disease associations (Open Targets)

  • developmental and epileptic encephalopathy, 43

    0.78
  • epilepsy

    0.71
  • childhood absence epilepsy

    0.70
  • Lennox-Gastaut syndrome

    0.67
  • Seizure

    0.66
  • insomnia

    0.63
  • major depressive disorder

    0.61
  • migraine disorder

    0.61
  • panic disorder

    0.61
  • Agitation

    0.60

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

Protein function (UniProt)

Gamma-aminobutyric acid receptor subunit beta-3

Beta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:14993607, PubMed:18514161, PubMed:22243422, PubMed:22303015, PubMed:24909990, PubMed:26950270, PubMed:30602789). 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:24909990, PubMed:30140029, PubMed:30602789). GABAARs containing beta-3/GABRB3 subunit are found at both synaptic and extrasynaptic sites (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:14993607, PubMed:22303015, PubMed:26950270, PubMed:30602789). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (PubMed:22303015, PubMed:26950270). GABAARs containing alpha-1 and beta-3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (PubMed:25489750). Extrasynaptic beta-3 receptors contribute to the tonic GABAergic inhibition (By similarity). GABAARs containing alpha-1, beta-3 and epsilon subunits may also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity). Beta-containing GABAARs 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:18281286, PubMed:24909990, PubMed:35355020). Plays an important role in somatosensation and in the production of antinociception (By similarity)

Curated MONDO disease pages that list GABRB3 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.