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GABRA1

Chr 5q34

gamma-aminobutyric acid type A receptor subunit alpha1

Aliases:
EJM5
MANE:
ENST00000393943.10

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, 19

    0.76
  • juvenile myoclonic epilepsy

    0.74
  • epilepsy

    0.74
  • major depressive disorder

    0.67
  • Seizure

    0.63
  • insomnia

    0.61
  • migraine disorder

    0.61
  • panic disorder

    0.60
  • Agitation

    0.60
  • anxiety disorder

    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 alpha-1

Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:23909897, PubMed:25489750, PubMed:29950725, 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:29950725, PubMed:30602789). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:23909897, PubMed:29950725, PubMed:30602789). Alpha-1/GABRA1-containing GABAARs are largely synaptic (By similarity). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). GABAARs containing alpha-1 and beta-2 or -3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (PubMed:23909897, PubMed:25489750). GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response (By similarity). GABAARs containing alpha, beta and epsilon subunits also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity). Alpha-1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (By similarity). Together with rho subunits, may also control neuronal and glial GABAergic transmission in the cerebellum (By similarity)

Curated MONDO disease pages that list GABRA1 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.