GABRA1 Gene: GABA-A Receptor Alpha1 Subunit – Function, Mutations & Disease

GABRA1 encodes the alpha1 subunit of the gamma-aminobutyric acid type A (GABA-A) receptor, a pentameric ligand-gated chloride channel that mediates fast inhibitory neurotransmission in the central nervous system. The alpha1 subunit is the most abundant alpha subunit in the brain and is essential for benzodiazepine sensitivity and receptor clustering at synapses. Mutations in GABRA1 are associated with several epilepsy syndromes, including juvenile myoclonic epilepsy and childhood absence epilepsy.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• GABAergic synapse (KEGG: hsa04727)

• Neuroactive ligand-receptor interaction (KEGG: hsa04080)

• Transmission across Chemical Synapses (Reactome: R-HSA-112315)

The GABRA1 protein (UniProt P14867) is a 456-amino-acid transmembrane subunit that forms part of the GABA-A receptor pentamer. It contains an extracellular N-terminal domain with a signal peptide, four transmembrane domains (M1-M4), and a large intracellular loop between M3 and M4 that mediates phosphorylation and interactions with scaffolding proteins. The alpha1 subunit confers high affinity for GABA and benzodiazepine sensitivity when co-assembled with beta2/3 and gamma2 subunits. Post-translational modifications include N-glycosylation and palmitoylation.