Gamma-aminobutyric acid receptor subunit alpha-1

GABRA1 encodes the gamma-1 subunit of GABA(A) receptors, ligand-gated chloride channels that mediate inhibitory neurotransmission in the brain (UniProt: P14867). When activated by GABA, these pentameric receptors allow chloride influx into postsynaptic neurons, suppressing action potential generation. Alpha-1-containing receptors are predominantly synaptic and regulate plasticity in circuits including the orbitofrontal cortex.

GABRA1 is widely expressed in the central nervous system and associated with several neurological disorders. UniProt documents mutations linked to idiopathic generalized epilepsies—including childhood absence epilepsy, juvenile myoclonic epilepsy, and developmental epileptic encephalopathy—indicating critical roles in seizure threshold and cortical synchronization (UniProt: P14867).

In Alzheimer's Disease, GABRA1 is downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC −0.47, Chaparral AD proteomics). This reduction in inhibitory GABAergic signaling may contribute to the neuronal hyperexcitability and network dysfunction observed in AD pathophysiology.