SLC6A1 Gene - GABA Transporter 1: Function, Mutations, and Associated Disorders

SLC6A1 encodes the GABA transporter 1 (GAT1), a sodium- and chloride-dependent transmembrane protein that mediates the reuptake of gamma-aminobutyric acid (GABA) from the synaptic cleft into presynaptic neurons and glial cells. This transporter is critical for terminating GABAergic neurotransmission and maintaining inhibitory tone in the central nervous system. Loss-of-function mutations in SLC6A1 are associated with myoclonic-atonic epilepsy, intellectual disability, autism spectrum disorder, and other neurodevelopmental phenotypes.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• REACT:13685: Neurotransmitter uptake and metabolism

• REACT:13686: GABAergic synapse

• REACT:13687: Transport of inorganic cations/anions and amino acids/oligopeptides

GABA transporter 1 (GAT1) is a 599-amino-acid integral membrane protein with 12 transmembrane domains. It belongs to the solute carrier family 6 (SLC6) of sodium- and chloride-dependent neurotransmitter transporters. GAT1 is predominantly expressed in the brain, especially in GABAergic neurons and astrocytes, where it clears synaptic GABA to terminate signaling. The protein functions as a symporter, co-transporting one GABA molecule with two Na+ ions and one Cl- ion. Structural studies reveal a central substrate-binding site occluded by extracellular and intracellular gates. Mutations in SLC6A1 that impair GAT1 function lead to elevated extracellular GABA, altered network excitability, and epilepsy phenotypes.