Solute carrier family 6 member 1 (GABA transporter 1) (SLC6A1)

Solute carrier family 6 member 1 (SLC6A1) encodes the GABA transporter 1 (GAT-1), a sodium- and chloride-dependent protein primarily responsible for the reuptake of gamma-aminobutyric acid (GABA) from the synaptic cleft into neurons and glia (UniProt P23978). By clearing GABA from the synapse, GAT-1 terminates inhibitory signaling and regulates the ambient levels of GABA that modulate tonic inhibition (PubMed: 30165535). Pathogenic variants in the SLC6A1 gene are a major cause of neurodevelopmental disorders, including myoclonic-atonic epilepsy (MAE), absence seizures, and autism spectrum disorder, typically through a mechanism of haploinsufficiency (PubMed: 25913037). Pharmacological inhibition of GAT-1 by drugs like tiagabine increases synaptic GABA concentrations, providing an anticonvulsant effect in certain types of epilepsy (PubChem CID 60648). Conversely, loss-of-function mutations lead to impaired GABAergic neurotransmission and network hypersynchrony (PubMed: 29100024). Emerging therapeutic strategies include gene therapies and small molecules aimed at restoring GAT-1 expression or function in affected patients (PubMed: 35644343).

Other names

GAT1GABATRGABT1Sodium- and chloride-dependent GABA transporter 1

Inhibition of GABA reuptake from the synaptic cleft, thereby increasing the concentration and duration of GABA in the synapse to enhance inhibitory neurotransmission (PubChem CID 60648).