protein
Sodium- and chloride-dependent GABA transporter 1
aka GAT-1
Gene
SLC6A1
Organism
Homo sapiens(9606)
Length
599 aa
Mass
67,074 Da
SLC6A1 encodes a sodium- and chloride-dependent GABA transporter (GAT-1) that mediates the reuptake of gamma-aminobutyric acid from the synapse, a critical inhibitory neurotransmitter in the central nervous system (UniProt: P30531). The transporter can also function bidirectionally to release GABA, with transport direction determined by membrane potential and intracellular and extracellular ion and GABA concentrations. Secondary transport of hypotaurine has been documented but occurs at substantially lower efficiency.
SLC6A1 is associated with myoclonic-atonic epilepsy (MAE), a form of early-childhood epilepsy characterized by myoclonic-atonic and absence seizures accompanied by developmental delay and intellectual disability (UniProt: P30531). The protein functions as a crucial regulator of GABAergic neurotransmission, making it essential for normal neuronal inhibitory signaling.
SLC6A1 is classified as a Category 1 (high confidence) autism spectrum disorder risk gene with syndromic features (SFARI Cat 1, syndromic). This curated association reflects evidence linking SLC6A1 variants to neurodevelopmental phenotypes overlapping with autism, particularly in the context of seizure disorders and developmental abnormalities.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
not detected
S2
+0.690
S3
not detected
Mean log₂FC across detected fractions: +0.6897 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Genetic Evidence · ASD
High confidence — strong genetic evidence from multiple studies
Source: SFARI Gene database · gene.sfari.org
This protein is implicated in both ASD and Alzheimer's Disease. View all cross-disease proteins →
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Mediates transport of gamma-aminobutyric acid (GABA) together with sodium and chloride and is responsible for the reuptake of GABA from the synapse (PubMed:30132828). The translocation of GABA, however, may also occur in the reverse direction leading to the release of GABA (By similarity). The direction and magnitude of GABA transport is a consequence of the prevailing thermodynamic conditions, determined by membrane potential and the intracellular and extracellular concentrations of Na(+), Cl(-) and GABA (By similarity). Can also mediate sodium- and chloride-dependent transport of hypotaurine but to a much lower extent as compared to GABA (By similarity)
Disease associations
Myoclonic-atonic epilepsyMAE
A form of epilepsy characterized by myoclonic-atonic and absence seizures, appearing in early childhood. Patients have delayed development before the onset of seizures and show varying degrees of intellectual disability following seizure onset.
Sources
Last updated 5/8/2026, 1:12:33 AM