SLC32A1: Solute Carrier Family 32 Member 1 (VGAT)
The vesicular GABA and glycine transporter essential for inhibitory neurotransmission
Gene Information Card
| Symbol | SLC32A1 |
|---|---|
| Full Name | Solute Carrier Family 32 Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 20q11.23 |
| NCBI Gene ID | 140679 ncbi.nlm.nih.gov/gene/140679 |
| Ensembl ID | ENSG00000101438 |
| UniProt ID | Q9H598 |
| OMIM ID | 616440 |
| HGNC ID | 11018 |
| Aliases | VGAT, VIAAT, bA121O18.1 |
Description
SLC32A1 (Solute Carrier Family 32 Member 1), also known as VGAT (vesicular GABA transporter) or VIAAT (vesicular inhibitory amino acid transporter), is a transmembrane protein that transports GABA and glycine from the cytoplasm into synaptic vesicles. This loading is essential for inhibitory neurotransmission in the central nervous system. The protein is a member of the SLC32 family and uses a proton gradient generated by V-ATPase to drive neurotransmitter uptake. Loss-of-function mutations in SLC32A1 are associated with epilepsy, hyperekplexia, and other neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epileptic encephalopathy, early infantile, 79 (EIEE79) | Loss-of-function mutations impair GABA/glycine vesicular loading, reducing inhibitory neurotransmission and causing hyperexcitability | ClinVar, OMIM |
| Hyperekplexia 4 (HKPX4) | Dominant-negative or loss-of-function variants disrupt transporter activity, leading to exaggerated startle responses and stiffness | OMIM |
| Developmental and epileptic encephalopathy (DEE) | Heterozygous missense mutations reduce transporter expression or function, contributing to seizure phenotypes | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Cerebral cortex | 15.2 | High |
| Cerebellum | 10.8 | High |
| Spinal cord | 8.3 | Medium |
| Retina | 6.1 | Medium |
| Testis | 0.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 9.8 | High expression in neuronal models |
| U-87 MG (glioblastoma) | 2.1 | Low expression |
| HEK293 (embryonic kidney) | 0.3 | Not expressed endogenously |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.539G>A (p.Arg180His) | Missense | Rare | Reduced transporter activity; associated with EIEE79 |
| c.1006C>T (p.Arg336Trp) | Missense | Rare | Dominant-negative effect; linked to hyperekplexia |
| c.1123G>A (p.Gly375Arg) | Missense | Rare | Loss of function; reported in DEE |
| c.1A>G (p.Met1?) | Start loss | Very rare | Complete loss of protein; severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg180His) reduce or abolish GABA/glycine transport, leading to decreased inhibitory vesicle filling.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SLC32A1.
Dominant Negative (DN)
p.Arg336Trp exerts a dominant-negative effect, likely by disrupting oligomerization or trafficking of the transporter.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Neurotransmitter release cycle (R-HSA-112310)
• Transmission across Chemical Synapses (R-HSA-112315)
• GABAergic synapse (KEGG:04727)
• Synaptic vesicle cycle (KEGG:04721)
Protein Summary
SLC32A1 encodes a 525-amino acid integral membrane protein with 10 transmembrane domains. It functions as a proton-coupled antiporter that exchanges luminal H+ for cytoplasmic GABA or glycine, accumulating these neurotransmitters in synaptic vesicles. The protein is highly expressed in inhibitory neurons and is essential for normal inhibitory neurotransmission. Structural studies show that the transporter adopts an inward-open conformation for substrate binding and an occluded state during transport. Mutations that disrupt its function lead to reduced inhibitory tone and are causative for several neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC32A1 Knockout HEK293 Cell Line | EDJ-KQ9792 | Human | 140679 | Details Get a Quote |
| SLC32A1 Knockout HeLa Cell Line | EDJ-KQ58442 | Human | 140679 | Details Get a Quote |
| SLC32A1 Knockout A-549 Cell Line | EDJ-KQ66929 | Human | 140679 | Details Get a Quote |
| SLC32A1 Knockout HCT 116 Cell Line | EDJ-KQ75333 | Human | 140679 | Details Get a Quote |
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