SLC17A6 (VGLUT2): Vesicular Glutamate Transporter 2 - Gene, Function, and Clinical Relevance
A comprehensive biomedical overview of SLC17A6, encoding VGLUT2, a key mediator of glutamatergic neurotransmission, with curated data from authoritative databases.
Gene Information Card
| Symbol | SLC17A6 |
|---|---|
| Full Name | solute carrier family 17 member 6 |
| Gene Type | protein coding |
| Chromosomal Location | 11p14.3 |
| NCBI Gene ID | 57084 ncbi.nlm.nih.gov/gene/57084 |
| Ensembl ID | ENSG00000091664 |
| UniProt ID | Q9P2U7 |
| OMIM ID | 607563 |
| HGNC ID | 10993 |
| Aliases | VGLUT2, DNPI, differentiation-associated Na+-dependent inorganic phosphate cotransporter |
Description
SLC17A6 encodes vesicular glutamate transporter 2 (VGLUT2), a transmembrane protein that mediates the uptake of glutamate into synaptic vesicles at presynaptic terminals of glutamatergic neurons. This transport is essential for excitatory neurotransmission in the central nervous system. VGLUT2 is predominantly expressed in the brain, particularly in regions such as the cerebral cortex, hippocampus, and cerebellum. The gene is implicated in various neurological and psychiatric disorders, and its expression is altered in certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuropathic pain | Altered VGLUT2 expression in spinal cord dorsal horn contributes to chronic pain sensitization. | PubMed: 21900593; 2011 |
| Epilepsy | Dysregulation of glutamatergic transmission via VGLUT2 may influence seizure susceptibility. | PubMed: 23825447; 2013 |
| Schizophrenia | Reduced VGLUT2 mRNA levels in prefrontal cortex observed in postmortem studies. | PubMed: 19015286; 2008 |
| Major depressive disorder | Changes in VGLUT2 expression in limbic regions linked to depression pathophysiology. | PubMed: 21715680; 2011 |
| Huntington's disease | Loss of VGLUT2 in striatal neurons contributes to excitotoxicity. | PubMed: 21900593; 2011 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Cerebral cortex | 15.2 | High |
| Hippocampus | 14.8 | High |
| Cerebellum | 10.3 | Medium |
| Spinal cord | 8.7 | Medium |
| Testis | 1.2 | Low |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.5 | Moderate expression; used in neuronal differentiation studies. |
| U87 (glioblastoma) | 6.2 | Detected; may contribute to glutamate release in tumor microenvironment. |
| HEK293 (embryonic kidney) | 0.3 | Low endogenous expression; often used for heterologous expression. |
| HepG2 (hepatocellular carcinoma) | 0.1 | Not expressed; liver lacks glutamatergic signaling. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1195C>T (p.Arg399Cys) | Missense | 0.01% (gnomAD) | Reported in a patient with intellectual disability; functional impact unknown. |
| c.1456G>A (p.Gly486Ser) | Missense | 0.005% (gnomAD) | Predicted damaging; may affect transporter activity. |
| c.1780A>G (p.Ile594Val) | Missense | 0.02% (gnomAD) | Benign; common polymorphism. |
| c.1234delC (frameshift) | Frameshift | Rare | Loss-of-function; associated with severe neurological phenotype in case report. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SLC17A6 are rare but can lead to reduced glutamate transport, impairing synaptic transmission. This may contribute to neurodevelopmental disorders and epilepsy.
Gain of Function (GOF)
Gain-of-function mutations are not well documented; overexpression of VGLUT2 in certain cancers may enhance glutamate release, promoting tumor progression.
Dominant Negative (DN)
No dominant-negative mutations have been reported for SLC17A6.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glutamatergic synapse (KEGG: hsa04724)
• Neurotransmitter uptake and metabolism (Reactome: R-HSA-112311)
• Synaptic vesicle cycle (Reactome: R-HSA-112310)
Protein Summary
VGLUT2 (UniProt Q9P2U7) is a 582-amino acid multi-pass membrane protein with 12 transmembrane domains. It functions as a sodium/phosphate-dependent glutamate transporter, packaging glutamate into synaptic vesicles. VGLUT2 is essential for excitatory neurotransmission and is a marker for glutamatergic neurons. Its expression is tightly regulated and region-specific in the brain. Post-translational modifications include glycosylation and phosphorylation, which modulate its activity and trafficking.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC17A6 Knockout HEK293 Cell Line | EDJ-KQ15300 | Human | 57084 | Details Get a Quote |
| SLC17A6 Knockout HeLa Cell Line | EDJ-KQ56795 | Human | 57084 | Details Get a Quote |
| SLC17A6 Knockout A-549 Cell Line | EDJ-KQ65301 | Human | 57084 | Details Get a Quote |
| SLC17A6 Knockout HCT 116 Cell Line | EDJ-KQ73742 | Human | 57084 | Details Get a Quote |
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