SLC18A3: Vesicular Acetylcholine Transporter
Key regulator of cholinergic neurotransmission and neuromuscular junction function
Gene Information Card
| Symbol | SLC18A3 |
|---|---|
| Full Name | Solute carrier family 18 member A3 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q11.23 |
| NCBI Gene ID | 6572 ncbi.nlm.nih.gov/gene/6572 |
| Ensembl ID | ENSG00000187714 |
| UniProt ID | Q16572 |
| OMIM ID | 600336 |
| HGNC ID | 10936 |
| Aliases | VAChT, VACHT, CGI-62, dJ55C23.6 |
Description
SLC18A3 encodes the vesicular acetylcholine transporter (VAChT), a transmembrane protein that transports acetylcholine from the cytoplasm into synaptic vesicles in cholinergic neurons. This transport is essential for quantal release of acetylcholine at the neuromuscular junction and in the autonomic nervous system. The gene is located within the first intron of the choline acetyltransferase (CHAT) gene, allowing coordinated expression. Mutations in SLC18A3 cause presynaptic congenital myasthenic syndrome (CMS) due to impaired acetylcholine loading.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Presynaptic congenital myasthenic syndrome (CMS) | Loss-of-function mutations reduce acetylcholine transport into synaptic vesicles, leading to decreased quantal release and neuromuscular transmission failure | Multiple families with biallelic missense/nonsense variants; functional studies show reduced acetylcholine uptake |
| Myasthenia gravis (autoimmune) | Autoantibodies against VAChT may contribute to cholinergic dysfunction in some patients | Case reports; limited evidence |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Spinal cord | 8.7 | Medium |
| Skeletal muscle | 0.2 | Not detected |
| Heart | 0.1 | Not detected |
| Liver | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 45.2 | High expression; cholinergic phenotype |
| SK-N-SH (neuroblastoma) | 22.1 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 0.0 | No expression |
| HeLa (cervical carcinoma) | 0.0 | No expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.4A>G (p.Met1?) | Start loss | Rare | Loss of translation initiation; severe CMS |
| c.107G>A (p.Arg36His) | Missense | Rare | Reduced acetylcholine transport activity |
| c.1165C>T (p.Arg389*) | Nonsense | Rare | Truncated protein; loss of function |
| c.1262T>C (p.Leu421Pro) | Missense | Rare | Impaired vesicular targeting and transport |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations are loss-of-function, reducing acetylcholine uptake into synaptic vesicles, leading to presynaptic CMS.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • transporter activity (GO:0005215) | • acetylcholine transmembrane transporter activity (GO:0005326) |
| • symporter activity (GO:0015293) | • acetylcholine transport (GO:0015844) |
| • neurotransmitter transport (GO:0006836) | • gamma-aminobutyric acid secretion (GO:0014051) |
| • synapse (GO:0045202) | • synaptic vesicle membrane (GO:0030672) |
Pathways
• Acetylcholine synthesis and transport (Reactome: R-HSA-264642)
• Neurotransmitter release cycle (Reactome: R-HSA-112310)
• Cholinergic synapse (KEGG: hsa04725)
Protein Summary
The vesicular acetylcholine transporter (VAChT) is a 530-amino acid integral membrane protein with 12 transmembrane domains. It uses a proton gradient generated by vacuolar ATPase to drive acetylcholine uptake into synaptic vesicles. VAChT is expressed exclusively in cholinergic neurons and is essential for efficient neuromuscular transmission. Its expression is tightly co-regulated with choline acetyltransferase (CHAT).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC18A3 Knockout HEK293 Cell Line | EDJ-KQ5794 | Human | 6572 | Details Get a Quote |
| SLC18A3 Knockout HeLa Cell Line | EDJ-KQ54516 | Human | 6572 | Details Get a Quote |
| SLC18A3 Knockout A-549 Cell Line | EDJ-KQ63001 | Human | 6572 | Details Get a Quote |
| SLC18A3 Knockout HCT 116 Cell Line | EDJ-KQ71471 | Human | 6572 | Details Get a Quote |
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