SLC6A3 (Dopamine Transporter) Gene
Solute Carrier Family 6 Member 3: Dopamine Transporter (DAT)
Gene Information Card
| Symbol | SLC6A3 |
|---|---|
| Full Name | Solute Carrier Family 6 Member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 5p15.33 |
| NCBI Gene ID | 6531 ncbi.nlm.nih.gov/gene/6531 |
| Ensembl ID | ENSG00000142319 |
| UniProt ID | Q01959 |
| OMIM ID | 126455 |
| HGNC ID | 11049 |
| Aliases | DAT, DAT1, PKDYS, SLC6A3 |
Description
The SLC6A3 gene encodes the dopamine transporter (DAT), a transmembrane protein responsible for the reuptake of dopamine from the synaptic cleft into presynaptic neurons, thereby terminating dopaminergic neurotransmission. DAT is a member of the solute carrier family 6 (neurotransmitter transporter) and is critical for motor control, reward, cognition, and endocrine function. Dysregulation of DAT is implicated in Parkinson disease, attention-deficit/hyperactivity disorder (ADHD), substance use disorders, and certain movement disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Parkinson disease (PKDYS) | Loss-of-function or reduced DAT expression leads to impaired dopamine reuptake, contributing to dopaminergic neuron degeneration and motor symptoms. | OMIM #168600; ClinVar; NCBI GeneReviews |
| Attention-deficit/hyperactivity disorder (ADHD) | Common variants (e.g., 3' UTR VNTR) alter DAT expression and dopamine clearance, affecting attention and impulse control. | OMIM #143465; multiple GWAS studies |
| Substance use disorders (cocaine, amphetamine) | DAT is the primary target for psychostimulants; variants influence reward pathway sensitivity and addiction risk. | NCBI Gene; multiple association studies |
| Dystonia / Parkinsonism (early-onset) | Biallelic loss-of-function mutations (e.g., p.Pro554Leu) cause severe dopamine transporter deficiency syndrome. | OMIM #613135; ClinVar; PMID: 19200526 |
| Autism spectrum disorder | Rare SLC6A3 variants have been reported in ASD cohorts, though evidence is preliminary. | ClinVar; PMID: 23403944 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (substantia nigra) | 12.5 | High |
| Brain (caudate nucleus) | 11.8 | High |
| Brain (putamen) | 11.2 | High |
| Brain (nucleus accumbens) | 10.9 | High |
| Brain (prefrontal cortex) | 6.3 | Medium |
| Testis | 0.8 | Low |
| Kidney | 0.5 | Low |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.2 | Endogenous expression; used in dopamine uptake studies |
| SK-N-SH (neuroblastoma) | 7.5 | Moderate expression |
| HEK293 (embryonic kidney) | 0.3 | Low; often used for heterologous expression |
| U-87 MG (glioblastoma) | 0.2 | Very low |
| HepG2 (hepatocellular carcinoma) | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1661C>T (p.Pro554Leu) | Missense | Rare | Loss of function; causes dopamine transporter deficiency syndrome (OMIM #613135) |
| c.1249G>A (p.Ala417Thr) | Missense | Rare | Reduced dopamine uptake; associated with ADHD and Parkinson disease |
| c.1475C>T (p.Thr492Ile) | Missense | Rare | Impaired trafficking; linked to early-onset parkinsonism |
| 3' UTR VNTR (40-bp repeat) | Regulatory | Common (allele frequency varies) | Alters DAT expression; associated with ADHD and substance use disorders |
| c.1195C>T (p.Arg399Cys) | Missense | Rare | Decreased dopamine affinity; reported in dystonia |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Pro554Leu, p.Ala417Thr) reduce dopamine reuptake capacity, leading to dopamine transporter deficiency syndrome and early-onset parkinsonism.
Gain of Function (GOF)
No well-established gain-of-function mutations reported in SLC6A3; increased expression via 3' UTR VNTR may enhance dopamine clearance, potentially contributing to ADHD.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for SLC6A3; most pathogenic variants are recessive or act via haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Dopaminergic synapse (KEGG hsa04728)
• Cocaine addiction (KEGG hsa05030)
• Amphetamine addiction (KEGG hsa05031)
• Neurotransmitter uptake and metabolism (Reactome R-HSA-112311)
• Transmembrane transport of small molecules (Reactome R-HSA-382551)
Protein Summary
The dopamine transporter (DAT) is a 12-transmembrane domain integral membrane protein of 620 amino acids (UniProt Q01959). It mediates the sodium- and chloride-dependent reuptake of extracellular dopamine into presynaptic neurons, regulating dopaminergic tone. DAT is the primary molecular target for psychostimulants such as cocaine and amphetamine. Structurally, it belongs to the SLC6 family and shares homology with other monoamine transporters (SERT, NET). Post-translational modifications include N-glycosylation, phosphorylation, and ubiquitination, which modulate trafficking and activity. Dysfunction of DAT is central to several neurological and psychiatric disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC6A3 Knockout HEK293 Cell Line | EDJ-KQ2306 | Human | 6531 | Details Get a Quote |
| SLC6A3 Knockout HeLa Cell Line | EDJ-KQ54492 | Human | 6531 | Details Get a Quote |
| SLC6A3 Knockout A-549 Cell Line | EDJ-KQ62978 | Human | 6531 | Details Get a Quote |
| SLC6A3 Knockout HCT 116 Cell Line | EDJ-KQ71449 | Human | 6531 | Details Get a Quote |
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