SLC6A3

Chr 5AR

solute carrier family 6 member 3

Also known as: DAT, DAT1, PKDYS, PKDYS1

NCBI Gene: 6531ENSG00000142319UniProt: Q01959OMIM: 126455

This gene encodes a dopamine transporter which is a member of the sodium- and chloride-dependent neurotransmitter transporter family. The 3' UTR of this gene contains a 40 bp tandem repeat, referred to as a variable number tandem repeat or VNTR, which can be present in 3 to 11 copies. Variation in the number of repeats is associated with idiopathic epilepsy, attention-deficit hyperactivity disorder, dependence on alcohol and cocaine, susceptibility to Parkinson disease and protection against nicotine dependence.[provided by RefSeq, Nov 2009]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Nicotine dependence, protection against}MIM #188890
Parkinsonism-dystonia, infantile, 1MIM #613135
AR

Clinical highlights

Gene-disease validity (ClinGen)
SLC6A3-related dopamine transporter deficiency syndrome · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the established mechanism and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
4
Active trials
82
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.25
LOEUF· LoF intol.
LOF
Mechanism· annotated
📖
GeneReview available — SLC6A3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.25LOEUF
pLI 0.998
Z-score 4.65
OE 0.10 (0.04–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.29Z-score
OE missense 0.67 (0.60–0.74)
249 obs / 373.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.10 (0.04–0.25)
0≤0.351.4
Missense OE?0.67 (0.60–0.74)
0≤0.61.4
Synonymous OE?1.19
0≤1.21.6
LoF obs/exp: 3 / 30.9Missense obs/exp: 249 / 373.7Syn Z: -1.92

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SLC6A3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients