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…
LOFmechanismARLOEUF 0.252 OMIM phenotypes
Clinical Summary— SLC6A3
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Gene-Disease Validity (ClinGen)
SLC6A3-related dopamine transporter deficiency syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 168 VUS of 568 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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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
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSLC6A3-related parkinsonism-dystonia, infantileLOFAR
Mechanism Note (expert annotation)
LOF

Dopamine transporter (DAT). Biallelic LOF causes infantile parkinsonism-dystonia (DTDS). Reduced dopamine reuptake leads to dopaminergic dysfunction.1

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6260th %ile
GOF
0.78top 25%
LOF
0.4234th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

  1. 1.PMID 19608709 ↗

ClinVar Variant Classifications

568 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic9
VUS168
Likely Benign284
Benign78
Conflicting13
12
Pathogenic
9
Likely Pathogenic
168
VUS
284
Likely Benign
78
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
3
3
0
12
Likely Pathogenic
6
2
1
0
9
VUS
2
149
15
2
168
Likely Benign
0
7
129
148
284
Benign
0
0
68
10
78
Conflicting
—13
Total14161216160564

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

136 pathogenic / likely-pathogenic (of 150) ClinVar copy-number / structural variants overlap SLC6A3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

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