SLC6A3

Chr 5AR

solute carrier family 6 member 3

Also known as: DAT, DAT1, PKDYS, PKDYS1

This gene encodes the dopamine transporter that mediates sodium- and chloride-dependent reuptake of dopamine from synapses. Mutations cause autosomal recessive infantile parkinsonism-dystonia through loss-of-function, resulting in impaired dopamine clearance and disrupted dopaminergic signaling. The gene shows high constraint against loss-of-function variants, consistent with the severe phenotype when both alleles are affected.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.252 OMIM phenotypes
Clinical SummarySLC6A3
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Gene-Disease Validity (ClinGen)
SLC6A3-related dopamine transporter deficiency syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.25LOEUF
pLI 0.998
Z-score 4.65
OE 0.10 (0.040.25)
Highly constrained

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

Missense Constraint
2.29Z-score
OE missense 0.67 (0.600.74)
249 obs / 373.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.040.25)
00.351.4
Missense OE0.67 (0.600.74)
00.61.4
Synonymous OE1.19
01.21.6
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.

References:PMID:19608709

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.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗