SLC18A2

Chr 10AR

solute carrier family 18 member A2

The protein is a vesicular monoamine transporter that concentrates neurotransmitters including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles for regulated release. Autosomal recessive mutations cause infantile parkinsonism-dystonia with onset in early childhood. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.511), reflecting its critical role in monoaminergic neurotransmission.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.511 OMIM phenotype
Clinical SummarySLC18A2
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Gene-Disease Validity (ClinGen)
brain dopamine-serotonin vesicular transport disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.076
Z-score 3.42
OE 0.27 (0.150.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.25Z-score
OE missense 0.80 (0.720.89)
240 obs / 301.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.27 (0.150.51)
00.351.4
Missense OE0.80 (0.720.89)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 7 / 25.7Missense obs/exp: 240 / 301.2Syn Z: -0.03
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSLC18A2-related neurotransmitter disorder with dystonia and oculogyric crisisOTHERAR

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

DN
0.79top 25%
GOF
0.6833th %ile
LOF
0.2776th %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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC18A2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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