SLC18A2

Chr 10AR

solute carrier family 18 member A2

Also known as: PKDYS2, SVAT, SVMT, VAT2, VMAT2

NCBI Gene: 6571 ENSG00000165646 UniProt: Q05940 OMIM: 193001

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an transmembrane protein that functions as an ATP-dependent transporter of monoamines, such as dopamine, norepinephrine, serotonin, and histamine. This protein transports amine neurotransmitters into synaptic vesicles. Polymorphisms in this gene may be associated with schizophrenia, bipolar disorder, and other neurological/psychiatric ailments. [provided by RefSeq, Jun 2018]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.511 OMIM phenotype

Clinical Summary— SLC18A2

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Gene-Disease Validity (ClinGen)

brain dopamine-serotonin vesicular transport disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

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GeneReview available — SLC18A2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.076

Z-score 3.42

OE 0.27 (0.15–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.25Z-score

OE missense 0.80 (0.72–0.89)

240 obs / 301.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.15–0.51)

0≤0.351.4

Missense OE?0.80 (0.72–0.89)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

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

This gene — mechanism propensity

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

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.