SLC30A10

Chr 1AR

solute carrier family 30 member 10

Also known as: HMDPC, HMNDYT1, ZNT10, ZNT8, ZRC1, ZnT-10

The protein functions as a calcium:manganese antiporter that mediates manganese efflux from cells and is required for intracellular manganese homeostasis. Autosomal recessive mutations cause hypermanganesemia with dystonia 1, which presents with dystonia and can progress to adult-onset parkinsonism due to manganese accumulation and toxicity. The gene is highly expressed in liver and is particularly important for neuronal metabolism since manganese is essential for neurotransmitter metabolism but becomes cytotoxic when accumulated.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.251 OMIM phenotype
Clinical SummarySLC30A10
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.25LOEUF
pLI 0.980
Z-score 3.20
OE 0.00 (0.000.25)
Highly constrained

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

Missense Constraint
1.58Z-score
OE missense 0.73 (0.650.82)
197 obs / 269.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.25)
00.351.4
Missense OE0.73 (0.650.82)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 0 / 11.9Missense obs/exp: 197 / 269.8Syn Z: 0.13
DN
0.6452th %ile
GOF
0.6639th %ile
LOF
0.4825th %ile

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.25
GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

SLC30A10 · 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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