SLC30A10

Chr 1

solute carrier family 30 member 10

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

NCBI Gene: 55532 ENSG00000196660 UniProt: Q6XR72

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene is highly expressed in the liver and is inducible by manganese. Its protein product appears to be critical in maintaining manganese levels, and has higher specificity for manganese than zinc. Loss of function mutations appear to result in a pleomorphic phenotype, including dystonia and adult-onset parkinsonism. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Mar 2012]

GeneReviews ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.25

Clinical Summary— SLC30A10

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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.

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ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 149 VUS of 316 total submissions

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GeneReview available — SLC30A10

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.25LOEUF

pLI 0.980

Z-score 3.20

OE 0.00 (0.00–0.25)

Highly constrained

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

Missense Constraint?

1.58Z-score

OE missense 0.73 (0.65–0.82)

197 obs / 269.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.25)

0≤0.351.4

Missense OE?0.73 (0.65–0.82)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 0 / 11.9Missense obs/exp: 197 / 269.8Syn Z: 0.13

This gene — mechanism propensity

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.

LOF64% of P/LP variants are LoF · LOEUF 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

316 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic4

VUS149

Likely Benign105

Benign32

Conflicting10

Pathogenic

Likely Pathogenic

149

VUS

105

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	2	1	0	7
Likely Pathogenic	3	1	0	0	4
VUS	3	123	22	1	149
Likely Benign	0	5	30	70	105
Benign	0	0	32	0	32
Conflicting	—				10
Total	10	131	85	71	307

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

View in ClinVar →

32 pathogenic / likely-pathogenic (of 43) ClinVar copy-number / structural variants overlap SLC30A10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →