SLC30A6

Chr 2

solute carrier family 30 member 6

Also known as: MST103, MSTP103, ZNT6

NCBI Gene: 55676 ENSG00000152683 UniProt: Q6NXT4 OMIM: 611148

This protein forms a functional zinc transporter with SLC30A5 that moves zinc into organelles of the secretory pathway, regulating zinc homeostasis and the proper folding of enzymes like alkaline phosphatases. Biallelic mutations cause hyperphosphatasia with impaired intellectual development and seizures (HPMRS), an autosomal recessive disorder presenting in infancy with developmental delay, seizures, and elevated alkaline phosphatase levels. The gene is not highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of a family of proteins that function as zinc transporters. This protein can regulate subcellular levels of zinc in the Golgi and vesicles. Expression of this gene is altered in the Alzheimer's disease brain plaques. [provided by RefSeq, Aug 2016]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.87

Clinical Summary— SLC30A6

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 64 VUS of 95 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

opentargets: Error: Open Targets API error: 502

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.87LOEUF

pLI 0.000

Z-score 2.13

OE 0.59 (0.40–0.87)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.03Z-score

OE missense 1.00 (0.90–1.11)

248 obs / 249.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.40–0.87)

0≤0.351.4

Missense OE?1.00 (0.90–1.11)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 18 / 30.8Missense obs/exp: 248 / 249.2Syn Z: -2.09

This gene — mechanism propensity

0.81top 10%

GOF

0.6932th %ile

LOF

0.3067th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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.

ClinVar Variant Classifications

95 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic1

VUS64

Likely Benign5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	8	0	8
Likely Pathogenic	0	1	0	1
VUS	62	2	0	64
Likely Benign	4	0	1	5
Benign	0	0	0	0
Total	66	11	1	78

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

View in ClinVar →

32 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap SLC30A6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →