SLC30A6

Chr 2

solute carrier family 30 member 6

Also known as: MST103, MSTP103, ZNT6

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.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.87
Clinical SummarySLC30A6
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 71 VUS of 135 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.000
Z-score 2.13
OE 0.59 (0.400.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.03Z-score
OE missense 1.00 (0.901.11)
248 obs / 249.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.400.87)
00.351.4
Missense OE1.00 (0.901.11)
00.61.4
Synonymous OE1.29
01.21.6
LoF obs/exp: 18 / 30.8Missense obs/exp: 248 / 249.2Syn Z: -2.09
DN
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

135 submitted variants in ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic4
VUS71
Likely Benign5
Benign1
37
Pathogenic
4
Likely Pathogenic
71
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
0
4
0
4
VUS
0
62
9
0
71
Likely Benign
0
4
0
1
5
Benign
0
0
1
0
1
Total066511118

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC30A6 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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