SLC30A2

Chr 1AD

solute carrier family 30 member 2

Also known as: PP12488, TNZD, ZNT2, ZnT-2

NCBI Gene: 7780ENSG00000158014UniProt: Q9BRI3OMIM: 609617

The protein is a zinc transporter that regulates cellular zinc homeostasis by concentrating zinc ions into intracellular organelles and secretory vesicles, and is crucial for zinc secretion into breast milk. Mutations cause transient neonatal zinc deficiency, typically presenting in newborns with zinc deficiency symptoms that resolve as dietary zinc sources become available. The condition follows autosomal dominant inheritance, and the gene shows moderate constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.611 OMIM phenotype
Clinical Summary— SLC30A2
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Gene-Disease Validity (ClinGen)
zinc deficiency, transient neonatal · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
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ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 49 VUS of 67 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.61LOEUF
pLI 0.081
Z-score 2.71
OE 0.29 (0.15–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.93Z-score
OE missense 0.83 (0.73–0.93)
185 obs / 224.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.15–0.61)
0≤0.351.4
Missense OE0.83 (0.73–0.93)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 5 / 17.1Missense obs/exp: 185 / 224.1Syn Z: 0.23
DN
0.83top 10%
GOF
0.74top 25%
LOF
0.2581th %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 · 1 literature citation
GOFprediction above median · 1 literature citation

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.

Literature Evidence

DNA dominant negative heterozygous G87R mutation in the zinc transporter, ZnT-2 (SLC30A2), results in transient neonatal zinc deficiency.PMID:22733820
GOFExome Sequencingof SLC30A2 Identifies Novel Loss- and Gain-of-Function Variants Associated with Breast Cell Dysfunction.PMID:26293594

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS49
Likely Benign4
Benign1
9
Pathogenic
1
Likely Pathogenic
49
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
5
0
9
Likely Pathogenic
1
0
0
0
1
VUS
0
45
4
0
49
Likely Benign
0
0
1
3
4
Benign
0
1
0
0
1
Total34810364

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC30A2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Milk-derived miRNA profiles elucidate molecular pathways that underlie breast dysfunction in women with common genetic variants in SLC30A2.
Kelleher SL et al.·Sci Rep
2019
A genetic variant in SLC30A2 causes breast dysfunction during lactation by inducing ER stress, oxidative stress and epithelial barrier defects.
Lee S et al.·Sci Rep
2018
A novel homozygous mutation p.E88K in maternal SLC30A2 gene as a cause of transient neonatal zinc deficiency.
Li Z et al.·Exp Dermatol
2020Case report
Interaction between glycolysis‒cholesterol synthesis axis and tumor microenvironment reveal that gamma-glutamyl hydrolase suppresses glycolysis in colon cancer.
Chen YJ et al.·Front Immunol
2022
Molecular Patterns Discriminate Accommodation and Subclinical Antibody-mediated Rejection in Kidney Transplantation.
Hruba P et al.·Transplantation
2019
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Transient Neonatal Zinc Deficiency due to Maternal Variants in SLC30A2: An Emerging and Atypical Candidate Gene for Maternal Carrier Screening.
Carter C et al.·Am J Med Genet A
2026
SLC30A2-Mediated Zinc Metabolism Modulates Gastric Cancer Progression via the Wnt/β-Catenin Signaling Pathway.
Li F et al.·Front Biosci (Landmark Ed)
2024
Think zinc: Transient nutritional deficiency related to novel maternal SLC30A2 mutation potentially precipitated by antenatal proton pump inhibitor exposure.
Porter E et al.·Clin Case Rep
2023Open Access
Novel SLC30A2 mutations in the pathogenesis of transient neonatal zinc deficiency.
Muto T et al.·Pediatr Investig
2023Open Access
Loss-of-function SLC30A2 mutants are associated with gut dysbiosis and alterations in intestinal gene expression in preterm infants.
Kelleher SL et al.·Gut Microbes
2022Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients