SLC39A4

Chr 8AR

solute carrier family 39 member 4

Also known as: AEZ, AWMS2, ZIP4

NCBI Gene: 55630ENSG00000147804UniProt: Q6P5W5

This protein functions as a selective zinc transporter that mediates zinc uptake in the intestinal tract, playing an essential role in dietary zinc absorption. Mutations cause acrodermatitis enteropathica, a disorder characterized by zinc deficiency affecting the skin, gastrointestinal system, and immune function. The condition follows autosomal recessive inheritance and typically presents in early infancy.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Acrodermatitis enteropathicaMIM #201100
AR
0
Active trials
11
Pubs (1 yr)
42
P/LP submissions
3%
P/LP missense
0.70
LOEUF
LOF
Mechanism· G2P
Clinical Summary— SLC39A4
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Gene-Disease Validity (ClinGen)
acrodermatitis enteropathica · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 130 VUS of 400 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
0.70LOEUF
pLI 0.000
Z-score 2.66
OE 0.42 (0.26–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.30Z-score
OE missense 1.04 (0.96–1.13)
412 obs / 395.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.42 (0.26–0.70)
0≤0.351.4
Missense OE1.04 (0.96–1.13)
0≤0.61.4
Synonymous OE1.33
0≤1.21.6
LoF obs/exp: 10 / 24.1Missense obs/exp: 412 / 395.5Syn Z: -3.75
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSLC39A4-related acrodermatitis enteropathica, zinc deficiency typeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.75top 25%
GOF
0.77top 25%
LOF
0.2092th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic23
VUS130
Likely Benign209
Benign7
Conflicting1
17
Pathogenic
23
Likely Pathogenic
130
VUS
209
Likely Benign
7
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
10
0
17
Likely Pathogenic
20
1
2
0
23
VUS
0
110
11
9
130
Likely Benign
0
8
83
118
209
Benign
0
2
5
0
7
Conflicting
—1
Total27121111127387

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC39A4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

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
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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