SLC39A7

Chr 6AR

solute carrier family 39 member 7

Also known as: AGM9, D6S115E, D6S2244E, H2-KE4, HKE4, KE4, RING5, ZIP7

NCBI Gene: 7922ENSG00000112473UniProt: Q92504

The protein encoded by this gene transports zinc from the Golgi and endoplasmic reticulum to the cytoplasm. This transport may be important for activation of tyrosine kinases, some of which could be involved in cancer progression. Therefore, modulation of the encoded protein could be useful as a therapeutic agent against cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

Primary Disease Associations & Inheritance

Agammaglobulinemia 9, autosomal recessiveMIM #619693
AR
264
ClinVar variants
11
Pathogenic / LP
0.08
pLI score
0
Active trials
Clinical Summary— SLC39A7
🧬
Gene-Disease Validity (ClinGen)
agammaglobulinemia · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 131 VUS of 264 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.61LOEUF
pLI 0.082
Z-score 2.72
OE 0.29 (0.15–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.53Z-score
OE missense 0.74 (0.66–0.83)
198 obs / 268.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.29 (0.15–0.61)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.66–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.71
0≤1.21.6
LoF obs/exp: 5 / 17.1Missense obs/exp: 198 / 268.6Syn Z: 2.38

ClinVar Variant Classifications

264 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic4
VUS131
Likely Benign112
Benign6
Conflicting4
7
Pathogenic
4
Likely Pathogenic
131
VUS
112
Likely Benign
6
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
4
0
7
Likely Pathogenic
0
0
4
0
4
VUS
6
108
16
1
131
Likely Benign
1
9
38
64
112
Benign
0
1
1
4
6
Conflicting
—4
Total71216369264

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC39A7 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Agammaglobulinemia 9, autosomal recessive

MIM #619693

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The NLRX1-SLC39A7 complex orchestrates mitochondrial dynamics and mitophagy to rejuvenate intervertebral disc by modulating mitochondrial Zn(2+) trafficking.
Song Y et al.·Autophagy
2024
Monogenic Common Variable Immunodeficiency (Mo-CVID) Score for Optimizing the Genetic Diagnosis in Pediatric CVID Cohort.
Barbati F et al.·Eur J Immunol
2025Cohort
Immunotherapy landscape analyses of necroptosis characteristics for breast cancer patients.
Yu H et al.·J Transl Med
2022Cohort
The emerging role of the LIV-1 subfamily of zinc transporters in breast cancer.
Taylor KM et al.·Mol Med
2007Review
PSMB8 as a Candidate Marker of Responsiveness to Preoperative Radiation Therapy in Rectal Cancer Patients.
Ha YJ et al.·Int J Radiat Oncol Biol Phys
2017Cohort
Identification of a Gene Panel Predictive of Triple-Negative Breast Cancer Response to Neoadjuvant Chemotherapy Employing Transcriptomic and Functional Validation.
Vishnubalaji R et al.·Int J Mol Sci
2022Functional
ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in antihormone-resistant breast cancer Cells.
Taylor KM et al.·Endocrinology
2008
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools