SLC39A5

Chr 12AD

solute carrier family 39 member 5

Also known as: LZT-Hs7, MYP24, ZIP5

NCBI Gene: 283375ENSG00000139540UniProt: Q6ZMH5

The protein encoded by this gene belongs to the ZIP family of zinc transporters that transport zinc into cells from outside, and play a crucial role in controlling intracellular zinc levels. Zinc is an essential cofactor for many enzymes and proteins involved in gene transcription, growth, development and differentiation. Mutations in this gene have been associated with autosomal dominant high myopia (MYP24). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

Primary Disease Associations & Inheritance

Myopia 24, autosomal dominantMIM #615946
AD
132
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC39A5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 92 VUS of 132 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.
1.20LOEUF
pLI 0.000
Z-score 0.83
OE 0.81 (0.56–1.20)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.24Z-score
OE missense 0.96 (0.88–1.06)
310 obs / 322.0 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.0.81 (0.56–1.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.88–1.06)
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.0.96
0≤1.21.6
LoF obs/exp: 18 / 22.2Missense obs/exp: 310 / 322.0Syn Z: 0.40

ClinVar Variant Classifications

132 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS92
Likely Benign20
Benign7
Conflicting3
8
Pathogenic
2
Likely Pathogenic
92
VUS
20
Likely Benign
7
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
7
0
8
Likely Pathogenic
1
0
1
0
2
VUS
4
85
3
0
92
Likely Benign
0
12
1
7
20
Benign
0
4
1
2
7
Conflicting
—3
Total5102139132

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC39A5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SLC39A5-related myopia

strong
ADUndeterminedUncertain
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Myopia 24, autosomal dominant

MIM #615946

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Familial Whole Exome Sequencing Study of 30 Families With Early-Onset High Myopia.
Yang E et al.·Invest Ophthalmol Vis Sci
2023
SLC39A5 dysfunction impairs extracellular matrix synthesis in high myopia pathogenesis.
Dong S et al.·J Cell Mol Med
2021
Blocking IL-6 signaling improves glucose tolerance via SLC39A5-mediated suppression of glucagon secretion.
Chen W et al.·Metabolism
2023
SLC39A5 promotes lung adenocarcinoma cell proliferation by activating PI3K/AKT signaling.
Liu Z et al.·Pathol Res Pract
2021
Mutation screening of 17 candidate genes in a cohort of 67 probands with early-onset high myopia.
Liu F et al.·Ophthalmic Physiol Opt
2020Cohort
Mutational screening of SLC39A5, LEPREL1 and LRPAP1 in a cohort of 187 high myopia patients.
Feng CY et al.·Sci Rep
2017Cohort
Detection of mutations in LRPAP1, CTSH, LEPREL1, ZNF644, SLC39A5, and SCO2 in 298 families with early-onset high myopia by exome sequencing.
Jiang D et al.·Invest Ophthalmol Vis Sci
2014
Mutational screening of AGRN, SLC39A5, SCO2, P4HA2, BSG, ZNF644, and CPSF1 in a Chinese cohort of 103 patients with nonsyndromic high myopia.
Zheng YH et al.·Mol Vis
2021Cohort
SLC39A5 mutations interfering with the BMP/TGF-β pathway in non-syndromic high myopia.
Guo H et al.·J Med Genet
2014
Induction of the metal transporter ZIP8 by interferon gamma in intestinal epithelial cells: Potential role of metal dyshomeostasis in Crohn's disease.
Melia JMP et al.·Biochem Biophys Res Commun
2019
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