HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SLC39A14
solute carrier family 39 member 14
Chromosome 8 Β· 8p21.3
NCBI Gene: 23516Ensembl: ENSG00000104635.16HGNC: HGNC:20858UniProt: A0A0S2Z534
111PubMed Papers
22Diseases
0Drugs
13Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
iron import into celliron ion transmembrane transportzinc ion transmembrane transporter activityearly endosome membranehypermanganesemia with dystonia 2hyperostosis cranialis internadystonia 16genetic disorder
✦AI Summary

SLC39A14 (ZIP14) is an electroneutral membrane transporter mediating cellular uptake of divalent metal cations, primarily zinc, manganese, and iron, which are essential for tissue homeostasis and metabolism 123. The transporter functions as an energy-dependent symporter, transporting metal-bicarbonate complexes across the plasma membrane [UniProt]. SLC39A14 regulates intestinal zinc uptake critical for maintaining tight junctions and permeability, and controls insulin receptor signaling and glucose metabolism in hepatocytes through zinc-dependent intracellular processes 4. It serves as the major manganese transporter in intestinal epithelial cells and participates in blood-brain barrier manganese uptake 56. Additionally, SLC39A14 mediates non-transferrin-bound iron (NTBI) uptake and endosomal iron transport 78. Clinically, SLC39A14 dysfunction is associated with ferroptosis-related pathologies. SLC39A14 upregulation promotes hepatocyte ferroptosis in liver ischemia-reperfusion injury and cirrhosis 91011. In skeletal muscle aging, elevated SLC39A14 combined with declining transferrin receptor 1 drives labile iron accumulation and ferroptosis-mediated regeneration impairment 12. SLC39A14 also facilitates ferroptosis during acute lung injury 13. In cancer, SLC39A14 promotes zinc uptake by tumor cells, depleting the tumor microenvironment and impairing T cell immunity in nasopharyngeal carcinoma 14. These findings identify SLC39A14 as a therapeutic target for ferroptosis-related diseases and cancer immunotherapy.

Sources cited
1
SLC39A14 regulates intestinal zinc uptake critical for maintaining tight junctions and permeability, and controls insulin receptor signaling and glucose metabolism in hepatocytes through zinc-dependent intracellular processes .
PMID: 27703010
2
In skeletal muscle aging, elevated SLC39A14 combined with declining transferrin receptor 1 drives labile iron accumulation and ferroptosis-mediated regeneration impairment .
PMID: 33955709
3
SLC39A14 also facilitates ferroptosis during acute lung injury .
PMID: 37301835
4
In cancer, SLC39A14 promotes zinc uptake by tumor cells, depleting the tumor microenvironment and impairing T cell immunity in nasopharyngeal carcinoma .
PMID: 40818459
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜22
hypermanganesemia with dystonia 2Open Targets
0.79Strong
hyperostosis cranialis internaOpen Targets
0.55Moderate
dystonia 16Open Targets
0.37Weak
genetic disorderOpen Targets
0.34Weak
intracranial hemorrhageOpen Targets
0.16Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
polycystic ovary syndromeOpen Targets
0.07Suggestive
gliomaOpen Targets
0.07Suggestive
posterior cortical atrophyOpen Targets
0.07Suggestive
cancerOpen Targets
0.07Suggestive
renal cell carcinomaOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
obesityOpen Targets
0.06Suggestive
isolated hyperferritinemiaOpen Targets
0.06Suggestive
Hypocalcemic vitamin D-resistant ricketsOpen Targets
0.06Suggestive
esophageal squamous cell carcinomaOpen Targets
0.05Suggestive
glycine N-methyltransferase deficiencyOpen Targets
0.05Suggestive
multiple epiphyseal dysplasia type 1Open Targets
0.05Suggestive
acute myeloid leukemiaOpen Targets
0.05Suggestive
spondyloepimetaphyseal dysplasia with multiple dislocationsOpen Targets
0.05Suggestive
Hypermanganesemia with dystonia 2UniProt
Hyperostosis cranialis internaUniProt
Pathogenic Variants13
NM_001128431.4(SLC39A14):c.751-9C>GLikely pathogenic
Hypermanganesemia with dystonia 2|Hyperostosis cranialis interna
β˜…β˜…β˜†β˜†2024
NM_001128431.4(SLC39A14):c.971G>A (p.Trp324Ter)Likely pathogenic
Hypermanganesemia with dystonia 2
β˜…β˜†β˜†β˜†2026β†’ Residue 324
NM_001128431.4(SLC39A14):c.152A>G (p.Tyr51Cys)Likely pathogenic
Hypermanganesemia with dystonia 2
β˜…β˜†β˜†β˜†2025β†’ Residue 51
NM_001128431.4(SLC39A14):c.178C>T (p.Gln60Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 60
NM_015359.6(SLC39A14):c.520dup (p.Val174fs)Pathogenic
Hypermanganesemia with dystonia 2
β˜…β˜†β˜†β˜†2023β†’ Residue 174
NM_001128431.4(SLC39A14):c.628-2A>GLikely pathogenic
Hypermanganesemia with dystonia 2
β˜…β˜†β˜†β˜†2023
NM_001128431.4(SLC39A14):c.1322T>G (p.Leu441Arg)Pathogenic
Hyperostosis cranialis interna
β˜†β˜†β˜†β˜†2022β†’ Residue 441
NM_001128431.4(SLC39A14):c.313G>T (p.Glu105Ter)Pathogenic
Hypermanganesemia with dystonia 2
β˜†β˜†β˜†β˜†2022β†’ Residue 105
NM_001128431.4(SLC39A14):c.1336C>T (p.Pro446Ser)Pathogenic
Hypermanganesemia with dystonia 2
β˜†β˜†β˜†β˜†2022β†’ Residue 446
NM_001128431.4(SLC39A14):c.1147G>A (p.Gly383Arg)Pathogenic
Hypermanganesemia with dystonia 2
β˜†β˜†β˜†β˜†2018β†’ Residue 383
NM_001128431.4(SLC39A14):c.1407C>G (p.Asn469Lys)Pathogenic
Hypermanganesemia with dystonia 2
β˜†β˜†β˜†β˜†2018β†’ Residue 469
NM_001128431.4(SLC39A14):c.292T>G (p.Phe98Val)Pathogenic
Hypermanganesemia with dystonia 2
β˜†β˜†β˜†β˜†2018β†’ Residue 98
NM_015359.6(SLC39A14):c.477_478del (p.Ser160fs)Pathogenic
Hypermanganesemia with dystonia 2
β˜†β˜†β˜†β˜†2018β†’ Residue 160
View on ClinVar β†—
Related Genes
HAMPProtein interaction100%SLC30A6Protein interaction89%SLC30A5Protein interaction87%SLC30A7Protein interaction85%TFRCProtein interaction79%SLC40A1Protein interaction79%
Tissue Expression6 tissues
Liver
100%
Heart
16%
Ovary
4%
Brain
4%
Lung
3%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
SLC39A14HAMPSLC30A6SLC30A5SLC30A7TFRCSLC40A1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q15043
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.59Moderately Constrained
pLIβ“˜
0.37Tolerant
Observed/Expected LoF0.40 [0.28–0.59]
RankingsWhere SLC39A14 stands among ~20K protein-coding genes
  • #4,294of 20,598
    Most Researched111 Β· top quartile
  • #2,586of 5,498
    Most Pathogenic Variants13
  • #4,020of 17,882
    Most Constrained (LOEUF)0.59 Β· top quartile
Genes detectedSLC39A14
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Ferroptosis-related signature and immune infiltration characterization in acute lung injury/acute respiratory distress syndrome.
PMID: 37301835
Respir Res Β· 2023
1.00
2
Hepatic transferrin plays a role in systemic iron homeostasis and liver ferroptosis.
PMID: 32374849
Blood Β· 2020
0.90
3
Mesenchymal Stem Cells Prevent SLC39A14-Dependent Hepatocyte Ferroptosis through Exosomal miR-16-5p in Liver Graft.
PMID: 39680749
Adv Sci (Weinh) Β· 2025
0.80
4
Transferrin receptor 1 ablation in satellite cells impedes skeletal muscle regeneration through activation of ferroptosis.
PMID: 33955709
J Cachexia Sarcopenia Muscle Β· 2021
0.70
5
Mesenchymal stem cell-derived extracellular vesicles attenuate ferroptosis in aged hepatic ischemia/reperfusion injury by transferring miR-1275.
PMID: 39986119
Redox Biol Β· 2025
0.60