SLC39A14 (ZIP14): Manganese and Zinc Transporter in Hypermanganesemia and Metabolic Disease
A comprehensive biomedical reference for SLC39A14, covering gene structure, expression, disease associations, mutations, and functional classification.
Gene Information Card
| Symbol | SLC39A14 |
|---|---|
| Full Name | Solute carrier family 39 member 14 |
| Gene Type | Protein coding |
| Chromosomal Location | 8p21.3 |
| NCBI Gene ID | 23516 ncbi.nlm.nih.gov/gene/23516 |
| Ensembl ID | ENSG00000104635 |
| UniProt ID | Q15043 |
| OMIM ID | 608736 |
| HGNC ID | 20858 |
| Aliases | ZIP14, LZT-Hs4, cig19, HZ4 |
Description
SLC39A14 (ZIP14) encodes a member of the SLC39 family of metal transporters, primarily mediating the cellular uptake of zinc and manganese. It is widely expressed, with high levels in the liver, intestine, and brain. Mutations in SLC39A14 cause autosomal recessive hypermanganesemia with dystonia, a severe neurological disorder characterized by manganese accumulation in the brain. The protein also plays roles in iron metabolism and systemic metal homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypermanganesemia with dystonia 2 (HMNDYT2) | Loss-of-function mutations impair manganese transport, leading to manganese accumulation in the brain, particularly in the basal ganglia, causing neurodegeneration and dystonia. | OMIM #617013; multiple case reports (e.g., Tuschl et al., 2016; Rodan et al., 2018) |
| SLC39A14-related parkinsonism | Similar to HMNDYT2, mutations cause manganese-induced dopaminergic neuron dysfunction, presenting with parkinsonian features. | ClinVar submissions; case studies (e.g., Zaki et al., 2017) |
| Non-alcoholic fatty liver disease (NAFLD) susceptibility | Altered zinc transport may affect hepatic lipid metabolism and insulin signaling, contributing to NAFLD progression. | GWAS and expression studies (e.g., Kim et al., 2014; Liuzzi et al., 2005) |
| Iron overload disorders (modifier) | ZIP14 can transport iron; dysregulation may exacerbate iron accumulation in conditions like hemochromatosis. | Functional studies (e.g., Jenkitkasemwong et al., 2015) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High (e.g., ~30-50 nTPM) | High |
| Small intestine | High (e.g., ~20-40 nTPM) | High |
| Kidney | Moderate (e.g., ~10-20 nTPM) | Medium |
| Brain (cerebellum, basal ganglia) | Moderate (e.g., ~5-15 nTPM) | Medium |
| Pancreas | Moderate (e.g., ~5-10 nTPM) | Medium |
| Lung | Low (e.g., <5 nTPM) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | ~20-30 nTPM | High expression; used for metal transport studies |
| Caco-2 (intestinal) | ~15-25 nTPM | High; relevant for dietary metal absorption |
| SH-SY5Y (neuroblastoma) | ~5-10 nTPM | Moderate; neuronal model for manganese toxicity |
| HEK293 (embryonic kidney) | ~10-15 nTPM | Moderate; commonly used for overexpression studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112G>A (p.Gly38Arg) | Missense | Rare (found in HMNDYT2 families) | Loss of function; impaired manganese transport |
| c.208C>T (p.Arg70Ter) | Nonsense | Rare (found in HMNDYT2) | Loss of function; truncated protein |
| c.1007T>C (p.Leu336Pro) | Missense | Rare (found in HMNDYT2) | Loss of function; altered protein folding |
| c.1225G>A (p.Gly409Arg) | Missense | Rare (found in HMNDYT2) | Loss of function; reduced cell surface expression |
Mutation functional classification
Loss of Function (LOF)
Most SLC39A14 mutations are loss-of-function, leading to impaired manganese and zinc transport. This results in manganese accumulation in the brain, causing neurodegeneration and dystonia. Examples include missense, nonsense, and frameshift mutations that reduce protein stability, trafficking, or transport activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SLC39A14. All known pathogenic variants are loss-of-function.
Dominant Negative (DN)
No dominant-negative effects have been described; the disease is inherited in an autosomal recessive manner, requiring biallelic mutations.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005385 - zinc ion transmembrane transporter activity | • GO:0005384 - manganese ion transmembrane transporter activity |
| • GO:0006811 - ion transport | • GO:0006812 - cation transport |
| • GO:0016021 - integral component of membrane | • GO:0005886 - plasma membrane |
| • GO:0035434 - copper ion transmembrane transport | • GO:0070838 - divalent metal ion transport |
Pathways
• Metal ion homeostasis (e.g.
• zinc
• manganese
• iron)
• Manganese transport and toxicity
• Zinc uptake and distribution
• Iron metabolism and erythropoiesis
Protein Summary
SLC39A14 (ZIP14) is a 489-amino acid transmembrane protein with eight predicted transmembrane domains. It functions as a metal transporter, primarily importing zinc and manganese into cells. It forms homo- or heterodimers and localizes to the plasma membrane and intracellular vesicles. The protein is critical for systemic manganese homeostasis, particularly in the liver and brain. Mutations causing loss of function lead to hypermanganesemia with dystonia, a severe autosomal recessive disorder. ZIP14 also participates in iron uptake and may influence metabolic diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC39A14 Knockout HEK293 Cell Line | EDJ-KQ2426 | Human | 23516 | Details Get a Quote |
| SLC39A14 Knockout HCT 116 Cell Line | EDJ-KQ22938 | Human | 23516 | Details Get a Quote |
| SLC39A14 Knockout HeLa Cell Line | EDJ-KQ22939 | Human | 23516 | Details Get a Quote |
| SLC39A14 Knockout A-549 Cell Line | EDJ-KQ21615 | Human | 23516 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
