SLC39A8
Solute Carrier Family 39 Member 8: A Key Manganese and Zinc Transporter
Gene Information Card
| Symbol | SLC39A8 |
|---|---|
| Full Name | Solute Carrier Family 39 Member 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q24 |
| NCBI Gene ID | 64116 ncbi.nlm.nih.gov/gene/64116 |
| Ensembl ID | ENSG00000138821 |
| UniProt ID | Q9C0K1 |
| OMIM ID | 608732 |
| HGNC ID | 20862 |
| Aliases | ZIP8, BIGM103, LZT-Hs6, PP3105 |
Description
SLC39A8 encodes the ZIP8 (Zrt- and Irt-like protein 8) transporter, which mediates the cellular uptake of divalent metal ions, particularly manganese (Mn2+) and zinc (Zn2+). It is essential for manganese homeostasis, especially in the brain and liver. Loss-of-function mutations cause a congenital disorder of glycosylation (SLC39A8-CDG) characterized by severe neurological impairment.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| SLC39A8 deficiency (Congenital disorder of glycosylation type IIn) | Loss-of-function mutations impair manganese uptake, leading to deficient activity of manganese-dependent enzymes (e.g., β-1,4-galactosyltransferase), causing abnormal protein glycosylation and neurological dysfunction. | OMIM #616721; ClinVar; multiple case reports |
| Schizophrenia | Common variant rs13107325 (Ala391Thr) in SLC39A8 is associated with increased risk; altered manganese transport may affect dopaminergic signaling. | GWAS catalog; PMID: 25056061 |
| Crohn's disease | The same missense variant rs13107325 is associated with increased risk, possibly via altered zinc/manganese homeostasis affecting intestinal barrier function. | GWAS catalog; PMID: 26192919 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 17.8 | Medium |
| Kidney | 12.3 | Medium |
| Brain (cerebellum) | 9.5 | Medium |
| Lung | 8.1 | Low |
| Pancreas | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.2 | High expression |
| SH-SY5Y (neuroblastoma) | 8.7 | Moderate expression |
| A549 (lung) | 5.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112G>C (p.Gly38Arg) | Missense | Rare | Loss of function; causes SLC39A8-CDG |
| c.746G>A (p.Gly249Asp) | Missense | Rare | Loss of function; causes SLC39A8-CDG |
| rs13107325 (c.1171G>A, p.Ala391Thr) | Missense | Common (allele frequency ~0.07 in Europeans) | Reduced manganese transport; associated with schizophrenia and Crohn's disease |
Mutation functional classification
Loss of Function (LOF)
p.Gly38Arg and p.Gly249Asp reduce or abolish manganese uptake, leading to SLC39A8-CDG.
Gain of Function (GOF)
Not described.
Dominant Negative (DN)
Not described.
View complete mutation data：
Gene Ontology (GO)
| • zinc ion transmembrane transporter activity (GO:0005385) | • ferrous iron transmembrane transporter activity (GO:0015093) |
| • cobalt ion transmembrane transporter activity (GO:0015087) | • manganese ion transmembrane transporter activity (GO:0015089) |
| • integral component of membrane (GO:0016021) | • manganese ion transmembrane transport (GO:0070834) |
Pathways
• Metal ion transport (SLC39 family)
• Manganese homeostasis
Protein Summary
ZIP8 is a transmembrane protein with eight predicted transmembrane domains, localized to the plasma membrane and intracellular vesicles. It functions as a symporter of divalent metal ions with bicarbonate. The protein is critical for manganese uptake in the brain and liver, and its deficiency disrupts glycosylation pathways.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC39A8 Knockout HEK293 Cell Line | EDJ-KQ15342 | Human | 64116 | Details Get a Quote |
| SLC39A8 Knockout A-549 Cell Line | EDJ-KQ17917 | Human | 64116 | Details Get a Quote |
| SLC39A8 Knockout HCT 116 Cell Line | EDJ-KQ46063 | Human | 64116 | Details Get a Quote |
| SLC39A8 Knockout HeLa Cell Line | EDJ-KQ46064 | Human | 64116 | Details Get a Quote |
| SLC39A8 Knockout Caco-2 Cell Line | EDJ-KZ475 | Human | 64116 | Details Get a Quote |
| SLC39A8 Knockout K-562 Cell Line | EDJ-KZ476 | Human | 64116 | Details Get a Quote |
| SLC39A8 Knockout THP-1 Cell Line | EDJ-KZ477 | Human | 64116 | Details Get a Quote |
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