Ask about this productRelated genes to: SLC39A8 antibody
- Gene:
- SLC39A8 NIH gene
- Name:
- solute carrier family 39 member 8
- Previous symbol:
- -
- Synonyms:
- BIGM103
- Chromosome:
- 4q24
- Locus Type:
- gene with protein product
- Date approved:
- 2003-10-08
- Date modifiied:
- 2016-02-17
Related products to: SLC39A8 antibody
Related articles to: SLC39A8 antibody
- The rapid expansion of human genomic data has revealed a large number of naturally occurring variants, creating a major challenge for functional annotation. The human metal transporter SLC39A8 (ZIP8) is a clinically important divalent metal transporter, yet most of its documented variants remain uncharacterized. Here, we developed a workflow to functionally evaluate ZIP8 variants by integrating laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOF-MS) with scaled-up cell-based transport assays. Using this method, we systematically analyzed 33 naturally occurring missense variants located in the extracellular domain (ECD) of ZIP8. The assay enables direct quantification of intracellular metal accumulation with substantially improved throughput (∼150 samples per hour). Functional screening identified 14 potential pathogenic variants with significantly reduced transport activity. Comparison with computational predictions revealed a moderate correlation between activity and AlphaMissense pathogenicity scores (R = 0.423), while an error rate of ∼20% for AlphaMissense underscores the need for experimental validation. Flow cytometry analysis showed that most loss-of-function variants exhibit impaired trafficking of the protein to the cell surface possibly due to mutation-caused protein misfolding or instability. Structural mapping of activity-compromised variants, together with functional assessment of the ZIP8-ECD, highlights the importance of this domain in ZIP8 expression and intracellular protein trafficking. Together, this work establishes a scalable approach for functional screening of metal transporter variants and provides new insights into the structure-function relationships of ZIP8. - Source: PubMed
Publication date: 2026/09/08
Nikolovski MichaelWang TianqiSue AaronMacRenaris KeithZhao HongyanO'Halloran Thomas VHu Jian - Solute carrier family 39 member 8 (SLC39A8) exhibits abnormal expression in a broad range of tumors and is closely associated with the progression of malignant tumors. However, its expression patterns and functional roles in glioma remain unexplored. This research aimed to investigate the key regulatory function of SLC39A8 in the malignant phenotypes of glioma and its possible value as a therapeutic candidate for this malignancy. Bioinformatics analysis and experimental validation revealed elevated SLC39A8 levels in gliomas, with strong associations with clinicopathological traits and patient prognostic status. The results of functional assays revealed that SLC39A8 knockdown elicits robust anti-glioma effects. Notably, re-expression of SLC39A8 in SLC39A8-depleted glioma cells markedly reversed these anti-tumor effects. Further investigation demonstrated that SLC39A8 knockdown enhances lipid peroxidation and induces ferroptosis and that treatment with ferroptosis inhibitors significantly counteracts the tumor-suppressive impact of SLC39A8 knockdown. Mechanistically, SLC39A8 mediates zinc influx, which activates cyclic adenosine monophosphate-responsive element-binding protein (CREB)-mediated glutathione peroxidase 4 (GPX4) transcription, thereby modulating ferroptosis. Overexpression of GPX4 strongly reversed the ferroptosis induction resulting from SLC39A8 knockdown. In vivo glioma xenograft models further confirmed that SLC39A8 knockdown suppressed tumor formation and increased ferroptosis in tumor tissues. Collectively, our findings indicate that SLC39A8 plays a protumorigenic role in glioma and that its knockdown suppresses tumor progression, likely by modulating CREB/GPX4-mediated ferroptosis. This study offers new perspectives on the molecular pathogenic mechanisms of glioma and highlights SLC39A8 as a potential promising target for treating this malignant tumor. - Source: PubMed
Publication date: 2026/08/29
Feng ZibinWu LinShen YingHu YuqiZhang Zhiguo - Infectious bovine rhinotracheitis virus (IBRV) causes highly contagious bovine respiratory disease and threatens the global cattle industry. Ferroptosis, an iron-dependent regulated cell death, is involved in multiple viral infections, but its role and mechanism in IBRV infection remain unclear. This study investigated IBRV-induced ferroptosis and the axis in MDBK cells and examined the effect of ferroptosis on IBRV replication. Ferroptotic phenotypes and molecules were detected by biochemical assays, qPCR, Western blotting and TEM. Gain- and loss-of-function assays were performed to modulate gene expression, and their transcriptional relationship was verified by dual-luciferase assay. IBRV induced typical ferroptosis in MDBK cells, including Fe overload, excessive ROS and MDA accumulation, GSH depletion and mitochondrial damage. Ferrostatin-1 reversed these changes and reduced viral titers, suggesting that ferroptosis contributes to IBRV replication. overexpression aggravated ferroptosis, whereas its knockdown suppressed it. Mechanistically, our data support that positively regulates transcription, and silencing inhibited IBRV-induced ferroptosis. In conclusion, this in vitro study shows that IBRV induces ferroptosis in MDBK cells via the axis, and ferroptosis may contribute to viral replication. These findings provide insights into IBRV-host cellular interaction and identify potential candidate molecular targets for future antiviral research. - Source: PubMed
Publication date: 2026/08/18
Wei YimingHao WenKou WantingYu WenwenWang XinLi JianmingHu GuixueWang KaiLeng Xue - Manganese (Mn) is an essential metal required for many physiological functions, and deficiency or overexposure is associated with neurological dysfunction and neuropathology. Tight homeostatic control of Mn in the body is required to maintain optimal physiological levels and protect against toxicity. Mn homeostasis has been studied for decades, but there has been limited knowledge of the molecular mechanisms until recently, when the first human genetic disorders of Mn metabolism were described. These discoveries led to the identification of the Mn transporters SLC30A10, SLC39A14, and SLC39A8, which spurred a transformation of research into Mn homeostatic mechanisms. This review provides an overview of Mn physiology and homeostasis and the role of the critical Mn transporters and discusses the progress made within recent years toward understanding how these transporters work together to regulate brain Mn biology under both physiological and pathophysiological Mn conditions. - Source: PubMed
Publication date: 2026/08/08
Melkote AshviniAschner MichaelBowman Aaron BMukhopadhyay Somshuvra - ZIP8, encoded by SLC39A8, mediates cellular uptake of divalent metal ions, including manganese (Mn). Mutations in SLC39A8 cause a congenital disorder of glycosylation (CDG) associated with Mn deficiency (SLC39A8-CDG). Here, we report a novel case of SLC39A8-CDG harboring a previously unreported mutation (p.F206I) in the transmembrane domain 3 (TMD3). The patient showed markedly low serum Mn levels and abnormal glycosylation. To evaluate the functional consequences of this variant, we generated cells expressing hZIP8-F206I. Mn, cadmium, and zinc uptake levels in cells expressing hZIP8-F206I were approximately half of those in cells expressing wild-type hZIP8. The mutant hZIP8 also showed reduced plasma membrane localization. These findings suggest that this previously unreported mutation in TMD3 significantly impairs ZIP8-mediated metal transport, leading to CDG. - Source: PubMed
Publication date: 2026/07/22
Fujishiro HitomiMorisada NaoyaMitani NaoNakayama RinaGoto NatsukiNishito YukinaKambe TaihoOkamoto NobuhikoWada YoshinaoIshida YusukeSuzuki HisatoNozu KandaiKosaki KenjiroHimeno SeiichiroSumi Daigo