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
- Iron and manganese are essential nutrients yet toxic in excess. Given this, levels of these metals are carefully regulated in the body by specific molecular mechanisms. In this review, we discuss recently reported overlaps in iron and manganese homeostasis in mammalian systems, with a focus on intestinal absorption and gastrointestinal excretion. We begin with the current understanding of iron and manganese homeostasis, then present causes and consequences of imbalances in levels of these metals in the body. Notably, while manganese is best known as a neurotoxicant, multiple recent studies have reported that variations in manganese levels correlate with a wide variety of parameters of health and disease. We then highlight deficiency in the manganese transport protein SLC30A10, the first reported inherited cause of manganese excess, and recent studies of SLC30A10 from our group and others that demonstrate three intriguing overlaps between iron and manganese homeostasis. First, intestinal iron transporters DMT1 and ferroportin are essential for manganese absorption and overload in SLC30A10 deficiency. Second, intestinal SLC30A10 downregulates manganese absorption when pathways of iron absorption are upregulated. Third, manganese excess promotes SLC30A10 expression by perturbing regulation of hypoxia-inducible factors, transcription factors that are essential for the cellular response to iron imbalance. We also briefly review SLC39A14 and SLC39A8 deficiency, two other inherited diseases of manganese imbalance, and the current understanding of the function of SLC39A14 and SLC39A8. We conclude with a discussion of active, unresolved questions in need of further investigation that will enhance our understanding of the interplay between iron and manganese homeostasis in mammalian systems. - Source: PubMed
Publication date: 2026/04/14
Prajapati MilankumarChiu LaurenAkpengbe JaydynCosteas ChristosBartnikas Thomas B - Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor deficits, dopaminergic neuron loss, and α-synuclein (α-syn) aggregation. While rare mutations underlie familial PD, around 85% of cases are idiopathic. Emerging evidence implicates common genetic variants and the gut microbiome in PD risk, but their interaction has not been studied. We previously demonstrated that the PD-protective SLC39A8 variant rs13107325 (human A391T, corresponding to A393T in mouse) is associated with microbial compositional shifts in humans and reshapes the microbiome in SLC39A8 A393T knock-in mice. Here, we test whether this SNP modifies PD phenotypes in two α-synucleinopathy mouse models. In the human α-synuclein overexpression model, A393T carrier mice show reduced motor deficits, consistent with a protective role. However, in the α-synuclein preformed fibril (PFF) injection model, A393T carriers exhibit worsened motor deficits, increased dopaminergic terminal loss, and enhanced α-synuclein pathology spread. SNP- and model-specific microbiome changes correlated with motor outcomes. These included enrichment of Lactobacillus and Lactobacillaceae HT002 genera in A393T carriers with α-synuclein overexpression, and enrichment of Erysipelatoclostridium in PFF-injected A393T carriers. These findings suggest that SLC39A8 A393T-induced microbiome alterations are associated with differential disease outcomes depending on context. Our results are consistent with a model in which susceptibility gene SNPs may influence PD progression via the gut microbiome, though direct causal effects remain to be tested. - Source: PubMed
Yang Julianne CSitu JamillaTroutman RyanZhu RuoweiBlack MargaretBuri HeidiGutta ArjunTian FengruiKang AllysonAja EzinneZeng AmberLai Rochelle WTan JiaLiang FengtingBrahim CaitlynMurphy GraceAhdoot AaronPeng ChaoJacobs Jonathan P - Colorectal cancer (CRC) remains a significant global health challenge due to its high prevalence and mortality rates. Zinc transporter proteins of the SLC39A family are crucial mediators of metal ion transport and have been implicated in numerous diseases, including cancer. However, the specific molecular mechanisms underpinning their impact on CRC progression remain poorly understood. By analyzing thousands of CRC patient samples from large-scale public databases, we constructed a SLC39A family-related signature (SFRS) for prognostic prediction through the integration of 101 combinations of 10 machine learning algorithms. This model was utilized to explore tumor biology, immune microenvironment composition, mutation patterns, and responses to immunotherapy in CRC patients. To reinforce these findings, immunohistochemistry (IHC) analyses were conducted on our in-house cohort (RJ-TMA-Cohort) to examine expression levels of two key molecules, SLC39A8 and SLC39A14, and their associations with CRC progression. The SFRS model demonstrated excellent predictive performance, effectively stratifying CRC patients based on tumor characteristics, immune microenvironment, mutation features, and immunotherapy responses. Moreover, IHC and bioinformatic analyses revealed that SLC39A8 and SLC39A14 expression levels are closely associated with CRC progression, emphasizing their potential roles in tumor microenvironment regulation and their value as biomarkers and therapeutic targets. This study is the first to comprehensively investigate the functions of the SLC39A family in CRC, offering novel insights into their roles in tumor development, prognosis, and potential relevance to immunotherapy response. The SFRS model represents a powerful tool for clinical applications, while SLC39A8 and SLC39A14 present promising avenues for future research and therapeutic strategies. - Source: PubMed
Publication date: 2026/03/21
Chen HaizhenChen ChaozhaoChen JieZheng HuangZhu XinhaoYu QianruZhou JiajieZong JiashengLu TingyanSun JingShao YanfeiZheng Minhua - SLC39A8-congenital disorder of glycosylation (SLC39A8-CDG) is a rare autosomal recessive metabolic disease of manganese transport, leading to defective glycosylation and mitochondrial dysfunction. An eight-month-old male infant with severe hypotonia, developmental delay, and dystonic episodes was initially misdiagnosed as epilepsy. Genetic testing identified a homozygous pathogenic variant in the gene, and biochemical analysis confirmed low manganese levels. Upon initiation of oral manganese sulfate therapy, the patient demonstrated significant clinical improvement, including the achievement of new motor milestones. To our knowledge, this is the first documented case in Bulgaria. This case underscores the importance of early genetic diagnosis and targeted metabolic treatment in altering the clinical trajectory of SLC39A8-CDG. Timely recognition allows for intervention in a disorder that, despite its rarity, has a modifiable course and potential for meaningful developmental gains. - Source: PubMed
Publication date: 2026/01/09
Varbanova ValentinaTacheva GenovevaPaneva TeodoraKrasteva MarinaStamatov DimitarLitvinenko Ivan - NPs (natriuretic peptides) are bioactive hormones crucial for regulating blood pressure, glucose homeostasis, and lipid metabolism. Despite the high heritability of circulating NP levels, the genetic determinants of NP regulation, particularly across ancestries and sexes, remain poorly understood. The objective of the current study was to identify genetic variants associated with NT-proBNP (N-terminal pro-B-type NP) levels in a multiancestry study population. - Source: PubMed
Publication date: 2026/01/28
Shetty Naman SPampana AkhilGaonkar MokshadNayak AmritaBal Harshvir SPatel NiravVekariya NehalSmith J GustavMorrison Alanna CYu BingPsaty Bruce MBoerwinkle EricFloyd James SRotter Jerome ITaylor Kent DLange Leslie AIrvin Marguerite RCushman MaryRich Stephen SVasan Ramachandran SWang Thomas JGuo XiuqingLi PengArora GarimaArora Pankaj