Ask about this productRelated genes to: SLC39A4 antibody
- Gene:
- SLC39A4 NIH gene
- Name:
- solute carrier family 39 member 4
- Previous symbol:
- AEZ
- Synonyms:
- ZIP4, AWMS2
- Chromosome:
- 8q24.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-02-13
- Date modifiied:
- 2016-11-01
Related products to: SLC39A4 antibody
Related articles to: SLC39A4 antibody
- Liver fibrosis is a progressive pathological process driven by chronic liver injury, with limited effective therapies. Zinc transporter ZIP4 (SLC39A4) is critical for zinc homeostasis, but its role in liver fibrosis remains unclear. Here, we show that ZIP4 expression is significantly downregulated in fibrotic human liver tissues. Using hepatocyte-specific Zip4 knockout and AAV8-mediated ZIP4 overexpression mouse models, we demonstrate that ZIP4 deficiency exacerbates CCl-induced liver injury, fibrosis, oxidative stress, apoptosis, and ferroptosis, whereas ZIP4 overexpression alleviates these lesions. Mechanistically, ZIP4 maintains hepatic zinc homeostasis, upregulates antioxidant enzymes (PRDXs, SODs), and inhibits ferroptosis by regulating p53, SLC7A11, SLC40A1, and GPX4. Furthermore, zinc gluconate (Zn-Glu) combined with GCN2 inhibitor (GCN2iB) synergistically increases ZIP4 expression and intracellular zinc levels in HepG2 cells. In CCl-treated mice, Zn-Glu plus GCN2iB upregulates hepatic ZIP4, enhances antioxidant capacity, suppresses ferroptosis, and mitigates liver fibrosis. Collectively, our findings identify ZIP4 as a novel anti-fibrotic regulator that protects against liver fibrosis by maintaining zinc homeostasis, restraining oxidative stress, and inhibiting ferroptosis. The Zn-Glu/GCN2iB combination exerts anti-fibrotic effects by activating ZIP4 signaling, representing a promising strategy for clinical intervention. - Source: PubMed
Publication date: 2026/04/20
Luo JialiYu ZhuoranGao JunlingZhao YueZhang BingqiLuo KaiJianggewaer YierxiatiWang SiyuLu Zhongbing - Interventional therapy and surgery play important roles in the treatment of various diseases, but they cause varying degrees of vascular injury. Currently, the side effects are often overlooked. Here, we observed abnormal nuclear morphology (nuclear dysmorphism) and vascular aging in injured human and rodent arteries. Platelet-derived microvesicles (PMVs) adhere to injured blood vessels, leading to nuclear dysmorphism and cell senescence in vascular smooth muscle cells (VSMCs). This occurs because PMV adherence reduces intracellular Zn levels, which impairs Zn-dependent processing of prelamin A by the enzyme ZMPSTE24. Consequently, prelamin A accumulates in VSMCs, contributing to the observed nuclear dysmorphism and cell senescence. RNA sequencing and loss-of-function assays revealed that Zinc transporter solute carrier family 39 member 4 (SLC39A4, also called ZIP4) deficiency accounts for the decreased Zinc concentration. Consistently, Zmpste24 and Zmpste24 mice displayed significant cumulative prelamin A, deteriorated nuclear dysmorphism and vascular aging. Whole genome bisulfite sequencing (WGBS) and bioinformatic analysis illustrated that demethylation of genes within Lamina-associated domains (LADs) participates in nuclear dysmorphism and cell senescence. Of note, Zinc supplementation, especially using platelet membrane-coated Zn-MOF nanoparticles, robustly alleviated nuclear dysmorphism and vascular aging. Our data established a novel and significant role of pMVs/ZIP4/zinc/prelamin A axis in promoting nuclear dysmorphism and vascular aging after injury. - Source: PubMed
Ma TengzhiBao HanXu ZhijueRen HeTian WenhaoChen JiaheLiu ZhongqianLu XinwuLv FanYao QingpingQi YingxinHuang Kai - Acrodermatitis enteropathica (AE) is a clinical disorder that manifests due to severe zinc deficiency, which can be either genetic or acquired. The acquired form has been reported in patients with poor dietary intake, alcoholism, chronic liver disease, malabsorption syndrome, sickle cell anemia, or chronic renal failure, which usually presents at a later stage in life and has similar clinical features to the inherited defect. On the other hand, the genetic form is an autosomal recessive disorder, characterized by periorificial dermatitis, alopecia, and diarrhea caused by a defect in the SLC39A4 gene located on human chromosome 8, band 8q24.3, which impairs zinc absorption in the small intestine. Zinc is necessary for the functioning of many regulatory genes and enzymes; its deficiency presents with diverse manifestations in childhood, most commonly. Genetic testing is usually not available in many places, so the diagnosis is made clinically, along with measurement of zinc levels in serum or hair, and replenishing with supplements as soon as possible. This case report also depicts a case of inherited acrodermatitis enteropathica in an infant, which was managed successfully with zinc supplementation. - Source: PubMed
Publication date: 2025/12/31
Sushantika SushantikaSethi Jyoti - Acrodermatitis enteropathica (AE) is a rare disorder of zinc deficiency which may be hereditary or acquired. Hereditary AE is an autosomal recessive disorder caused by defects in the zinc transporter gene SLC39A4, resulting in impaired intestinal absorption of zinc. Acquired AE arises secondary to reduced intake, increased demand, or malabsorption. Zinc, an essential micronutrient plays a key role in immune status, wound repair, gastrointestinal and metabolic function. AE is characterised by diarrhoea, recurrent infections, growth delay and skin manifestations including periorificial and acrodermatitis. We report six cases of AE seen in a tertiary centre. The mean age at presentation was 8 months (5-13 months). All patients presented with a characteristic well-demarcated crusted orofacial erythematous rash together with persistent erosive symmetrical anogenital involvement. One patient had an identified defect in the zinc transporter gene. Four patients (66%) patients were exclusively breast fed and three (50%) were born prematurely. The mean age of presentation among breastfed infants was earlier, at 3.25 months (range: 3-5 months). Low serum zinc levels were documented in 66% of cases. All patients were treated with zinc supplementation and showed rapid clinical improvement following initiation of therapy. This series highlights risk factors for developing acquired AE, including prematurity and exclusive breastfeeding. Breast milk is highest in zinc in the first 1-2 months after which zinc content declines 1, corresponding with the typical age of presentation in breastfed infants. Diagnoses is primality based upon the dermatological presentation demonstrating the importance of clinician familiarity of the presenting -features. - Source: PubMed
Jassal-Prior PoojaCarson LukeLeech SuzyDubois AnnaGoodhead Charlotte - BACKGROUND Acrodermatitis enteropathica (AE) is a rare autosomal recessive disorder caused by solute carrier family 39 member 4 (SLC39A4) gene variants that impair zinc absorption. Although typically associated with bacterial or fungal superinfection, its concurrence with Kaposi's varicelliform eruption (KVE) is exceptionally rare - only 1 case was previously reported. This report describes a case of KVE complicating AE in a patient with novel compound heterozygous SLC39A4 variants, highlighting the immunovirological implications of zinc deficiency. CASE REPORT An 8-year-old girl who had chronic dermatitis since infancy presented with a diffuse vesiculobullous rash. Physical examination revealed perioral and acral dermatitis, alopecia, and crusted vesicles consistent with KVE. Laboratory testing showed normal serum zinc levels (76.13 µg/dL) but reduced alkaline phosphatase (32 U/L). Genetic analysis identified compound heterozygous SLC39A4 variants: a maternal frameshift variant (c.522_523dup) and 3 paternal variants (c.925T>C, c.1782C>T, and c.1843C>T). The patient received oral zinc gluconate and topical crisaborole ointment, achieving complete resolution within 2 weeks. CONCLUSIONS This case demonstrates that AE may present with normal zinc concentrations, underscoring the diagnostic value of alkaline phosphatase. Genetic confirmation remains essential in atypical presentations. These novel variants broaden the mutational spectrum of SLC39A4 and emphasize the importance of early zinc supplementation and antiviral prophylaxis in patients with AE who display KVE risk. - Source: PubMed
Publication date: 2025/12/12
He YuanBai LiuLi Junyou