ArticleJCI insight2020
Pleiotropic ZIP8 A391T implicates abnormal manganese homeostasis in complex human disease.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Functional characterization of a novel ZIP8 variant causing impaired manganese homeostasis and congenital disorders of glycosylation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- Common genetic mechanisms between obesity and COVID-19 severity: unravelling pleiotropic loci and biological pathways.Royal Society open science · 2026Article
- Article
- A microbiome quantitative trait locus in SLC39A8 modulates disease severity in synucleinopathy-induced models of Parkinson's disease.Human molecular genetics · 2026Article
- A homology-based 3D model and structure-function studies reveal key elements for divalent metal ion transporter ZIP8 (SLC39A8) function.The Journal of biological chemistry · 2025Article
- Allosteric modulation of the solute carrier transporter SLC39A8 potentiates manganese and cadmium uptake.The Journal of clinical investigation · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Metal Transporter GeneNutrients · 2025Article
- Systematic analysis of naturally occurring missense mutations in human manganese transporters: prediction and structural insights.bioRxiv : the preprint server for biology · 2025Article
- Alcohol use disorder and body mass index show genetic pleiotropy and shared neural associations.Nature human behaviour · 2025Article
- ZIP8 Regulates Inflammation and Macrophage Polarisation in Intervertebral Disc Degeneration via the Wnt/β-Catenin Pathway.Journal of cellular and molecular medicine · 2025Article
- Roles of zinc and zinc transporters in development, progression, and treatment of inflammatory bowel disease (IBD).Frontiers in nutrition · 2025Review
- Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.Frontiers in physiology · 2025Review
- The restricted N-glycome of neurons is programmed during differentiation.bioRxiv : the preprint server for biology · 2024Article
- Crohn's Disease-Associated Pathogenic Mutation in the Manganese Transporter ZIP8 Shifts the Ileal and Rectal Mucosal Microbiota Implicating Aberrant Bile Acid Metabolism.Inflammatory bowel diseases · 2024Article
- The manganese transporter SLC39A8 links alkaline ceramidase 1 to inflammatory bowel disease.Nature communications · 2024Article
- Noninvasive assessment of organ-specific and shared pathways in multi-organ fibrosis using T1 mapping.Nature medicine · 2024Article
- Nutritional Immunity and Fungal Pathogens: a New Role for Manganese.Current clinical microbiology reports · 2024Article
- Effects ofInternational journal of molecular sciences · 2023Article
- Metal transporter SLC39A14/ZIP14 modulates regulation between the gut microbiome and host metabolism.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
ZIP8 is a metal transporter with a role in manganese (Mn) homeostasis. A common genetic variant in ZIP8 (rs13107325; A391T) ranks in the top 10 of pleiotropic SNPs identified in GWAS; A391T has associations with an increased risk of schizophrenia, obesity, Crohn's disease, and reduced blood Mn. Here, we used CRISPR/Cas9-mediated knockin (KI) to generate a mouse model of ZIP8 A391T (Zip8 393T-KI mice). Recapitulating the SNP association with blood Mn, blood Mn was reduced in Zip8 393T-KI mice. There was restricted abnormal tissue Mn homeostasis, with decreases in liver and kidney Mn and a reciprocal increase in biliary Mn, providing in vivo evidence of hypomorphic Zip8 function. Upon challenge in a chemically induced colitis model, male Zip8 393T-KI mice exhibited enhanced disease susceptibility. ZIP8 391-Thr associated with reduced triantennary plasma N-glycan species in a population-based cohort to define a genotype-specific glycophenotype hypothesized to be linked to Mn-dependent glycosyltransferase activity. This glycophenotype was maintained in a cohort of patients with Crohn's disease. These data and the pleiotropic disease associations with ZIP8 391-Thr suggest underappreciated roles of Mn homeostasis in complex human disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.