ArticleNature immunology2019
An essential role for the Zn
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In one paragraph
Article in Nature immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 1 pooled it
10.5field-weighted citation impact, top 1% of its field
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Gut microbiota bridges dietary nutrients and host immunity.Science China. Life sciences · 2023Pooled it
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- SLC4A7/NBCn1 maintains intracellular pH to support mTORC1 activity and antibody-secreting cell differentiation.Nature communications · 2026Article
- Machine Learning-Based Identification of Immune Inflammation-Related Genes as Shared Potential Diagnostic Biomarkers in Autism Spectrum Disorder and Atopic Dermatitis.Biomedicines · 2026Article
- Zinc-redox crosstalk regulates proteostasis in the endoplasmic reticulum.Nature communications · 2026Article
- The role of metal ions iron, copper, and zinc in the immune microenvironment of gastric cancer.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Zinc excess promotes lysosome remodeling by activating HLH-30/TFEB through the action of the high zinc sensor HIZR-1.bioRxiv : the preprint server for biology · 2026Article
- ZIP3 is essential for the encephalitogenic function of pTh17 cells by regulating intracellular zinc levels.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2026Article
- Zinc Transporter Gene Variants (SLC30A and SLC39A) in Human Disease: From Metal Homeostasis Disruption to Convergent Signaling Pathways.Human mutation · 2026Review
- Probing of substrate binding-induced conformational switch of a ZIP metal transporter using sandwich ELISA.Scientific reports · 2025Article
- Human genetic influences on early B cell development.Journal of human immunity · 2025Review
- Zinc deficiency as possible link between immunosenescence and age-related diseases.Immunity & ageing : I & A · 2025Review
- Zinc and its binding proteins: essential roles and therapeutic potential.Archives of toxicology · 2025Review
- SLC30 (ZnT) and SLC39 (ZIP) zinc transporter families: from gatekeepers of zinc homeostasis to promoters of tumorigenesis and targets for clinical therapy.Frontiers in immunology · 2025Review
- Dietary Zinc Supplementation in Steers Modulates Labile Zinc Concentration and Zinc Transporter Gene Expression in Circulating Immune Cells.Biological trace element research · 2024Article
- Molecular insights into substrate translocation in an elevator-type metal transporter.Nature communications · 2024Article
- ZIP7 contributes to the pathogenesis of diabetic cardiomyopathy by suppressing mitophagy in mouse hearts.Cardiovascular diabetology · 2024Article
- SENP1 mediates zinc-induced ZnT6 deSUMOylation at Lys-409 involved in the regulation of zinc metabolism in Golgi apparatus.Cellular and molecular life sciences : CMLS · 2024Article
- Evolution, classification, and mechanisms of transport, activity regulation, and substrate specificity of ZIP metal transporters.Critical reviews in biochemistry and molecular biology · 2024Review
- Molecular insights into substrate translocation in an elevator-type metal transporter.bioRxiv : the preprint server for biology · 2024Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
45 authors at 16 institutions in 6 countries.
Consuelo AnzilottiMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-4528-0651
David J SwanPrimary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Bertrand BoissonSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0001-5240-3555
Mukta Deobagkar-LeleMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-8543-6801
Catarina OliveiraWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-9060-5112
Pauline ChabosseauSection of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College, London, UK.
Karin R EngelhardtPrimary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Xijin XuMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Rui ChenPrimary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Luis AlvarezWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-1316-1906
Rolando Berlinguer-PalminiBioimaging Unit, Newcastle University Medical School, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0002-1786-496X
Katherine R BullMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Eleanor CawthorneMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Adam P CribbsMRC WIMM Centre for Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Tanya L CrockfordMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Tarana Singh DangPrimary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Amy FearnInstitute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
Emma J FenechLudwig Institute for Cancer Research, University of Oxford, Oxford, UK.
Sarah J de JongSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
B Christoffer LagerholmMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Cindy S MaGarvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
David SimsMRC WIMM Centre for Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Bert van den BergInstitute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
Yaobo XuInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Andrew J CantGreat North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Gary KleinerPediatric Allergy and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA.
T Ronan LeahyPaediatric Immunology and Infectious Diseases, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
M Teresa de la MorenaDivision of Immunology, Department of Pediatrics, University of Washington and Seattle Children's Hospital, Seattle, WA, USA.
Jennifer M PuckDepartment of Pediatrics, Division of Allergy, Immunology, and Blood and Bone Marrow Transplantation, University of California, San Francisco, CA, USA.
Ralph S ShapiroMidwest Immunology Clinic, Plymouth, MN, USA.
Mirjam van der BurgDepartment of Immunology, Erasmus University Medical Centre, Rotterdam, the Netherlands.
J Ross ChapmanWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
John C ChristiansonLudwig Institute for Cancer Research, University of Oxford, Oxford, UK.
Benjamin DaviesWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-3623-600X
John A McGrathSt John's Institute of Dermatology, King's College London, London, UK.ORCID http://orcid.org/0000-0002-3708-9964
Stefan PrzyborskiDepartment of Biosciences, Durham University, Durham, UK.
Mauro Santibanez KorefInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Stuart G TangyeGarvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.ORCID http://orcid.org/0000-0002-5360-5180
Andreas WernerInstitute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
Guy A RutterSection of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College, London, UK.
Sergi Padilla-ParraWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Jean-Laurent CasanovaSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
Richard J CornallMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. richard.cornall@ndm.ox.ac.uk.ORCID http://orcid.org/0000-0002-6213-3269
Mary Ellen ConleySt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. conley.maryellen@gmail.com.ORCID http://orcid.org/0000-0003-1933-0723
Sophie HambletonPrimary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. sophie.hambleton@newcastle.ac.uk.ORCID http://orcid.org/0000-0001-7954-3267
University of Oxford · GBNewcastle University · GBCentre for Human Genetics · GBGarvan Institute of Medical Research · AUGenomics (United Kingdom) · GBNewcastle upon Tyne Hospitals NHS Foundation Trust · GBRockefeller University · USChildren's Health Ireland at Crumlin · IEDurham University · GBHoward Hughes Medical Institute · USIkerbasque · ESInserm · FRKing's College London · GBSeattle Children's Hospital · USUniversity of California, San Francisco · USUniversity of Miami · US
Funding
Regulation of IgA class switching in the intestinal mucosaP01AI061093 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI CUNNINGHAM-RUNDLES, CHARLOTTE · 2004 to 2021
$29.8MGenetic Etiology of Agammaglobulinemia with Absent B CellsR01AI104857 · NIAID · ROCKEFELLER UNIVERSITY · PI CONLEY, MARY ELLEN · 2014 to 2015
$792kCancer Research UK 19270Howard Hughes Medical InstituteMedical Research Council MC_PC_15065Medical Research Council MC_UU_00008/6Medical Research Council MR/K001981/1Medical Research Council MR/K023667/1Medical Research Council MR/L001209/1Medical Research Council MR/L020149/1Medical Research Council MR/L02036X/1Medical Research Council MR/M009971/1Medical Research Council MR/M012646/1Medical Research Council MR/N00275X/1Medical Research Council MR/N020472/1Medical Research Council MR/R007748/1Medical Research Council MR/R010676/1Medical Research Council MR/R017549/1NIAID NIH HHS P01 AI061093NIAID NIH HHS R01 AI104857
Abstract
Despite the known importance of zinc for human immunity, molecular insights into its roles have remained limited. Here we report a novel autosomal recessive disease characterized by absent B cells, agammaglobulinemia and early onset infections in five unrelated families. The immunodeficiency results from hypomorphic mutations of SLC39A7, which encodes the endoplasmic reticulum-to-cytoplasm zinc transporter ZIP7. Using CRISPR-Cas9 mutagenesis we have precisely modeled ZIP7 deficiency in mice. Homozygosity for a null allele caused embryonic death, but hypomorphic alleles reproduced the block in B cell development seen in patients. B cells from mutant mice exhibited a diminished concentration of cytoplasmic free zinc, increased phosphatase activity and decreased phosphorylation of signaling molecules downstream of the pre-B cell and B cell receptors. Our findings highlight a specific role for cytosolic Zn
Indexed as
AgammaglobulinemiaAnimalsB-LymphocytesCation Transport ProteinsChild, PreschoolCytosolDisease Models, AnimalEndoplasmic ReticulumFemaleGene Expression ProfilingHumansInfantMaleMice, Inbred C57BLMice, TransgenicMutationCation Transport ProteinsSLC39A7 protein, humanZinc
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