ArticleBlood2018
Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin.
Article in Blood, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
194 citing papers in PubMed, 2 syntheses or guidelines pooled it, 321 citations in OpenAlex.
- The role of TMPRSS6 gene polymorphism in iron resistance iron deficiency anaemia (IRIDA): a systematic review.Annals of hematology · 2024Pooled it
- The Relationship Between Hepcidin-Mediated Iron Dysmetabolism and COVID-19 Severity: A Meta-Analysis.Frontiers in public health · 2022Pooled it
- A TMPRSS6-inhibiting mAb improves disease in a β-thalassemia mouse model and reduces iron in healthy humans.JCI insight · 2025Trial
- Effect of roxadustat on iron metabolism in patients with peritoneal dialysis: a real-world 24-week study.European journal of medical research · 2023Trial
- Hepcidin is a relevant iron status indicator in infancy: results from a randomized trial of early vs. delayed cord clamping.Pediatric research · 2021Trial
- Targeting the hepcidin-ferroportin pathway in anaemia of chronic kidney disease.British journal of clinical pharmacology · 2019Trial
- Exploring Ferroptosis: A Key Mechanism in Respiratory System Diseases and its Therapeutic Potential.Applied biochemistry and biotechnology · 2026Review
- The neogenin-hemojuvelin axis in murine liver is crucial for hepcidin expression.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Ferroportin at the Crossroads of Iron Biology: Disease, Regulation and Modulation.Biomolecules · 2026Review
- GSH-Related Enzymes GPx4, Chac1, and GSTs and Redox Regulation of Ferroptosis in Cancer.International journal of molecular sciences · 2026Review
- Article
- Hepcidin as a Molecular Hub of Iron Homeostasis: From BMP-SMAD Signaling to Therapeutic Modulation.Biomolecules · 2026Review
- Identification and characterization of novel hepcidin mimetics that modulate ferroportin function.Blood red cells & iron · 2026Article
- Vamifeport, a clinical stage oral ferroportin inhibitor, alleviates murine lupus nephritis: A pilot study.Clinical immunology (Orlando, Fla.) · 2026Article
- Kupffer cells: Orchestrators of liver physiology.Liver research (Beijing, China) · 2026Review
- Halofuginone suppresses hepcidin by a heparan sulfate-dependent mechanism to treat iron disorders in mice.Blood advances · 2026Article
- Iron Biology in Acute Kidney Injury: Catalytic Iron, Hepcidin-Ferroportin Axis, and NGAL-A Narrative Review.International journal of molecular sciences · 2026Review
- Article
- The role of hepcidin in the inflammatory and iron homeostasis axis in inflammatory bowel diseases: a systematic review.Translational gastroenterology and hepatology · 2026Review
- Iron: Regulation, redox homeostasis, and ferroptosis in cancer.Ferroptosis and oxidative stress · 2026Article
134 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Nonclassical ferroportin disease (FD) is a form of hereditary hemochromatosis caused by mutations in the iron transporter ferroportin (Fpn), resulting in parenchymal iron overload. Fpn is regulated by the hormone hepcidin, which induces Fpn endocytosis and cellular iron retention. We characterized 11 clinically relevant and 5 nonclinical Fpn mutations using stably transfected, inducible isogenic cell lines. All clinical mutants were functionally resistant to hepcidin as a consequence of either impaired hepcidin binding or impaired hepcidin-dependent ubiquitination despite intact hepcidin binding. Mapping the residues onto 2 computational models of the human Fpn structure indicated that (1) mutations that caused ubiquitination-resistance were positioned at helix-helix interfaces, likely preventing the hepcidin-induced conformational change, (2) hepcidin binding occurred within the central cavity of Fpn, (3) hepcidin interacted with up to 4 helices, and (4) hepcidin binding should occlude Fpn and interfere with iron export independently of endocytosis. We experimentally confirmed hepcidin-mediated occlusion of Fpn in the absence of endocytosis in multiple cellular systems: HEK293 cells expressing an endocytosis-defective Fpn mutant (K8R),
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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.