ArticleProceedings of the National Academy of Sciences of the United States of America2003
Contribution of the H63D mutation in HFE to murine hereditary hemochromatosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Hemochromatosis gene and nonalcoholic fatty liver disease: a systematic review and meta-analysis.Journal of hepatology · 2011Pooled it
- Neuroprotection From Intracerebral Hemorrhage Following Pharmacological Inhibition of GSK3β Depends on HFE Gene Status.Journal of neurochemistry · 2026Article
- Liver Iron Content in Individuals With B-Thalassemia Trait and Hyperferritinemia: Role of Metabolic Alterations,Mediterranean journal of hematology and infectious diseases · 2026Article
- A Common Mutation in the Homeostatic Iron Regulatory Gene Alters Astrocyte Migration and Redox Profile.FASEB bioAdvances · 2025Article
- Control of Systemic Iron Homeostasis: Insights Gained from Studying Mouse Models.Advances in experimental medicine and biology · 2025Review
- HFE Mutations in Neurodegenerative Disease as a Model of Hormesis.International journal of molecular sciences · 2024Review
- Hereditary hemochromatosis with homozygous C282Y HFE mutation: possible clinical model to assess effects of elevated reactive oxygen species on the development of cardiovascular disease.Molecular and cellular biochemistry · 2024Review
- Whole exome sequencing reveal 83 novel Mendelian disorders carrier P/LP variants in Chinese adult patients.Journal of human genetics · 2023Article
- Elevated transferrin saturation in individuals with alcohol use disorder: Association with HFE polymorphism and alcohol withdrawal severity.Addiction biology · 2022Article
- Lobe specificity of iron binding to transferrin modulates murine erythropoiesis and iron homeostasis.Blood · 2019Article
- Emerging and Dynamic Biomedical Uses of Ferritin.Pharmaceuticals (Basel, Switzerland) · 2018Review
- A role for sex and a common HFE gene variant in brain iron uptake.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Article
- The role of HFE genotype in macrophage phenotype.Journal of neuroinflammation · 2018Article
- Reduced white matter MRI transverse relaxation rate in cognitively normal H63D-HFE human carriers and H67D-HFE mice.Brain imaging and behavior · 2016Article
- Mutation in HFE gene decreases manganese accumulation and oxidative stress in the brain after olfactory manganese exposure.Metallomics : integrated biometal science · 2016Article
- Review
- Regulation of HFE expression by poly(ADP-ribose) polymerase-1 (PARP1) through an inverted repeat DNA sequence in the distal promoter.Biochimica et biophysica acta · 2013Article
- Ferritin upregulates hepatic expression of bone morphogenetic protein 6 and hepcidin in mice.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
- Mutant HFE H63D protein is associated with prolonged endoplasmic reticulum stress and increased neuronal vulnerability.The Journal of biological chemistry · 2011Article
- Clinical assessment incorporating a personal genome.Lancet (London, England) · 2010Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Hereditary hemochromatosis (HH) is an autosomal recessive disease characterized by iron accumulation in several organs, followed by organ damage and failure. The C282Y mutation in the HFE gene explains 80-90% of all diagnosed cases of HH in populations of northwestern European ancestry. Targeted disruption of the mouse Hfe gene (or introduction of the murine mutation analogous to the C282Y human mutation) produces a murine model of HH. Another mutation in the HFE gene, H63D, is more prevalent than C282Y. However, the physiological consequences of the H63D mutation (as well as C282Y/H63D compound heterozygosity) on iron homeostasis are less well established. To evaluate the phenotypic consequences of the C282Y/H63D and H63D/H63D genotypes, we produced H67D (corresponding to H63D in humans) and C294Y (corresponding to C282Y in humans) knock-in mice. H67D homozygous mice, C294Y homozygous mice, and H67D/C294Y compound heterozygous mice each demonstrated hepatic iron loading. Even on a standard diet, by 10 weeks of age, hepatic iron levels in mice of these three genotypes were significantly higher than those of wild-type littermates. The relative severity of hepatic iron loading was C294Y/C294Y > C294Y/H67D > H67D/H67D. We conclude that the H67D allele, when homozygous or combined with a more consequential mutation like C294Y, leads to hepatic iron loading. These observations indicate that the H67D mutation leads to partial loss of Hfe function and can contribute to murine HH.
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