ArticleNature genetics2016
A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency.
Article in Nature genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 3 of them syntheses that pooled it.
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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
173 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Gut microbiota bridges dietary nutrients and host immunity.Science China. Life sciences · 2023Pooled it
- The Role of Nutrition in COVID-19 Susceptibility and Severity of Disease: A Systematic Review.The Journal of nutrition · 2021Pooled it
- Iron Deficiency Is Associated With Reduced Levels of Plasmodium falciparum-specific Antibodies in African Children.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Pooled it
- Iron Deficiency Anemia at Time of Vaccination Predicts Decreased Vaccine Response and Iron Supplementation at Time of Vaccination Increases Humoral Vaccine Response: A Birth Cohort Study and a Randomized Trial Follow-Up Study in Kenyan Infants.Frontiers in immunology · 2020Trial
- Immunodeficiency and EBV-induced lymphoproliferation caused by 4-1BB deficiency.The Journal of allergy and clinical immunology · 2019Trial
- TfR1 deficiency beyond combined immunodeficiency. Pivotal role of mitochondrial function and iron-sulfur cluster biogenesis in disease pathogenesis.Genes & diseases · 2027Article
- Histone chaperone HIRA restrains ferroptosis susceptibility through epigenetic control of iron metabolism in prostate cancer.Science China. Life sciences · 2026Article
- Inherited microcytic anemias due to disorders of iron and heme metabolism: An updated clinical review.HemaSphere · 2026Review
- Review
- Prognostic Biomarker Signature of Relapse in Neuromyelitis Optica Spectrum Disorders in the CIRCLES Observational Study.Neurology(R) neuroimmunology & neuroinflammation · 2026Observational
- Article
- Multiplexed Transcriptomics for Screening Drug Combinations and Defining the Mechanism of Action of HCC Therapeutics at Single-Cell Resolution.Cell proliferation · 2026Article
- Plasmacytoid Dendritic Cells Exhibit High Transferrin Receptor Expression Without Iron Accumulation.European journal of immunology · 2026Article
- An Iron-Complement Network Model of Thromboinflammation and Humoral Immune Remodeling in Severe COVID-19.Current issues in molecular biology · 2026Article
- Impaired iron balance and erythrocytosis: a complex relationship.Blood cancer journal · 2026Review
- Metabolic modulation of immune cell function: mechanisms and therapeutic implications in cancer immunotherapy.Oncogenesis · 2026Review
- Single-cell assessment of iron content in primary human T cells using laser ablation inductively coupled plasma mass spectrometry.Cell reports methods · 2026Article
- African-specific genetic loci determine iron status and risk of severe malaria and bacteremia in African children.Nature communications · 2026Article
- Heme enhances B-cell proliferation and plasma cell formation through reduced p21 and Rb expression.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Faecalibacterium prausnitzii, depleted in the Parkinson's disease microbiome, improves motor deficits in α-synuclein overexpressing mice.NPJ Parkinson's disease · 2026Article
113 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors.
Funding
Abstract
Patients with a combined immunodeficiency characterized by normal numbers but impaired function of T and B cells had a homozygous p.Tyr20His substitution in transferrin receptor 1 (TfR1), encoded by TFRC. The substitution disrupts the TfR1 internalization motif, resulting in defective receptor endocytosis and markedly increased TfR1 expression on the cell surface. Iron citrate rescued the lymphocyte defects, and expression of wild-type but not mutant TfR1 rescued impaired transferrin uptake in patient-derived fibroblasts. Tfrc(Y20H/Y20H) mice recapitulated the immunological defects of patients. Despite the critical role of TfR1 in erythrocyte development and function, patients had only mild anemia and only slightly increased TfR1 expression in erythroid precursors. We show that STEAP3, a metalloreductase expressed in erythroblasts, associates with TfR1 and partially rescues transferrin uptake in patient-derived fibroblasts, suggesting that STEAP3 may provide an accessory TfR1 endocytosis signal that spares patients from severe anemia. These findings demonstrate the importance of TfR1 in adaptive immunity.
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