Affinage

TFR2

Transferrin receptor protein 2 · UniProt Q9UP52

Length
801 aa
Mass
88.8 kDa
Annotated
2026-04-28
67 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TFR2 is a hepatocyte membrane iron sensor that transduces circulating diferric transferrin signals into transcriptional activation of hepcidin, the master regulator of systemic iron homeostasis. The alpha isoform forms a multi-protein complex with HFE and HJV on hepatocyte membranes—via extracellular residues 120–139—and is required for both Bmp6 upregulation in response to parenchymal iron and downstream Smad1/5/9 phosphorylation leading to hepcidin induction, while HFE and TFR2 exert non-redundant functions in this pathway (PMID:15345587, PMID:20177050, PMID:22728873, PMID:24284962, PMID:41662592). A distinct beta isoform expressed in the spleen controls ferroportin-mediated iron egress, and in erythroid cells TFR2 partners with the erythropoietin receptor to couple iron availability with erythropoiesis (PMID:20179178, PMID:24847265). Loss-of-function mutations in TFR2 cause type 3 hereditary hemochromatosis, characterized by absent hepcidin response to iron and progressive iron overload (PMID:10802645, PMID:21173098).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2000 High

    Identifying TFR2 as a hemochromatosis gene established that it is essential for human iron homeostasis, opening the question of where it acts in the regulatory hierarchy.

    Evidence Homozygous nonsense mutation identified by genetic mapping in affected families

    PMID:10802645

    Open questions at the time
    • Downstream mechanism by which TFR2 loss causes iron overload was unknown
    • Relationship to hepcidin not yet established
  2. 2004 High

    Positioning TFR2 upstream of hepcidin resolved its place in the iron regulatory hierarchy and showed that inflammatory hepcidin induction operates independently of TFR2.

    Evidence Hepcidin mRNA measurement in Tfr2 mutant vs wild-type mice and isolated hepatocytes stimulated with IL-6/LPS; urinary hepcidin in TFR2-mutant patients

    PMID:15345587 PMID:15486069

    Open questions at the time
    • Molecular mechanism linking TFR2 to hepcidin transcription was unknown
    • Whether TFR2 acts via BMP-SMAD signaling was unresolved
  3. 2006 High

    Demonstrating that BMP-stimulated hepcidin induction occurs independently of TFR2 positioned TFR2 outside the direct BMP receptor axis, while discovery of TFR2 in lipid rafts with ERK/p38 MAPK signaling identified a candidate downstream pathway.

    Evidence BMP stimulation of wild-type vs Tfr2-mutant hepatocytes; lipid raft fractionation, co-IP with caveolin-1/CD81, MAPK phosphorylation assays in HepG2/K562 cells

    PMID:16801541 PMID:17046995

    Open questions at the time
    • Whether MAPK signaling downstream of TFR2 is required for hepcidin induction in vivo was untested
    • Nature of TFR2's relationship with HFE at the molecular level remained unclear
  4. 2010 High

    Hepatocyte-specific rescue and clinical iron-challenge experiments established that TFR2 and HFE are both required in liver for hepcidin regulation but are non-redundant, and that distinct isoforms (alpha in liver, beta in spleen) serve tissue-specific iron-regulatory functions.

    Evidence AAV-mediated hepatocyte-specific gene delivery in KO mice; oral iron challenge with serum hepcidin measurement in patients; comparison of Tfr2 KO vs beta-knockin mice with conditional liver KO

    PMID:20177050 PMID:20179178 PMID:21173098

    Open questions at the time
    • Whether HFE and TFR2 physically interact as a complex was unresolved
    • Mechanism by which beta-TFR2 controls splenic ferroportin was unclear
  5. 2012 High

    Identification of an HFE–TFR2–HJV ternary membrane complex and mapping of the critical TFR2 interaction domain (residues 120–139) provided a structural basis for the cooperative hepcidin regulation; epistasis with Tmprss6 revealed TFR2 additionally promotes erythropoiesis independently of hepcidin.

    Evidence Glycerol gradient sedimentation and reciprocal co-IP with TFR2 mutant constructs in hepatoma cells; Hfe/Tmprss6 and Tfr2/Tmprss6 double KO mice

    PMID:22244935 PMID:22728873

    Open questions at the time
    • Whether HFE directly contacts TFR2 was challenged by subsequent PLA data
    • Structural resolution of the ternary complex was lacking
  6. 2013 High

    Demonstrating that TFR2 is required for parenchymal iron–induced Bmp6 upregulation placed TFR2 upstream of BMP6 ligand production, revising the initial view that TFR2 acts wholly outside the BMP pathway; meanwhile, proximity ligation data questioned direct HFE–TFR2 contact.

    Evidence Dietary vs parenteral iron loading in WT, Hfe−/−, Tfr2−/−, and double KO mice; proximity ligation assay in stably co-expressing cells

    PMID:24155934 PMID:24284962

    Open questions at the time
    • Whether TFR2 and HFE physically interact or signal through parallel arms remains debated
    • Mechanism by which TFR2 senses parenchymal iron to induce Bmp6 is unknown
  7. 2015 High

    Identification of CD81 as a TFR2 partner that controls TFR2 turnover and sustains hepcidin expression independently of BMP and ERK pathways revealed an additional layer of TFR2-dependent hepcidin regulation.

    Evidence Yeast two-hybrid, co-precipitation domain mapping, CD81/GRAIL siRNA knockdown with hepcidin and signaling readouts in Hep3B-TfR2 cells

    PMID:25635054

    Open questions at the time
    • In vivo relevance of CD81-dependent TFR2 regulation not demonstrated
    • Whether GRAIL-mediated CD81 degradation is iron-responsive is unknown
  8. 2018 High

    Structural dissection of holo-transferrin binding showed that TFR2 uses a mechanistically distinct recognition mode from TFR1, with critical apical arm junction residues, explaining TFR2's selective role as a transferrin saturation sensor rather than an iron uptake receptor.

    Evidence Binding kinetics with full-length receptors, TFR2–TFR1 chimeras, and mutagenesis of apical arm junction residues

    PMID:29388418

    Open questions at the time
    • Atomic-resolution structure of TFR2–holo-Tf complex not available
    • How conformational change upon Tf binding propagates intracellularly is unknown
  9. 2023 Medium

    Discovery that DENND3-activated RAB12 targets TFR2 for lysosomal degradation, reducing pSMAD1/5 and hepcidin, identified a new degradation pathway controlling TFR2 protein levels and causing hemochromatosis.

    Evidence DENND3 variant transfection with RAB12, TFR2 lysosomal degradation, pSMAD1/5, and hepcidin readouts; AAV mouse model

    PMID:36729283

    Open questions at the time
    • Whether RAB12-mediated TFR2 degradation is a physiological iron-responsive mechanism is unknown
    • Single-lab finding, not independently replicated
  10. 2026 High

    Epistasis analysis in hepatocyte-specific Tfr1/Tfr2 double knockouts demonstrated that liberated HFE requires TFR2 to activate Smad1/5/9 phosphorylation and acute hepcidin induction, while TFR2 is dispensable for transferrin-bound iron uptake, cementing TFR2's role as a signaling sensor rather than an iron transporter.

    Evidence Hepatocyte-specific double Tfr1/Tfr2 KO mice; fluorescent holo-Tf uptake assays; dietary iron challenge with Hamp mRNA and pSmad1/5/9 measurement

    PMID:41662592

    Open questions at the time
    • Molecular mechanism by which TFR2 activates Smad1/5/9 phosphorylation upon Tf binding remains unresolved
    • Whether TFR2 signaling requires kinase activity or acts as a scaffold is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The signal transduction mechanism linking holotransferrin-bound TFR2 to Smad1/5/9 phosphorylation and Bmp6 upregulation—including the identity of intermediary kinases or scaffolds, the atomic structure of the TFR2–HFE–HJV complex, and the mechanism of beta-TFR2 control of splenic ferroportin—remains unresolved.
  • No structural model of the TFR2–HFE–HJV ternary complex exists
  • Signaling intermediates between TFR2 and Smad phosphorylation are unidentified
  • Mechanism of beta-TFR2 regulation of ferroportin in spleen is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005739 mitochondrion 1 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-382551 Transport of small molecules 5 R-HSA-1643685 Disease 3
Partners
ATP5BCD81EPORHFEHJVRGMATFR1
Complex memberships
HFE-TFR2-HJV complexTFR2-CD81 complexTFR2-EPOR complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Homozygous nonsense mutation in TFR2 causes hereditary hemochromatosis (type 3), establishing TFR2 as essential for iron homeostasis in humans. Genetic mapping and mutation analysis in affected families Nature genetics High 10802645
2004 TFR2 is upstream of hepcidin in the iron regulatory pathway; TfR2 mutant mice show reduced hepcidin mRNA expression and elevated duodenal DMT1, and inflammatory stimuli (IL-6, LPS) can induce hepcidin independently of TfR2. Northern blot analysis of hepcidin and DMT1 mRNA in TfR2(Y245X) mutant vs wild-type mice; isolated hepatocyte stimulation with IL-6 and LPS Blood High 15345587
2004 TFR2 mutations in patients result in low or absent urinary hepcidin, indicating TFR2 is a modulator of hepcidin production in response to iron. Urinary hepcidin measurement in patients homozygous for TFR2 mutations Blood High 15486069
2006 BMP2, BMP4, and BMP9 stimulate hepcidin expression independently of Tfr2 (and Hfe, IL-6), as shown by equivalent BMP responses in isolated hepatocytes from wild-type and Tfr2 mutant mice, placing Tfr2 outside the BMP-direct signaling axis. Primary hepatocyte stimulation assays with BMPs in wild-type vs Tfr2 mutant mice; comparison of hepcidin transcription responses Proceedings of the National Academy of Sciences of the United States of America High 16801541
2006 TfR2 localizes in lipid raft (low-density Triton-insoluble) plasma membrane domains, co-immunoprecipitates with caveolin-1 and CD81, and activation by holotransferrin or anti-TfR2 antibody triggers ERK1/ERK2 and p38 MAPK signaling in a lipid raft-dependent manner. TfR2 is also exported via exosomes. Lipid raft biochemical fractionation, co-immunoprecipitation, subcellular fractionation, MAPK phosphorylation assays, raft disruption, exosome isolation from HepG2 and K562 cells Journal of cell science High 17046995
2009 TfR2 contains a mitochondrial targeting sequence and localizes to mitochondria of substantia nigra dopamine neurons, where it participates in a transferrin/TfR2-mediated mitochondrial iron transport pathway that can deliver iron to respiratory complex I; this pathway is redox-sensitive and is disrupted in Parkinson's disease. Subcellular fractionation, mitochondrial targeting sequence identification, iron delivery assays to mitochondria and complex I, rotenone PD model, human SN immunolocalization Neurobiology of disease Medium 19250966
2010 Hepatocyte-specific expression of Tfr2 in Tfr2-deficient mice increases hepcidin mRNA and lowers hepatic iron and transferrin saturation, confirming the liver as the site of TfR2 action on hepcidin. HFE and TFR2 have non-redundant roles: expressing HFE in Tfr2-deficient mice or Tfr2 in HFE-null mice has no effect, suggesting both are required together (likely as a complex). AAV2/8-mediated hepatocyte-specific gene delivery of Hfe or Tfr2 in knockout mice; measurement of hepcidin mRNA, liver iron, transferrin saturation Blood High 20177050
2010 The two TFR2 isoforms (alpha and beta) have distinct functions: hepatic alpha-Tfr2 senses diferric transferrin and activates hepcidin, while beta-Tfr2 (expressed in spleen) specifically controls splenic iron efflux by regulating ferroportin-1 expression. Comparison of Tfr2 knockout vs. beta-isoform knockin mice; measurement of iron parameters, hepcidin, BMP6, ferroportin-1 in liver and spleen; liver-specific Tfr2 conditional knockout in knockin mice Blood High 20179178
2010 TFR2-hemochromatosis patients show absent hepcidin response to oral iron challenge, whereas HFE-hemochromatosis patients show a blunted but detectable response, establishing TFR2 as playing a prominent role (and HFE a contributory role) in acute hepcidin induction by iron. Oral iron challenge test with time-course measurement of serum iron, transferrin saturation, and serum hepcidin by ELISA and mass spectrometry Haematologica High 21173098
2012 HFE, TfR2, and HJV form a multi-protein membrane complex on hepatocytes. TfR2 residues 120-139 of the extracellular domain are critical for binding both HFE and HJV. HJV competes with TfR1 for HFE binding (as does TfR2). RGMA (a CNS homologue of HJV) can substitute for HJV in the complex. Glycerol gradient sedimentation assays, co-immunoprecipitation in transfected HuH7 hepatoma cells, domain mapping with TfR2 mutant constructs Journal of hepatology High 22728873
2012 Hfe and Tfr2 are not substrates for Tmprss6 (matriptase-2); double mutant mice lacking both Hfe or Tfr2 and Tmprss6 show the Tmprss6-null phenotype for hepcidin but with greater erythropoiesis, indicating Hfe and Tfr2 allow increased erythropoiesis independently of liver hepcidin regulation. Generation of Hfe/Tmprss6 and Tfr2/Tmprss6 double knockout mice; measurement of hepcidin, iron parameters, and erythropoiesis Blood cells, molecules & diseases High 22244935
2013 In stably co-expressing cells, HFE and TFR2 do not directly interact (no signal detected by proximity ligation assay), whereas HFE-TFR1 and TFR1-TFR2 heterodimer interactions are detected, suggesting HFE and TFR2 can regulate hepcidin independently. Proximity ligation assay in stably co-expressing cell lines; comparison with known HFE-TfR1 interaction as positive control PloS one Medium 24155934
2013 Tfr2 is required for upregulation of Bmp6 in response to hepatocyte iron (parenchymal iron), but not non-parenchymal iron; Hfe is not required for Bmp6 upregulation but is required for efficient downstream transmission of the regulatory signal. Dietary vs parenteral iron loading in wild-type, Hfe-/-, Tfr2-/-, and Hfe-/-/Tfr2-/- mice; measurement of Bmp6, hepcidin, and iron parameters American journal of physiology. Gastrointestinal and liver physiology High 24284962
2015 CD81 interacts with TfR2 via both the cytoplasmic and ecto-transmembrane domains, promotes TfR2 degradation (increasing TfR2 half-life when knocked down), and the TfR2/CD81 complex is required for maintenance of hepcidin mRNA expression independently of BMP and ERK1/2 pathways. CD81 is itself targeted for degradation by the ubiquitin E3 ligase GRAIL. Yeast two-hybrid screen, co-precipitation with TfR2 domain constructs, siRNA knockdown of CD81 and GRAIL, hepcidin expression assay, BMP6 stimulation, ID1 and SMAD7 expression, ERK1/2 phosphorylation in Hep3B-TfR2 cells The Journal of biological chemistry High 25635054
2016 In hereditary tyrosinemia type 1 mice, transcription factor Sp1 regulates Tfr2 expression; downregulation of Sp1 reduces Tfr2, which decreases hepcidin, leading to iron overload. Forced expression of Tfr2 in the liver reduces iron accumulation. qRT-PCR, immunoblotting, adenovirus-mediated Tfr2 overexpression in Fah-/- mice; transferrin-sensitive hepcidin induction assay in hepatocytes Journal of hepatology Medium 27013087
2018 TfR2 binds holotransferrin (holo-Tf) through a mechanism different from TfR1: the helical domain differences account for differences in Tf on-rate, and conserved apical arm junction residues are critical for TfR2-Tf (but not TfR1-Tf) interaction stabilization. Apo-Tf binds TfR2 only very weakly at serum pH. Binding studies with full-length receptors, TfR2-TfR1 chimeras containing the TfR1 helical domain, mutagenesis of apical arm junction residues; kinetic binding analysis Biochemistry High 29388418
2003 HFE and TfR2 co-localize in duodenal crypt cells (but not mature enterocytes) and in a CD63-negative early endosomal compartment in Caco-2 cells; HFE deficiency disrupts TfR2 cellular distribution; signal enhancement occurs on exposure to iron-saturated transferrin, indicating HFE preferentially interacts with TfR2 in a specialized early endosomal iron-transferrin transport pathway in intestinal crypts. Confocal microscopy with specific peptide antisera in human/mouse duodenum and Caco-2 cells; comparison with HFE-deficient tissue; iron-saturated transferrin stimulation The journal of histochemistry and cytochemistry Medium 12704209
2023 DENND3 p.L708V activating variant causes TFR2 degradation in lysosomes via upregulation of RAB12 (a GTPase), leading to decreased TFR2 and reduced pSMAD1/5 signaling and hepcidin expression, causing hereditary hemochromatosis. Cell transfection with DENND3 p.L708V vector; measurement of RAB12 expression, TfR2 lysosomal degradation, pSMAD1/5, hepcidin; adeno-associated virus mouse model Hepatology international Medium 36729283
2024 EZH2 suppresses TFR2 expression via H3K27me3 epigenetic modification at the TFR2 promoter, reducing RNA polymerase II binding, which in turn suppresses ferroptosis in hepatocellular carcinoma. EZH2 overexpression/knockdown, H3K27me3 ChIP-like analysis, RNA polymerase II binding at TFR2 promoter, ferroptosis assays in HCC cells and sorafenib-resistant cells Cancer science Medium 38623968
2023 PFOS exposure causes ATP5B to interact with TFR2 and both proteins to translocate from the plasma membrane to mitochondria, leading to mitochondrial iron overload and hepatic insulin resistance; inhibiting TfR2 translocation or stabilizing ATP5B on the plasma membrane prevents this. Co-immunoprecipitation of ATP5B and TfR2, subcellular fractionation, TfR2 knockdown/overexpression, pharmacological inhibition of mitochondrial iron, PFOS-treated L-O2 cells and mouse liver Ecotoxicology and environmental safety Medium 36801541
2026 Tfr2 is required for acute hepcidin induction in response to dietary iron challenge: in Tfr1-deficient hepatocytes, 'liberated' HFE requires Tfr2 to become functionally active for Smad1/5/9 phosphorylation and hepcidin induction. Under chronic iron loading, Tfr2 and Hfe have non-redundant functions; Tfr2 is dispensable for hepatocellular transferrin-bound iron uptake. Hepatocyte-specific double Tfr1/Tfr2 knockout mice; fluorescent holo-transferrin uptake assays in primary hepatocytes; dietary iron restriction/challenge experiments; Hamp mRNA and Smad1/5/9 phosphorylation measurement Blood High 41662592
2014 In erythroid cells, TFR2 is a binding partner of the erythropoietin receptor (EPOR) and stabilizes EPOR on the cell surface, modulating EPO signaling and red blood cell production in response to iron availability. Review/synthesis citing erythroid TFR2-EPOR interaction studies; Tfr2-Tmprss6 double knockout phenotype analysis Frontiers in pharmacology Medium 24847265

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nature genetics 626 10802645
2004 Hepcidin is decreased in TFR2 hemochromatosis. Blood 305 15486069
2006 Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proceedings of the National Academy of Sciences of the United States of America 259 16801541
2004 Expression of hepcidin is down-regulated in TfR2 mutant mice manifesting a phenotype of hereditary hemochromatosis. Blood 175 15345587
2009 A novel transferrin/TfR2-mediated mitochondrial iron transport system is disrupted in Parkinson's disease. Neurobiology of disease 154 19250966
2006 TfR2 localizes in lipid raft domains and is released in exosomes to activate signal transduction along the MAPK pathway. Journal of cell science 146 17046995
2012 The hemochromatosis proteins HFE, TfR2, and HJV form a membrane-associated protein complex for hepcidin regulation. Journal of hepatology 144 22728873
2002 Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation. Blood 78 12130528
2018 Transferrin Receptors TfR1 and TfR2 Bind Transferrin through Differing Mechanisms. Biochemistry 76 29388418
2010 Hepatocyte-targeted HFE and TFR2 control hepcidin expression in mice. Blood 71 20177050
2010 A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis. Haematologica 66 21173098
2010 Comparison of 3 Tfr2-deficient murine models suggests distinct functions for Tfr2-alpha and Tfr2-beta isoforms in different tissues. Blood 65 20179178
2010 Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels. Human molecular genetics 62 21208937
2004 Early onset hereditary hemochromatosis resulting from a novel TFR2 gene nonsense mutation (R105X) in two siblings of north French descent. British journal of haematology 52 15147384
2001 Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5. Nucleic acids research 52 11239002
2003 Co-localization of the mammalian hemochromatosis gene product (HFE) and a newly identified transferrin receptor (TfR2) in intestinal tissue and cells. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 45 12704209
2003 AVAQ 594-597 deletion of the TfR2 gene in a Japanese family with hemochromatosis. Hepatology research : the official journal of the Japan Society of Hepatology 44 12809944
2014 The extrahepatic role of TFR2 in iron homeostasis. Frontiers in pharmacology 38 24847265
2013 In situ proximity ligation assays indicate that hemochromatosis proteins Hfe and transferrin receptor 2 (Tfr2) do not interact. PloS one 37 24155934
2021 IL-6 Regulates Hepcidin Expression Via the BMP/SMAD Pathway by Altering BMP6, TMPRSS6 and TfR2 Expressions at Normal and Inflammatory Conditions in BV2 Microglia. Neurochemical research 31 33835366
2024 EZH2 suppresses ferroptosis in hepatocellular carcinoma and reduces sorafenib sensitivity through epigenetic regulation of TFR2. Cancer science 28 38623968
2023 TFR2 regulates ferroptosis and enhances temozolomide chemo-sensitization in gliomas. Experimental cell research 27 36702193
2008 New TFR2 mutations in young Italian patients with hemochromatosis. Haematologica 27 18245657
2016 Iron overload in hereditary tyrosinemia type 1 induces liver injury through the Sp1/Tfr2/hepcidin axis. Journal of hepatology 26 27013087
2012 Severe microcytic anemia but increased erythropoiesis in mice lacking Hfe or Tfr2 and Tmprss6. Blood cells, molecules & diseases 26 22244935
2012 Mutations in the HFE, TFR2, and SLC40A1 genes in patients with hemochromatosis. Gene 26 22890139
2001 Transferrin receptor-2 (TFR2) mutation Y250X in Alabama Caucasian and African American subjects with and without primary iron overload. Blood cells, molecules & diseases 26 11358388
2009 TfR2 expression in human colon carcinomas. Blood cells, molecules & diseases 25 19729324
2016 Identification of novel mutations in HFE, HFE2, TfR2, and SLC40A1 genes in Chinese patients affected by hereditary hemochromatosis. International journal of hematology 23 27896572
2018 Long-Term High-Fat Diet Decreases Hepatic Iron Storage Associated with Suppressing TFR2 and ZIP14 Expression in Rats. Journal of agricultural and food chemistry 20 30350980
2006 Homozygous p.M172K mutation of the TFR2 gene in an Italian family with type 3 hereditary hemochromatosis and early onset iron overload. Haematologica 19 16923517
2015 CD81 promotes both the degradation of transferrin receptor 2 (TfR2) and the Tfr2-mediated maintenance of hepcidin expression. The Journal of biological chemistry 15 25635054
2013 Parenteral vs. oral iron: influence on hepcidin signaling pathways through analysis of Hfe/Tfr2-null mice. American journal of physiology. Gastrointestinal and liver physiology 15 24284962
2006 Hemochromatosis and severe iron overload associated with compound heterozygosity for TFR2 R455Q and two novel mutations TFR2 R396X and G792R. Acta haematologica 15 16424658
2003 Analysis of HFE and TFR2 mutations in selected blood donors with biochemical parameters of iron overload. Haematologica 15 12681966
2023 Mitochondrial iron overload mediated by cooperative transfer of plasma membrane ATP5B and TFR2 to mitochondria triggers hepatic insulin resistance under PFOS exposure. Ecotoxicology and environmental safety 14 36801541
2013 TFR2-related hereditary hemochromatosis as a frequent cause of primary iron overload in patients from Central-Southern Italy. Blood cells, molecules & diseases 14 24055163
2023 Circ-STC2 promotes the ferroptosis of nucleus pulposus cells via targeting miR-486-3p/TFR2 axis. Journal of orthopaedic surgery and research 11 37480032
2011 Genetic polymorphisms in bovine transferrin receptor 2 (TFR2) and solute carrier family 40 (iron-regulated transporter), member 1 (SLC40A1) genes and their association with beef iron content. Animal genetics 10 22404347
2022 Transferrin receptor 2 (Tfr2) genetic deletion makes transfusion-independent a murine model of transfusion-dependent β-thalassemia. American journal of hematology 9 36071579
2021 New Mutations in HFE2 and TFR2 Genes Causing Non HFE-Related Hereditary Hemochromatosis. Genes 9 34946929
2019 Repeated Restraint Stress Enhances Hepatic TFR2 Expression and Induces Hepatic Iron Accumulation in Rats. Biological trace element research 9 31707638
2005 Analysis of HFE and TFR2 gene mutations in patients with acute leukemia. Leukemia research 8 15863206
2022 Genetic variants in promoter region of TFR2 is associated with the risk of non-alcoholic fatty liver disease in a Chinese Han population: a case-control study. Gastroenterology report 7 36324614
2011 Mutations in HFE and TFR2 genes in a Spanish patient with hemochromatosis. Revista espanola de enfermedades digestivas 7 21770687
2024 Lack of Hfe and TfR2 in Macrophages Impairs Iron Metabolism in the Spleen and the Bone Marrow. International journal of molecular sciences 6 39273097
2020 Global loss of Tfr2 with concomitant induced iron deficiency greatly ameliorates the phenotype of a murine thalassemia intermedia model. American journal of hematology 6 33180328
2024 Biomimetic peroxidase MOF-Fe promotes bone defect repair by inhibiting TfR2 and activating the BMP2 pathway. Biology direct 5 38654256
2024 Bone marrow Tfr2 deletion improves the therapeutic efficacy of the activin-receptor ligand trap RAP-536 in β-thalassemic mice. American journal of hematology 4 38629683
2023 DENND3 p.L708V activating variant is involved in the pathogenesis of hereditary hemochromatosis via the RAB12/TFR2 signaling pathway. Hepatology international 4 36729283
2022 Association of CFI, IL-8, TF and TFR2 Genetic Polymorphisms with Age-Related Macular Degeneration in a Northeastern Chinese Population. Current eye research 4 35180024
2004 Prevalence of HFE and TFR2 gene mutation in 118 Ligurian rheumatic patients. Minerva medica 4 15785438
2022 Assessment of iron overload in a cohort of Sri Lankan patients with transfusion dependent beta thalassaemia and its correlation with pathogenic variants in HBB, HFE, SLC40A1, and TFR2 genes. BMC pediatrics 3 35705926
2020 Role of Slc19a1 and Tfr2 in liver transport of iron and folate: A rat model of folate/iron deficiency followed by supplementation. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 3 32521439
2020 The Proteomics Study of Compounded HFE/TF/TfR2/HJV Genetic Variations in a Thai Family with Iron Overload, Chronic Anemia, and Motor Neuron Disorder. Journal of molecular neuroscience : MN 3 32895881
2018 Tfr2 suppression benefits β-thalassemic erythropoiesis. Blood 3 30467188
2011 [Hyperferritinemia, ferropenia and metabolic syndrome in a patient with a new mutation of gene TFR2 and another in gene FTL. A family study]. Medicina clinica 3 21524769
2001 A rapid PCR-SSP assay for the hemochromatosis-associated Tyr250Stop mutation in the TFR2 gene. Genetic testing 3 11551099
2017 TFR2-related haemochromatosis in the Netherlands: a cause of arthralgia in young adulthood. The Netherlands journal of medicine 1 28276324
2011 [TfR2 mRNA expression in bone marrow mononuclear cells of children with hyperplastic anemia and its implications]. Zhongguo shi yan xue ye xue za zhi 1 21518504
2026 Maternal Adiposity and DNA Methylation of TfR2 and HJV Genes in Early Pregnancy: Mediating Role of Inflammation and Consequences for Iron Status. The Journal of nutrition 0 41651072
2026 Tfr2 is necessary for acute iron-dependent hepcidin induction in mice with Tfr1-deficient hepatocytes. Blood 0 41662592
2026 TFR2 p.A75V mutation aggravates liver iron overload in alcoholic liver disease via ERK pathway. Journal of molecular medicine (Berlin, Germany) 0 41677839
2025 Next Generation Sequencing Allows Identification of a Novel Mutation in the TfR2 Gene and Outperforms the Conventional Diagnostic Techniques. EJHaem 0 40574988
2025 Immunohistochemical investigation of transferrin receptor 2 (TFR2) immunoreactivity in patients with cutaneous lichen planus. Irish journal of medical science 0 41430519
2019 Role of TfR2-Y250X and TfR1- rs3817672 Single Nucleotide Polymorphism on Pathophysiology of Iron Deficiency Anemia. The Journal of the Association of Physicians of India 0 31793267
2014 Association between genetic variations in TFR2 gene and coronary heart disease in Chinese: a case-control study. Journal of cardiovascular medicine (Hagerstown, Md.) 0 23751596