TMPRSS6

Summary

Gene Symbol: TMPRSS6
Description: transmembrane protease, serine 6
Alias: IRIDA, matriptase-2, membrane-bound mosaic serine proteinase matriptase-2, transmembrane protease serine 6, type II transmembrane serine protease 6
Species: human

Top Publications

  1. doi Pathogenesis and management of iron deficiency anemia: emerging role of celiac disease, helicobacter pylori, and autoimmune gastritis
    Chaim Hershko
    Department of Hematology, Shaare Zedek Medical Center and Hebrew University of Jerusalem, Israel
    Semin Hematol 46:339-50. 2009
  2. pmc Down-regulation of Bmp/Smad signaling by Tmprss6 is required for maintenance of systemic iron homeostasis
    Karin E Finberg
    Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA
    Blood 115:3817-26. 2010
  3. pmc Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels
    Irene Pichler
    Institute of Genetic Medicine, European Academy Bozen Bolzano, 39100 Bolzano, Italy
    Hum Mol Genet 20:1232-40. 2011
  4. doi Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations
    Michela Traglia
    Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano, Italy
    J Med Genet 48:629-34. 2011
  5. pmc Common variants in TMPRSS6 are associated with iron status and erythrocyte volume
    Beben Benyamin
    Queensland Institute of Medical Research, Brisbane, Queensland, Australia
    Nat Genet 41:1173-5. 2009
  6. pmc Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels
    Beben Benyamin
    Queensland Institute of Medical Research, Brisbane 4029, Australia
    Am J Hum Genet 84:60-5. 2009
  7. pmc Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)
    Karin E Finberg
    Pathology Service, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Nat Genet 40:569-71. 2008
  8. doi Genetic variability of TMPRSS6 and its association with iron deficiency anaemia
    Paola Delbini
    Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, University of Milan, Italy
    Br J Haematol 151:281–4. 2010
  9. doi Inherited disorders of iron metabolism
    Clara Camaschella
    Vita Salute University, San Raffaele Scientific Institute, Milan, Italy
    Curr Opin Pediatr 23:14-20. 2011
  10. doi TMPRSS6 rs855791 modulates hepcidin transcription in vitro and serum hepcidin levels in normal individuals
    Antonella Nai
    Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Verona, Italy
    Blood 118:4459-62. 2011

Scientific Experts

Detail Information

Publications90

  1. doi Pathogenesis and management of iron deficiency anemia: emerging role of celiac disease, helicobacter pylori, and autoimmune gastritis
    Chaim Hershko
    Department of Hematology, Shaare Zedek Medical Center and Hebrew University of Jerusalem, Israel
    Semin Hematol 46:339-50. 2009
    ..However, abnormal iron absorption caused by hereditary iron-refractory iron deficiency anemia (IRIDA) or acquired disease is increasingly recognized as an important cause of unexplained iron deficiency...
  2. pmc Down-regulation of Bmp/Smad signaling by Tmprss6 is required for maintenance of systemic iron homeostasis
    Karin E Finberg
    Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA
    Blood 115:3817-26. 2010
    ..Previously, we showed that IRIDA patients harbor loss-of-function mutations in TMPRSS6, a type II transmembrane serine protease primarily expressed by the liver...
  3. pmc Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels
    Irene Pichler
    Institute of Genetic Medicine, European Academy Bozen Bolzano, 39100 Bolzano, Italy
    Hum Mol Genet 20:1232-40. 2011
    ..an association between the HFE locus and ferritin and confirmed previously reported associations with the TF, TMPRSS6 and HFE genes...
  4. doi Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations
    Michela Traglia
    Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano, Italy
    J Med Genet 48:629-34. 2011
    ..Hepcidin is the main regulator of iron homeostasis: inappropriate production of hepcidin results in iron overload or iron deficiency and anaemia...
  5. pmc Common variants in TMPRSS6 are associated with iron status and erythrocyte volume
    Beben Benyamin
    Queensland Institute of Medical Research, Brisbane, Queensland, Australia
    Nat Genet 41:1173-5. 2009
    ..1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.
  6. pmc Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels
    Beben Benyamin
    Queensland Institute of Medical Research, Brisbane 4029, Australia
    Am J Hum Genet 84:60-5. 2009
    ....
  7. pmc Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)
    Karin E Finberg
    Pathology Service, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Nat Genet 40:569-71. 2008
    ..Here, we show that iron deficiency anemia refractory to oral iron therapy can be caused by germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the ..
  8. doi Genetic variability of TMPRSS6 and its association with iron deficiency anaemia
    Paola Delbini
    Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, University of Milan, Italy
    Br J Haematol 151:281–4. 2010
    Transmembrane Protease, Serine 6 (TMPRSS6) has an important role in iron homeostasis and its mutations, performed in TMPRSS6-deficient mice, have been recently associated with iron-refractory iron deficiency anaemia (IRIDA)...
  9. doi Inherited disorders of iron metabolism
    Clara Camaschella
    Vita Salute University, San Raffaele Scientific Institute, Milan, Italy
    Curr Opin Pediatr 23:14-20. 2011
    ..To discuss inherited iron disorders, their pathophysiology and clinical implications in the light of the recent advances in our knowledge of iron metabolism and its regulation...
  10. doi TMPRSS6 rs855791 modulates hepcidin transcription in vitro and serum hepcidin levels in normal individuals
    Antonella Nai
    Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Verona, Italy
    Blood 118:4459-62. 2011
    The iron hormone hepcidin is inhibited by matriptase-2 (MT2), a liver serine protease encoded by the TMPRSS6 gene...
  11. pmc A genome-wide association analysis of serum iron concentrations
    Toshiko Tanaka
    MedStar Research Institute, Baltimore, MD, USA
    Blood 115:94-6. 2010
    ..12 x 10(-9)), located in exon 13 of the transmembrane protease serine 6 (TMPRSS6) gene, an enzyme that promotes iron absorption and recycling by inhibiting hepcidin ..
  12. pmc Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis
    Andrew J Ramsay
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
    Haematologica 94:840-9. 2009
    ..The type-two transmembrane serine protease (TTSP), matriptase-2 (also known as TMPRSS6), is attracting significant amounts of interest due to its recently described role in iron homeostasis...
  13. doi Matriptase-2 (TMPRSS6) is directly up-regulated by hypoxia inducible factor-1: identification of a hypoxia-responsive element in the TMPRSS6 promoter region
    Eva Maurer
    Pharmaceutical Institute, University of Bonn, An der Immenburg 4, D 53121 Bonn, Germany
    Biol Chem 393:535-40. 2012
    The type II transmembrane serine protease matriptase-2 (TMPRSS6) down-regulates the expression of hepcidin, the main regulator of systemic iron homeostasis, and increases in this way iron plasma levels...
  14. pmc The A736V TMPRSS6 polymorphism influences hepatic iron overload in nonalcoholic fatty liver disease
    Luca Valenti
    Department of Pathophysiology and Transplantation, Section Internal Medicine, Universita degli Studi, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico, Milano, Italy
    PLoS ONE 7:e48804. 2012
    ..The p.Ala736Val TMPRSS6 variant influences iron metabolism regulating the transcription of the hepatic hormone hepcidin, but its role in ..
  15. doi Effect of the A736V TMPRSS6 polymorphism on the penetrance and clinical expression of hereditary hemochromatosis
    Luca Valenti
    Department of Internal Medicine, UO Medicina Interna 1B, Universita degli Studi, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico, Milano, Italy
    J Hepatol 57:1319-25. 2012
    ..The rs855791 polymorphism, encoding for the p.A736V variant of TMPRSS6 regulating hepcidin, influences iron status in the population...
  16. pmc Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels
    John C Chambers
    Department of Epidemiology and Public Health, Imperial College London, London, UK
    Nat Genet 41:1170-2. 2009
    ..most closely associated SNP (rs855791) results in nonsynonymous (V736A) change in the serine protease domain of TMPRSS6 and a blood hemoglobin concentration 0.13 (95% CI 0.09-0.17) g/dl lower per copy of allele A (P = 1.6 x 10(-13))...
  17. pmc A novel TMPRSS6 mutation that prevents protease auto-activation causes IRIDA
    Sandro Altamura
    Department of Pediatric Oncology, Haematology and Immunology, University Hospital of Heidelberg, Germany
    Biochem J 431:363-71. 2010
    ..The disease is caused by mutations in the transmembrane serine protease TMPRSS6 (transmembrane protease serine 6) that prevent inactivation of HJV (haemojuvelin), an activator of hepcidin transcription...
  18. pmc The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin
    Laura Silvestri
    Vita Salute San Raffaele University, Istituto di Ricovero e Cura a Carattere Scientifico IRCCS San Raffaele, Milan, Italy
    Cell Metab 8:502-11. 2008
    ..The transmembrane serine protease matriptase-2 (TMPRSS6) inhibits the hepcidin response and its mutational inactivation causes iron-deficient anemia in mice and humans...
  19. doi Novel TMPRSS6 mutations associated with iron-refractory iron deficiency anemia (IRIDA)
    Luigia De Falco
    CEINGE, Centro di Ingegneria Genetica e Biotecnologie Avanzate, Via Comunale Margherita 482, Naples, Italy
    Hum Mutat 31:E1390-405. 2010
    ..In this paper we describe 12 IRIDA patients belonging to 7 unrelated families and identify 10 (9 novel) TMPRSS6 mutations spread along the gene sequence: 5 missense, 1 non sense and 4 frameshift...
  20. doi A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron
    Maria Antonietta Melis
    Dipartimento di Scienze Biomediche e Biotecnologie, Universita di Cagliari, Cagliari, Italy
    Haematologica 93:1473-9. 2008
    ..Defective hepcidin synthesis causes iron loading, while overproduction results in defective reticuloendothelial iron release and iron absorption...
  21. doi Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia
    Laura Silvestri
    Vita Salute University, San Raffaele Scientific Institute, Milan, Italy
    Blood 113:5605-8. 2009
    ..Our results underline the importance of LDLRA and CUB domains of matriptase-2...
  22. pmc Role of matriptase-2 (TMPRSS6) in iron metabolism
    Pauline Lee
    Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA
    Acta Haematol 122:87-96. 2009
    ..Mutations in a type II serine protease, matriptase-2/TMPRSS6, were recently identified to be associated with severe iron deficiency caused by inappropriately high levels of ..
  23. ncbi The type II transmembrane serine protease matriptase-2--identification, structural features, enzymology, expression pattern and potential roles
    Andrew J Ramsay
    Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland 4059, Australia
    Front Biosci 13:569-79. 2008
    Matriptase-2 (also known as TMPRSS6) is a recently identified member of the type II transmembrane serine protease (TTSP) family...
  24. ncbi Matriptase-2, a membrane-bound mosaic serine proteinase predominantly expressed in human liver and showing degrading activity against extracellular matrix proteins
    Gloria Velasco
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Biol Chem 277:37637-46. 2002
    ....
  25. doi Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanisms
    Andrew J Ramsay
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Hum Mol Genet 18:3673-83. 2009
    ..Here we describe two novel heterozygous mutations within the matriptase-2 (TMPRSS6) gene of monozygotic twin girls exhibiting an IRIDA phenotype...
  26. pmc Inflammation Regulates TMPRSS6 Expression via STAT5
    Delphine Meynard
    Program in Anemia Signaling Research, Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 8:e82127. 2013
    b>TMPRSS6 is a regulated gene, with a crucial role in the regulation of iron homeostasis by inhibiting hepcidin expression...
  27. ncbi Is the acronym IRIDA acceptable for slow responders to iron in the presence of TMPRSS6 mutations?
    Ebru Yımaz Keskin
    Division of Pediatric Hematology, Department of Pediatrics, Gazi University Faculty of Medicine, Ankara, Turkey
    Turk J Pediatr 55:479-84. 2013
    ..iron deficiency anemia (IRIDA) is a recently described autosomal recessive disorder caused by mutations in TMPRSS6, the gene encoding matriptase-2. Patients have inappropriately high levels of hepcidin...
  28. doi Liver iron modulates hepcidin expression during chronically elevated erythropoiesis in mice
    Victor Díaz
    Institute of Veterinary Physiology, Vetsuisse Faculty, and Zurich Center for Integrative Human Physiology ZIHP, and University of Zurich, Switzerland Department of Health and Human Performance, Faculty of Sports Science, INEF, Technical University of Madrid, Spain
    Hepatology 58:2122-32. 2013
    ..pathway targets showed that inhibitor of DNA binding 1 (ID1) and SMAD7, but not transmembrane serine protease 6 (TMPRSS6), were up-regulated by increased iron availability and thus may be involved in setting the upper limit of ..
  29. doi Associations of common variants in HFE and TMPRSS6 with iron parameters are independent of serum hepcidin in a general population: a replication study
    Tessel E Galesloot
    Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands
    J Med Genet 50:593-8. 2013
    Genome-wide association studies have convincingly shown that single nucleotide polymorphisms (SNPs) in HFE and TMPRSS6 are associated with iron parameters...
  30. doi Hepatocyte growth factor activator inhibitor type 2 (HAI-2) modulates hepcidin expression by inhibiting the cell surface protease matriptase-2
    Eva Maurer
    Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany
    Biochem J 450:583-93. 2013
    ....
  31. pmc A strong anti-inflammatory signature revealed by liver transcription profiling of Tmprss6-/- mice
    Michela Riba
    Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy
    PLoS ONE 8:e69694. 2013
    ..anemia (IDA)-low hepcidin show a pro-inflammatory response that is blunted in iron deficient-high hepcidin Tmprss6 KO mice...
  32. doi TMPRSS6, but not TF, TFR2 or BMP2 variants are associated with increased risk of iron-deficiency anemia
    Peng An
    Key Laboratory of Nutrition and Metabolism, Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
    Hum Mol Genet 21:2124-31. 2012
    ..elderly Chinese women: rs3811647 (TF), rs7385804 (TFR2), rs235756 (BMP2), and rs855791(V736A) and rs4820268 (TMPRSS6, encoding matriptase-2)...
  33. pmc Deletion of TMPRSS6 attenuates the phenotype in a mouse model of β-thalassemia
    Antonella Nai
    Vita Salute San Raffaele University, Milan, Italy
    Blood 119:5021-9. 2012
    ..The BMP pathway is inactivated by the serine protease TMPRSS6 that cleaves the BMP coreceptor hemojuvelin...
  34. pmc Iron refractory iron deficiency anemia
    Luigia De Falco
    CEINGE, Biotecnologie Avanzate, Naples, Italy
    Haematologica 98:845-53. 2013
    Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2...
  35. ncbi Decreased hemojuvelin protein levels in mask mice lacking matriptase-2-dependent proteolytic activity
    J Frýdlová
    Institute of Pathophysiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
    Physiol Res 62:405-11. 2013
    Matriptase-2, a membrane protein encoded by the Tmprss6 gene, is a negative regulator of hepcidin expression...
  36. doi Administration of recombinant erythropoietin alone does not improve the phenotype in iron refractory iron deficiency anemia patients
    Kai Lehmberg
    Department of Pediatric Hematology and Oncology, University Medical Center Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany
    Ann Hematol 92:387-94. 2013
    Mutations in transmembrane protease, serine 6 (TMPRSS6) cause iron refractory iron deficiency anemia (IRIDA). Parenteral iron administration may slightly improve hemoglobin level but is troublesome for patients...
  37. ncbi Matriptase-2, a regulatory protease of iron homeostasis: possible substrates, cleavage sites and inhibitors
    Marit Stirnberg
    Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, D 53121 Bonn, Germany
    Curr Pharm Des 19:1052-61. 2013
    ..Mutations in matriptase- 2 cause iron-refractory iron deficiency anemia (IRIDA), an iron deficiency disorder where the level of hepcidin is inappropriately high...
  38. pmc Neogenin interacts with matriptase-2 to facilitate hemojuvelin cleavage
    Caroline A Enns
    Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Biol Chem 287:35104-17. 2012
    ..The complex facilitates HJV cleavage by MT2, and release of the cleaved HJV from the cell occurs after a retrograde trafficking through the TGN/Golgi compartments...
  39. pmc Genetic variants influencing biomarkers of nutrition are not associated with cognitive capability in middle-aged and older adults
    Tamuno Alfred
    School of Social and Community Medicine, University of Bristol, Bristol, UK
    J Nutr 143:606-12. 2013
    ..for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([..
  40. doi The influence of matriptase-2 on prostate cancer in vitro: a possible role for β-catenin
    Siobhan L Webb
    Metastasis and Angiogenesis Research Group, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK
    Oncol Rep 28:1491-7. 2012
    ....
  41. pmc Reducing TMPRSS6 ameliorates hemochromatosis and β-thalassemia in mice
    Shuling Guo
    Isis Pharmaceuticals, Carlsbad, California 92010, USA
    J Clin Invest 123:1531-41. 2013
    ..HAMP expression is controlled by activation of the SMAD1,5,8/SMAD4 complex. TMPRSS6 is a serine protease that reduces SMAD activation and blocks HAMP expression...
  42. pmc Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III)
    Jonna L Grimsby
    General Medicine Division, Massachusetts General Hospital, Boston, MA, USA
    BMC Med Genet 13:30. 2012
    ..is race-ethnic variation in 1) HbA1c-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA1c and 3) association of SNPs with mortality.
  43. pmc An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe(-/-) mice and ameliorates anemia and iron overload in murine β-thalassemia intermedia
    Paul J Schmidt
    Department of Pathology, Children s Hospital Boston and Harvard Medical School, Boston, MA 02115, USA
    Blood 121:1200-8. 2013
    ..b>Tmprss6 is postulated to regulate hepcidin production by cleaving Hemojuvelin (Hjv), a key modulator of hepcidin ..
  44. doi A novel mutation Gly603Arg of TMPRSS6 in a Korean female with iron-refractory iron deficiency anemia
    Hyoung Soo Choi
    Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea
    Pediatr Blood Cancer 58:640-2. 2012
    ..The genetic background of IRIDA is mutations in the TMPRSS6 gene encoding matriptase-2 (TMPRSS6) that prevent inactivation of hemojuvelin, an activator of hepcidin ..
  45. pmc Common TMPRSS6 mutations and iron, erythrocyte, and pica phenotypes in 48 women with iron deficiency or depletion
    Pauline L Lee
    Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA, USA
    Blood Cells Mol Dis 48:124-7. 2012
    b>TMPRSS6 A736V is associated with lower transferrin saturation (TS), hemoglobin (Hb), and mean corpuscular volume (MCV) levels in general adult populations...
  46. pmc Severe microcytic anemia but increased erythropoiesis in mice lacking Hfe or Tfr2 and Tmprss6
    Pauline Lee
    The Scripps Research Institute, Department of Molecular and Experimental Medicine, La Jolla, CA, USA
    Blood Cells Mol Dis 48:173-8. 2012
    Cell surface proteins Hfe, Tfr2, hemojuvelin and Tmprss6 play key roles in iron homeostasis. Hfe and Tfr2 induce transcription of hepcidin, a small peptide that promotes the degradation of the iron transporter ferroportin...
  47. doi Responsiveness to oral iron and ascorbic acid in a patient with IRIDA
    Milena Cau
    Dipartimento di Scienze Biomediche e Biotecnologie, Universita di Cagliari, Italy
    Blood Cells Mol Dis 48:121-3. 2012
    Mutations in TMPRSS6 gene cause iron-refractory iron deficiency anemia, a rare autosomal recessive disorder characterized by hypochromic microcytic anemia not responsive to oral iron therapy and partially responsive to parenteral iron ..
  48. doi Association of TMPRSS6 polymorphisms with ferritin, hemoglobin, and type 2 diabetes risk in a Chinese Han population
    Wei Gan
    Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China
    Am J Clin Nutr 95:626-32. 2012
    b>Transmembrane protease serine 6 (TMPRSS6) regulates iron homeostasis by inhibiting the expression of hepcidin...
  49. pmc Candidate gene sequencing of SLC11A2 and TMPRSS6 in a family with severe anaemia: common SNPs, rare haplotypes, no causative mutation
    Anita Kloss-Brandstätter
    Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
    PLoS ONE 7:e35015. 2012
    ..iron deficiency anaemia (IRIDA) is a rare disorder which was linked to mutations in two genes (SLC11A2 and TMPRSS6). Common polymorphisms within these genes were associated with serum iron levels...
  50. doi Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis
    Alicia R Folgueras
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Spain
    Blood 112:2539-45. 2008
    ..Here we show that matriptase-2 (Tmprss6), a recently described member of the TTSP family, is an essential regulator of iron homeostasis...
  51. doi Iron-refractory iron deficiency anemia
    Karin E Finberg
    Department of Pathology, Duke University Medical Center, Durham, NC
    Semin Hematol 46:378-86. 2009
    ..IRIDA has recently been shown to be caused by mutations in the gene TMPRSS6, which encodes a transmembrane serine protease (also known as matriptase-2) expressed by the liver...
  52. doi Genetic upregulation of matriptase-2 reduces the aggressiveness of prostate cancer cells in vitro and in vivo and affects FAK and paxillin localisation
    Andrew J Sanders
    Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff, UK
    J Cell Physiol 216:780-9. 2008
    ..Furthermore, the data presented implies a possible connection between matriptase-2 and the paxillin and FAK adhesion molecules which may ultimately contribute to the reduced migration rates seen in this study...
  53. pmc Polymorphisms and mutations of human TMPRSS6 in iron deficiency anemia
    E Beutler
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Blood Cells Mol Dis 44:16-21. 2010
    ..with iron deficiency from the general population were examined for polymorphisms or sporadic mutations in TMPRSS6 to identify genetic risk factors for iron deficiency anemia...
  54. pmc Sequence variants in three loci influence monocyte counts and erythrocyte volume
    Manuel A R Ferreira
    Queensland Institute of Medical Research QIMR, Brisbane, QLD 4029, Australia
    Am J Hum Genet 85:745-9. 2009
    ..001, 9.9x10(-5), and 7x10(-5), respectively). The identification of these QTL provides new opportunities for furthering our understanding of the mechanisms regulating hemopoietic cell fate...
  55. ncbi Matriptase-2 inhibits breast tumor growth and invasion and correlates with favorable prognosis for breast cancer patients
    Christian Parr
    Metastasis and Angiogenesis Research Group, School of Medicine, Cardiff University, Cardiff, United Kingdom
    Clin Cancer Res 13:3568-76. 2007
    ..The role of matriptase-2 and its cellular function in cancer is unknown. This study aimed to provide new insights into the significance of matriptase-2 in cancer...
  56. ncbi Refinement of the 22q12-q13 breast cancer--associated region: evidence of TMPRSS6 as a candidate gene in an eastern Finnish population
    Jaana M Hartikainen
    Department of Pathology, University of Kuopio, Finland
    Clin Cancer Res 12:1454-62. 2006
    ..A SNP (rs733655) in matriptase-2 gene (TMPRSS6) was detected to associate with breast cancer risk...
  57. ncbi Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer
    Sarah Netzel-Arnett
    Vascular Biology Department, Jerome H Holland Laboratory for the Biological Sciences, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855, USA
    Cancer Metastasis Rev 22:237-58. 2003
    ..Diagnostic or therapeutic targeting of the membrane anchored serine proteases has potential as promising new approaches for the treatment of cancer and other diseases...
  58. pmc Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium
    Santhi K Ganesh
    National Human Genome Research Institute, Division of Intramural Research, Bethesda, MD, USA
    Nat Genet 41:1191-8. 2009
    ..Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci)...
  59. pmc Iron-refractory iron deficiency anemia: new molecular mechanisms
    Yujie Cui
    Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou, China
    Kidney Int 76:1137-41. 2009
    ..In mice, defects in the Tmprss6 gene encoding matriptase-2 result in high hepcidin expression and cause severe microcytic anemia...
  60. doi Fine tuning of hepcidin expression by positive and negative regulators
    Martina U Muckenthaler
    Department of Pediatric Oncology, Haematology and Immunology, University Hospital of Heidelberg, Molecular Medicine Partnership Unit, Im Neuenheimer Feld 156, 69120 Heidelberg, Germany
    Cell Metab 8:1-3. 2008
    ..Three recent publications now identify a novel hepcidin suppressor, the transmembrane serine protease TMPRSS6 (also known as matriptase-2), which is required to sense iron deficiency.
  61. doi Two nonsense mutations in the TMPRSS6 gene in a patient with microcytic anemia and iron deficiency
    Flavia Guillem
    Assistance publique des Hôpitaux de Paris APHP, Laboratoire de Génétique et Biochimie Hormonale, Hopital Bichat, Paris, France
    Blood 112:2089-91. 2008
    ..with poor intestinal absorption and defective iron utilization of IV iron is caused by inherited mutations in TMPRSS6, a liver-expressed gene that encodes a membrane-bound serine protease of previously unknown role that was ..
  62. doi Interacting signals in the control of hepcidin expression
    Deepak Darshan
    Iron Metabolism Laboratory, Queensland Institute of Medical Research and the University of Queensland, PO Royal Brisbane Hospital, Brisbane, QLD, Australia
    Biometals 22:77-87. 2009
    ..levels by acting through hepatocyte cell surface proteins including HFE, transferrin receptor 2, hemojuvelin, TMPRSS6 and the IL-6R...
  63. ncbi Hepcidin downregulation by repeated bleeding is not mediated by soluble hemojuvelin
    J Krijt
    Institute of Pathophysiology and Center of Experimental Hematology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic
    Physiol Res 59:53-9. 2010
    ..Liver and muscle furin mRNA content was not significantly changed. No effect on hepatic Tmprss6 mRNA content was observed...
  64. doi SELDI-TOF MS detection of urinary hepcidin
    Sandro Altamura
    Department of Pediatric Oncology, Haematology and Immunology, University Hospital of Heidelberg Molecular Medicine Partnership Unit, Im Neuenheimer Feld 156, 69120 Heidelberg, Germany
    Biochimie 91:1335-8. 2009
    ..retention in the anemias of inflammation and plays a pathogenic role in iron-refractory iron-deficiency anemia (IRIDA)...
  65. pmc Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasis
    Samira Lakhal
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom
    J Biol Chem 286:4090-7. 2011
    ..Type II transmembrane serine proteinase (TMPRSS6) antagonizes hepcidin induction by BMPs by cleaving HJV from the cell membrane...
  66. pmc The serine protease TMPRSS6 is required to sense iron deficiency
    Xin Du
    Department of Genetics, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 320:1088-92. 2008
    ..caused by high levels of hepcidin and is due to a splicing defect in the transmembrane serine protease 6 gene Tmprss6. Overexpression of normal TMPRSS6 protein suppresses activation of the Hamp promoter, and the TMPRSS6 cytoplasmic ..
  67. doi Suppression of the hepcidin-encoding gene Hamp permits iron overload in mice lacking both hemojuvelin and matriptase-2/TMPRSS6
    Jaroslav Truksa
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Br J Haematol 147:571-81. 2009
    ..is countered through a pathway involving the hepatocyte-specific plasma membrane protease matriptase-2 encoded by TMPRSS6, leading to suppression of HAMP expression...
  68. doi Haematologic data, iron parameters and molecular findings in two new cases of iron-refractory iron deficiency anaemia
    Isabelle Tchou
    Geneva University Hospitals, Switzerland
    Eur J Haematol 83:595-602. 2009
    Matriptase-2 (Tmprss6), a type II transmembrane serine protease, has an essential role in iron homoeostasis as a hepcidin regulator...
  69. doi Recent advances in iron metabolism and related disorders
    Clara Camaschella
    Università Vita Salute e IRCCS San Raffaele, Via Olgettina 60, Milan, Italy
    Intern Emerg Med 5:393-400. 2010
    ..The study of genetic conditions such as hemochromatosis and iron-refractory-iron-deficiency anemia (IRIDA) has provided crucial insights into the molecular mechanisms controlling iron homeostasis...
  70. pmc Immunoassay for human serum hemojuvelin
    Carole Brasse-Lagnel
    Laboratoire de Biochimie Medicale, hôpital universitaire de Rouen, EA4309 Endothélium Microvasculaire et Lésions Cérébrales Néonatales, Universite de Rouen, Rouen, France
    Haematologica 95:2031-7. 2010
    ..can be produced by secretion following furin cleavage or by proteolytic cleavage of the membrane-bound form by matriptase 2 (TMPRSS6). These forms contribute to down-regulation of hepcidin expression upon iron deficiency or hypoxia...
  71. doi A novel SNaPshot assay to detect genetic mutations related to iron metabolism
    Stefania Bertoncini
    Department of Biology, Anthropology Unit, University of Pisa, Pisa, Italy
    Genet Test Mol Biomarkers 15:173-9. 2011
    ..targets 10 autosomal mutations in genes, or regions near to them, reported to be involved in iron metabolism: TMPRSS6, TF, and HFE...
  72. ncbi [Iron deficiency anaemia due to a matriptase-2 mutation]
    M L H Marloes Cuijpers
    Universitair Medisch Centrum St Radboud, Nijmegen, Afd Hematologie, The Netherlands
    Ned Tijdschr Geneeskd 154:A1038. 2010
    ..hepcidin-regulating proteins the patient was found to be compound heterozygous for two different mutations in the TMPRSS6 gene. This leads to a dysfunctional matriptase-2 protein for which the gene codes...
  73. pmc Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels
    Konrad Oexle
    Institute of Human Genetics, MRI, Technische Universitat Munchen, Munich, Germany
    Hum Mol Genet 20:1042-7. 2011
    ..of five genome-wide association studies on sTfR and ferritin revealed novel association to the PCSK7 and TMPRSS6 loci for sTfR and the HFE locus for both parameters...
  74. pmc Suppression of hepatic hepcidin expression in response to acute iron deprivation is associated with an increase of matriptase-2 protein
    An Sheng Zhang
    Department of Cell and Developmental Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Blood 117:1687-99. 2011
    ..demonstrate a pivotal role for bone morphogenic protein-6 (BMP6) and matriptase-2, a protein encoded by the TMPRSS6 gene, in the induction and suppression of hepatic hepcidin expression, respectively...
  75. doi Iron-deficiency anemia secondary to mutations in genes controlling hepcidin
    Milena Cau
    Dipartimento di Scienze Biomediche e Biotecnologie Università di Cagliari, Ospedale Regionale Microcitemie ASL Cagliari, Via Jenner s n, Cagliari, Italy
    Expert Rev Hematol 3:205-16. 2010
    ..In 2008, a new gene, TMPRSS6, was identified that encodes a negative regulator of hepcidin expression...
  76. pmc Common variants at 10 genomic loci influence hemoglobin A₁(C) levels via glycemic and nonglycemic pathways
    Nicole Soranzo
    Human Genetics, Wellcome Trust Sanger Institute, Hinxton, U K
    Diabetes 59:3229-39. 2010
    ..We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA₁(c) levels...
  77. pmc Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice
    Karin E Finberg
    Department of Pathology, Duke University School of Medicine, Durham, NC, USA
    Blood 117:4590-9. 2011
    ..b>TMPRSS6, a transmembrane serine protease mutated in iron-refractory iron deficiency anemia, inhibits hepcidin expression ..
  78. doi Liver hemojuvelin protein levels in mice deficient in matriptase-2 (Tmprss6)
    Jan Krijt
    Institute of Pathophysiology and Center of Experimental Hematology, Charles University in Prague, Czech Republic
    Blood Cells Mol Dis 47:133-7. 2011
    Mutations of the TMPRSS6 gene, encoding the serine protease matriptase-2, lead to iron-refractory iron deficiency anemia. Matriptase-2 is a potent negative regulator of hepcidin...
  79. ncbi A close association of abnormal iron metabolism with steatosis in the mice fed a choline-deficient diet
    Hiroyuki Tsuchiya
    Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Tottori 683 8504, Japan
    Biol Pharm Bull 33:1101-4. 2010
    ..significantly downregulated hepcidin while increases in hemojuvelin and transferrin receptor 2 and a decrease in Tmprss6 expression were observed...
  80. doi Molecular mechanisms of hepcidin regulation in sea bass (Dicentrarchus labrax)
    J V Neves
    Iron and Innate Immunity, Instituto de Biologia Molecular e Celular IBMC, Rua do Campo Alegre 823, 4150 180 Porto, Portugal
    Fish Shellfish Immunol 31:1154-61. 2011
    ..labrax) several coding sequences of known molecules involved on these pathways in mammals, namely jak3, stat3, tmprss6, bmp6, bmpr2, hjv, smad4, smad5, tfr1 and tfr2...
  81. ncbi [Iron deficiency and overload. Implications in oxidative stress and cardiovascular health]
    L Toxqui
    Departamento de Metabolismo y Nutricion, Instituto de Ciencia y Tecnología de Alimentos y Nutrición ICTAN, Instituto del Frio, Consejo Superior de Investigaciones Cientificas CSIC, Madrid, Spain
    Nutr Hosp 25:350-65. 2010
    ..overload and iron deficiency anaemia, involves mutations in several genes such as HFE, TFR2,HAMP, HJV, Tf and TMPRSS6. Iron has the capacity to accept and donate electrons easily and can catalyze reactions of free radicals ..
  82. doi Rapid, accurate detection of TMPRSS6 gene causative mutations with a high-resolution melting assay
    He ming Wu
    Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, PR China
    Blood Cells Mol Dis 47:198-204. 2011
    Mutations of the TMPRSS6 gene are considered the major genetic factors for iron-refractory iron deficiency anemia (IRIDA)...
  83. pmc Essential role of endocytosis of the type II transmembrane serine protease TMPRSS6 in regulating its functionality
    François Béliveau
    Department of Pharmacology, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada
    J Biol Chem 286:29035-43. 2011
    The type II transmembrane serine protease TMPRSS6 (also known as matriptase-2) controls iron homeostasis through its negative regulation of expression of hepcidin, a key hormone involved in iron metabolism...
  84. doi Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemia
    Tsutomu Sato
    Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, South 1, West 16, Chuo Ku, Sapporo, 060 8543, Japan
    Int J Hematol 94:101-3. 2011
    ..The disease is caused by mutations in TMPRSS6 (transmembrane protease serine 6) that prevent inactivation of membrane-bound hemojuvelin, an activator of hepcidin transcription...
  85. doi Low hepcidin accounts for the proinflammatory status associated with iron deficiency
    Alessia Pagani
    Vita Salute San Raffaele University and Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy
    Blood 118:736-46. 2011
    ..b>Tmprss6(-/-) mice, characterized by iron deficiency and high hepcidin, show a blunted inflammatory response when ..
  86. pmc Regulation of TMPRSS6 by BMP6 and iron in human cells and mice
    Delphine Meynard
    Program in Membrane Biology, Division of Nephrology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Blood 118:747-56. 2011
    Mutations in transmembrane protease, serine 6 (TMPRSS6), encoding matriptase-2, are responsible for the familial anemia disorder iron-refractory iron deficiency anemia (IRIDA)...
  87. pmc Matriptase-2- and proprotein convertase-cleaved forms of hemojuvelin have different roles in the down-regulation of hepcidin expression
    Julia E Maxson
    Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Biol Chem 285:39021-8. 2010
    ..These results suggest that the matriptase-2 and proprotein convertase-cleavage products have different roles in the regulation of hepcidin expression...

Research Grants19

  1. Hemochromatosis - Epidemiology and Molecular Mechanisms
    Pauline Lee; Fiscal Year: 2009
    ..We have recently discovered that a serum protease encoded by the Tmprss6 gene is a potent downregulator of hepcidin...
  2. Hemochromatosis - Epidemiology and Molecular Mechanisms
    Pauline L Lee; Fiscal Year: 2010
    ..We have recently discovered that a serum protease encoded by the Tmprss6 gene is a potent downregulator of hepcidin...
  3. Mechanistic Characterization and Genetic Analysis of Systemic Iron Homeostasis
    Xin Du; Fiscal Year: 2010
    ..Mask phenotype was traced to a splicing error affecting the type II transmembrane serine protease 6 (TMPRSS6)...
  4. Mechanistic Characterization and Genetic Analysis of Systemic Iron Homeostasis
    Xin Du; Fiscal Year: 2009
    ..Mask phenotype was traced to a splicing error affecting the type II transmembrane serine protease 6 (TMPRSS6)...
  5. Genes that modify Iron loading in mice
    Nancy Catherine Andrews; Fiscal Year: 2010
    ..iron content and (2) carry out genetic screens for novel genes involved in iron homeostasis using mice lacking Tmprss6, a key inhibitor of production of the iron regulatory hormone hepcidin...
  6. Iron Status: A Pathway Analysis in Multiple Ethnicities
    Christine McLaren; Fiscal Year: 2009
    ..Potential study results could be used to identify individuals at risk for iron deficiency and to develop innovative prevention and treatment strategies. ..
  7. Study of the HFE Transferrin Receptor interaction in mammalian iron homeostasis
    Paul Schmidt; Fiscal Year: 2007
    ..Most importantly, this award will assist in the transition of the candidate to become a fully independent investigator in the field of iron metabolism. ..
  8. Iron Status: A Pathway Analysis in Multiple Ethnicities
    Christine McLaren; Fiscal Year: 2007
    ..Potential study results could be used to identify individuals at risk for iron deficiency and to develop innovative prevention and treatment strategies. ..
  9. Functional investigation of hemojuvelin in regulation of hepcidin expression
    An Sheng Zhang; Fiscal Year: 2010
    ..Elucidation of the role of HFE2, the juvenile HH-causing gene (Papanikolaou et al., 2004), will lead to a full understanding of the regulation of body iron homeostasis as well as more effective cures for iron overload disorders. ..
  10. Functional investigation of hemojuvelin in regulation of hepcidin expression
    An Sheng Zhang; Fiscal Year: 2009
    ..Elucidation of the role of HFE2, the juvenile HH-causing gene (Papanikolaou et al., 2004), will lead to a full understanding of the regulation of body iron homeostasis as well as more effective cures for iron overload disorders. ..