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TFR2 gene

transferrin receptor 2
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Normal Function

The TFR2 gene provides instructions for making a protein called transferrin receptor 2. The main function of this protein is to help iron enter liver cells (hepatocytes). On the surface of hepatocytes, the receptor binds to a protein called transferrin, which transports iron through the blood to tissues throughout the body. When transferrin binds to transferrin receptor 2, iron is allowed to enter the cell.

Additionally, transferrin receptor 2 can bind to other proteins to help regulate iron storage levels in the body by controlling the levels of another protein called hepcidin. Hepcidin is a protein that determines how much iron is absorbed from the diet and released from storage sites in the body in response to iron levels.

Health Conditions Related to Genetic Changes

Hereditary hemochromatosis

About 50 mutations in the TFR2 gene cause type 3 hemochromatosis, a form of hereditary hemochromatosis that begins in early adulthood, usually before age 30. Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. The excess iron accumulates in, and eventually damages, the body's tissues and organs.

Some TFR2 gene mutations prevent the production of transferrin receptor 2. Other mutations result in proteins that have an incorrect sequence of protein building blocks (amino acids) or proteins that are too short to function normally. These mutations prevent the protein from binding to transferrin, blocking iron from entering hepatocytes.

Mutations in the TFR2 gene are also thought to contribute to low levels of hepcidin in the body, which results in too much iron being absorbed from the diet. When this occurs, the excess iron is stored in the body's tissues, especially the liver. Iron overload leads to the organ damage and other signs and symptoms of type 3 hemochromatosis.

More About This Health Condition

Other Names for This Gene

  • HFE3
  • TFR2_HUMAN
  • Transferrin Receptor Protein 2

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • Camaschella C, Roetto A, Calì A, De Gobbi M, Garozzo G, Carella M, Majorano N, Totaro A, Gasparini P. The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat Genet. 2000 May;25(1):14-5. Citation on PubMed
  • Deicher R, Hörl WH. New insights into the regulation of iron homeostasis. Eur J Clin Invest. 2006 May;36(5):301-9. Review. Citation on PubMed
  • Gerhard GS, Paynton BV, DiStefano JK. Identification of Genes for Hereditary Hemochromatosis. Methods Mol Biol. 2018;1706:353-365. doi: 10.1007/978-1-4939-7471-9_19. Review. Citation on PubMed
  • Kleven MD, Jue S, Enns CA. Transferrin Receptors TfR1 and TfR2 Bind Transferrin through Differing Mechanisms. Biochemistry. 2018 Mar 6;57(9):1552-1559. doi: 10.1021/acs.biochem.8b00006. Epub 2018 Feb 12. Citation on PubMed or Free article on PubMed Central
  • Le Gac G, Mons F, Jacolot S, Scotet V, Férec C, Frébourg T. Early onset hereditary hemochromatosis resulting from a novel TFR2 gene nonsense mutation (R105X) in two siblings of north French descent. Br J Haematol. 2004 Jun;125(5):674-8. Citation on PubMed
  • Peters TM, Meulders AF, Redert K, Cuijpers ML, Rennings AJ, Janssen MC, Blijlevens NM, Swinkels DW. TFR2-related haemochromatosis in the Netherlands: a cause of arthralgia in young adulthood. Neth J Med. 2017 Mar;75(2):56-64. Citation on PubMed
  • Pietrangelo A. Non-HFE hemochromatosis. Semin Liver Dis. 2005 Nov;25(4):450-60. Review. Citation on PubMed
  • Roetto A, Daraio F, Alberti F, Porporato P, Calì A, De Gobbi M, Camaschella C. Hemochromatosis due to mutations in transferrin receptor 2. Blood Cells Mol Dis. 2002 Nov-Dec;29(3):465-70. Citation on PubMed
  • Trinder D, Baker E. Transferrin receptor 2: a new molecule in iron metabolism. Int J Biochem Cell Biol. 2003 Mar;35(3):292-6. Review. Citation on PubMed
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