Normal Function
The TMPRSS6 gene provides instructions for making a protein called matriptase-2. This protein is part of a signaling pathway that controls the levels of another protein called hepcidin, which is a key regulator of iron balance in the body. When blood iron levels are low, this signaling pathway reduces hepcidin production, allowing more iron from the diet to be absorbed through the intestines and transported out of storage sites (particularly in the liver and spleen) into the bloodstream. Iron is an essential component of hemoglobin, which is the molecule in red blood cells that carries oxygen.
Health Conditions Related to Genetic Changes
Iron-refractory iron deficiency anemia
At least 40 mutations in the TMPRSS6 gene have been found to cause an inherited form of anemia called iron-refractory iron deficiency anemia. This condition is characterized by a shortage (deficiency) of iron in the bloodstream that is resistant (refractory) to treatment with iron.
TMPRSS6 gene mutations greatly reduce the amount of functional matriptase-2, preventing it from controlling hepcidin levels. The resulting elevation in hepcidin activity blocks the absorption of iron through the intestines and the release of iron from storage. When not enough iron is available in the bloodstream, less hemoglobin is produced and red blood cells cannot carry oxygen to the body's cells and tissues effectively. The shortage of oxygen causes the signs and symptoms of anemia, which can include tiredness (fatigue), weakness, and pale skin.
More About This Health ConditionOther Names for This Gene
- matriptase 2
- matriptase-2
- membrane-bound mosaic serine proteinase matriptase-2
- transmembrane protease serine 6
- transmembrane protease, serine 6
- type II transmembrane serine protease 6
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Camaschella C, Silvestri L. Molecular mechanisms regulating hepcidin revealed by hepcidin disorders. ScientificWorldJournal. 2011 Jul 7;11:1357-66. doi: 10.1100/tsw.2011.130. Citation on PubMed
- De Falco L, Totaro F, Nai A, Pagani A, Girelli D, Silvestri L, Piscopo C, Campostrini N, Dufour C, Al Manjomi F, Minkov M, Van Vuurden DG, Feliu A, Kattamis A, Camaschella C, Iolascon A. Novel TMPRSS6 mutations associated with iron-refractory iron deficiency anemia (IRIDA). Hum Mutat. 2010 May;31(5):E1390-405. doi: 10.1002/humu.21243. Citation on PubMed
- Du X, She E, Gelbart T, Truksa J, Lee P, Xia Y, Khovananth K, Mudd S, Mann N, Moresco EM, Beutler E, Beutler B. The serine protease TMPRSS6 is required to sense iron deficiency. Science. 2008 May 23;320(5879):1088-92. doi: 10.1126/science.1157121. Epub 2008 May 1. Citation on PubMed or Free article on PubMed Central
- Meynard D, Vaja V, Sun CC, Corradini E, Chen S, Lopez-Otin C, Grgurevic L, Hong CC, Stirnberg M, Gutschow M, Vukicevic S, Babitt JL, Lin HY. Regulation of TMPRSS6 by BMP6 and iron in human cells and mice. Blood. 2011 Jul 21;118(3):747-56. doi: 10.1182/blood-2011-04-348698. Epub 2011 May 26. Citation on PubMed or Free article on PubMed Central
- Ramsay AJ, Hooper JD, Folgueras AR, Velasco G, Lopez-Otin C. Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis. Haematologica. 2009 Jun;94(6):840-9. doi: 10.3324/haematol.2008.001867. Epub 2009 Apr 18. Citation on PubMed or Free article on PubMed Central
- Stirnberg M, Gutschow M. Matriptase-2, a regulatory protease of iron homeostasis: possible substrates, cleavage sites and inhibitors. Curr Pharm Des. 2013;19(6):1052-61. doi: 10.2174/1381612811319060007. Citation on PubMed
- Zhao N, Zhang AS, Enns CA. Iron regulation by hepcidin. J Clin Invest. 2013 Jun;123(6):2337-43. doi: 10.1172/JCI67225. Epub 2013 Jun 3. Citation on PubMed or Free article on PubMed Central
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