The link between genetics, health, and a life-sustaining metal

The Weekly Gene: TMPRSS6

The Weekly Gene: TMPRSS6

Welcome to The Weekly Gene, a blog series brought to you by Helix that introduces a different human gene each week. We’ll share important facts, relevant research, and how these genes might be related to certain conditions and traits. It’s a great way to build your DNA vocabulary, learn more about the code that makes all of us unique, and find a path to the genetic insights that are important to you.

Want to know more about a specific gene? Let us know by tweeting @my_helix with #WeeklyGene.

Whether it’s in our cars and bicycles, gleaming in the hilts of swords, or personified as a nearly indestructible, high-tech superhero, iron touches our lives every single day. In fact, we cannot live without it—literally. Iron is essential to life, and its dysregulation can have profound effects on the human body. An iron imbalance can occur in humans for a number of reasons, but research indicates that heritable changes in a gene called TMPRSS6 can predispose a person to iron irregularities.

Iron is one of the most abundant molecules in the earth’s crust and is critically involved in many processes within the body. It integrates into the structure of proteins, allowing them to perform functions like oxygen transportation, synthesizing DNA precursors, and neutralizing toxins. Maintaining iron levels is essential to our survival, because the absorption of too much iron (hemochromatosis) can result in the formation of dangerous oxygen radicals that destroy organs. On the other hand, low levels of iron (anemia) result in a decreased ability to transport oxygen throughout the body.

To maintain iron levels within the normal range, our bodies have developed a complex method for regulating the absorption and recycling of iron. Humans have no significant way to expel iron (very little iron leaves the body in a given day)2, therefore regulation of iron levels occurs via limiting its absorption and storage. Iron is present in both meats and vegetables, but the type of iron present within foods can differ. Plants contain iron that is primarily integrated into plant-specific protein structures that are poorly soluble, making them difficult for the human body to absorb. In contrast, iron in the form of hemoglobin and myoglobin is readily absorbed, which makes meat a rich source of it.

When a person’s body senses high levels of iron, it releases a hormone known as hepcidin. This signaling molecule is made in the liver and stimulates a decrease in blood iron levels by limiting intestinal absorption and the release of iron from body stores. The regulation of hepcidin levels can thus affect the amount of iron present within the body.

One protein with significant influence over iron levels is matriptase-2 (MT2) which inhibits the production of hepcidin. MT-2 is a protein encoded by the gene TMPRSS6, and research into the genetics of iron metabolism has revealed that some people inherit the TMPRSS6 gene with an altered DNA sequence that results in anemia3,4,5. To correct this deficiency, it is sometimes sufficient to increase dietary intake of iron. In other cases, therapeutic treatments6 are available. Some changes within the TMPRSS6 gene do not cause anemia on their own, but can affect iron levels. One such change causes the MT2 protein to be built with a different sequence of amino acids, which may result in elevated levels of hepcidin. This change may disrupt iron regulation leading to potentially lower levels of iron but not so low as to cause anemia (relative to individuals without this base change).

Identifying whether a person is predisposed to misregulation of iron as a result of a TMPRSS6 variant can be done using DNA testing kits offered through the Helix Store. These products assess multiple genes involved in nutrient metabolism with the ultimate goal of helping individuals improve their nutrition using DNA-based insights. These tests do not report on medical conditions but rather explore how your genetics can cause minor changes in iron metabolism. DNA is not destiny, but understanding the genetics behind your body’s metabolism of nutrients may help you pursue a healthier you.

Check out nutrition products in the Helix Store >


1Zimmermann, Michael B, and Richard F Hurrell. “Nutritional iron deficiency.” The Lancet, vol. 370, no. 9586, 11 Aug. 2007, pp. 511–520., doi:10.1016/s0140-6736(07)61235-5. Web. 18 Oct. 2017.

2Ganz, T. “Systemic Iron Homeostasis.” Physiological Reviews, vol. 93, no. 4, Jan. 2013, pp. 1721–1741., doi:10.1152/physrev.00008.2013. Web. 17 Oct. 2017

3Finberg, Karin E et al. “Mutations in TMPRSS6 Cause Iron-Refractory Iron Deficiency Anemia (IRIDA).” Nature genetics 40.5 (2008): 569–571. PMC. Web. 17 Oct. 2017.

4Benyamin, Beben et al. “Common Variants in TMPRSS6 Are Associated with Iron Status and Erythrocyte Volume.” Nature genetics 41.11 (2009): 1173–1175. PMC. Web. 17 Oct. 2017.

5Tanaka, Toshiko et al. “A Genome-Wide Association Analysis of Serum Iron Concentrations.” Blood 115.1 (2010): 94–96. PMC. Web. 17 Oct. 2017.

6Johnson-Wimbley, Terri D., and David Y. Graham. “Diagnosis and Management of Iron Deficiency Anemia in the 21st Century.” Therapeutic Advances in Gastroenterology 4.3 (2011): 177–184. PMC. Web. 17 Oct. 2017.

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