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TMPRSS6 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

TMPRSS6 gene

The TMPRSS6 gene encodes the protein matriptase-2, which regulates iron balance by controlling hepcidin levels in the body.

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 of iron in the bloodstream that is resistant 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, leading to symptoms of anemia, which can include:

  • Tiredness (fatigue)
  • Weakness
  • Pale skin

Other 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

Frequently Asked Questions

Diagnosis relies on a combination of clinical anemia, low serum iron, low transferrin saturation, normal or elevated ferritin, and a poor rise in hemoglobin after a trial of oral iron. Genetic testing for TMPRSS6 mutations confirms IRIDA. Additional tests may include serum hepcidin (often elevated) and a complete blood count with red‑cell indices.
Mutations in TMPRSS6 cause over‑production of hepcidin, the hormone that blocks iron absorption in the duodenum and iron release from macrophages. Even large oral iron doses cannot overcome this hepcidin‑mediated blockade, so hemoglobin levels remain low despite supplementation.
Experimental approaches include hepcidin antagonists (e.g., monoclonal antibodies or Spiegelmers), small‑molecule inhibitors of the BMP‑SMAD pathway that drives hepcidin transcription, and intravenous iron formulations that deliver iron directly to the bloodstream. Some patients benefit from periodic IV iron infusions, but long‑term efficacy varies and should be managed by a hematologist.
IRIDA follows an autosomal‑recessive pattern; both parents must carry a pathogenic TMPRSS6 allele for a child to be affected. Siblings have a 25 % chance of being affected, a 50 % chance of being carriers, and a 25 % chance of being unaffected non‑carriers. Targeted genetic testing of at‑risk relatives is recommended, especially if they have unexplained microcytic anemia that does not respond to oral iron.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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