TMPRSS6- Mutation in Iron Deficiency Anemia: A Review

Introduction: Iron is one of the metals involved in a variety of physiological reactions, including the construction of haemoglobin, which transports oxygen to the tissues. Chronic blood loss or insufficient food intake are the most common causes of iron insufficiency.. A germline mutation in TMPRSS6, which encodes type two transmembrane serine protease generated by the liver and helps regulate the expression of systemic iron, can induce anaemia that is resistant to oral iron treatment.

Structure: The plasma membrane is cleaved by TMPRSS6 in vitro. The signalling mechanism required for iron-dependent hepcidin transcription regulation is thought to be downregulated by TMPRSS6. They also investigated whether the robust physiologic inducer of hepcidin, iron, can affect TMPRSS6 mRNA levels in vivo, as one of the most important activators of hepcidin expression in vitro and in vivo.

Role of TMPRSS6: Overexpression of normal TMPRSS6 protein reduces Hamp promoter activity, and the TMPRSS6 cytoplasmic domain mediates Hamp suppression via the proximal promoter element. TMPRSS6 polymorphisms are more common than mutations and have been linked to variations in iron and hematologic markers.

Conclusion: Because TMPRSS6 is linked to haematological factors, it is essential for maintaining iron homeostasis and proper erythropoiesis. Overproduction of hepcidin is caused by the TMPRSS6 mutation, which contributes to poor iron absorption and utilisation. Patients with poor transferrin saturation, normal ferritin levels, high amounts of hepcidin molecules, and a family history of iron deficiency anemia should be aware of TMPRSS6 gene mutations.