TFR2

The TFR2 gene provides instructions for making a protein called transferrin receptor 2. Studies suggest that this receptor helps iron enter liver cells (hepatocytes). In the blood, iron binds to a protein called transferrin for transport and delivery to the liver and other tissues. On the cell surface, transferrin binds to transferrin receptor 2, and iron is allowed to enter the cell. Additionally, this receptor helps sense and 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.

hemochromatosis - caused by mutations in the TFR2 gene

At least nine different mutations that cause type 3 hemochromatosis have been identified in the TFR2 gene. Some mutations in the TFR2 gene 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 likely impair the ability to regulate importation of iron into certain cells.

Mutations in the TFR2 gene are also thought to contribute to low levels of hepcidin in the body, which allows too much iron to be 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.