Transferrin receptor 2 (TfR2)

Transferrin receptor 2 is a type II transmembrane glycoprotein encoded by the TFR2 gene on chromosome 7q22.1, consisting of 801 amino acids with structural homology to transferrin receptor 1 (TfR1), but displaying distinct regulatory functions. Unlike TfR1, TfR2 is primarily expressed in the liver (especially hepatocytes) and certain erythroid cells, and is essential for the hormonal regulation of systemic iron via its effect on hepcidin production. Mutations in TFR2 cause type 3 hereditary hemochromatosis, a genetic disorder characterized by excessive iron absorption and deposition, especially in the liver. Biochemically, TfR2 binds to transferrin-bound iron with lower affinity than TfR1 and participates in iron sensing rather than primary transport. It comprises domains mediating endocytosis, dimerization, and protein-protein interactions important for iron metabolism and signaling. TfR2 is widely studied both as a disease gene and as a potential, though not yet clinically validated, therapeutic target for iron overload syndromes[1][2][3][4][5][6].

Other names

TFR2HFE3transferrin receptor protein 2CD71L

Therapeutic modulation could occur via interfering with transferrin binding or stabilizing/destabilizing TfR2 to alter iron uptake and hepcidin response[1][5][6].