Transferrin receptor-2, TfR2 or TFR2 of 801 aas and 1 TMS.  TFR2, is predominantly expressed in hepatocytes and erythroid precursor cells. In the liver, TFR2 forms a complex with HFE, a hereditary hemochromatosis-associated protein, and acts as an iron sensor. In mice, hepatocyte-specific knockout of the TFR2 gene has been shown to cause systemic iron-overload with decreased expression of hepcidin, the central regulator of iron homeostasis. In erythroid cells, TFR2 forms a complex with the erythropoietin receptor and facilitates its trafficking to the cell membrane. Hematopoietic cell-specific knockout of the TFR2 gene causes microcytic erythrocytosis in mice (Kawabata et al. 2016). Hereditary hemochromatosis (HH), also known as ferroportin disease, is caused by mutations in the SLC4OA1 gene. Ferroportin is an iron transmembrane transport protein, and Type 4 HH is the only known form of hemochromatosis that can be inherited in an autosomal dominant fashion (Sonagra AD, Zubair M, 2023, PMiD 37603641).

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