Function is modulated by other proteins under the control of genes for haemochromatosis (HFE) heamojuvelin and transferrin receptor 2
Although the exact function of transferrin binding protein transferrin receptor 2
(TfR2) is not fully known, homozygous mutations are also a cause of hereditary hemochromatosis.
Kawabata H, Yang R, Hirama T, Vuong PT, Kawano S, Gombart AF, Koeffler HP Molecular cloning of transferrin receptor 2.
Kawabata H, Nakamaki T, Ikonomi P, Smith RD, Germain RS, Koeffler HP Expression of transferrin receptor 2 in normal and neoplastic hematopoietic cells.
Several proteins mediating iron uptake into cells have been identified, including the ubiquitously expressed transferrin receptor 1, which binds iron complexed to transferrin (31); transferrin receptor 2, the expression of which is restricted to hepatocytes, duodenal crypt cells, and erythroid precursors; divalent metal transporter 1, a H+/divalent metal symporter found in duodenal enterocytes, which mediates uptake of dietary iron (32,33); cubilin, a protein expressed in polarized epithelial cells in the kidney, which mediates endocytosis of iron and transferrin with its coreceptor megalin (34); and the hemoglobin scavenger receptor CD163, which is expressed on the surface of monocytes and macrophages and receives plasma hemoglobin bound to haptoglobin.
The transcription of hepcidin mRNA is controlled by signaling pathways initiated by several proteins, including hereditary hemochromatosis protein HFE, transferrin receptor 2, and hemojuvelin.
Since the identification of the C282Y mutation in the HFE gene as the most common cause of hemochromatosis, mutations in the genes encoding the hepcidin, hemojuvelin, transferrin receptor 2, and ferroportin proteins have been identified as causes of hereditary hemochromatosis.
Indeed, available data do suggest that HFE/TfR1 in parallel to transferrin receptor 2 (TfR2) is implicated in the iron-sensing pathway of hepatocytes that controls hepcidin synthesis (Fig.
The gene coding for transferrin receptor 2 (TfR2) was described in 1999 (8).
3 Hemochromatosis Type 2 Type 2A HJV Hemojuvelin 1q21 Type 2B HAMP Hepcidin 19q13 Hemochromatosis Type 3 TFR2 Transferrin receptor 2
7q22 Hemochromatosis Type 4 SLC40A1 Ferroportin 2q32 Disorder Treatment Hemochromatosis Type 1 Phlebotomy, iron chelating therapy Hemochromatosis Type 2 Phlebotomy, iron chelating therapy Type 2A Type 2B Hemochromatosis Type 3 Phlebotomy, iron chelating therapy Hemochromatosis Type 4 Phlebotomy, erythropoietin
One involves homozygous mutations of the transferrin receptor 2 gene (TfR2; OMIM 604720) on chromosome 7.
Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene.