New mutations inactivating transferrin receptor 2 in hemochromatosis type 3

Genetic Loci Implicated in Erythroid Differentiation and Cell Cycle Regulation Are Associated With Red Blood Cell Traits

“…TFR2 is a member of the transferrin receptor-like family that mediates cellular uptake of transferrin-bound iron, and mutations in this gene have been associated with hereditary hemochromatosis type III. 33 TFR2, a homolog of TFR1 with expression restricted to hepatocytes and erythroid cells, binds transferrin at lower affinity than TFR1 and is involved in iron homeostasis. In addition, imputation-based association analyses identified a SNP (rs551238, r 2 ϭ0.31 with rs4434553 in TFR2) in the 3= flanking region of the erythropoietin gene (EPO) to be associated with MCV (Pϭ4.6ϫ10 Ϫ8 ) and MCH (Pϭ9.7ϫ10 Ϫ9 ).…”

Defective trafficking and localization of mutated transferrin receptor 2: implications for type 3 hereditary hemochromatosis

“…A homologue of TfR1, termed transferrin receptor 2 (TfR2), was identified in 1999 (22). While the exact role of TfR2 in iron metabolism is unknown, it is evident that it plays an important function in maintaining iron homeostasis, because mutations in TfR2 lead to a form of hereditary hemochromatosis (type 3) (3,11,14,24,29). TfR2 is highly expressed in the liver (22).…”

Non-classical hereditary hemochromatosis in Portugal: novel mutations identified in iron metabolism-related genes

“…Other very rare or private HFE variants have been reported in affected individuals, contributing to the HH genetic heterogeneity [3][4][5][6][7][8][9][10]. Moreover, an association of HH with other genes, such as the transferrin receptor 2 (TFR2) [11][12][13][14][15][16], the hemojuvelin (HJV) [17][18][19][20][21][22][23][24][25] and the hepcidin (HAMP) [14,[26][27][28][29][30][31] genes, has also been documented. These latter two genes are mainly associated with the juvenile form of the disease (Juvenile Hemochromatosis, JH).…”