A study in patients affected by type 1 (HFE-related) or type 3 (TFR2-related) hemochromatosis showed a different role for TFR2 and HFE in hepcidin activation in response to a single oral iron challenge able to increase transferrin saturation: HFE patients showed a blunted hepcidin response, whereas TFR2 patients showed no response (Girelli et al., 2011). This evidence concerns the gene TF and hemochromatosis type 1.