Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin. Binds TFR through the extracellular domain in a pH-dependent manner. Additional isoforms seem to exist. Expressed in all tissues tested except brain. Genetic variations in HFE define the transferrin serum level quantitative trait locus 2 (TFQTL2) [MIM:614193]. Iron is essential for biochemical functions such as oxygen transport and oxidative phosphorylation. Excessive iron can cause iron-overload-related liver diseases, whereas iron deficiency can lead to anemia. Iron status can be assessed by measuring the levels of serum iron, serum transferrin, transferrin saturation with iron, and serum ferritin. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. Iron overload due to HFE variants is a precipitating or exacerbating factor in variegate porphyria. Disease susceptibility is associated with variants affecting the gene represented in this entry. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Belongs to the MHC class I family.