The HFE gene at 6p22.2 codes for the 348 amino acid pro-peptide to hereditary haemochromatosis protein which has at least 11 isoforms created by alternative splicing. This glycoprotein binds to the transferrin receptor and reduces its affinity for iron-loaded transferrin. It is not expressed in the brain.
Mutations cause haemochromatosis 1 (HFE1, hereditary haemochromatosis, HH, hemochromatosis 1, OMIM:235200) and variants modulate serum transferrin. Variants also influence disease susceptibility to variegate porphyria, porphyria cutanea tarda, Alzheimers disease, and ocular microvascular complications of diabetes mellitus.