The hereditary hemochromatosis gene (HFE) - A MHC class I-like gene that functions in the regulation of iron homeostasis

The iron overload disorder, hereditary hemochromatosis, is one of the most common genetic diseases of individuals of Northern European descent. The di sorder is characterized by the progressive accumulation of dietary iron in the major organs of the body, which if not diagnosed, leads to numerous med ical maladies and eventually death. The locus for this disorder was mapped by genetic linkage to the short arm of chromosome over twenty years ago, bu t it was not until 1996 that the gene for this disorder was cloned by an id entity-by-descent positional cloning approach. The gene, called HFE, encode s a major histocompatibility complex (MHC) class like protein that is mutat ed in approx 85% of all individuals known to have hereditary hemochromatosi s (HH). Since the cloning of the HFE gene, considerable work has been carri ed out which has furthered our understanding of the genetics of this preval ent disorder. In addition, with the identification of the transferrin recep tor as a protein capable of interacting with HFE we are now beginning to un derstand how a protein with the structural characteristics of an MHC class I molecule can influence cellular iron homeostasis.