Molecular aspects of iron absorption and HFE expression

Gastroenterology. 2001 Dec;121(6):1489-96. doi: 10.1053/gast.2001.29617.


Hereditary hemochromatosis, a disease of iron overload, occurs in about 1 in 200-400 Caucasians. The gene mutated in this disorder is termed HFE. The product of this gene, HFE protein, is homologous to major histocompatibility complex class I proteins, but HFE does not present peptides to T cells. Based on recent structural, biochemical, and cell biological studies, transferrin receptor (TfR) is a ligand for HFE. This association directly links HFE protein to the TfR-mediated regulation of iron homeostasis. Although evidence is accumulating that binding of HFE to TfR is critical for the effects of HFE, the final pieces in the HFE puzzle have not been established. This review focuses on recent advances in HFE research and presents a hypothetical model of HFE function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Absorption
  • Animals
  • HLA Antigens / genetics*
  • HLA Antigens / physiology
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / physiology
  • Homeostasis
  • Humans
  • Iron / metabolism
  • Iron / pharmacokinetics*
  • Iron Overload / genetics
  • Membrane Proteins*
  • Mutation / physiology*


  • HFE protein, human
  • HLA Antigens
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Iron