Molecular genetics and control of iron metabolism in hemochromatosis

Antonello Pietrangelo, Clara Camaschella

Research output: Contribution to journalArticlepeer-review


Background and Objectives. Hereditary hemochromatosis (HC) is an inborn error of iron metabolism that leads to progressive Iron overload. Considerable advances in the knowledge of molecular events in iron metabolism have been recently obtained. These molecular findings, the cloning of the gene responsible for HC (HFE gene) and the results of preliminary studies on the HFE protein prompted us to review this topic. Information Sources. The material examined in this review article includes papers and abstracts published in the Journals covered by the Science Citation Index and Medline. The authors have been working in the field of HC for several years and have contributed eleven of the quoted papers. State of Art and Perspective. HC is now recognized as the genetic disease characterized by the homozygosity for the Cys→Tyr substitution at position 282 (C282Y) of the HFE protein. The mutation abolishes the association of the HFE protein with β2-microglobulin (β2M), making the complex unable to gain the cell surface. Thus HC is an example of abnormal trafficking of the corresponding proteins. It is clear by the analysis of its structure that HFE protein is not an iron transporter itself, but has a regulatory role in iron metabolism. Its pecullar localization in the crypt cells of the small intestine suggests an important role in iron trafficking at this level. However, other proteins are involved in iron uptake, as the recently cloned Nramp2, the first iron transporter discovered in mammalians. Nramp2 has a recognized role both in the intestinal iron uptake and in the iron transport within the erythroblast. The relationships between HFE and Nramp2 are still unexplored. The recent association of HFE gene with transferrin receptor (TfR) in trophoblast cells opens new possibilities on its role in cellular iron uptake. The existence of other forms of genetic iron overload suggests that the scenario of iron proteins is not yet fully defined. Further studies in this field will contribute to our knowledge of iron metabolism regulation in humans.

Original languageEnglish
Pages (from-to)456-461
Number of pages6
Issue number5
Publication statusPublished - May 1998


  • Hemochromatosis
  • HFE gene
  • Iron metabolism

ASJC Scopus subject areas

  • Hematology


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