title: HFE gene: Structure, function, mutations, and associated iron abnormalities.
abstract: The hemochromatosis gene HFE was discovered in 1996, more than a century after clinical and pathologic manifestations of hemochromatosis were reported. Linked to the major histocompatibility complex (MHC) on chromosome 6p, HFE encodes the MHC class I-like protein HFE that binds beta-2 microglobulin. HFE influences iron absorption by modulating the expression of hepcidin, the main controller of iron metabolism. Common HFE mutations account for ~90% of hemochromatosis phenotypes in whites of western European descent. We review HFE mapping and cloning, structure, promoters and controllers, and coding region mutations, HFE protein structure, cell and tissue expression and function, mouse Hfe knockouts and knockins, and HFE mutations in other mammals with iron overload. We describe the pertinence of HFE and HFE to mechanisms of iron homeostasis, the origin and fixation of HFE polymorphisms in European and other populations, and the genetic and biochemical basis of HFE hemochromatosis and iron overload.
authors.affiliation: Southern Iron Disorders Center, Birmingham, AL, USA and Department of Medicine; University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: ironmd@isp.com.
authors.forename: James C
authors.initials: JC
authors.lastname: Barton
authors.affiliation: Department of Medicine, Intermountain Medical Center and University of Utah, Salt Lake City, UT, USA. Electronic address: corwin.edwards@imail.org.
authors.forename: Corwin Q
authors.initials: CQ
authors.lastname: Edwards
authors.affiliation: Southern Iron Disorders Center, Birmingham, AL, USA and Department of Medicine; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: rtakma@bellsouth.net.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Acton
mesh_terms: D000818:Animals; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D006801:Humans; D019189:Iron Metabolism Disorders / Q000235:genetics*; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins
keywords: Hemochromatosis; Iron; Major histocompatibility complex; Transferrin receptor