Hemochromatosis: a genetic defect in iron metabolism.
Hemochromatosis (HC), the common inherited disorder in iron metabolism, affects at least 1 in 300 Caucasians. The disorder causes inappropriately high iron absorption and accumulation of excess iron in the parenchymal cells of the major organs of the body. The gene responsible for HC has recently been cloned and is termed HFE; two missense mutations have been reported in the gene, both cause amino acid substitutions (H63D and C282Y), but to date only the C282Y mutation has been found to clearly correlate with HC in all affected populations. HFE is highly homologous to genes in the major histocompatibility complex (MHC) class I family; all of these genes encode a heterodimeric protein which is complexed to beta 2-microglobulin, a coupling essential for cell surface expression of a functional molecule. The first important step toward establishing the role of HFE in the pathogenesis of HC came with the recent observation that the C282Y mutation disrupts the binding of beta 2-microglobulin to the HFE protein and as a result the mutant molecule is not expressed on the cell surface.
Jazwinska
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Queensland Institute of Medical Research, Brisbane, Australia.
D000818:Animals; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005828:Genetics, Population; D006680:HLA Antigens / Q000235:genetics; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D001613:beta 2-Microglobulin / Q000235:genetics
C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D001613:beta 2-Microglobulin; D007501:Iron