Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages)

Stable Identifier
Homo sapiens
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SLC40A1 (MTP1 aka ferroportin or IREG1) is highly expressed on macrophages where it mediates iron efflux from the breakdown of haem. SLC40A1 colocalises with ceruloplasmin (CP) which stablizes SLC40A1 and is necessary for the efflux reaction to occur. Six copper ions are required by ceruloplasmin as a cofactor.
Defects in SLC40A1 can cause hemochromatosis 4 (HFE4; MIM:606069), a disorder of iron metabolism characterised by iron overload. Excess iron is deposited in a variety of organs leading to their failure, resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis and hypogonadotropic hypogonadism. Severe effects of the disease don't usually appear until after decades of progressive iron overloading (De Domenico et al. 2005, 2006, 2011, Kaplan et al. 2011).

Literature References
PubMed ID Title Journal Year
21901657 Hepcidin and ferroportin: the new players in iron metabolism

De Domenico, I, Ward, DM, Kaplan, J

Semin. Liver Dis. 2011
16434376 Iron overload due to mutations in ferroportin

De Domenico, I, Ward, DM, Musci, G, Kaplan, J

Haematologica 2006
21210258 The molecular basis of iron overload disorders and iron-linked anemias

Kaplan, J, Ward, DM, De Domenico, I

Int. J. Hematol. 2011
15956209 The molecular basis of ferroportin-linked hemochromatosis

De Domenico, I, Ward, DM, Nemeth, E, Vaughn, MB, Musci, G, Ganz, T, Kaplan, J

Proc. Natl. Acad. Sci. U.S.A. 2005
Name Identifier Synonyms
hemochromatosis DOID:2352 iron storage disorder, Hemochromatosis (disorder), diabetes bronze, Bronze diabetes (disorder), HEMOCHROMATOSIS, Hemochromatosis (disorder), Bronzed diabetes, Haemochromatosis, Haemochromatosis
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