Defective SLC40A1 causes hemochromatosis 4 (HFE4) (duodenum)

Stable Identifier
Homo sapiens
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The primary site for absorption of dietary iron is the duodenum. Ferrous iron (Fe2+) is taken up from the gut lumen across the apical membranes of enterocytes and released into the portal vein circulation across basolateral membranes. The human gene SLC40A1 encodes the metal transporter protein MTP1 (aka ferroportin or IREG1). This protein resides on the basolateral membrane of enterocytes and mediates ferrous iron efflux into the portal vein. SLC40A1 colocalises with hephaestin (HEPH) which stablises it and is necessary for the efflux reaction to occur.
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
16434376 Iron overload due to mutations in ferroportin

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

Haematologica 2006
21901657 Hepcidin and ferroportin: the new players in iron metabolism

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

Semin. Liver Dis. 2011
21210258 The molecular basis of iron overload disorders and iron-linked anemias

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

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

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

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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