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. Mutations causing HFE4 include N144H, A77D, V162del, G80V, D181V and D157G (Njajou et al. 2001, Agarwal et al. 2006, Wallace et al. 2002, Cremonesi et al. 2005, Hetet et al. 2003).