Positional cloning has been carried out to identify the gene responsible
for the hypochromic anemia of the zebrafish mutant weissherbst. The gene,
ferroportin1, encodes a novel multiple-transmembrane domain protein,
expressed in the yolk sac. Zebrafish ferroportin1 is required for the
transport of iron from maternally-derived yolk stores to the circulation,
and functions as an iron exporter when expressed in Xenopus oocytes.
Human and mouse homologs of the ferroportin1 gene have been identified.
The invention includes isolated polynucleotides, vectors and host cells
comprising nucleotide sequences encoding Ferroportin1 proteins and
variants thereof, including those having iron transport function. The
invention also includes polypeptides encoded by ferroportin1 genes and
variants of such polypeptides, and fusion polypeptides comprising a
Ferroportin1 or a portion thereof. Methods to produce a Ferroportin1,
methods to produce antibodies to a Ferroportin1 and methods to identify
agents binding to a Ferroportin1, which can be inhibitors or enhancers of
Ferroportin1 iron transport activity, are also described. Inhibitors of
Ferroportin1 activity can be used in a therapy for hemochromatosis.