Juvenile hemochromatosis gene (HFE2A) cleavage products and uses thereof

Abstract

Isolated fragments of the HFE2A protein able to bind and modulate HFE2A and other proteins, such as hepcidin, involved in the iron metabolism pathway are disclosed, such fragments being of molecular weight of approximately 7 kDa to 43 kDa. Also disclosed are corresponding isolated polynucleotides encoding the fragments of the HFE2A protein. The invention includes derivatives and analogs of the polypeptide fragments of HFE2A, along with compositions of these, that are functionally active, i.e. capable of interacting with the HFE2A, as well as methods of production of the HFE2A cleavage products, derivatives and analogs, e.g. by recombinant means. Methods for identifying modulators of HFE2A, comprising contacting a test compound with HFE2A and determining a change in HFE2A activity due to the compound, are provided. Also taught are methods of diagnosing an animal afflicted with or at risk of developing a disease of iron metabolism comprising determining a change in the level, amount or activity of a fragment of an HFE2A obtained in a sample from said animal relative to the level, amount or activity of a fragment of an HFE2A obtained in a control sample from an unaffected animal, wherein a change identifies said individual as being affect by or at risk of developing a disease of iron metabolism. Methods for treating and/or preventing a disorder in animals comprising administering to an animal afflicted therewith, or at risk of developing said disorder, a therapeutically effective amount of an HFE2A modulator are provided.

Dependencies are inferred from the claim text.