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. Also disclosed are corresponding isolated polynucleotides encoding the fragments of the HFE2A protein. 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. 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.

Abstract: The present invention relates to the discovery that mutations in SCN9A are causative of Congenital Indifference to Pain (CIP) in humans. The invention also relates to methods of utilizing the SCN9A gene and expression products thereof for the screening and identification of therapeutic agents, including small organic compounds, which are selective for SCN9A, and are useful in the treatment of pain and other disorders. The invention also relates to methods of using these compounds to treat or otherwise ameliorate such disorders.

Abstract: Polynucleotide and polypeptide sequences for HFE2A, as well as mutations associated with juvenile hemochromatosis, and methods of utilizing these for the screening and identification of agents for the treatment of diseases of iron metabolism, including small organic compounds, are disclosed along with methods of treating and/or ameliorating diseases of iron metabolism, especially in human patients are disclosed. Diagnostic compounds, kits and methods using HFE2A are also described.

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.