However, to comply with the observation of our cohort, in which IRIDA is the predominant disease, such mutations would have to possess certain characteristics: (i) the mutations themselves should not have a significant clinical effect on their own (i.e., not be disease-causing themselves); (ii) they should have an overall stimulating effect within the hepcidin expression pathway or an inhibiting effect on ferroportin activity; and (iii) in combination with a TMPRSS6 variant, they should resist any attenuation by cellular feedback mechanisms. The gene discussed is TMPRSS6; the disease is IRIDA syndrome.