The genetic background of IRIDA is mutations in the TMPRSS6 gene encoding matriptase-2 (TMPRSS6) that prevent inactivation of hemojuvelin, an activator of hepcidin transcription.
Patients with iron-refractory iron-deficiency anemia with a mutation in the TMPRSS6 gene were found to have lower levels of circulating hemojuvelin than those in healthy patients.