As Hif1a and Hif2a are regulated by oxygen and iron, this upregulation could be a result of inactivation of iron-dependent prolyl hydroxylases needed to mark HIF proteins for degradation due to functional iron deficiency, and in vivo by induced anemia in addition to the regulation of Hif2a by IRP/IRE binding [107,108]. This evidence concerns the gene EPAS1 and anemia (phenotype).