Conversely, HIF2A (EPAS1) gain-of-function mutations can predispose to PH; a Hif2a variant in high altitude cattle increases susceptibility to brisket disease (85), whilst a HIF2A mutation causing familial erythrocytosis is also associated with elevated systolic PAP in humans (86). This evidence concerns the gene EPAS1 and primary familial polycythemia due to EPO receptor mutation.