EPAS1 and pulmonary arterial hypertension: Hif2a haploinsufficiency and endothelial cell conditional knockout of Hif2a are protective (Brusselmans et al. 2003; Kapitsinou et al. 2016; Tang et al. 2018), whereas a hypermorphic Hif2a knockin mutation that stabilizes the protein leads to pulmonary hypertension under normoxia (Tan et al. 2013).