While these findings provide insight into altered transcriptional activity as a result of this missense variant in vitro, previous EPAS1 loss-of-function studies in animal models suggest a protective effect against chronic hypoxia, in which heterozygous knockout mice (Epas1+/−) exhibit lower [Hb] and reduced risk of pulmonary hypertension and right ventricular hypertrophy relative to wild-type mice following exposure to sustained hypoxia (54). Here, EPAS1 is linked to Right ventricular hypertrophy.