TABLE 1.

Amino acid variants in EPAS1 among species.

Species	Region	Variation in EPAS1	Disease State (if associated)	Predicted effect of variation	References
Human	Andean	H194R			Eichstaedt et al., 2017
	Tibetan	N203H	Patent ductus arteriosus	Decreased transcriptional activity, enhanced interactions with PHD2 and VHL	Pan et al., 2018
		G724W	Ventricular septal defect
	Patients with erythrocytosis	F374Y I533V P534L	Erythrocytosis	Reduction of hydroxylation by PHD2 and decreased recognition by VHL	Gardie et al., 2014
		M535T M535V M535I		Disruption of PHD2 interaction
		G537W G537R D539E F540L		Reduction of hydroxylation by PHD2 and decreased recognition by VHL
Horse	Tibetan	R144C		Gain-of-function, increased affinity for ARNT binding	Liu et al., 2019
		G263D
Dog	Tibetan	G305S		Predicted destabilization of the PAS domain	Gou et al., 2014; Wang et al., 2014
		D494E V500M P750S
Chicken	Tibetan	Y333C*			Li et al., 2017
Hot spring snake	Tibetan	R65H			Li J. T. et al., 2018
Beef cattle	United States	E270Q P362L A671G L701F A606T G610S	Pulmonary hypertension		Heaton et al., 2016
Cashmere goat	Tibetan	Q579L**		Reduction of hydroxylation by PHD2 and decreased recognition by VHL	Song et al., 2016

Variants in bold have been identified in high-altitude adapted studies and correspond to residues mapped on to the crystal structure in Figure 3. *Y333 corresponds to Y342 in humans and mice. **Q579 Corresponds to Q557 in humans.