Although, disruption of ACO1 has not been linked to Mendelian condition in humans, our data are consistent with Aco1 homozygous knockout mice that show symptoms of polycythemia and pulmonary hypertension, suggested to be caused by translational derepression of HIF2α (EPAS1) and subsequent elevation of serum EPO levels from the kidney and endothelin-1 levels from pulmonary endothelial cells21,22. Here, EPAS1 is linked to pulmonary arterial hypertension.