EPAS1 and neoplasm: This is associated with bi-allelic inactivation of the von Hippel Lindau (VHL) tumour suppressor, which forms part of an E3 ubiquitin ligase complex that targets HIF-α subunits (HIF-1α and HIF-2α; also known as EPAS-1) for proteasomal degradation in the presence of oxygen (9).