As HIF-2α regulates mTORC1 activity to promote proliferation, this connection could prove relevant in pathological situations; for example, both somatic and germline EPAS1 gain-of-function mutations have been found in patients with paraganglioma, a catecholamine-secreting tumor of neural crest origin (Lorenzo et al., 2013; Zhuang et al., 2012). This evidence concerns the gene EPAS1 and paraganglioma.