Three missense mutants (V155A, L158Q, and Q164R) sustained E3 ligase activity as indicated by their ability for the VBC complex and degrade HIF-2 α thereby decreased the expression VEGF, Glut-1 and Epo, which are target genes of HIF-2α [40] which promotes tumor cell growth, invasion and regulates glucose metabolism [41]. The gene discussed is EPAS1; the disease is neoplasm.