VHL and neoplasm: Germline and somatic mutations in major susceptibility genes associated with hypoxia signaling involved in the PCC development, include the tumor suppressors such as VHL1, the SDH complex (genes encoding the four subunits, A,B,C,D) and occasionally, the egl-9 family hypoxia-inducible factor 1/Prolyl hydroxylase domain 2 protein (EGLN1/PHD2) (62, 63).