Von Hippel-Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign tumors. A germline mutation of this gene is the basis of familial inheritance of VHL syndrome. The protein encoded by this gene is a component of the protein complex that includes elongin B, elongin C, and cullin-2, and possesses ubiquitin ligase E3 activity. This protein is involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the regulation of gene expression by oxygen. RNA polymerase II subunit POLR2G/RPB7 is also reported to be a target of this protein. Alternatively spliced transcript variants encoding distinct isoforms have been observed.,VHL,HRCA1,RCA1,VHL1,pVHL,PVHL,Epigenetics & Nuclear Signaling,Cancer,Tumor suppressors,Cell Biology & Developmental Biology,Apoptosis,Cell Cycle,Cell cycle inhibitors,Cell differentiation,Ubiquitin,Ubiquitin-Proteasome Signaling Pathway,Endocrine & Metabolism,Immunology & Inflammation,Cardiovascular,Angiogenesis,VHL