HIF1A and von Hippel-Lindau disease: In von Hippel–Lindau (VHL) syndrome, mutated VHL breaks its interaction to adaptor protein and inactivates the CRL2 E3 ligase, which leads to the accumulation of HIF1α and promotes angiogenesis, proliferation and cell survival by transactivating many of its target genes involved in regulation of these processes [54, 55].