HIF1A and von Hippel-Lindau disease: In VHL disease, the loss of function in the VCB-CR complex prevents its binding to the ubiquitous unstable subunit HIF1α, which subsequently heterodimerizes with the stable HIF1β to form HIF1, which translocates to the nucleus and acts as a transcription factor binding the hypoxia-response elements, leading to the constitutive activation of expressed downstream effectors that would physiologically be activated only in hypoxic conditions.