Von Hippel-Lindau Syndrome

A 32-year-old man presents with progressive occipital headaches, gait ataxia, and vertigo. Fundoscopy reveals bilateral retinal hemangioblastomas. MRI brain shows a cystic posterior fossa lesion with an enhancing mural nodule. Abdominal imaging demonstrates multiple bilateral renal cysts and a solid enhancing renal mass. Laboratory studies show hemoglobin 19.2 g/dL with elevated 24-hour urine metanephrines, and MIBG scan localizes an occult adrenal pheochromocytoma. Genetic testing confirms a heterozygous pathogenic variant at the locus marked **A** in the diagram. Which of the following best describes the molecular consequence of biallelic loss of the VHL tumor suppressor gene at this locus?