The VHL HIF1α inactivator and tumour suppressor also exhibits hypoxia-regulated alternative splicing, characterized by inactivating mutations in the cryptic exon (E1) deep in intron 1 that promotes excessive E1 retention and VHL protein repression, within the context of pre-neoplastic von Hippel Landau disease, leading to aberrant HIF activation (Fig. 3a) [149]. This evidence concerns the gene VHL and neoplasm.