The effects of hypoxia on the general splicing machinery, include de-regulation of SRSF1, SRSF2, SRSF3, SAM68, HuR, hnRNPA1, hnRNPM, PRPF40B and RBM4 splice factor expression, activation and increased expression of the SR protein kinases Cdc2-like kinase-1 (CLK1) and SRPK1, that promote SR splice factor hyper-phosphorylation and activity, alter splice factor intracellular localization, and capacity to interact with other proteins and pre-mRNAs, resulting in hypoxia-adapted gene transcription and promotion of tumour progression [58–63]. The gene discussed is CLK1; the disease is neoplasm.