Screening based on sequencing data after HIF2a knockdown and three independent mitochondrial metabolism‐related gene sets showed that nicotinamide nucleotide transhydrogenase (NNT) was a mediator between HIF2a and tumor cells “slimming.” Further research showed that NNT had significant prognostic predictive value and was downregulated in ccRCC. Here, EPAS1 is linked to neoplasm.