Oncogenes and tumor suppressor genes play a key role in cancer induction and progression. Theydirectly or indirectly regulate critical metabolic pathways, phosphatidylinositol‐3 kinase pathwaybeing frequently activated pathway in cancer. The catalytic subunit of phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K), p110α, is the most frequently mutated kinase in human cancer, E542K,E545K, and H1047R mutations being the most common. Expression of hepatic E545K and H1047Rp110α mutants in vivo shows marked and rapid increase in hepatic lipid and glycogen accumulationin mice with developmental (chronic) liver‐specific deletion of p110α, which was not seen in micewhen wildtype p110α is overexpressed. To investigate the logical pathways that could explain thelipid accumulation in mutant expressing mice, RNA sequencing from wildtype, knockout and mutatedmouse livers was performed. Read alignment and count quantification was done using the Rsubreadpackage and the statistical analyses are performed using the DeSeq2 package. Differentiallyexpressed genes were identified with adjusted p‐value of 0.05. Gene ontology analysis wasperformed on the differentially expressed genes using clusterProfiler, an R package to identifyseveral key pathways which were upregulated and downregulated among the different samplegroups. Signaling pathways related to cell cycle processes were mainly upregulated in the mutatedsamples when compared with the wildtype as well as knockout samples while signaling pathwaysrelated to many metabolic processes seem to be downregulated in mutated samples, even thoughthese mutants showed upregulated metabolism by accumulation of lipids and glycogenphysiologically. To confirm the results of gene expression data the results have to be cross validatedwith the gold standard quantitative Real Time Polymerase Chain Reaction.