In-silico analysis of BCL2 gene using multiple bioinformatics tools to identify the most lethal mutations that are crucial for its structural and functional integrity

Abstract

BCL2 was the first ever known gene for anti-apoptotic activity, that encodes for essential proteins of the external mitochondrial membrane. Regarding tumorigenesis, deregulated BCL2 expression and related proteins have been recognized as characteristic of several human cancers and there is concrete evidence that the deregulated expression of BCL2 like proteins plays a vital role in tumor development, persistence and therapeutic resistance. Therefore, it is important to identify the polymorphisms of BCL2 that are both structurally and functionally important for research to find their possible malfunctions and therapeutics. For this reason, in our research, we have used a variety of bioinformatics tools to recognize the most destructive nsSNPs that may be important for the structure and function of BCL2. In silico tools, PROVEAN, SIFT, SNP&GO, PhD SNP, and PolyPhen2 included a variety of other tools such as I Mutant, MutPred, and ConSurf, to study their conservation profiles to validate their stability, structural, and functional impacts. Post-transcriptional alteration sites were also predicted followed by application of 3-D mapping with I-TASSER and Phyre2 tools. Furthermore, the gene interactions were mapped via STRING and GeneMANIA. We also found that nsSNPs Q118R (rs759928495), G193R (rs1197820694), R129C (rs777784952), and Ll81V (rs752310933) are the most destructive nsSNPs in BCL2 genes that can have a vital part in BCL2 protein defects and possibly cause different cancers. Gene-gene interactions showed relation of BCL2 with other genes depicting its importance in several pathways and co-expressions. This research is the first of its kind and offers future prospects for the development of dedicated medicines as well. In the animal models, the effects of BCL2 can also be tested in diseases. Such should be the study of BCL2 proteins from cancer patients. The effects of BCL2 can also be tested on animal models.