In silico SNP Analysis and 3D Structure Prediction of Human ERG Proto-Oncogene

Single-nucleotide polymorphisms (SNPs) are the major source of attraction for researchers as they significantly contribute to an individual's susceptibility to various diseases, as well as provide an insight into new diseases associated with a particular gene.

In this study, the data were retrieved from dbSNP till July 2021. DbSNP showed 103738 total SNPs in the human ERG gene, and out of them, 377 missense SNPs were selected for analysis. Twenty-six missense SNPs were found to be deleterious in all five SNP tools (SIFT, PolyPhen-2, Condel, PHD-SNP, SNPs&GO). These 26 SNPs were further checked for protein stability by iStable, I-Mutant, and MuPro. Collectively, 23 SNPs showed to decrease the protein stability. A comparison of the 3D structures of the wild type (predicted by trRosetta) and the mutated type was visualized using the Chimera tool.

Post-translational modifications identified T180, R302, S356, and Y452 as clinically significant sites, as they were involved in phosphorylation and methylation.

In this study, in silico SNP analysis was performed on the human ERG gene. ERG's involvement in various types of diseases, as well as cancer, has made it a source of interest. It is an oncogene that is not only involved in the germ line differentiation of hemo-poietic stem cells, but is also involved in cell proliferation, embryonic development, angiogenesis, inflammation, and apoptosis.

This study has provided detailed information on missense SNPs of the ERG gene. This work can be significant in the detection of genetic diseases and drug discovery, as it has shown involvement of the ERG gene.