In Silico Post Translational Analysis of Functional Single Nucleotide Alterations in Human TERT Gene Associated with Acute Myeloid Leukemia

Acute myeloid leukemia (AML) refers to a diverse assemblage of hematological malignancies that constitute clonal expansion of immature myeloid progenitor cells in the peripheral blood and bone marrow. TERT gene ensures telomeres maintenance, chromosome stability and prevention of malignancy. The TERT gene has several single nucleotide polymorphisms (SNPs) that have been linked to a number of diseases, including AML. Objective: To classify the harmful TERT gene mutations, and to analyze them using various computational approaches at structural, functional and translational expression levels Methods: National Centre for Biotechnology Information (NCBI) database was used to retrieve nsSNPs of TERT gene (Q53H, V170M, A184T, S255Y, A288V, H412Y, I540M, R631W) reported in AML and they were analyzed using various bioinformatics tools. Results: In this in silico analysis, it was observed that seven out of eight SNPs had a damaging effect; they could affect the protein stability, protein-protein interactions, hydrophobicity, protein folding, three-dimensional structure, secondary structure and conservation profile. 3D models were generated and validated by various tools and the structural effect of these alterations was observed on protein function that was destabilizing to the RNA folding, protein-protein interactions and other functionally associated proteins. Analysis of post translational modifications showed no significant effect of these mutations. Conclusions: These SNPs could be used in future as potential targets in disease diagnosis, biological markers and protein studies.