Bioinformatics Prediction of rs۱۴۸۹۴۸۰۸۷۳Pathogenicity in TAL۱ Gene which is Associated with AcuteLymphoblastic Leukemia (ALL)

Introduction: Acute lymphoblastic leukemia (ALL) is themost common childhood cancer, and despite cure rates exceeding۹۰% in children, it remains an important cause of morbidityand mortality in children and adults. TAL۱ is one of the mostfrequently deregulated oncogenes in T-cell acute lymphoblasticleukemia (T-ALL). Its deregulation can occur through diverseCis-alterations, including SIL-TAL۱ micro-deletions, translocationswith T cell Receptor (TCR) loci and, more recently describedupstream intergenic non-coding mutations. These mutationsconsist of recurrent focal micro insertions that create anoncogenic neo-enhancer accompanied by activating epigeneticmarks. The structure of TAL۱ is helix-loop-helix and its geneis positioned on ۱p۳۳. Our purpose is the evaluation the pathogenicityeffect of a missense mutation (rs۱۴۸۹۴۸۰۸۷۳) in ALL.This mutation causes the arginine amino acid at position ۱۸۹to change to proline. This assessment has been analyzed usingseveral bioinformatics tools such as polyphen-۲, I-Mutant ۲.۰,and SIFT.Methods: PolyPhen-۲ is a web-based tool that predicts the impactof amino acid substitutions on protein structure and functionbased on multiple sequence alignments of ۳D protein structures.I-Mutant can evaluate the stability change upon singlesite mutation starting from the protein structure or the proteinsequence. This tool correctly predicts whether the protein mutationstabilizes or destabilizes the protein. The SIFT tool predictswhether an amino acid substitution affects protein functionbased on the sequence.Results: Polyphen-۲ analysis indicated that this mutation(rs۱۴۸۹۴۸۰۸۷۳) was likely deleterious and probably damagingwith a PSIC index score of ۱,۰۰۰. I-Mutant proved thatrs۱۴۸۹۴۸۰۸۷۳ missense mutation will increase the stability ofthe TAL۱. The rs۴۸۹۴۸۰۸۷۳ affected the protein function witha score of ۰.۰ by the SIFT.Conclusion: According to this consideration, rs۱۴۸۹۴۸۰۸۷۳might have pathogenic effects on the Tal۱ protein. This theoryshould be proved with experimental studies because the score of pathogenicity of this SNP is very high