In-silico Pathogenicity Assays for p. Arg-۱۶۶Gln Missense Mutation (rs۱۰۶۰۴۹۹۶۱۶) in the HumanRUNX۱ Gene Involved in Acute Myeloid Leukemia (AML)

Background: Acute myeloid leukemia (AML) is one type ofblood cancer. It is characterized by the clonal expansion of immatureblast cells in the peripheral blood and bone marrow,resulting in ineffective erythropoiesis and bone marrow failure.Several genes are involved in AML. One of these genesis RUNX۱. RUNX۱ is located at chromosome ۲۱q۲۲.۱۲. Itsprotein is Runt-related transcription factor۱ which contains ۴۸۰amino acids. A runt-related transcription factor is an essentialcomponent of hematopoiesis. It is also known as core-bindingfactor subunit alpha-۲ (CBFA۲) and binds to enhancers andpromoters. Any nucleotide changes in this gene are associated with several types of leukemia.Materials and Methods: In this study, we have evaluated amissense variation c. ۴۹۷G>A (p. Arg۱۶۶Gln; rs۱۰۶۰۴۹۹۶۱۶)in RUNX۱ gene. The rs۱۰۶۰۴۹۹۶۱۶ affected the protein functionwith a score of ۰.۰۰۰ by the SIFT and was predicted to beprobably damaging with a score of ۱.۰۰۰ by the PolyPhen-۲programs. This variation is reported as a disease caused by MutationTaster and in Clinvar it has been reported as pathogenic.The score of variation R۱۶۶Q by Panther was reported as ۰.۹۱۷,and for PHD-SNP it is ۰.۸۷۴. The score obtained by SNAP is۰.۸۳۵ and by Meta-SNP is ۰.۸۸۳. We evaluated this missensevariation in PredictSNP and our results showed pathogenicityscores for ۷۵% MAPP, ۸۶% PHD-SNP, ۷۴% PolyPhen-۱, ۸۱%PolyPhen-۲, ۷۹% SIFT, and ۸۹% SNAP. Eigen score for codingSNV that report in varsome is ۰.۹۳۹۷. Hydrophobicity of proteinwas measured by PEPTIDE.۲ and the number that showedwas ۴۲.۵%. The hydrophobicity value for arginine is -۴.۵۰۰ andfor glutamine, it is -۳.۵۰۰.Results: According to this study, rs۱۰۶۰۴۹۹۶۱۶ might havepathogenic effects on the RUNX۱ protein. This theory shouldbe proved with experimental studies because the score of pathogenicityof this SNP is very high.