Donya Ghazi - Department of Biology, Faculty of science, Yazd University, Yazd, Iran.
Mehri khatami - Department of Biology, Faculty of science, Yazd University, Yazd, Iran.
Mohammad Mehdi Heidari - Department of Biology, Faculty of science, Yazd University, Yazd, Iran.

Introduction: NKX2-6 gene encodes a homeobox-containing protein that belongs to the NK-2 homeobox family. This gene plays critical roles in regulating tissue-specific gene expression, as well as determining the temporal and spatial patterns of heart development. Several SNPs in the NKX2.6 gene have been identified that associated with congenital heart disease. Determining the protein structure is one of the important issues in the field of bioinformatics assays. PyMOL, a cross-platform molecular graphics tool, has been widely used for 3-D visualization of proteins. The PolyPhen-2 score predicts the possible impact of an amino acid substitution on the structure and function of a human protein. SIFT is able to distinguish mutations involved in disease from neutral polymorphisms.Method: We identified four non-synonymous single nucleotide polymorphisms in the NKX2.6 gene (rs759945353، rs761239489، rs267606914، rs777859360) using dbSNP and then analyzed their effect on the protein structure using PyMOL software and SIFT and polyphen-2 databases.Results: Our results showed that non-synonymous single nucleotide polymorphisms change the polar groups, and also, number and length of hydrogen bonds. rs777859360 (Leu147Pro), rs759945353 (Thr172Met) and rs761239489 (Arg162Cys) SNPs caused to a hydrogen bond disappearing in protein structure. rs759945353 leads to polar R group into a nonpolar R group conversion. rs761239489 Changes the polar positively charged into a polar uncharged amino acid. Pathogenic rs754763080 (Phe151Leu) SNP changes the length of hydrogen bond.Conclusions: The results of the SNP analysis with the Pymol software and the SIFT and Polyphen-2 database indicate that all four mentioned SNPs can be deleterious and damaging and change the structure of the protein.

NKX2.6, Non-synonymous single nucleotid polymorphisms, Pymol, Polyphen-2,SIFT