Identification of functional SNPs in PAX3 gene and in silico analysis of damaging SNPs in relation to neural tube defect

Abstract

Introduction: PAX3 gene belongs to the class of transcription factor and has a significant role in neural tube development. There are a number of SNP which are associated with neural tube defect. Hence, we must sort functional SNP for a population study. To fulfill this goal data from dbSNP and literature review can be used. Methods: In this study we analyzed the functional and structural impact of SNPs through computational prediction tool. A total of 8947 SNPs were observed from dbSNP in which SNP associated with neural tube defect having missense mutation is rs2234675. This nsSNP was found to be damaging by sequence homology based tool (Provean) and structural homology based tool (Polyphen). Modeling of wild and mutant protein structure were done using RMSD of wild and mutant protein structure were determined using Swiss PDB viewer and then the protein structure stability was determined using I-mutant 3. Results: The nsSNP present in dbSNP i.e., rs2234675 was identified as deleterious, which lead too decrease in stability of PAX3 protein. Discussion: A change of Thr315Lys, i.e. from polar neutral amino acid to polar basic amino acid showed a change in charge to positive and size of amino acid lead to change in structure. The modeled structure further, showed a decrease in stability. The result obtained from insilico study would open new prospect for association of PAX3 with neural tube defect. © 2015 Anatomical Society of India.