First ComprehensiveIn SilicoAnalysis of the Functional and Structural Consequences of SNPs in HumanGalNAc-T1Gene

Abstract

GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-typeO-linked glycosylation pathway, is expressed in most biological tissues and cell types. Despite the reported association ofGalNAc-T1gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs ofGalNAc-T1gene in order to identify and characterize them. Our concordantin silicoanalysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs ofGalNAc-T1. Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified inGalNAc-T1by using FastSNP tool. Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function ofGalNAc-T1enzyme. These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases.