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In-silico analysis of phylogenetic relationship and potentially damaging nsSNPs in human SLC2A2 gene
Journal of King Saud University-Science ( IF 3.7 ) Pub Date : 2021-06-29 , DOI: 10.1016/j.jksus.2021.101529
Tehmina Fiayyaz , Mamoona Noreen , Naureen Ehsan Ilahi , Farkhanda Zaib , Afrah Fahad Alkhuriji , Suliman Yousef Alomar

Transport of glucose across the eukaryotic cell membranes is carried out by members of the glucose transporter (GLUT) family which is mainly divided into three classes (I, II and III) on the basis of phylogenetic relationship. In humans, one member of Class I called GLUT2 is encoded by solute carrier family 2, facilitated glucose transporter member 2 (SLC2A2) gene located on third chromosome. Protein mediated glucose movement across cell membranes is made possible through GLUT2 that is a trans-membrane carrier protein. It regulates the entry of glucose and secretion of insulin in the pancreatic cell. It has three isoforms and the longest isoform consists of 524 amino acid. There are 13 extracellular, 12 transmembrane and 5 cytoplasmic domains in human GLUT2. The risk of Fanconi-Bickel syndrome (FBS), diabetes, breast cancer (BC) and Alzheimer disease (AD) is associated with improper functioning of GLUT2. The most frequent form of genetic changes is single nucleotide polymorphism (SNPs). Non synonymous SNPs (nsSNPs) can result in alterations of amino acids and subsequent changes in phenotype. In this study, in-silico analysis was done to find phylogenetic relationship of human GLUT2 protein and possible deleterious effect of nsSNPs of its coding region. Clustal Omega was used to make phylogenetic tree. SIFT, PolyPhen, PROVEAN and SNPeffect were used to predict deleterious or tolerated SNPs. 167 nsSNPs were predicted to be damaging by SIFT, 65 to be possibly damaging and 77 to be probably damaging by PolyPhen. PROVEAN predicted 162 nsSNPs to be neutral and 138 to be deleterious. 101 SNPs were found to be damaging by three algorithms; SIFT, PolyPhen and PROVEAN.



中文翻译:

人类 SLC2A2 基因系统发育关系和潜在破坏性 nsSNP 的计算机内分析

葡萄糖跨真核细胞膜的转运是由葡萄糖转运蛋白 (GLUT) 家族的成员进行的,葡萄糖转运蛋白家族根据系统发育关系主要分为三类(I、II 和 III)。在人类中,称为 GLUT2 的 I 类成员由溶质载体家族 2 编码,即位于第三条染色体上的促进葡萄糖转运蛋白成员 2 (SLC2A2) 基因。蛋白介导的 葡萄糖 整个运动 细胞膜通过GLUT2这是一个成为可能-membrane载体  蛋白质。它调节胰腺细胞中葡萄糖的进入和胰岛素的分泌。它具有三个同种型,最长的同种型由 524 个氨基酸组成。在人类 GLUT2 中有 13 个细胞外结构域、12 个跨膜结构域和 5 个细胞质结构域。Fanconi-Bickel 综合征 (FBS)、糖尿病、乳腺癌 (BC) 和阿尔茨海默病 (AD) 的风险与 GLUT2 的功能不当有关。最常见的遗传变化形式是单核苷酸多态性 (SNP)。非同义 SNP (nsSNP) 可导致氨基酸的改变和随后的表型变化。在这项研究中,在硅进行分析以发现人类 GLUT2 蛋白的系统发育关系及其编码区 nsSNP 的可能有害影响。Clustal Omega被用来制作系统发育树。SIFT、PolyPhen、PROVEAN 和 SNPeffect 用于预测有害或耐受的 SNP。167 个 nsSNP 被 SIFT 预测为具有破坏性,65 个可能具有破坏性,77 个可能被 PolyPhen 破坏。PROVEAN 预测 162 个 nsSNP 是中性的,138 个是有害的。三种算法发现 101 个 SNP 具有破坏性;SIFT、PolyPhen 和 PROVEAN。

更新日期:2021-08-23
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