In silico analysis and high-risk pathogenic phenotype predictions of non-synonymous single nucleotide polymorphisms in human Crystallin beta A4 gene associated with congenital cataract
In order to provide a cost-effective method to narrow down the number of pathogenic Crystallin beta A4 (CRYBA4) non-synonymous single nucleotide polymorphisms (nsSNPs), we collected nsSNP information of the CRYBA4 gene from SNP databases and literature, predicting the pathogenicity and possible changes of protein properties and structures using multiple bioinformatics tools. The nsSNP data of the CRYBA4 gene were collected from 4 databases and published literature. According to 12 criteria, six bioinformatics tools were chosen to predict the pathogenicity. I-Mutant 2.0, Mupro and INPS online tools were used to analyze the effects of amino acid substitution on protein stability by calculating the value of Delta Delta G. ConSurf, SOPMA, GETAREA and HOPE online tools were used to predict the evolutionary conservation of amino acids, solvent accessible surface areas, and the physical and chemical properties and changes of protein structure. All 157 CRYBA4 nsSNPs were analyzed. Forty-four CRYBA4 high-risk pathogenic nsSNPs (predicted to be pathogenic by all six software tools) were detected out of the 157 CRYBA4 nsSNPs, four of which (c.283C>T, p.R95W; c.449T>A, p.V150D; c.475G>A, p.G159R; c.575G>C, p.R192P) should be focused on because of their high potential pathogenicity and possibility of changing protein properties. Thirty high-risk nsSNPs were predicted to cause a decrease of protein stability. Twenty-nine high-risk nsSNPs occurred in evolutionary conserved positions. Twenty-two high-risk nsSNPs occurred in the core of the protein. It is predicted that these high-risk pathogenic nsSNPs can cause changes in the physical and chemical properties of amino acids, resulting in structural changes of proteins and changes in the interactions between domains and other molecules, thus affecting the function of proteins. This study provides important reference value when narrowing down the number of pathogenic CRYBA4 nsSNPs and studying the pathogenesis of congenital cataracts. By using this method, we can easily find 44 high-risk pathogenic nsSNPs out of 157 CRYBA4 nsSNPs.
基金：
National Science and Technology Major Project [2018ZX10101004]
基金编号：2018ZX10101004
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|3 区综合性期刊
小类|3 区综合性期刊
最新[2025]版：
大类|3 区综合性期刊
小类|3 区综合性期刊
第一作者：
第一作者机构：[1]Peking Univ, Hosp 3, Dept Ophthalmol, Beijing, Peoples R China[2]Peking Univ, Hosp 3, Beijing Key Lab Restorat Damaged Ocular Nerve, Beijing, Peoples R China
通讯作者：
通讯机构：[1]Peking Univ, Hosp 3, Dept Ophthalmol, Beijing, Peoples R China[*1]Peking Univ, Hosp 3, Dept Ophthalmol, Beijing, Peoples R China[2]Peking Univ, Hosp 3, Beijing Key Lab Restorat Damaged Ocular Nerve, Beijing, Peoples R China[*2]Peking Univ, Hosp 3, Beijing Key Lab Restorat Damaged Ocular Nerve, Beijing, Peoples R China
推荐引用方式(GB/T 7714)：
Wang Zhenyu,Huang Chen,Lv Huibin,et al.In silico analysis and high-risk pathogenic phenotype predictions of non-synonymous single nucleotide polymorphisms in human Crystallin beta A4 gene associated with congenital cataract[J].PLOS ONE.2020,15(1):e0227859.doi:10.1371/journal.pone.0227859.
APA：
Wang, Zhenyu,Huang, Chen,Lv, Huibin,Zhang, Mingzhou&Li, Xuemin.(2020).In silico analysis and high-risk pathogenic phenotype predictions of non-synonymous single nucleotide polymorphisms in human Crystallin beta A4 gene associated with congenital cataract.PLOS ONE,15,(1)
MLA：
Wang, Zhenyu,et al."In silico analysis and high-risk pathogenic phenotype predictions of non-synonymous single nucleotide polymorphisms in human Crystallin beta A4 gene associated with congenital cataract".PLOS ONE 15..1(2020)
