In silico analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the human GJA3 gene associated with congenital cataract

BMC Molecular and Cell Biology

article

Zhang, Mingzhou¹  Huang, Chen¹  Wang, Zhenyu¹  Lv, Huibin¹  Li, Xuemin¹ 

[1] Department of Ophthalmology, Peking University Third Hospital;Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital;Medical Research Center, Peking University Third Hospital

关键词: Congenital cataract;    Gap junction protein alpha 3;    GJA3;    Pathogenicity prediction;    Bioinformatics;   

DOI  :  10.1186/s12860-020-00252-7

学科分类：内科医学

来源: Colegio Oficial de Psicologos

【 摘 要 】

Gap junction protein alpha 3 (GJA3), an important pathogenic gene of congenital cataracts, encodes the transmembrane protein connexin46, which functions as an intercellular channel for voltage and chemical gating by forming dodecamers. This study systematically collected nsSNP information for the GJA3 gene from SNP databases and literature and screened for nsSNPs with high risks of pathogenicity. A total of 379 nsSNPs of GJA3 were identified. A total of 88 high-risk pathogenic GJA3 nsSNPs were found, including 31 published nsSNPs associated with congenital cataracts and 57 novel nsSNPs predicted by all eight online tools. The 88 high-risk pathogenic mutations, which are related to 67 amino acids in the wild-type sequences, cause a decrease in protein stability according to I-Mutant 3.0, MUpro and INPS. G2 and R33 were predicted to participate in post-translational modification and ligand binding by ModPred, RaptorX Binding and COACH. Additionally, high-risk mutations were likely to involve highly conserved sites, random coils, alpha helixes, and extracellular loops and were accompanied by changes in amino acid size, charge, hydrophobicity and spatial structure. Eighty-eight high-risk pathogenic nsSNPs of GJA3 were screened out in the study, 57 of which were newly reported. The combination of multiple in silico tools is highly efficient for targeting pathogenic sites.

【 授权许可】

CC BY|CC0