In silico analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the human GJA3 gene associated with congenital cataract
Abstract Background 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 in...
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doaj-c3d46cc6260d4894b865bdee188903822020-11-25T03:03:19ZengBMCBMC Molecular and Cell Biology2661-88502020-03-0121111310.1186/s12860-020-00252-7In silico analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the human GJA3 gene associated with congenital cataractMingzhou Zhang0Chen Huang1Zhenyu Wang2Huibin Lv3Xuemin Li4Department of Ophthalmology, Peking University Third HospitalDepartment of Ophthalmology, Peking University Third HospitalDepartment of Ophthalmology, Peking University Third HospitalDepartment of Ophthalmology, Peking University Third HospitalDepartment of Ophthalmology, Peking University Third HospitalAbstract Background 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s12860-020-00252-7Congenital cataractGap junction protein alpha 3, GJA3Pathogenicity predictionBioinformatics |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mingzhou Zhang Chen Huang Zhenyu Wang Huibin Lv Xuemin Li |
spellingShingle |
Mingzhou Zhang Chen Huang Zhenyu Wang Huibin Lv Xuemin Li In silico analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the human GJA3 gene associated with congenital cataract BMC Molecular and Cell Biology Congenital cataract Gap junction protein alpha 3, GJA3 Pathogenicity prediction Bioinformatics |
author_facet |
Mingzhou Zhang Chen Huang Zhenyu Wang Huibin Lv Xuemin Li |
author_sort |
Mingzhou Zhang |
title |
In silico analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the human GJA3 gene associated with congenital cataract |
title_short |
In silico analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the human GJA3 gene associated with congenital cataract |
title_full |
In silico analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the human GJA3 gene associated with congenital cataract |
title_fullStr |
In silico analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the human GJA3 gene associated with congenital cataract |
title_full_unstemmed |
In silico analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the human GJA3 gene associated with congenital cataract |
title_sort |
in silico analysis of non-synonymous single nucleotide polymorphisms (nssnps) in the human gja3 gene associated with congenital cataract |
publisher |
BMC |
series |
BMC Molecular and Cell Biology |
issn |
2661-8850 |
publishDate |
2020-03-01 |
description |
Abstract Background 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. Results 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. Conclusions 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. |
topic |
Congenital cataract Gap junction protein alpha 3, GJA3 Pathogenicity prediction Bioinformatics |
url |
http://link.springer.com/article/10.1186/s12860-020-00252-7 |
work_keys_str_mv |
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