Insilico prediction and functional analysis of nonsynonymous SNPs in human CTLA4 gene
Abstract The CTLA4 receptor is an immune checkpoint involved in the downregulation of T cells. Polymorphisms in this gene have been found to be associated with different diseases like rheumatoid arthritis, autosomal dominant immune dysregulation syndrome, juvenile idiopathic arthritis and autoimmune...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-24699-0 |
| _version_ | 1828123362469085184 |
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| author | Muhammad Irfan Talha Iqbal Sakina Hashmi Uzma Ghani Attya Bhatti |
| author_facet | Muhammad Irfan Talha Iqbal Sakina Hashmi Uzma Ghani Attya Bhatti |
| author_sort | Muhammad Irfan |
| collection | DOAJ |
| description | Abstract The CTLA4 receptor is an immune checkpoint involved in the downregulation of T cells. Polymorphisms in this gene have been found to be associated with different diseases like rheumatoid arthritis, autosomal dominant immune dysregulation syndrome, juvenile idiopathic arthritis and autoimmune Addison's disease. Therefore, the identification of polymorphisms that have an effect on the structure and function of CTLA4 gene is important. Here we identified the most damaging missense or non-synonymous SNPs (nsSNPs) that might be crucial for the structure and function of CTLA4 using different bioinformatics tools. These in silico tools included SIFT, PROVEAN, PhD-SNP, PolyPhen-2 followed by MutPred2, I-Mutant 2.0 and ConSurf. The protein structures were predicted using Phyre2 and I-TASSER, while the gene–gene interactions were predicted by GeneMANIA and STRING. Our study identified three damaging missense SNPs rs1553657429, rs1559591863 and rs778534474 in coding region of CTLA4 gene. Among these SNPs the rs1553657429 showed a loss of potential phosphorylation site and was found to be highly conserved. The prediction of gene–gene interaction showed the interaction of CTlA4 with other genes and its importance in different pathways. This investigation of damaging nsSNPs can be considered in future while studying CTLA4 related diseases and can be of great importance in precision medicine. |
| first_indexed | 2024-04-11T14:50:24Z |
| format | Article |
| id | doaj.art-27841c52068c4b6295afab257fbcf5e0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T14:50:24Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-27841c52068c4b6295afab257fbcf5e02022-12-22T04:17:28ZengNature PortfolioScientific Reports2045-23222022-11-0112111110.1038/s41598-022-24699-0Insilico prediction and functional analysis of nonsynonymous SNPs in human CTLA4 geneMuhammad Irfan0Talha Iqbal1Sakina Hashmi2Uzma Ghani3Attya Bhatti4Healthcare Biotechnology, National University of Science and TechnologyHealthcare Biotechnology, National University of Science and TechnologyHealthcare Biotechnology, National University of Science and TechnologyHealthcare Biotechnology, National University of Science and TechnologyHealthcare Biotechnology, National University of Science and TechnologyAbstract The CTLA4 receptor is an immune checkpoint involved in the downregulation of T cells. Polymorphisms in this gene have been found to be associated with different diseases like rheumatoid arthritis, autosomal dominant immune dysregulation syndrome, juvenile idiopathic arthritis and autoimmune Addison's disease. Therefore, the identification of polymorphisms that have an effect on the structure and function of CTLA4 gene is important. Here we identified the most damaging missense or non-synonymous SNPs (nsSNPs) that might be crucial for the structure and function of CTLA4 using different bioinformatics tools. These in silico tools included SIFT, PROVEAN, PhD-SNP, PolyPhen-2 followed by MutPred2, I-Mutant 2.0 and ConSurf. The protein structures were predicted using Phyre2 and I-TASSER, while the gene–gene interactions were predicted by GeneMANIA and STRING. Our study identified three damaging missense SNPs rs1553657429, rs1559591863 and rs778534474 in coding region of CTLA4 gene. Among these SNPs the rs1553657429 showed a loss of potential phosphorylation site and was found to be highly conserved. The prediction of gene–gene interaction showed the interaction of CTlA4 with other genes and its importance in different pathways. This investigation of damaging nsSNPs can be considered in future while studying CTLA4 related diseases and can be of great importance in precision medicine.https://doi.org/10.1038/s41598-022-24699-0 |
| spellingShingle | Muhammad Irfan Talha Iqbal Sakina Hashmi Uzma Ghani Attya Bhatti Insilico prediction and functional analysis of nonsynonymous SNPs in human CTLA4 gene Scientific Reports |
| title | Insilico prediction and functional analysis of nonsynonymous SNPs in human CTLA4 gene |
| title_full | Insilico prediction and functional analysis of nonsynonymous SNPs in human CTLA4 gene |
| title_fullStr | Insilico prediction and functional analysis of nonsynonymous SNPs in human CTLA4 gene |
| title_full_unstemmed | Insilico prediction and functional analysis of nonsynonymous SNPs in human CTLA4 gene |
| title_short | Insilico prediction and functional analysis of nonsynonymous SNPs in human CTLA4 gene |
| title_sort | insilico prediction and functional analysis of nonsynonymous snps in human ctla4 gene |
| url | https://doi.org/10.1038/s41598-022-24699-0 |
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