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In Silico Analysis Identified Putative Pathogenic Missense nsSNPs in Human SLITRK1 Gene
Human DNA contains several variations, which can affect the structure and normal functioning of a protein. These variations could be single nucleotide polymorphisms (SNPs) or insertion-deletions (InDels). SNPs, as opposed to InDels, are more commonly present in DNA and may cause genetic disorders. I...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030497/ https://www.ncbi.nlm.nih.gov/pubmed/35456478 http://dx.doi.org/10.3390/genes13040672 |
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author | Ali, Muhammad Zeeshan Farid, Arshad Ahmad, Safeer Muzammal, Muhammad Mohaini, Mohammed Al Alsalman, Abdulkhaliq J. Al Hawaj, Maitham A. Alhashem, Yousef N. Alsaleh, Abdulmonem A. Almusalami, Eman M. Maryam, Mahpara Khan, Muzammil Ahmad |
author_facet | Ali, Muhammad Zeeshan Farid, Arshad Ahmad, Safeer Muzammal, Muhammad Mohaini, Mohammed Al Alsalman, Abdulkhaliq J. Al Hawaj, Maitham A. Alhashem, Yousef N. Alsaleh, Abdulmonem A. Almusalami, Eman M. Maryam, Mahpara Khan, Muzammil Ahmad |
author_sort | Ali, Muhammad Zeeshan |
collection | PubMed |
description | Human DNA contains several variations, which can affect the structure and normal functioning of a protein. These variations could be single nucleotide polymorphisms (SNPs) or insertion-deletions (InDels). SNPs, as opposed to InDels, are more commonly present in DNA and may cause genetic disorders. In the current study, several bioinformatic tools were used to prioritize the pathogenic variants in the SLITRK1 gene. Out of all of the variants, 16 were commonly predicted to be pathogenic by these tools. All the variants had very low frequency, i.e., <0.0001 in the global population. The secondary structure of all filtered variants was predicted, but no structural change was observed at the site of variation in any variant. Protein stability analysis of these variants was then performed, which determined a decrease in protein stability of 10 of the variants. Amino acid conservation analysis revealed that all the amino acids were highly conserved, indicating their structural and functional importance. Protein 3D structure of wildtype SLITRK1 and all of its variants was predicted using I-TASSER, and the effect of variation on 3D structure of the protein was observed using the Missense3D tool, which presented the probable structural loss in three variants, i.e., Asn529Lys, Leu496Pro and Leu94Phe. The wildtype SLITRK1 protein and these three variants were independently docked with their close interactor protein PTPRD, and remarkable differences were observed in the docking sites of normal and variants, which will ultimately affect the functional activity of the SLITRK1 protein. Previous studies have shown that mutations in SLITRK1 are involved in Tourette syndrome. The present study may assist a molecular geneticist in interpreting the variant pathogenicity in research as well as diagnostic setup. |
format | Online Article Text |
id | pubmed-9030497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90304972022-04-23 In Silico Analysis Identified Putative Pathogenic Missense nsSNPs in Human SLITRK1 Gene Ali, Muhammad Zeeshan Farid, Arshad Ahmad, Safeer Muzammal, Muhammad Mohaini, Mohammed Al Alsalman, Abdulkhaliq J. Al Hawaj, Maitham A. Alhashem, Yousef N. Alsaleh, Abdulmonem A. Almusalami, Eman M. Maryam, Mahpara Khan, Muzammil Ahmad Genes (Basel) Article Human DNA contains several variations, which can affect the structure and normal functioning of a protein. These variations could be single nucleotide polymorphisms (SNPs) or insertion-deletions (InDels). SNPs, as opposed to InDels, are more commonly present in DNA and may cause genetic disorders. In the current study, several bioinformatic tools were used to prioritize the pathogenic variants in the SLITRK1 gene. Out of all of the variants, 16 were commonly predicted to be pathogenic by these tools. All the variants had very low frequency, i.e., <0.0001 in the global population. The secondary structure of all filtered variants was predicted, but no structural change was observed at the site of variation in any variant. Protein stability analysis of these variants was then performed, which determined a decrease in protein stability of 10 of the variants. Amino acid conservation analysis revealed that all the amino acids were highly conserved, indicating their structural and functional importance. Protein 3D structure of wildtype SLITRK1 and all of its variants was predicted using I-TASSER, and the effect of variation on 3D structure of the protein was observed using the Missense3D tool, which presented the probable structural loss in three variants, i.e., Asn529Lys, Leu496Pro and Leu94Phe. The wildtype SLITRK1 protein and these three variants were independently docked with their close interactor protein PTPRD, and remarkable differences were observed in the docking sites of normal and variants, which will ultimately affect the functional activity of the SLITRK1 protein. Previous studies have shown that mutations in SLITRK1 are involved in Tourette syndrome. The present study may assist a molecular geneticist in interpreting the variant pathogenicity in research as well as diagnostic setup. MDPI 2022-04-11 /pmc/articles/PMC9030497/ /pubmed/35456478 http://dx.doi.org/10.3390/genes13040672 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ali, Muhammad Zeeshan Farid, Arshad Ahmad, Safeer Muzammal, Muhammad Mohaini, Mohammed Al Alsalman, Abdulkhaliq J. Al Hawaj, Maitham A. Alhashem, Yousef N. Alsaleh, Abdulmonem A. Almusalami, Eman M. Maryam, Mahpara Khan, Muzammil Ahmad In Silico Analysis Identified Putative Pathogenic Missense nsSNPs in Human SLITRK1 Gene |
title | In Silico Analysis Identified Putative Pathogenic Missense nsSNPs in Human SLITRK1 Gene |
title_full | In Silico Analysis Identified Putative Pathogenic Missense nsSNPs in Human SLITRK1 Gene |
title_fullStr | In Silico Analysis Identified Putative Pathogenic Missense nsSNPs in Human SLITRK1 Gene |
title_full_unstemmed | In Silico Analysis Identified Putative Pathogenic Missense nsSNPs in Human SLITRK1 Gene |
title_short | In Silico Analysis Identified Putative Pathogenic Missense nsSNPs in Human SLITRK1 Gene |
title_sort | in silico analysis identified putative pathogenic missense nssnps in human slitrk1 gene |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030497/ https://www.ncbi.nlm.nih.gov/pubmed/35456478 http://dx.doi.org/10.3390/genes13040672 |
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