In Silico Analysis Revealed Five Novel High-Risk Single-Nucleotide Polymorphisms (rs200384291, rs201163886, rs193141883, rs201139487, and rs201723157) in ELANE Gene Causing Autosomal Dominant Severe Congenital Neutropenia 1 and Cyclic Hematopoiesis
Single-nucleotide polymorphisms in the ELANE (Elastase, Neutrophil Expressed) gene are associated with severe congenital neutropenia, while the ELANE gene provides instructions for making a protein called neutrophil elastase. We identified disease susceptibility single-nucleotide polymorphisms (SNPs...
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| Format: | Article |
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Wiley
2022-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2022/3356835 |
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| author | Khyber Shinwari Mikhail A. Bolkov Muhammad Yasir Akbar Liu Guojun Svetlana S. Deryabina Irina A. Tuzankina Valery. A. Chereshnev |
| author_facet | Khyber Shinwari Mikhail A. Bolkov Muhammad Yasir Akbar Liu Guojun Svetlana S. Deryabina Irina A. Tuzankina Valery. A. Chereshnev |
| author_sort | Khyber Shinwari |
| collection | DOAJ |
| description | Single-nucleotide polymorphisms in the ELANE (Elastase, Neutrophil Expressed) gene are associated with severe congenital neutropenia, while the ELANE gene provides instructions for making a protein called neutrophil elastase. We identified disease susceptibility single-nucleotide polymorphisms (SNPs) in the ELANE gene using several computational tools. We used cutting-edge computational techniques to investigate the effects of ELANE mutations on the sequence and structure of the protein. Our study suggested that eight nsSNPs (rs28931611, rs57246956, rs137854448, rs193141883, rs201723157, rs201139487, rs137854451, and rs200384291) are the most deleterious in ELANE gene and disturb protein structure and function. The mutants F218L, R34W, G203S, R193W, and T175M have not yet been identified in patients suffering from SCN and cyclic hematopoiesis, while C71Y, P139R, C151Y, G214R, and G203C reported in our study are already associated with both of the disorders. These mutations are shown to destabilize structure and disrupt ELANE protein activation, splicing, and folding and might diminish trypsin-like serine protease efficiency. Prediction of posttranslation modifications highlighted the significance of deleterious nsSNPs because some of nsSNPs affect potential phosphorylation sites. Gene-gene interactions showed the relation of ELANE with other genes depicting its importance in numerous pathways and coexpressions. We identified the deleterious nsSNPs, constructed mutant protein structures, and evaluated the impact of mutation by employing molecular docking. This research sheds light on how ELANE failure upon mutation results in disease progression, including congenital neutropenia, and validation of these novel predicted nsSNPs is required through the wet lab. |
| format | Article |
| id | doaj-art-075b1086ec974a19844e82f01ac8d544 |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-075b1086ec974a19844e82f01ac8d5442025-02-03T05:53:49ZengWileyThe Scientific World Journal1537-744X2022-01-01202210.1155/2022/3356835In Silico Analysis Revealed Five Novel High-Risk Single-Nucleotide Polymorphisms (rs200384291, rs201163886, rs193141883, rs201139487, and rs201723157) in ELANE Gene Causing Autosomal Dominant Severe Congenital Neutropenia 1 and Cyclic HematopoiesisKhyber Shinwari0Mikhail A. Bolkov1Muhammad Yasir Akbar2Liu Guojun3Svetlana S. Deryabina4Irina A. Tuzankina5Valery. A. Chereshnev6Institute of Chemical EngineeringInstitute of Chemical EngineeringNational Center for Bioinformatics Quaid-i-Azam University IslamabadSchool of Life Science and TechnologyMedical Center Healthcare of Mother and ChildInstitute of Immunology and Physiology of the Ural Branch of the Russian Academy of SciencesInstitute of Immunology and Physiology of the Ural Branch of the Russian Academy of SciencesSingle-nucleotide polymorphisms in the ELANE (Elastase, Neutrophil Expressed) gene are associated with severe congenital neutropenia, while the ELANE gene provides instructions for making a protein called neutrophil elastase. We identified disease susceptibility single-nucleotide polymorphisms (SNPs) in the ELANE gene using several computational tools. We used cutting-edge computational techniques to investigate the effects of ELANE mutations on the sequence and structure of the protein. Our study suggested that eight nsSNPs (rs28931611, rs57246956, rs137854448, rs193141883, rs201723157, rs201139487, rs137854451, and rs200384291) are the most deleterious in ELANE gene and disturb protein structure and function. The mutants F218L, R34W, G203S, R193W, and T175M have not yet been identified in patients suffering from SCN and cyclic hematopoiesis, while C71Y, P139R, C151Y, G214R, and G203C reported in our study are already associated with both of the disorders. These mutations are shown to destabilize structure and disrupt ELANE protein activation, splicing, and folding and might diminish trypsin-like serine protease efficiency. Prediction of posttranslation modifications highlighted the significance of deleterious nsSNPs because some of nsSNPs affect potential phosphorylation sites. Gene-gene interactions showed the relation of ELANE with other genes depicting its importance in numerous pathways and coexpressions. We identified the deleterious nsSNPs, constructed mutant protein structures, and evaluated the impact of mutation by employing molecular docking. This research sheds light on how ELANE failure upon mutation results in disease progression, including congenital neutropenia, and validation of these novel predicted nsSNPs is required through the wet lab.http://dx.doi.org/10.1155/2022/3356835 |
| spellingShingle | Khyber Shinwari Mikhail A. Bolkov Muhammad Yasir Akbar Liu Guojun Svetlana S. Deryabina Irina A. Tuzankina Valery. A. Chereshnev In Silico Analysis Revealed Five Novel High-Risk Single-Nucleotide Polymorphisms (rs200384291, rs201163886, rs193141883, rs201139487, and rs201723157) in ELANE Gene Causing Autosomal Dominant Severe Congenital Neutropenia 1 and Cyclic Hematopoiesis The Scientific World Journal |
| title | In Silico Analysis Revealed Five Novel High-Risk Single-Nucleotide Polymorphisms (rs200384291, rs201163886, rs193141883, rs201139487, and rs201723157) in ELANE Gene Causing Autosomal Dominant Severe Congenital Neutropenia 1 and Cyclic Hematopoiesis |
| title_full | In Silico Analysis Revealed Five Novel High-Risk Single-Nucleotide Polymorphisms (rs200384291, rs201163886, rs193141883, rs201139487, and rs201723157) in ELANE Gene Causing Autosomal Dominant Severe Congenital Neutropenia 1 and Cyclic Hematopoiesis |
| title_fullStr | In Silico Analysis Revealed Five Novel High-Risk Single-Nucleotide Polymorphisms (rs200384291, rs201163886, rs193141883, rs201139487, and rs201723157) in ELANE Gene Causing Autosomal Dominant Severe Congenital Neutropenia 1 and Cyclic Hematopoiesis |
| title_full_unstemmed | In Silico Analysis Revealed Five Novel High-Risk Single-Nucleotide Polymorphisms (rs200384291, rs201163886, rs193141883, rs201139487, and rs201723157) in ELANE Gene Causing Autosomal Dominant Severe Congenital Neutropenia 1 and Cyclic Hematopoiesis |
| title_short | In Silico Analysis Revealed Five Novel High-Risk Single-Nucleotide Polymorphisms (rs200384291, rs201163886, rs193141883, rs201139487, and rs201723157) in ELANE Gene Causing Autosomal Dominant Severe Congenital Neutropenia 1 and Cyclic Hematopoiesis |
| title_sort | in silico analysis revealed five novel high risk single nucleotide polymorphisms rs200384291 rs201163886 rs193141883 rs201139487 and rs201723157 in elane gene causing autosomal dominant severe congenital neutropenia 1 and cyclic hematopoiesis |
| url | http://dx.doi.org/10.1155/2022/3356835 |
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