An In silico Approach towards Finding the Cancer-Causing Mutations in Human MET Gene
Mesenchymal–epithelial transition (MET) factor is a proto-oncogene encoding tyrosine kinase receptor with hepatocyte growth factor (HGF) or scatter factor (SF). It is found on the human chromosome number 7 and regulates the diverse cellular mechanisms of the human body. The impact of mutations occur...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | International Journal of Genomics |
| Online Access: | http://dx.doi.org/10.1155/2023/9705159 |
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| author | Fayeza Sadia Laskar Md. Nazmul Islam Bappy Md. Sowrov Hossain Zenifer Alam Dilruba Afrin Sudeb Saha Kazi Md. Ali Zinnah |
| author_facet | Fayeza Sadia Laskar Md. Nazmul Islam Bappy Md. Sowrov Hossain Zenifer Alam Dilruba Afrin Sudeb Saha Kazi Md. Ali Zinnah |
| author_sort | Fayeza Sadia Laskar |
| collection | DOAJ |
| description | Mesenchymal–epithelial transition (MET) factor is a proto-oncogene encoding tyrosine kinase receptor with hepatocyte growth factor (HGF) or scatter factor (SF). It is found on the human chromosome number 7 and regulates the diverse cellular mechanisms of the human body. The impact of mutations occurring in the MET gene is demonstrated by their detrimental effects on normal cellular functions. These mutations can change the structure and function of MET leading to different diseases such as lung cancer, neck cancer, colorectal cancer, and many other complex syndromes. Hence, the current study focused on finding deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) and their subsequent impact on the protein’s structure and functions, which may contribute to the emergence of cancers. These nsSNPs were first identified utilizing computational tools like SIFT, PROVEAN, PANTHER-PSEP, PolyPhen-2, I-Mutant 2.0, and MUpro. A total of 45359 SNPs of MET gene were accumulated from the database of dbSNP, and among them, 1306 SNPs were identified as non-synonymous or missense variants. Out of all 1306 nsSNPs, 18 were found to be the most deleterious. Moreover, these nsSNPs exhibited substantial effects on structure, binding affinity with ligand, phylogenetic conservation, secondary structure, and post-translational modification sites of MET, which were evaluated using MutPred2, RaptorX, ConSurf, PSIPRED, and MusiteDeep, respectively. Also, these deleterious nsSNPs were accompanied by changes in properties of MET like residue charge, size, and hydrophobicity. These findings along with the docking results are indicating the potency of the identified SNPs to alter the structure and function of the protein, which may lead to the development of cancers. Nonetheless, Genome-wide association study (GWAS) studies and experimental research are required to confirm the analysis of these nsSNPs. |
| format | Article |
| id | doaj-art-1351bd8d69b442e7abefbda5bb286afb |
| institution | Kabale University |
| issn | 2314-4378 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Genomics |
| spelling | doaj-art-1351bd8d69b442e7abefbda5bb286afb2025-02-03T06:42:44ZengWileyInternational Journal of Genomics2314-43782023-01-01202310.1155/2023/9705159An In silico Approach towards Finding the Cancer-Causing Mutations in Human MET GeneFayeza Sadia Laskar0Md. Nazmul Islam Bappy1Md. Sowrov Hossain2Zenifer Alam3Dilruba Afrin4Sudeb Saha5Kazi Md. Ali Zinnah6Faculty of Biotechnology and Genetic EngineeringFaculty of Biotechnology and Genetic EngineeringFaculty of Biotechnology and Genetic EngineeringFaculty of Biotechnology and Genetic EngineeringFaculty of Biotechnology and Genetic EngineeringFaculty of VeterinaryFaculty of Biotechnology and Genetic EngineeringMesenchymal–epithelial transition (MET) factor is a proto-oncogene encoding tyrosine kinase receptor with hepatocyte growth factor (HGF) or scatter factor (SF). It is found on the human chromosome number 7 and regulates the diverse cellular mechanisms of the human body. The impact of mutations occurring in the MET gene is demonstrated by their detrimental effects on normal cellular functions. These mutations can change the structure and function of MET leading to different diseases such as lung cancer, neck cancer, colorectal cancer, and many other complex syndromes. Hence, the current study focused on finding deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) and their subsequent impact on the protein’s structure and functions, which may contribute to the emergence of cancers. These nsSNPs were first identified utilizing computational tools like SIFT, PROVEAN, PANTHER-PSEP, PolyPhen-2, I-Mutant 2.0, and MUpro. A total of 45359 SNPs of MET gene were accumulated from the database of dbSNP, and among them, 1306 SNPs were identified as non-synonymous or missense variants. Out of all 1306 nsSNPs, 18 were found to be the most deleterious. Moreover, these nsSNPs exhibited substantial effects on structure, binding affinity with ligand, phylogenetic conservation, secondary structure, and post-translational modification sites of MET, which were evaluated using MutPred2, RaptorX, ConSurf, PSIPRED, and MusiteDeep, respectively. Also, these deleterious nsSNPs were accompanied by changes in properties of MET like residue charge, size, and hydrophobicity. These findings along with the docking results are indicating the potency of the identified SNPs to alter the structure and function of the protein, which may lead to the development of cancers. Nonetheless, Genome-wide association study (GWAS) studies and experimental research are required to confirm the analysis of these nsSNPs.http://dx.doi.org/10.1155/2023/9705159 |
| spellingShingle | Fayeza Sadia Laskar Md. Nazmul Islam Bappy Md. Sowrov Hossain Zenifer Alam Dilruba Afrin Sudeb Saha Kazi Md. Ali Zinnah An In silico Approach towards Finding the Cancer-Causing Mutations in Human MET Gene International Journal of Genomics |
| title | An In silico Approach towards Finding the Cancer-Causing Mutations in Human MET Gene |
| title_full | An In silico Approach towards Finding the Cancer-Causing Mutations in Human MET Gene |
| title_fullStr | An In silico Approach towards Finding the Cancer-Causing Mutations in Human MET Gene |
| title_full_unstemmed | An In silico Approach towards Finding the Cancer-Causing Mutations in Human MET Gene |
| title_short | An In silico Approach towards Finding the Cancer-Causing Mutations in Human MET Gene |
| title_sort | in silico approach towards finding the cancer causing mutations in human met gene |
| url | http://dx.doi.org/10.1155/2023/9705159 |
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