A comprehensive in silico investigation unravels the structural and functional consequences of non-synonymous single-nucleotide polymorphisms in human OXTR gene
Abstract Background The OXTR gene encodes oxytocin receptor (OXTR), a cell surface protein primarily found in the brain, uterus, and mammary glands. This receptor plays a crucial role in signal transduction by binding with the ligand oxytocin. Various polymorphisms in the OXTR have been linked to ca...
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SpringerOpen
2025-03-01
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| Series: | Egyptian Journal of Medical Human Genetics |
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| Online Access: | https://doi.org/10.1186/s43042-025-00680-0 |
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| author | Puja Mazumder Shuvo Chandra Das Sobuj Mondol Ibrahim Khalil Afif Mithu Howlader Shipan Das Gupta Md. Murad Hossain Md. Mijanur Rahman |
| author_facet | Puja Mazumder Shuvo Chandra Das Sobuj Mondol Ibrahim Khalil Afif Mithu Howlader Shipan Das Gupta Md. Murad Hossain Md. Mijanur Rahman |
| author_sort | Puja Mazumder |
| collection | DOAJ |
| description | Abstract Background The OXTR gene encodes oxytocin receptor (OXTR), a cell surface protein primarily found in the brain, uterus, and mammary glands. This receptor plays a crucial role in signal transduction by binding with the ligand oxytocin. Various polymorphisms in the OXTR have been linked to cause or exacerbation of specific diseases such as Asperger syndrome, Schizophrenia, and various psychotic disorders. However, the susceptibility of disease and aberrant function of the mutant OXTR variants remain unclear. Results In this study, a comprehensive in silico analysis was carried out to detect, characterize, and validate the harmful non-synonymous single-nucleotide polymorphisms (nsSNPs) of the human OXTR. Twenty different sequence and structure-based bioinformatics tools and algorithms were utilized to characterize the pathogenic impacts of nsSNPs on the structure, function, stability, and conservation of OXTR protein. Finally, a total of seven nsSNPs (P95L, Q119H, P170Q, P212Q, R272C, W288R, and C323G) were identified as the most pathogenic nsSNPs that were situated in the highly conserved region of the GPCR Rhodopsin 7 transmembrane (7TM) domain. Molecular docking studies revealed that three nsSNPs (P95L, P170Q, and R272C) had lower binding affinity with oxytocin which might cause the aberrant function of OXTR. Malfunctions of the OXTR protein might have detrimental effects on several signaling cascades that ultimately impact on several psychiatric or neurological disorders. Conclusion These consolidated findings of this computational analysis could aid in future studies to understand the roles of deleterious nsSNP variants in the alternation of OXTR function. |
| format | Article |
| id | doaj-art-a4b64bc778a54e678149f98db3ad9c4e |
| institution | DOAJ |
| issn | 2090-2441 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj-art-a4b64bc778a54e678149f98db3ad9c4e2025-08-20T02:41:34ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412025-03-0126112310.1186/s43042-025-00680-0A comprehensive in silico investigation unravels the structural and functional consequences of non-synonymous single-nucleotide polymorphisms in human OXTR genePuja Mazumder0Shuvo Chandra Das1Sobuj Mondol2Ibrahim Khalil Afif3Mithu Howlader4Shipan Das Gupta5Md. Murad Hossain6Md. Mijanur Rahman7Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology UniversityDepartment of Biotechnology and Genetic Engineering, Noakhali Science and Technology UniversityDepartment of Genetic Engineering & Biotechnology, University of ChittagongDepartment of Biotechnology, Bangladesh Agricultural UniversityDepartment of Biotechnology and Genetic Engineering, Noakhali Science and Technology UniversityDepartment of Biotechnology and Genetic Engineering, Noakhali Science and Technology UniversityDepartment of Biotechnology and Genetic Engineering, Noakhali Science and Technology UniversityDepartment of Microbiology, Noakhali Science and Technology UniversityAbstract Background The OXTR gene encodes oxytocin receptor (OXTR), a cell surface protein primarily found in the brain, uterus, and mammary glands. This receptor plays a crucial role in signal transduction by binding with the ligand oxytocin. Various polymorphisms in the OXTR have been linked to cause or exacerbation of specific diseases such as Asperger syndrome, Schizophrenia, and various psychotic disorders. However, the susceptibility of disease and aberrant function of the mutant OXTR variants remain unclear. Results In this study, a comprehensive in silico analysis was carried out to detect, characterize, and validate the harmful non-synonymous single-nucleotide polymorphisms (nsSNPs) of the human OXTR. Twenty different sequence and structure-based bioinformatics tools and algorithms were utilized to characterize the pathogenic impacts of nsSNPs on the structure, function, stability, and conservation of OXTR protein. Finally, a total of seven nsSNPs (P95L, Q119H, P170Q, P212Q, R272C, W288R, and C323G) were identified as the most pathogenic nsSNPs that were situated in the highly conserved region of the GPCR Rhodopsin 7 transmembrane (7TM) domain. Molecular docking studies revealed that three nsSNPs (P95L, P170Q, and R272C) had lower binding affinity with oxytocin which might cause the aberrant function of OXTR. Malfunctions of the OXTR protein might have detrimental effects on several signaling cascades that ultimately impact on several psychiatric or neurological disorders. Conclusion These consolidated findings of this computational analysis could aid in future studies to understand the roles of deleterious nsSNP variants in the alternation of OXTR function.https://doi.org/10.1186/s43042-025-00680-0Oxytocin receptornsSNPsMolecular dockingIn silico analysisPolymorphisms |
| spellingShingle | Puja Mazumder Shuvo Chandra Das Sobuj Mondol Ibrahim Khalil Afif Mithu Howlader Shipan Das Gupta Md. Murad Hossain Md. Mijanur Rahman A comprehensive in silico investigation unravels the structural and functional consequences of non-synonymous single-nucleotide polymorphisms in human OXTR gene Egyptian Journal of Medical Human Genetics Oxytocin receptor nsSNPs Molecular docking In silico analysis Polymorphisms |
| title | A comprehensive in silico investigation unravels the structural and functional consequences of non-synonymous single-nucleotide polymorphisms in human OXTR gene |
| title_full | A comprehensive in silico investigation unravels the structural and functional consequences of non-synonymous single-nucleotide polymorphisms in human OXTR gene |
| title_fullStr | A comprehensive in silico investigation unravels the structural and functional consequences of non-synonymous single-nucleotide polymorphisms in human OXTR gene |
| title_full_unstemmed | A comprehensive in silico investigation unravels the structural and functional consequences of non-synonymous single-nucleotide polymorphisms in human OXTR gene |
| title_short | A comprehensive in silico investigation unravels the structural and functional consequences of non-synonymous single-nucleotide polymorphisms in human OXTR gene |
| title_sort | comprehensive in silico investigation unravels the structural and functional consequences of non synonymous single nucleotide polymorphisms in human oxtr gene |
| topic | Oxytocin receptor nsSNPs Molecular docking In silico analysis Polymorphisms |
| url | https://doi.org/10.1186/s43042-025-00680-0 |
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