![conference banner](/images/conference-banner.jpeg)
Abstract
Aims: Perform in-silico analysis of human SOS1 mutations to elucidate their pathogenic role in Noonan syndrome (NS).
Background: NS is an autosomal dominant genetic disorder caused by single nucleotide mutation in PTPN11, SOS1, RAF1, and KRAS genes. NS is thought to affect approximately 1 in 1000. NS patients suffer different pathogenic effects depending on the mutations they carry. Analysis of the mutations would be a promising predictor in identifying the pathogenic effect of NS.
Methods: We performed computational analysis of the SOS1 gene to identify the pathogenic nonsynonymous single nucleotide polymorphisms (nsSNPs) th a t cause NS. SOS1 variants were retrieved from the SNP database (dbSNP) and analyzed by in-silico tools I-Mutant, iPTREESTAB, and MutPred to elucidate their structural and functional characteristics.
Results: We found that 11 nsSNPs of SOS1 that were linked to NS. 3D modeling of the wild-type and the 11 nsSNPs of SOS1 showed that SOS1 interacts with cardiac proteins GATA4, TNNT2, and ACTN2. We also found that GRB2 and HRAS act as intermediate molecules between SOS1 and cardiac proteins. Our in-silico analysis findings were further validated using induced cardiomyocytes (iCMCs) derived from NS patients carrying SOS1 gene variant c.1654A>G (NSiCMCs) and compared to control human skin fibroblast-derived iCMCs (C-iCMCs). Our in vitro data confirmed that the SOS1, GRB2 and HRAS gene expressions as well as the activated ERK protein, were significantly decreased in NS-iCMCs when compared to C-iCMCs.
Conclusion: This is the first in-silico and in vitro study demonstrating that 11 nsSNPs of SOS1 play deleterious pathogenic roles in causing NS.
Keywords: Noonan syndrome, SOS1 gene, in-silico analysis, post-translational modification, nonsynonymous SNP, pathogenicvariants.
Current Genomics
Title:In-Silico and In-Vitro Analysis of Human SOS1 Protein Causing Noonan Syndrome - A Novel Approach to Explore the Molecular Pathways
Volume: 22 Issue: 7
Author(s): Vinoth Sigamani, Sheeja Rajasingh, Narasimman Gurusamy, Arunima Panda and Johnson Rajasingh*
Affiliation:
- Department of Bioscience Research, University of Tennessee Health Science Center, Memphis, Tennessee
Keywords: Noonan syndrome, SOS1 gene, in-silico analysis, post-translational modification, nonsynonymous SNP, pathogenicvariants.
Abstract: Aims: Perform in-silico analysis of human SOS1 mutations to elucidate their pathogenic role in Noonan syndrome (NS).
Background: NS is an autosomal dominant genetic disorder caused by single nucleotide mutation in PTPN11, SOS1, RAF1, and KRAS genes. NS is thought to affect approximately 1 in 1000. NS patients suffer different pathogenic effects depending on the mutations they carry. Analysis of the mutations would be a promising predictor in identifying the pathogenic effect of NS.
Methods: We performed computational analysis of the SOS1 gene to identify the pathogenic nonsynonymous single nucleotide polymorphisms (nsSNPs) th a t cause NS. SOS1 variants were retrieved from the SNP database (dbSNP) and analyzed by in-silico tools I-Mutant, iPTREESTAB, and MutPred to elucidate their structural and functional characteristics.
Results: We found that 11 nsSNPs of SOS1 that were linked to NS. 3D modeling of the wild-type and the 11 nsSNPs of SOS1 showed that SOS1 interacts with cardiac proteins GATA4, TNNT2, and ACTN2. We also found that GRB2 and HRAS act as intermediate molecules between SOS1 and cardiac proteins. Our in-silico analysis findings were further validated using induced cardiomyocytes (iCMCs) derived from NS patients carrying SOS1 gene variant c.1654A>G (NSiCMCs) and compared to control human skin fibroblast-derived iCMCs (C-iCMCs). Our in vitro data confirmed that the SOS1, GRB2 and HRAS gene expressions as well as the activated ERK protein, were significantly decreased in NS-iCMCs when compared to C-iCMCs.
Conclusion: This is the first in-silico and in vitro study demonstrating that 11 nsSNPs of SOS1 play deleterious pathogenic roles in causing NS.
Export Options
About this article
Cite this article as:
Sigamani Vinoth, Rajasingh Sheeja , Gurusamy Narasimman , Panda Arunima and Rajasingh Johnson *, In-Silico and In-Vitro Analysis of Human SOS1 Protein Causing Noonan Syndrome - A Novel Approach to Explore the Molecular Pathways, Current Genomics 2021; 22 (7) . https://dx.doi.org/10.2174/1389202922666211130144221
DOI https://dx.doi.org/10.2174/1389202922666211130144221 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Current Genomics in Cardiovascular Research
Cardiovascular diseases are the main cause of death in the world, in recent years we have had important advances in the interaction between cardiovascular disease and genomics. In this Research Topic, we intend for researchers to present their results with a focus on basic, translational and clinical investigations associated with ...read more
Deep learning in Single Cell Analysis
The field of biology is undergoing a revolution in our ability to study individual cells at the molecular level, and to integrate data from multiple sources and modalities. This has been made possible by advances in technologies for single-cell sequencing, multi-omics profiling, spatial transcriptomics, and high-throughput imaging, as well as ...read more
Genomic Insights into Oncology: Harnessing Machine Learning for Breakthroughs in Cancer Genomics.
This special issue aims to explore the cutting-edge intersection of genomics and oncology, with a strong emphasis on original data and experimental validation. While maintaining the focus on how machine learning and advanced data analysis techniques are revolutionizing our understanding and treatment of cancer, this issue will prioritize contributions that ...read more
Related Journals
![Wayfinder Image](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Angiogenic and Vascular Modulation by Extracellular Matrix Cleavage Products
Current Pharmaceutical Design Lipid-Activated Nuclear Receptors and Sepsis
Endocrine, Metabolic & Immune Disorders - Drug Targets Anti-cancer and Anti-angiogenic Properties of Various Natural Pentacyclic Tri-terpenoids and Some of their Chemical Derivatives
Current Organic Chemistry Harnessing the Natural Pool of Polyketide and Non-ribosomal Peptide Family: A Route Map towards Novel Drug Development
Current Molecular Pharmacology The Application of High Throughput siRNA Screening Technology to Study Host-Pathogen Interactions
Combinatorial Chemistry & High Throughput Screening Lessons Learned from HIV Vaccine Clinical Efficacy Trials
Current HIV Research Recent Advances in Predicting Protein Classification and Their Applications to Drug Development
Current Topics in Medicinal Chemistry Tumor Protein p63/microRNA Network in Epithelial Cancer Cells
Current Genomics Mitochondrial Serine Protease HtrA2/Omi as a Potential Therapeutic Target
Current Drug Targets An Update on Overcoming MDR1-Mediated Multidrug Resistance in Cancer Chemotherapy
Current Pharmaceutical Design Ocular Drug Delivery - New Strategies for Targeting Anterior and Posterior Segments of the Eye
Current Pharmaceutical Design Diabetic CVD – Focus on Vitamin D
Cardiovascular & Hematological Agents in Medicinal Chemistry Biosafety Considerations Using Gamma-Retroviral Vectors in Gene Therapy
Current Gene Therapy The N-Terminal Region of HIV-1 Tat Protein Binds CD127 in Human CD8 T Cells to Target the Receptor for Down Regulation Through Tat's Basic Region
Current HIV Research Targeting the Immune Niche within the Bone Marrow Microenvironment: The Rise of Immunotherapy in Multiple Myeloma
Current Cancer Drug Targets Biochemical Markers of Renal Function
Current Medicinal Chemistry Recent Advances in Non-Steroidal FXR Antagonists Development for Therapeutic Applications
Current Topics in Medicinal Chemistry Current Treatment Options for HCC: From Pharmacokinetics to Efficacy and Adverse Events in Liver Cirrhosis
Current Drug Metabolism Adherence to Antiretroviral Therapies: State of the Science
Current HIV Research Targeting the RAS Signaling Pathway in Malignant Hematologic Diseases
Current Drug Targets