Related Experiment Video
Updated: Dec 10, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
In silico analysis predicting effects of deleterious SNPs of human RASSF5 gene on its structure and functions
Md Shahadat Hossain1, Arpita Singha Roy1, Md Sajedul Islam2
1Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh.
Abstract:
Ras association domain-containing protein 5 (RASSF5), one of the prospective biomarkers for tumors, generally plays a crucial role as a tumor suppressor. As deleterious effects can result from functional differences through SNPs, we sought to analyze the most deleterious SNPs of RASSF5 as well as predict the structural changes associated with the mutants that hamper the normal protein-protein interactions. We adopted both sequence and structure based approaches to analyze the SNPs of RASSF5 protein. We also analyzed the putative post translational modification sites as well as the altered protein-protein interactions that encompass various cascades of signals. Out of all the SNPs obtained from the NCBI database, only 25 were considered as highly deleterious by six in silico SNP prediction tools. Among them, upon analyzing the effect of these nsSNPs on the stability of the protein, we found 17 SNPs that decrease the stability. Significant deviation in the energy minimization score was observed in P350R, F321L, and R277W. Besides this, docking analysis confirmed that P350R, A319V, F321L, and R277W reduce the binding affinity of the protein with H-Ras, where P350R shows the most remarkable deviation. Protein-protein interaction analysis revealed that RASSF5 acts as a hub connecting two clusters consisting of 18 proteins and alteration in the RASSF5 may lead to disassociation of several signal cascades. Thus, based on these analyses, our study suggests that the reported functional SNPs may serve as potential targets for different proteomic studies, diagnosis and therapeutic interventions.
Insights
Single nucleotide polymorphisms (SNPs) in Ras association domain-containing protein 5 (RASSF5) can disrupt its tumor suppressor function. This study identifies key RASSF5 SNPs impacting protein stability and interactions, offering potential diagnostic and therapeutic targets.
Area of Science:
- Molecular Biology
- Genetics
- Bioinformatics
Background:
- Ras association domain-containing protein 5 (RASSF5) is a vital tumor suppressor. Single nucleotide polymorphisms (SNPs) can alter protein function, potentially contributing to cancer development.
- Understanding the impact of RASSF5 SNPs is crucial for identifying new biomarkers and therapeutic strategies in oncology.
Purpose of the Study:
- To identify and analyze the most deleterious SNPs in RASSF5.
- To predict structural changes caused by these SNPs and their effect on protein-protein interactions.
- To investigate the potential of functional RASSF5 SNPs as targets for cancer diagnosis and therapy.
Main Methods:
- Utilized sequence and structure-based bioinformatics approaches to analyze RASSF5 SNPs.
- Employed six in silico SNP prediction tools to identify deleterious variants.
- Performed stability analysis, energy minimization, docking analysis with H-Ras, and protein-protein interaction network analysis.
Main Results:
- Identified 25 highly deleterious RASSF5 SNPs, with 17 found to decrease protein stability.
- Observed significant energy deviations for P350R, F321L, and R277W mutations.
- Docking analysis revealed that P350R, A319V, F321L, and R277W reduce binding affinity with H-Ras, with P350R showing the most significant impact. RASSF5 acts as a hub in protein interaction networks, and alterations can disrupt signaling cascades.
Conclusions:
- Functional SNPs in RASSF5, particularly those affecting protein stability and H-Ras binding, are identified as potential targets for proteomic studies.
- These findings support the exploration of RASSF5 SNPs for cancer diagnosis and therapeutic interventions.
- The study highlights the importance of investigating genetic variations in tumor suppressor genes for understanding cancer mechanisms.
Related Concept Videos
Alternative RNA Splicing
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Single Nucleotide Polymorphisms-SNPs
The Ras Gene
Ras is a...

