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Published on: August 24, 2013
In silico analysis of deleterious SNPs of human MTUS1 gene and their impacts on subsequent protein structure and
Liza Teresa Rozario1, Tanima Sharker1, Tasnin Akter Nila2
1Department of Biochemistry and Molecular Biology, Noakhali Science and Technology University, Noakhali, Bangladesh.
Abstract:
The mitochondrial tumor suppressor 1 (MTUS1) gene acts as a crucial tumor suppressor by inhibiting growth and proliferation of eukaryotic cells including tumor cell lines. Down regulation of MTUS1 gene has been implicated in a wide range of cancers as well as various human diseases. Alteration through nsSNPs can potentially damage the structure and/or function of the protein. As characterization of functional SNPs in such disease linked genes is a major challenge, it is feasible to analyze putative functional SNPs prior to performing larger population studies. Hence, in this in silico study we differentiated the potentially harmful nsSNPs of the MTUS1 gene from the neutral ones by using various sequence and structure based bioinformatic tools. In a total of 215 nsSNPs, 9 were found to be most likely to exert deleterious effect using 7 prediction tools. From which, 5nsSNPs (S1259L, E960K, P503T, L1084V and L1143Q) were selected as potentially damaging due to their presence in the highly conserved region and ability to decrease protein stability. In fact, 2 nsSNPs (S1259L and E960K) among these 5 were found to be individually associated with two distinctive cancers named Stomach adenocarcinoma and Uterine corpus endometrial carcinoma. As this is the first comprehensive study analyzing the functional nsSNPs of MTUS1, the results of the current study would certainly be helpful in future prospects concerning large population-based studies as well as drug discovery, especially developing individualized medicine.
Insights
The mitochondrial tumor suppressor 1 (MTUS1) gene is vital for preventing cancer. This study identified specific genetic variations (nsSNPs) in MTUS1 that may harm its function and contribute to stomach and endometrial cancers.
Area of Science:
- Genetics
- Bioinformatics
- Oncology
Background:
- The mitochondrial tumor suppressor 1 (MTUS1) gene is a critical regulator of cell growth and proliferation.
- Downregulation of MTUS1 is linked to various cancers and human diseases.
- Non-synonymous single nucleotide polymorphisms (nsSNPs) can alter protein structure and function, potentially impacting disease risk.
Purpose of the Study:
- To computationally identify and differentiate deleterious nsSNPs in the MTUS1 gene from neutral ones.
- To investigate the functional impact of nsSNPs on MTUS1 protein stability and conserved regions.
- To correlate specific nsSNPs with cancer types.
Main Methods:
- Utilized a suite of sequence and structure-based bioinformatics tools for in silico analysis.
- Screened 215 nsSNPs within the MTUS1 gene using 7 prediction algorithms.
- Evaluated nsSNPs based on their location in conserved regions and predicted effect on protein stability.
Main Results:
- Identified 9 nsSNPs as potentially deleterious out of 215 analyzed.
- Selected 5 nsSNPs (S1259L, E960K, P503T, L1084V, L1143Q) as damaging due to conserved location and reduced protein stability.
- Found 2 nsSNPs (S1259L and E960K) associated with Stomach adenocarcinoma and Uterine corpus endometrial carcinoma, respectively.
Conclusions:
- This study provides the first comprehensive in silico analysis of functional nsSNPs in the MTUS1 gene.
- The identified potentially damaging nsSNPs offer valuable targets for future research and clinical applications.
- Results can guide large-scale population studies, drug discovery, and the development of personalized medicine strategies for MTUS1-associated cancers.
