Related Experiment Video
Updated: Feb 19, 2026
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Prediction of a highly deleterious mutation E17K in AKT-1 gene: An in silico approach
1Department of Biosciences, Integral University, Lucknow, INDIA.
Abstract:
The AKT1 (v-akt murine thymoma viral oncogene homologue 1) kinase is a member of most frequently activated proliferation and survival signaling pathway in cancer. Recently, hyperactivation of AKT1, due to functional point mutation in the pleckstrin homology (PH) domain of AKT1 gene, has been found to be associated with human colorectal, breast and ovarian cancer. Thus, considering its crucial role in cellular signaling pathway, a functional analysis of missense mutations of AKT1 gene was undertaken in this study. Twenty nine nsSNPs (non-synonymous single nucleotide polymorphism) within coding region of AKT1 gene were selected for our investigation and six SNPs were found to be deleterious by combinatorial predictions of various computational tools. RMSD values were calculated for the mutant models which predicted four substitutions (E17K, E319G, D32E and A255T) to be highly deleterious. The insight of the structural attribute was gained through analysis of, secondary structures, solvent accessibility and intermolecular hydrogen bond analysis which confirmed one missense mutation (E17K) to be highly deleterious nsSNPs. In conclusion, the investigated gene AKT1 has twenty nine SNPs in the coding region and through progressive analysis using different bioinformatics tools one highly deleterious SNP with rs121434592 was profiled. Thus, results of this study can pave a new platform to sort nsSNPs for several important regulatory genes that can be undertaken for the confirmation of their phenotype and their correlation with diseased status in case control studies.
Insights
The AKT1 gene has 29 non-synonymous single nucleotide polymorphisms (nsSNPs). Bioinformatics analysis identified one highly deleterious nsSNP (rs121434592), specifically the E17K mutation, which may impact cancer development.
Area of Science:
- Oncology
- Bioinformatics
- Molecular Biology
Background:
- The AKT1 kinase is a key component of proliferation and survival signaling pathways frequently activated in cancer.
- Hyperactivation of AKT1, often due to mutations in its pleckstrin homology (PH) domain, is linked to colorectal, breast, and ovarian cancers.
Purpose of the Study:
- To functionally analyze missense mutations in the AKT1 gene.
- To identify deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) within the AKT1 coding region.
Main Methods:
- Computational prediction tools were used to assess 29 nsSNPs in the AKT1 gene.
- Root Mean Square Deviation (RMSD) calculations evaluated the stability of mutant protein models.
- Analysis of secondary structures, solvent accessibility, and hydrogen bonds provided structural insights.
Main Results:
- Six AKT1 nsSNPs were predicted as deleterious by computational tools.
- Four substitutions (E17K, E319G, D32E, A255T) showed highly deleterious RMSD values.
- The E17K mutation (rs121434592) was confirmed as a highly deleterious nsSNP through structural analysis.
Conclusions:
- The study identified one highly deleterious nsSNP (rs121434592, E17K) in the AKT1 gene.
- This research provides a method for prioritizing nsSNPs in regulatory genes for further validation.
- Findings can aid in correlating genetic variations with disease status in case-control studies.
