In-silico predictions of deleterious SNPs in human ephrin type-A receptor 3 (EPHA3) gene

Ephrin type-A receptor 3 (EPHA3) is a receptor tyrosine kinase involved in many biological functions, including migration, adhesion, and so on. Dysregulation of the EPHA3 receptor gene can lead to various oncogenic events, such as prostate cancer and hepatocellular carcinoma. Therefore, in silico SNP analysis is required to screen out the deleterious SNPs. Using ten bioinformatics tools, 41 non-synonymous SNPs (nsSNPs) were predicted as potentially harmful among 631 nsSNPs retrieved from the dbSNP database and as non-synonymous SNPs alter the wild-type amino acids; these substitutions may lead to deformity of the structure and hamper proper functionality of the protein. ConSurf review showed that all 41 harmful SNPs were mainly found in heavily conserved regions. These predicted deleterious SNPs were studied extensively for their effects on protein stability, dynamic behavior, surface accessibility, secondary structure, and interactions with other molecules. Many of these predicted SNPs resided in the alpha-helix, extended sheet, and β turn of secondary structure, and they conferred a significant impact on the structure due to changes in charge density, hydrophobicity, hydrogen bond, and other favorable bonds. Using the phenotypic effect predicted by HOPE and combining it with modeled structures, R799C and R750Q were expected to have the most significant functional impact on the three-dimensional structure of proteins. 21SNPs related to the alteration of miRNA target site at 3’UTR region, which may affect post-transcriptional regulation of EPHA3 gene. These findings will provide necessary data to explore various diseases or cancer pertinent to the EPHA3 receptor protein, provide remedial biomarkers, aid in molecular diagnosis, and assist in designing target-specific therapeutic agents