Identification of novel key biomarkers in Simpson-Golabi-Behmel Syndrome: Evidence from bioinformatics analysis

AbstractBackgroundThe Simpson-Golabi-Behmel Syndrome (SGBS) or overgrowth Syndrome is a rare inherited X-linked condition characterized by pre- and postnatal overgrowth. The aim of the present study is to identify functional non-synonymous SNPs of GPC3 gene using various in silico approaches. These SNPs are supposed to have a direct effect on protein stability through conformation changes.Material and methodsThe SNPs were retrieved from the Single Nucleotide Polymorphism database (dbSNP) and further used to investigate a damaging effect using SIFT, PolyPhen, PROVEAN, SNAP2, SNPs&GO, PHD-SNP and P-mut, While we used I-mutant and MUPro to study the effect of SNPs on GPC3 protein structure. The 3D structure of human GPC3 protein is not available in the Protein Data Bank, so we used RaptorX to generate a 3D structural model for wild-type GPC3 to visualize the amino acids changes by UCSF Chimera. For biophysical validation we used project HOPE. Lastly we run conservational analysis by BioEdit and Consurf web server respectively.Resultsour results revealed three novel missense mutations (rs1460413167, rs1295603457 and rs757475450) that are found to be the most deleterious which effect on the GPC3 structure and function.ConclusionThis present study could provide a novel insight into the molecular basis of overgrowth Syndrome.