Abstract
PLA2R1 is a transmembrane glycoprotein that acts as an endogenous ligand which stimulates the processes including cell proliferation and cell migration. The SNPs in PLA2R1 is associated with idiopathic membranous nephropathy which is an autoimmune kidney disorder. The present study aimed to explore the structure-function analysis of high risk SNPs in PLA2R1 by using 12 different computational tools. First the functional annotation of SNPs were carried out by sequence based tools which were further subjected to evolutionary conservation analysis. Those SNPs which were predicted as deleterious in both categories were further considered for structure based analysis. The resultant SNPs were C1096S, C545S, C664S, F1257L, F734S, I1174T, I1114T, P177S, P384S, W1198G, W1328G, W692C, W692L, W962R, Y499H. One functional domain of PLA2R1 is already modelled in PDB (6JLI), the full 3D structure of the protein was predicted using I-TASSER homology modelling tool. The stability analysis, structure superimposition, RMSD calculation and docking studies were carried out. The structural analysis predicted four mutations F734S, F1246L, I1174T, W1198G as damaging to the structure of the protein. All these mutations are occurring at the conserved r...Continue Reading
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