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 region of CTL domain hence are more likely to abolish the function of the protein. Up to the best of our knowledge, this is the first study that provides in-depth and in-silico analysis of deleterious mutations on structure and function of PLA2R1.
Highlights
Phospholipases play a vital role in many cellular processes including phospholipids digestion and metabolism
This involves the analysis of single nucleotide polymorphism (SNPs) refers to as single base change that is present in 1% of the whole population
The experimental analysis carried out b y12 showed that rs6757188 and rs3577198 are highly associated with idiopathic membranous nephropathy (IMN) and that’s maybe the underlying cause of IMN
Summary
Phospholipases play a vital role in many cellular processes including phospholipids digestion and metabolism. Phospholipases which are activated by G-protein coupled receptors PLA2R1 results in releasing biologically active metabolite which further acts as first or second messengers to auxiliary modify or intensify the cell signals. It is involved in many patho-physical situations varying from acute inflammatory conditions ending to c ancer[5,6]. SNPs are more frequently observed in the non-coding regions of the genome including 5′UTR and 3′UTR and introns Those occurring at 5′UTR are involved in transcriptional activity while 3′UTR SNPs usually affects gene expression. The experimental analysis carried out b y12 showed that rs6757188 and rs3577198 are highly associated with idiopathic membranous nephropathy (IMN) and that’s maybe the underlying cause of IMN
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