Abstract
PLCG1 gene is responsible for many T-cell lymphoma subtypes, including peripheral T-cell lymphoma (PTCL), angioimmunoblastic T-cell lymphoma (AITL), cutaneous T-cell lymphoma (CTCL), adult T-cell leukemia/lymphoma along with other diseases. Missense mutations of this gene have already been found in patients of CTCL and AITL. The non-synonymous single nucleotide polymorphisms (nsSNPs) can alter the protein structure as well as its functions. In this study, probable deleterious and disease-related nsSNPs in PLCG1 were identified using SIFT, PROVEAN, PolyPhen-2, PhD-SNP, Pmut, and SNPS&GO tools. Further, their effect on protein stability was checked along with conservation and solvent accessibility analysis by I-mutant 2.0, MUpro, Consurf, and Netsurf 2.0 server. Some SNPs were finalized for structural analysis with PyMol and BIOVIA discovery studio visualizer. Out of the 16 nsSNPs which were found to be deleterious, ten nsSNPs had an effect on protein stability, and six mutations (L411P, R355C, G493D, R1158H, A401V and L455F) were predicted to be highly conserved. Among the six highly conserved mutations, four nsSNPs (R355C, A401V, L411P and L455F) were part of the catalytic domain. L411P, L455F and G493D made significant structural change in the protein structure. Two mutations-Y210C and R1158H had post-translational modification. In the 5’ and 3’ untranslated region, three SNPs, rs139043247, rs543804707, and rs62621919 showed possible miRNA target sites and DNA binding sites. This in silico analysis has provided a structured dataset of PLCG1 gene for further in vivo researches. With the limitation of computational study, it can still prove to be an asset for the identification and treatment of multiple diseases associated with the target gene.
Highlights
Single nucleotide polymorphisms (SNPs) are the most common genetic variations found in humans (3–5 million) [1]
We identified four potentially deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) (R355C, A401V, L411P and L455F) through our analysis, which form a part of the catalytic domain of Phospholipase C gamma-1 (PLCG1)
SNPs of the PLCG1 gene were retrieved from the dbSNP database
Summary
Single nucleotide polymorphisms (SNPs) are the most common genetic variations found in humans (3–5 million) [1]. It is a type of polymorphism in which a single nucleotide differs between individuals. Mutations in the highly structured non-coding regions of the gene can have a significant impact on gene expression. Mutations in the 5’ and 3’ untranslated region can alter the secondary structure of the protein, and the binding of proteins and ligands to these regions [4]
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