Functional Annotation of Missense Variants in CCR2 Gene: A computational approach to CKD susceptibility
DOI:
https://doi.org/10.63682/jns.v14i7.6080Keywords:
CCR2 gene, Missensevariants, chronic kidney disease, insilicoanalysis, Protein stability, Pathogenicity predictionAbstract
Background:Chronic kidney disease (CKD) affects approximately 9.1% of the global population and is increasingly recognized as a condition influenced by genetic predisposition. Among the genetic factors implicated, missense variants in the C-C motif chemokine receptor 2 (CCR2) gene are of particular interest due to CCR2's role in immune regulation. Variants in this gene may disrupt protein structure and function, potentially contributing to CKD pathogenesis. This study employs an in silico approach to investigate the structural and functional impact of CCR2 missense variants and their potential association with CKD susceptibility.
Methods:Missense single nucleotide polymorphisms (SNPs) in the CCR2 gene were retrieved from the dbSNP database. Ten computational tools—SIFT, PolyPhen-2, PANTHER, SNP&GO, I-Mutant 2.0, MUpro, MutPred2, ConSurf, Phyre2, and STRING—were employed to assess pathogenicity, protein stability, evolutionary conservation, structural alterations, and protein-protein interactions. Variants were classified as deleterious based on consensus predictions from at least six tools.
Results: Of the eight missense variants analysed, six (rs113340633, rs200491743, rs370278890, rs371121141, rs373211972, rs374045702) were consistently predicted to be deleterious. These variants were associated with reduced protein stability and significant structural alterations. Notably, substitutions such as L119P and M249K affected highly conserved residues and were predicted to disrupt chemokine-receptor interactions. Two variants (rs200575131 and rs368219093) yielded inconsistent results across tools, warranting further experimental validation.
Conclusion:This study highlights several CCR2 missense variants that may impair protein function and contribute to CKD susceptibility through dysregulation of immune responses. These computational findings provide a foundation for future experimental validation and may inform precision medicine strategies in CKD diagnosis and management.
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