A Simulation Analysis and Screening of Deleterious Non-Synonymous Single Nucleotide Polymorphisms (SNPs) in Human CDKN1A Gene

Abstract

CDKN1A also known as p21CIP1 /p21WAF1, a cyclin dependent kinase 1, interacts with proliferating cell nuclear antigen (PCNA) resulting in cell cycle inhibition in human. Non-synonymous single nucleotide polymorphisms (nsSNPs), which reside in the coding region of a gene, might distort the normal function of the corresponding protein. In silico analysis in this study followed many different algorithms. Following the final screening of 118 nsSNPs from dbSNP (NCBI), 12 missense SNPs (R19C (C[->]T), G23D (A[->]G), V25G (G[->]T), V25L (C[->]G), Q29P (A[->]C[->]G), F51L (C[->]T), E56K (A[->]G), T57I (C[->]T), G61R (C[->]G), G61D (A[->]G), Y151C (A[->]G) and R156W (C[->]G[->]T) were predicted to have deleterious effect by all the algorithms. Of them, R19C, G23D, F51L, Y151C and R156W occurred at the highly conserved site. G23D, F51L variants also occurred at the CDI domain. Homology structures of the protein predicted decrease of energy in mutant models. GV-GD scores predicted only two variants as neutral (V25L, F51L).