In-silico analysis of a missense SNP (rs۱۸۰۵۳۲۳ C>T) in human PMS۲ gene

Research has shown that the endometrial cancer is the most common type of uterine cancer, affecting mostoften women over ۵۵. The incidence rate of endometrial cancer is increasing rapidly, so much so that thecancer is estimated to increase by more than ۵۰% worldwide by ۲۰۴۰. About ۵% of endometrial cancers arelinked to hereditary factors. One of the genes playing a significant role in endometrial cancer is PMS۲. PMS۲(PMS۱ homolog ۲), which is located on chromosome ۷p. It encodes a protein that functions to correct DNAmismatches and deletions that can occur during DNA replication and homologous recombination. There is,however, little experimental research into the relationship between SNPs occurring within the PMS۲ andendometrial cancer. To address this gap, missense SNP and its FASTA sequence were first retrieved fromNCBI. It was subsequently evaluated through the following seven software: SIFT, POLYPHEN-۲,PORVERN, PhD-SNP, SNPs&GO, I-Mutant, and HOPE. The purpose was to determine whether theretrieved SNP affects the stability and functions of the protein encoded from the PMS۲ gene. According toI-Mutant report, a decrease in the stability of the encoded protein happens during the single-nuclotidpolymerization. HOPE confirms I-Mutant’s prediction that the wild-type residue is more hydrophobic thanthe mutant residue. While the mutant residue charge is positive, the wild-type residue charge was neutral. Asto the functions of the encoded protein, SIFT predicts that this SNP deleteriously affects the protein function.HOPE confirms SIFT prediction: the mutated residue is located in a domain that is important for the mainactivity of the protein. Hence, the mutation of the residue might disturb this function. According to the resultsof this study, with the decrease in the stability and disturbance in the function of the protein in the uterinecells, the probability of endometrial cancer increases.

کلیدواژه ها:

endometrial cancer ، PMS۲ ، single-nucleotide polymorphism (SNP) ، mutation effect prediction