A Bioinformatics study: predicting the pathogenicity of two SNPs in the CFTR gene which is associated with Cystic Fibrosis (CF) disease

Cystic fibrosis (CF) impacts various physiological systems, including respiratory, exocrinepancreas, digestive, hepatobiliary, and sweat glands, with the CFTR gene regulating ion and watersecretion and absorption in epithelial tissues. The most frequently encountered mutation associated withCF is DeltaF۵۰۸, which results in compromised folding and trafficking of the encoded protein. Ourstudy aimed to identify pathogenic single nucleotide polymorphisms (SNPs) within the CFTR geneusing bioinformatics servers. Two SNPs, rs۳۹۷۵۰۸۷۱۸ (G۱۴۹R) and rs۳۹۷۵۰۸۷۲۹ (T۱۶۱N and T۱۶۱D)were studied using SIFT, PolyPhen-۲, I-Mutant ۲.۰, and Hope servers. Results showed thatrs۳۹۷۵۰۸۷۱۸ affected protein function with a score of ۰.۰۲ by the SIFT and was predicted to be possiblydamaging with a score of ۱.۰۰۰ by PolyPhen-۲ programs. I-Mutant analysis showed an increase instability for the mutant state. In addition, the Hope server indicated that the wild-type (G۱۴۹) residue isthe most flexible amino acid. This flexibility might be necessary for the protein’s function. Thers۳۹۷۵۰۸۷۲۹ affected protein functions with a score of ۰.۰۰ by SIFT and was predicted to be damagingwith a score of ۱.۰۰۰ by PolyPhen-۲ programs. I-Mutant analysis showed also an increase in stability.Hope also indicated that the size difference between wild-type (T۱۶۱) and mutant residues (N۱۶۱ andD۱۶۱) causes the new residue to not be in the correct position to make the same hydrogen bond. Inconclusion, the study suggests that the G۱۴۹R, T۱۶۱N, and T۱۶۱D variants of CFTR could affectprotein function, potentially be pathogenic, and damage the protein.

کلیدواژه ها:

CFTR gene ، SIFT ، PolyPhen-۲ ، I-Mutant ۲.۰ ، Hope