Prediction of pathogenicity of rs۱۸۰۰۷۵۱ (Pro۱۸۱۲Thr) nucleotide change in BRCA۱ gene related to breast cancer by bioinformatics tools

Breast cancer is one of the most common types of cancer in women, and the BRCA۱ gene isassociated with an increased risk of developing this disease. Understanding the function of the BRCA۱gene and its role in the development of breast cancer has important implications for personalizedmedicine and targeted therapies for individuals at high risk. Ongoing research aims to uncover howBRCA۱ gene mutations contribute to cancer development and explore potential treatment options. Inthe present study, a missense mutation in this gene causes the proline amino acid at position ۱۸۱۲ tochange to Threonine. Its pathogenicity assessment has been analyzed using several bioinformatics toolssuch as polyphen-۲, I-Mutant ۲.۰, and SIFT .PolyPhen-۲ is an online tool designed to predict the impact of amino acid substitutions on proteinstructure and function. It does so by analyzing multiple sequence alignments of ۳D protein structures.The Expasy website can predict the effects of missense mutations on protein structure, function, andstability. The SIFT tool is also used to predict whether an amino acid substitution affects proteinfunction, based on the protein sequence .Polyphen-۲ analysis indicated that this mutation is predicted to be probably damaging with a score of۱.۰۰۰. Substitution at position ۱۸۱۲ from P to T is predicted to affect protein function with a score of۰.۰۰ by the SIFT. According to the results from Expasy, this mutation caused a change in thehydrophobicity index from -۱.۶۰۰ (proline) to -۰.۷۰۰ (threonine) .According to this consideration, rs۱۸۰۰۷۵۱ might have pathogenic effects on the BRCA۱ gene. Thistheory should be proved with experimental studies because the score of pathogenicity of this SNP isvery high.

کلیدواژه ها:

BRCA۱ gene ، Breast cancer ، rs۱۸۰۰۷۵۱ ، Missense mutation