Analyzing the Association of KPCD Gene’s Non-Synonymous Variants with Breast Cancer

Abstract

Breast cancer has the highest mortality rate among women, owing to its late diagnosis. Determining its susceptibility genes might lead to better outcomes. Several studies reported dysregulation of PKCδ in a variety of cancers. Therefore, variant rs1703863535 has also been linked to breast cancer. Thus, the study's primary purpose was to investigate the association of variant rs1703863535 with breast cancer and to analyze its impact on protein structure and function. Genotyping by ARMS PCR was done to study the variant association with breast cancer (cohort size =100). ENSEMBLE browser for data retrieval was used, and then filtering out the pathogenic variants based on scores of different tools, i.e., CADD, Mutation Accessor, Polyphen, SIFT, MetaLR, and Revel. To study the effect of missense mutation on PKCδ structure, DynaMut was used to determine the protein flexibility and interatomic interactions, HOPE and FATHMM were carried out to study the structure-functional analysis and protein stability, and in situ, mutagenesis was done by PyMOL. The molecular dynamic simulation was also done to study the impact of variant rs1703863535 on protein structure, i.e., wild and mutant. Protein stabilization, structure, and function were highly affected due to nsSNP. According to the MD results, RMSF, RMSD, and Rg values differed in wild and mutant. After the genotyping analysis, the variant showed highly significant results, which indicated that TT and TC genotypes were significantly associated with breast cancer as a significant risk factor. After accessing the results, variant rs1703863535 can be a potential diagnostic and prognostic marker for breast cancer and develop novel and successful therapeutic targets in clinical trials