Pathogenicity Prediction Assays of Human Missense Variant (rs۱۴۸۴۹۵۴۴۵۰) in CTLA-۴ Gene Based on Protein Sequence, Structure and Function

Globally, cancer is the main cause of death. During the occurrence of cancer, in themicroenvironment surrounding tumor cells, the process of identifying and connecting T cells byhistocompatibility complex( MHC) to antigens on the surface of antigen-presenting cells occurs, inorder to provide activation and cytotoxic activity of T cells. Binding of CD۸۰ and CD۸۲ molecules onantigen presenting cells with CD۲۸ receptor on T cell surface leads to T cell activation. Appropriatelevels of this connection cause the division of T cells and their differentiation through the secretion ofcytokines and increase the expression of genes related to cell survival, and the process of inhibitingtumor cells begins. Cytotoxic T lymphocyte antigen ۴ )CTLA۴ (is a negative regulator belonging to theimmunoglobulin subfamily. This gene is located at chromosomal position ۲q ۳۲.۲ and has ۴ exons.Upon receiving the signal from the side of the tumor cell, it is expressed in active T cells and regulatoryT cells and encodes a protein that transmits the inhibitory signal to these cells and helps the tumorspread. In this research we investigated the function and structure of this type of protein by studyingand checking bioinformatics servers, I-mutant-۲, Expasy.The A۱۱G variant (rs۱۴۸۴۹۵۴۴۵۰) pathogen polymorphism was selected from NCBI. By studying thisvariant in I- mutants, a decrease in protein stability was predicted. Hydrophobic index (score -۱.۷۵)increased and molecular weight (score ۱۳۸) decreased in Expasy tool.It was predicted that the missense variant replaces Alanine with Glycine can cause structural disorderand as a result protein dysfunction.

کلیدواژه ها:

Cancer ، T- cell ، CTLA-۴