The mutations in the Immunoglobulin V-set domain can alter the binding affinity of CTLA4 with CD80 and CD80 that are involve in the negative regulation of T-cells whereas, the polymorphism lied in the cytoplasmic domain may affect the binding of multiple proteins i.e., PI3K, lipid kinase phosphatidylinositol 3-kinase (PI3K), the phosphatases SH2 domain containing protein tyrosine phosphatases (SHP-2), the serine threonine phosphatase PP2A and clathrin adaptor proteins activator protein1 (AP-1) and AP-2 may results in cancer development49,50. Here, CTLA4 is linked to cancer.