For example, missense mutations predicted to have the most effect on structure are located near the Gβγ interface, such as P-Rex2 K634E (pancreatic cancer) and A1571E (colorectal cancer), suggesting that they would either interfere with activation by Gβγ or, alternatively, render constitutive activity (Fig. 2). This evidence concerns the gene CFB and familial pancreatic carcinoma.