Computational approach for predicting the functional effects of missense variants on Speckle-type BTB/POZ protein and association with prostate cancer

More than 10% of all prostate tumor cases have one mutation or more in speckle-type BTB/POZ protein ( SPOP ), with no significant differences through demographic or ethnic backgrounds. To explore the effects of missense variants on biochemical characteristics of SPOP protein; computational approach was used to predict the deleterious missense variants in SPOP gene and its significant pathogenic effects on the functions and structure of SPOP protein through SIFT, PolyPhen 2: HumDiv, PROVEAN, and I-Mutant 2.0 servers, followed by modeling native speckle-type POZ protein and the mutant proteins detected in a 3D structures, and finally finding the effects of these variants on protein characteristics: total minimizing energy, secondary structure, and solvent stability. Out of 54 missense variants; twelve substitutions showed a serious deviation range of energy minimization, solvent stability rates, and secondary structure from other missense variants tested. The deleterious variants probably affect the vital function of SPOP protein. Lab investigations and epidemiological researches recommended to study predicted pathogenic variants: F102C, F133L, F102V, F102L, F133S, F133C, Y87N, A220G, K286N, R370C, S197F, and R138C.