The effect of KLK2 nsSNPs on prostate related disease

Background: Kallikrein2 (KLK2) codes a serine protease enzyme that cleaves pro-PSA to active PSA which has an important role in liberation of sperm and fluidity of semen by shattering of semenogelin and fibronectin. Hence, any polymorphism of this gene could effect on serine protease activity, which means they can associate with any prostate disease such as prostate cancer and infertility.Methods: In this study, 5 nsSNPs were chosen which H65Y, and G214E are in active site; D207N, and S228A are in substrate binding site, and R250W that its GMAF is more than 1%. The influence of these substitution on function and stability of protein and being deleterious were predicted by Polyphen2.0, Provean, Imutant3.0 and SIFT.Result: All 5 nsSNPs were predicted as affected on protein function. The PolyPhen 2.0 predicts that D207N and S228A are possibly damaging, G214E, and H65Y are probably damaging and R250W is benign. Also D207N, G214E, and H65Y are deleterious while S228A, and R250W are neutral. The H65Y may increase the stability of protein, but other nsSNPs were checked, could decrease the stability.Conclusion: Among intended nsSNPs, D207N has destructive effect on this enzyme, while R250W may has less destruction. Change of hK2 enzyme function by mentioned nsSNPs could associate with some diseases like infertility and prostate cancer.

کلیدواژه ها:

Infertility ، In-silico ، KLK2 ، Deleterious nsSNPs