Accurate prediction of functional, structural, and stability changes in PITX2 mutations using in silico bioinformatics algorithms

摘要: Mutations in PITX2 have been implicated several genetic disorders, particularly Axenfeld-Rieger syndrome. In order to determine the most reliable bioinformatics tools assess likely pathogenicity of variants, results predictions were compared impact variants on structure and function. The MutPred, Provean, PMUT bioinformatic found highest performance predicting effects all 18 characterized missense PITX2, with sensitivity specificity >93%. Applying these three programs 13 previously uncharacterized predicted 12/13 as deleterious, except A30V which was benign variant for programs. Molecular modeling homoedomain predicts that 31 known L54Q, F58L, V83F, V83L, W86C, W86S, R91P alter PITX2’s structure. contrast, remaining 24 are not change molecular modeling, performed mutations located homeodomain, findings eight protein stability CUPSAT be effect stability. Our showed other members this homeodomain transcription factor family, PMUT, can reliably used predict pathogenicity.