Computational approach for predicting the functional effects of missense variants on Speckle-type BTB/POZ protein and as
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ORIGINAL ARTICLE
Computational approach for predicting the functional effects of missense variants on Speckle‑type BTB/POZ protein and association with prostate cancer Berjas Abumsimir1 · Yassine Kasmi1 · Moulay Mustapha Ennaji1 Received: 18 February 2020 / Revised: 11 June 2020 / Accepted: 10 July 2020 © Springer Nature Singapore Pte Ltd. 2020
Abstract 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. Keywords SPOP · Missense variants · Prostate cancer · Bioinformatics · Free energy Abbreviations SPOP Speckle-type POZ protein DAXX Death-associated protein 6 nsSNPs Non-synonymous single nucleotide polymorphisms SIFT Sorts intolerant from tolerant PSIC Position-specific independent count PolyPhen Polymorphism phenotyping SVM Support vector machine DDG Free energy change AAC Three state solvent accessibility DISO Disorder regions Electronic supplementary material The online version of this article (https://doi.org/10.1007/s42485-020-00042-x) contains supplementary material, which is available to authorized users. * Moulay Mustapha Ennaji [email protected] 1
Laboratory of Virology, Cancerology, Microbiology, Quality and Medical Biotechnologies/ETB–Faculty of Sciences and Techniques–Mohammedia, Hassan II University of Casablanca, Quarter Yasmina‑Mohammedia, P. O. Box 146, 20650 Casablanca, Morocco
Introduction Prostate cancer considers as one of the most common tumors among men in the world due to the increasing incidences and mortality rates, North America and Europe have the highest rates of incidences and predicted to contribute to 26.4% of all cancer deaths in the United States by 2020 (Weir et al. 2015). In addition to other non-genetic risk factors; inherited variations in dozens of genes have been considered as possible risk factors for prostate cancer, its work as tumor suppressors through different pathways. Alterations in these
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