In-silico analysis predicting the status of pathogenic SNPs of the human PAX۳ gene

Backgrounds: The paired box protein (PAX-۳) is a transcription factor encoded by PAX۳ gene.PAX۳ belongs to the family of PAX gene. They have a crucial role in developing tissues andorgans during embryogenesis. PAX۳ has two DNA binding sites and it can bind to DNA as ahomodimer or a heterodimer with PAX۷. Mutation in PAX۳ caused some diseases such asWaardenburg syndrome that involved abnormality in pigmentation, arms, hands, and hearingloss. Craniofacial-deafness-hand syndrome is characterized by distinctive facial features, severehearing loss. Rhabdomyosarcoma caused by chromosome aberration. It is the most common softtissue carcinoma in childhood (۵-۸% of all malignancies in children). In this study, ۲۴ singlenucleotide polymorphisms (SNP) for isoform PAX۳ are analyzed which are identified asmissense changes in the National center for biotechnology information (NCBI) on the SNPdatabase.Materials and Methods: In NCBI/SNP database ۴۷,۲۵۶ SNPs were found for PAX۳. Pathogenicand missense filters were applied and the result showed ۱۸rs (rs۷۵۸۱۳۶۸۲۶, rs۱۳۸۰۸۵۸۷۸۴rs۲۶۷۶۰۶۹۳۱,…). Their effect on the final protein product was checked.Results: The result of this research with bioinformatics tools (SIFT, PROVEAN, PANTHER,SNP&GO, FATHMM) shows that Reference SNP for instance rs۱۲۲۸۵۹۰۱۹۹ causes change R(Arg) to S (Ser) in ۲۷۰th amino acid residue in PAX۳ transcript, can produce an abnormalprotein that has a terrible effect on patients with this polymorphism.Conclusion: Based on the results were obtained these SNPs most probably deleterious and onlyrs۷۶۹۶۵۰۶۸۸ in the SIFT and SNP & GO databases were declared neutral.

کلیدواژه ها:

PAX۳ ، DNA-binding protein ، SNP ، Bioinformatics