Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.
PLoS One. 2024 Jan 2;19(1):e0296361. doi: 10.1371/journal.pone.0296361. eCollection 2024.
Genome-wide association studies (GWAS) identified a coding single nucleotide polymorphism, MYNN rs10936599, at chromosome 3q. MYNN gene encodes myoneurin protein, which has been associated with several cancer pathogenesis and disease development processes. However, there needed to be a more detailed characterization of this polymorphism's (and other coding and non-coding polymorphisms) structural, functional, and molecular impact. The current study addressed this gap and analyzed different properties of rs10936599 and non-coding SNPs of MYNN via a thorough computational method. The variant, rs10936599, was predicted functionally deleterious by nine functionality prediction approaches, like SIFT, PolyPhen-2, and REVEL, etc. Following that, structural modifications were estimated through the HOPE server and Mutation3D. Moreover, the mutation was found in a conserved and active residue, according to ConSurf and CPORT. Further, the secondary structures were predicted, followed by tertiary structures, and there was a significant deviation between the native and variant models. Similarly, molecular simulation also showed considerable differences in the dynamic pattern of the wildtype and mutant structures. Molecular docking revealed that the variant binds with better docking scores with ligand NOTCH2. In addition to that, non-coding SNPs located at the MYNN locus were retrieved from the ENSEMBL database. These were found to disrupt the transcription factor binding regulatory regions; nonetheless, only two affect miRNA target sites. Again, eight non-coding variants were detected in the testes with normalized expression, whereas HaploReg v4.1 unveiled annotations for non-coding variants. In summary, in silico comprehensive characterization of coding and non-coding single nucleotide polymorphisms of MYNN gene will assist researchers to work on MYNN gene and establish their association with certain types of cancers.
全基因组关联研究 (GWAS) 鉴定了位于 3 号染色体上的编码单核苷酸多态性 MYNN rs10936599。MYNN 基因编码肌神经元蛋白,该蛋白与多种癌症的发病机制和疾病发展过程有关。然而,需要更详细地描述该多态性(以及其他编码和非编码多态性)的结构、功能和分子影响。本研究填补了这一空白,并通过一种全面的计算方法分析了 rs10936599 及 MYNN 的非编码 SNP 的不同特性。该变体 rs10936599 通过 SIFT、PolyPhen-2 和 REVEL 等九种功能预测方法被预测为具有功能破坏性。随后,通过 HOPE 服务器和 Mutation3D 估计结构修饰。此外,根据 ConSurf 和 CPORT,突变发生在保守和活跃的残基上。此外,预测了二级结构,随后是三级结构,并且在天然和变体模型之间存在显著的偏差。同样,分子模拟也显示野生型和突变型结构的动态模式存在相当大的差异。分子对接表明,变体与配体 NOTCH2 的结合具有更好的对接评分。除此之外,还从 ENSEMBL 数据库中检索到位于 MYNN 基因座的非编码 SNP。这些 SNP 被发现破坏了转录因子结合的调控区域;然而,只有两个影响 miRNA 靶位点。同样,在睾丸中检测到 8 个具有正常表达的非编码变体,而 HaploReg v4.1 揭示了非编码变体的注释。总之,对 MYNN 基因的编码和非编码单核苷酸多态性进行计算机综合特征描述将有助于研究人员研究 MYNN 基因,并确定其与某些类型癌症的关联。
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