Department of Genetic Engineering and Biotechnology, Jagannath University, Dhaka, Bangladesh.
Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka, Bangladesh.
PLoS One. 2022 Aug 9;17(8):e0272625. doi: 10.1371/journal.pone.0272625. eCollection 2022.
FOXP2 encodes the forkhead transcription factor that plays a significant role in language development. Single nucleotide polymorphisms in FOXP2 have been linked to speech- language disorder, autism, cancer and schizophrenia. So, scrutinizing the functional SNPs to better understand their association in disease is an uphill task. The purpose of the current study was to identify the missense SNPs which have detrimental structural and functional effects on the FOXP2 protein. Multiple computational tools were employed to investigate the deleterious role of non-synonymous SNPs. Five variants as Y531H, L558P, R536G and R553C were found to be associated with diseases and located at the forkhead domain of the FOXP2 protein. Molecular docking analysis of FOXP2 DNA binding domain with its most common target sequence 5'-CAAATT-3' predicted that R553C and L558P mutant variants destabilize protein structure by changing protein-DNA interface interactions and disruption of hydrogen bonds that may reduce the specificity and affinity of the binding. Further experimental investigations may need to verify whether this kind of structural and functional variations dysregulate protein activities and induce formation of disease.
FOXP2 编码叉头转录因子，在语言发育中起着重要作用。FOXP2 中的单核苷酸多态性与言语-语言障碍、自闭症、癌症和精神分裂症有关。因此，仔细研究功能 SNP 以更好地了解它们在疾病中的关联是一项艰巨的任务。本研究的目的是确定错义 SNP，这些 SNP 对 FOXP2 蛋白具有有害的结构和功能影响。使用多种计算工具来研究非 synonymous SNP 的有害作用。发现五个变体 Y531H、L558P、R536G 和 R553C 与疾病相关，并且位于 FOXP2 蛋白的叉头结构域。FOXP2 DNA 结合域与其最常见的靶序列 5'-CAAATT-3'的分子对接分析预测 R553C 和 L558P 突变变体通过改变蛋白-DNA 界面相互作用和破坏氢键而使蛋白结构不稳定，这可能降低结合的特异性和亲和力。可能需要进一步的实验研究来验证这种结构和功能的变化是否会使蛋白活性失调并导致疾病的形成。
