School of Medical Science and Technology, Indian Institute of Technology Kharagpur, India.
School of Medical Science and Technology, Indian Institute of Technology Kharagpur, India.
Genomics. 2020 Jan;112(1):397-403. doi: 10.1016/j.ygeno.2019.03.002. Epub 2019 Mar 7.
The B-cell lymphoma/leukemia 11A protein (encoded by BCL11A gene) is a key regulator of fetal-to-adult hemoglobin switching as seen in post-natal life. Although genetic polymorphisms like SNPs in BCL11A gene are expected to affect fetal hemoglobin (HbF) expression levels, yet their implications are poorly studied. This study utilizes a computational approach to identify the deleterious SNPs which may affect the structure and function of BCL11A protein. The study also generated a 3D structure of native and mutants. The analysis identified two SNPs in BCL11A as highly deleterious: N391K and C414S which are expected to affect structure and stability of the protein. According to conservation analysis, both residues N391 and C414 were identified as highly conserved. Additionally, post-translational modification sites were predicted at both sites. Ligand binding sites were also predicted in N391 and C414. Therefore, N391K and C414S in BCL11A can considered as important candidates to mediate HbF variation.
B 细胞淋巴瘤/白血病 11A 蛋白（由 BCL11A 基因编码）是胎儿至成人血红蛋白转换的关键调节因子，这种转换可见于出生后生命中。尽管 BCL11A 基因中的遗传多态性（如单核苷酸多态性）预计会影响胎儿血红蛋白（HbF）的表达水平，但它们的影响尚未得到充分研究。本研究利用计算方法来鉴定可能影响 BCL11A 蛋白结构和功能的有害 SNP。该研究还生成了天然和突变体的 3D 结构。分析确定了 BCL11A 中的两个 SNP 为高度有害：N391K 和 C414S，预计会影响蛋白的结构和稳定性。根据保守性分析，N391 和 C414 两个残基均被鉴定为高度保守。此外，在两个位点均预测到了翻译后修饰位点。还在 N391 和 C414 预测到了配体结合位点。因此，BCL11A 中的 N391K 和 C414S 可以被认为是介导 HbF 变异的重要候选者。
