Identification of deleterious SNPs and their effects on BCL11A, the master regulator of fetal hemoglobin expression

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.