Mutational analysis and prediction of the potential impact of missense mutations in the HOXA9 gene in B-cell acute lymphoblastic leukemia

Background: The HOXA9 gene is an essential gene during the developmental stages of the embryo, and its mutations can result in different phenotypes in both fetal and adult life. Additionally, this gene encodes a transcription factor that plays a crucial role in hematopoietic processes. Deregulation of these pathways has been reported in some leukemia cases. This in-silico analysis aims to evaluate the pathogenic effect of missense mutations in the HOXA9 gene by utilizing various bioinformatics tools.

Methods: From dbSNP NCBI, 288 non-synonymous/missense mutations of the HOXA9 gene have been obtained. These missense mutations' functional impact was analyzed using various bioinformatics tools, including SIFT, Polyphen-2, PROVEAN, I-Mutant, PHD-SNP, and SNP&GO. Additionally, their structural impacts were investigated using Netsurf P-2.0, HOPE, ConSurf, and PyMOL. Furthermore, the analysis of protein hydrophobicity changes was examined using PEPTIDE 2.0 and ExPASy web tools.

Results: Out of the 288 non-synonymous mutations, 45 mutations have been identified as functional genetic variants that affect the structure and stability of the HOXA9 protein. According to the analysis, 10 out of the 45 missense mutations were more likely to be involved in changing the characteristics of the protein. These changes include absolute and relative solvent accessibility (ASA, RSA), classification secondary structure, surface accessibility, noncovalent interactions, and protein conformation.

Conclusion: Based on the results of this in-silico study, high-risk deleterious missense mutations have been predicted in the HOXA9 gene. These mutations may be potential candidates for future experimental investigations in various hematologic malignancy conditions.