In- silico Assessment of a Missense Mutation(p. Ala۱۰۲Pro) in HOXA۹ Gene and its Predicted Impactsin B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Background: B-Cell Acute lymphoblastic leukemia (B-ALL)has the highest annual prevalence rate of all diagnosed cancersin pediatric populations in developed countries. Homeobox(Hox) genes encoding transcription factors are vital in differentialand evolutionary processes, especially in hematopoiesis.Dysregulation of the Homeobox (HOX) transcription factorsincluding HOXA۹ is a dominant feature in most aggressiveacute leukemias. Significantly, Hoxa۹ is mainly dysregulated indifferent types of acute leukemia, including T- and B-cell acutelymphoblastic leukemia (B-ALL and T-ALL). A large part ofHOX cluster genes is considered oncogenes because of theirimplication in mutations, translocations, and improper expressionin some tissues. This study aimed to bioinformatics Analysisof a missense mutation in the HOXA۹ gene to predict theeffect of mutation on protein function.Materials and Methods: To pinpoint putatively pathogenicand causal variants we adopted the following filtering strategy:we first excluded variants with a minor allele frequency (MAF)>۱% in the dbSNP database. Then, we removed non‑codingand synonymous variants. Subsequently, the remaining variantswere filtered based on their in silico pathogenicity predictionand clinical relevance. Amino acid conservation was assessedby sequence alignments using CONSURF server.Results: The c.۳۰۴ G>C: p. Ala۱۰۲Pro variant is located inthe HOX۹ activation region and predicted tolerated by SIFT,benign by PolyPhen, probably pathogenic by SNP‑predictor,and has a score=۲۲.۸. This amino acid is conserved amongspecies. The p. Ala۱۰۲Pro is predicted probably pathogenicby UMD‑predictor with a high CADD score. Moreover, p. Ala۱۰۲Prois located in the activation domain of HOX۹ protein.Conclusion: HOXA۹ gene is part of the A cluster on chromosome۷ and encode a DNA‑binding transcription factor. Thepresent study identifies the association of a missense mutationin the HOXA۹ gene through bioinformatic predictions in leukemia.

کلیدواژه ها:

B-Cell Acute Lymphoblastic Leukemia ، HOXA۹ ، Mutation ، Bioinformatics