<i>In-Silico</i> Computing of the Most Deleterious nsSNPs in <i>HBA1</i> Gene

<div><p>Background</p><p>α-Thalassemia (α-thal) is a genetic disorder caused by the substitution of single amino acid or large deletions in the <i>HBA1</i> and/or <i>HBA2</i> genes.</p><p>Method</p><p>Using modern bioinformatics tools as a systematic <i>in-silico</i> approach to predict the deleterious SNPs in the <i>HBA1</i> gene and its significant pathogenic impact on the functions and structure of HBA1 protein was predicted.</p><p>Results and Discussion</p><p>A total of 389 SNPs in <i>HBA1</i> were retrieved from dbSNP database, which includes: 201 non-coding synonymous (nsSNPs), 43 human active SNPs, 16 intronic SNPs, 11 mRNA 3′ UTR SNPs, 9 coding synonymous SNPs, 9 5′ UTR SNPs and other types. Structural homology-based method (PolyPhen) and sequence homology-based tool (SIFT), SNPs&Go, PROVEAN and PANTHER revealed that 2.4% of the nsSNPs are pathogenic.</p><p>Conclusions</p><p>A total of 5 nsSNPs (G60V, K17M, K17T, L92F and W15R) were predicted to be responsible for the structural and functional modifications of HBA1 protein. It is evident from the deep comprehensive <i>in-silico</i> analysis that, two nsSNPs such as G60Vand W15R in <i>HBA1</i> are highly deleterious. These “2 pathogenic nsSNPs” can be considered for wet-lab confirmatory analysis.</p>