In-silico Analysis of Adenosine Deaminase: From Gene Sequence Retrieval to Clinical Implications and Drug Targets

Abstract

Background: Adenosine Deaminase (ADA) plays a critical role in purine metabolism and immune function. Its genetic and molecular characterization is essential for understanding its involvement in various physiological and pathological processes. The ADA gene has been implicated in immune system disorders and offers a potential target for therapeutic intervention. Objective: This study aims to comprehensively analyze the ADA gene and its protein product, detailing the genetic structure, physiochemical properties, subcellular localization, expression patterns, clinical variations, functional domains, splice variants, and potential as a drug target, to enhance the understanding of its function in human health. Methods: We utilized an array of in silico tools for gene sequence retrieval, including analysis of genomic databases for ADA's chromosomal location and gene structure. Physiochemical properties were determined using ProtParam, and subcellular localization was predicted with CELLO v.2.5. Gene expression levels across various tissues were ascertained using the Archive Ensemble TOOL. Clinical variations were categorized based on their potential pathogenicity, while splice variants and functional domains were predicted using domain-specific databases. Post-translational modifications were analyzed with prediction tools from the CBS server, and the STRING database facilitated protein interaction network analysis. Additionally, the DoG-Site Scorer predicted ADA's druggability profile. Results: ADA was localized to chromosome 12 (20q13.12), comprising 45940 base pairs encoding 363 amino acids. The protein's molecular weight was calculated as 37948.09, with a total atom count of 5396. Predictive localization indicated periplasmic and cytoplasmic presence with reliability scores of 1.437*, 1.210*, and 1.058*. Expression profiling revealed high ADA levels in the duodenum, with a notable expression in the lymphatic node. Clinical variations identified included 21 insertions and 23 inversions, with two pathogenic instances. Splice variant analysis predicted nine sites, and drug-binding potential was identified with scores as high as 0.81. Conclusion: Our study provides a detailed analysis of ADA, highlighting its genetic complexity and biological significance. The identification of clinically relevant gene variations and drug-binding pockets offers potential pathways for therapeutic intervention, emphasizing the importance of ADA in medical research and treatment strategies.