Abstract
Polymorphisms of the disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) are linked to pathophysiological changes in lung inflammation, cancer, Alzheimer’s disease (AD), encephalopathy, liver fibrosis, and cardiovascular diseases. In this study, we predicted the pathogenicity of ADAM10 non-synonymous single nucleotide polymorphisms (nsSNPs) in a wide array of mutation analyzing bioinformatics tools. We retrieved 423 nsSNPs from dbSNP-NCBI for the analysis, and 13 were predicted deleterious by each of the ten tools: SIFT, PROVEAN, CONDEL, PANTHER-PSEP, SNAP2, SuSPect, PolyPhen-2, Meta-SNP, Mutation Assessor and Predict-SNP. Further assessment of amino acid sequences, homology models, conservation profiles, and inter-atomic interactions identified C222G, G361E and C639Y as the most pathogenic mutations. We validated this prediction through structural stability analysis using DUET, I-Mutant Suite, SNPeffect and Dynamut. Molecular dynamics simulations and principal component analysis also indicated considerable instability of the C222G, G361E and C639Y variants. Therefore, these ADAM10 nsSNPs could be candidates for diagnostic genetic screening and therapeutic molecular targeting.
Communicated by Ramaswamy H. Sarma
Authors’ Contributions
Jannatun Namme: Conceptualization, Methodology, Resources, Software, Investigation, Data Collection & Interpretation, Validation, Writing- Manuscript draft. Asim Bepari: Conceptualization, Supervision, Investigation, Methodology, Resources, Data Interpretation, Software, Editing & Reviewing Manuscript. Hasan Reza: Visualization, Manuscript-Reviewing, and Editing. All authors reviewed and approved the final version of the manuscript.
Disclosure statement
The authors declare no competing interests.
Data availability statement
No datasets were generated in this study. The datasets analyzed during the current study are available in public repositories. ADAM10 genetic polymorphisms. Repository: dbSNP, Gene Name: ADAM10, Link: https://www.ncbi.nlm.nih.gov/snp/?term=Homo+sapiens+ADAM10. ADAM10 genetic polymorphisms in cancer. Repository: GDC Data Portal. Link: https://portal.gdc.cancer.gov/genes/ENSG00000137845. ADAM10 protein sequence. Repository: UniportKB, Accession no.: O14672. Link: https://www.uniprot.org/uniprotkb/O14672/entry. ADAM10 macromolecular structure. Repository: RCSB PDB, PDB ID: 6BDZ. Link: https://www.rcsb.org/structure/6BDZ