SNP based analysis depicts phenotypic variability in heme oxygenase-1 protein

Abstract

Abstract Objectives The heme oxygenase-1 (HMOX1) gene is a very critical player in cell homeostasis and takes part in heme catabolism. The HMOX1 gene possesses antioxidant, antiapoptotic anti-inflammatory, and antithrombotic properties. This study aimed to identify the deleterious SNPs which may alter the functional and structural attributes of the HMOX1 protein. Methods Deleterious SNPs were predicted using Polyphen-1, SIFT Blink, Polyphen-2, I-MUTANT 2.0, PROVEAN, PANTHER, MAPP, SNAP, and PhD-SNP. The 3D structure of the native protein was modelled using ITASSER and validated using PROCHECK. Mutant structures were created through SWISS PDB Viewer. All structures were energy-minimized using GROMACS. Protein-protein interaction (PPI) network was done using STRING. Results Three deleterious SNPs (rs146227657, rs373577583, and rs138349040 corresponding to A88D, A131V, and A206E respectively) in the HMOX1 gene were predicted. The structural analysis revealed notable differences in the structural attributes of wild-type and mutant structures. Furthermore, a PPI network was generated for the HMOX1 gene which predicts its interaction with other crucial cellular signaling molecules. Conclusions Three reported SNPs (A88D, A131V, and A206E) were identified as highly deleterious in the HMOX1 coding region that can alter the protein secondary structure, protein stability, and its conservation. This paves a new way to study the phenotype of the HMOX1 gene and its correlating diseases.