Pathogenicity Prediction of Potential Variants of Iba57 Gene Causing Heredity Spastic Paraplegia Through Mitochondrial Dysfunction by using Computational Tools

Abstract

IBA57 is the protein-coding gene that involves in the functional activity of mitochondria. IBA57 protein is related to the iron-sulfur cluster assembly pathway that regulates specific proteins. Mutation in the IBA57 gene damaged the functional activity of mitochondria and respiratory complexes. Heredity spastic paraplegia is a heterogeneous group of neurological disorders that affect the spinal cords and nerves in the human body. In this study, we use bioinformatics tools to analyze the structural and functional information of the IBA57 gene. Advanced in-silico approaches apply to find the pathogenic variants. To find these novel mutations, IBA57 protein data is retrieved through UniProt and gnomAD databases. Pathogenicity of variants was prognosticated through these software (SNP2, PhD-SNPg, and SNPs&go). Furthermore, the strategy applied to these variants is to check out the stability of IBA57 protein, by using DynaMut, CUPSAT, I-Stable, MAESTRO, and YASARA. IBA57 proteins are affected during the splicing mechanism. If mutation gets repeated on the splicing sites then there is a probability that the mutation can disturb the gene sequence as a result the protein formed also gets changed. ScanProsite protein databases and UCSF Chimera (PDB ID: 6QE4) were used to analyze the structural and functional domains of the protein. The deleterious effect of mutations on the structure of IBA57 protein with different parameters and contact/clashes among mutated residues also presented by chimera. These findings conclude that 34 high-risk pathogenic missense variants can cause the change of amino acid properties of IBA57 protein. Hence, this study revealed the importance of bioinformatics algorithms to figure out highly pathogenic variants linked with the structural and functional relationship of IBA57 protein.