title: Analysis of reported SCO2 gene mutations affecting cytochrome c oxidase activity in various diseases.
abstract: A large number of mutations have been reported in SCO2 (synthesis of cytochrome c oxidase) gene in association with COX deficiency reported in different diseases such as cardioencephalomyopathy, cardiomyopathy and Leigh syndrome. However, very few of these mutations have been functionally analyzed.SCO2 gene encodes for an essential assembly factor for the formation of cytochrome c oxidase (COX). It is a nuclear encoded protein that helps in transfer of copper ions to COX. This study is an attempt to understand the possible effect of these mutations on the structure and function of SCO2 protein, by using different in silico tools. As per Human Gene Mutation Database, total 11 non synonymous variations have been reported in SCO2 gene. Among these 11 variations, only E140K and R171W are functionally proven to cause COX deficiency. They have been used as controls in this study. The remaining variations were further analyzed using ClustalW, SIFT, PolyPhen-2, GOR4, MuPro and Panther softwares. As compared to the results of the controls, most of these variations were predicted to affect the structure of SCO2 protein and hence, may cause COX dysfunction. Thus, we hypothesize that these variations have the potential to result in a disease phenotype and should be investigated by subsequent functional analyses. This will help in an appropriate diagnosis and management of the wide spectrum of COX deficiency diseases.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, New Delhi.
authors.forename: Radhika
authors.initials: R
authors.lastname: Chadha
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, Noida.
authors.forename: Ritika
authors.initials: R
authors.lastname: Shah
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, Noida.
authors.forename: Shalini
authors.initials: S
authors.lastname: Mani
keywords: COX; OXPHOS; SCO2; in silico; mitochondrial diseases; mutations
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