Analysis of reported SCO2 gene mutations affecting cytochrome c oxidase activity in various diseases

A large number of mutations have been reported in SCO2 (synthesis of cytochrome c oxidase) gene in association with COXdeficiency reported in different diseases such as cardioencephalomyopathy, cardiomyopathy and Leigh syndrome. However, veryfew of these mutations have been functionally analyzed.SCO2 gene encodes for an essential assembly factor for the formation ofcytochrome c oxidase (COX). It is a nuclear encoded protein that helps in transfer of copper ions to COX. This study is an attemptto 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 11variations, 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. Ascompared 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 andshould be investigated by subsequent functional analyses. This will help in an appropriate diagnosis and management of the widespectrum of COX deficiency diseases.