Targeted gene under study:

OMIM: 603833


We previously reported the first human disease linked with COXFA4 mutations in four individuals from a consanguineous Pakistani family. They presented with congenital lactic acidosis and subsequent evolution into a Leigh syndrome neurological phenotype. Using muscle tissue and patient-derived fibroblasts harbouring homozygous loss-of-function COXFA4 mutations, we confirmed that deficiency of COXFA4 impairs Complex IV (cytochrome c oxidase, COX) activity.

Several in vitro studies have provided insights towards the role of COXFA4 in the oxidative phosphorylation pathway and mitochondria metabolism. However, the impact of COXFA4 on human mitochondrial pathophysiology and the role of COXFA4 in Complex IV assembly and activity have not been fully elucidated. We are working on a novel series of patients with COXFA4-related mitochondrial disorder to expand its phenotypic and genotypic spectrum and understand the precise biological function of COXFA4 protein and its interaction with the other COX subunits and assembly factors.

Coordinating clinicians

Robert Pitceathly –


Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK

Specific requirements beyond clinical data and genotype data sharing:

1- Re-analysis of DNA samples: No

2- Resampling of patients: No

3- Linked to a translational/basic research project: Yes