75 to 80 percent of Leigh syndrome is caused by mutations in nuclear DNA; mutations affecting the function or assembly of the fourth complex involved in oxidative phosphorylation, cytochrome c oxidase (COX), cause most cases of Leigh disease. Mutations in a gene called SURF1 (surfeit1) are the most common cause of this subtype of Leigh syndrome. The protein that SURF1 codes for is terminated early and therefore cannot perform its function, shepherding the subunits of COX together into a functional protein complex. This results in a deficit of COX protein, reducing the amount of energy produced by mitochondria. SURF1 is located on the long arm of chromosome 9. Another nuclear DNA mutation that causes Leigh syndrome affects another protein complex in the mitochondria, pyruvate dehydrogenase, which is an enzyme in the Link reaction pathway. Some types of SURF1 mutations cause a subtype of Leigh syndrome that has a particularly late onset but similarly variable clinical course.