The human gene COQ2 maps on chromosome 4q21 and it comprises seven exons. COQ2 encodes p-hydroxybenzoate polyprenyl transferase, the second enzyme involved in the biosynthesis of Coenzyme Q 10 (ubiquinone, CoQ, CoQ10), and is responsible for the condensation of the isoprenyl chain to the benzoquinone ring of the molecule. So far 19 mutations in COQ2 have been identified, mostly by exome sequencing.
Different pathomechanisms underly CoQ deficiency due to the multiple cell functions of CoQ10: it is an electron carrier in the mitochondrial respiratory chain, a powerful antioxidant, and a cofactor for Sulfide Quinone Reductase (SQR) and Dihydroorotate dehydrogenase (DHODH). However, in vitro studies point to oxidative stress as main mechanism of disease in COQ2 deficiency. Studies of genotype-phenotype correlation in yeast showed correlation between the CoQ content of the yeast expressing individual mutants (which reflects residual COQ2 function) and the phenotype. The less detrimental mutation, p. Met78Val, was found in the homozygous state in the two patients with the mildest phenotype. The other two relatively mild mutations, p.Asn178Ser and pTyr247Cys, were found in patients with the “intermediate” phenotypes characterized by SRNS +/- encephalopathy (in the homozygous state or in compound heterozygosity with a severe allele). On the contrary, all patients with the severe neonatal phenotype harboured two alleles associated with low CoQ production.