Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. Required for UMP biosynthesis via de novo pathway. (S)-dihydroorotate + a quinone = a quinol + orotate Binds 1 FMN per subunit. Pyrimidine metabolism; UMP biosynthesis via de novo pathway; orotate from (S)-dihydroorotate (quinone route): step 1/1. Monomer. The uncleaved transit peptide is required for mitochondrial targeting and proper membrane integration. The disease is caused by variants affecting the gene represented in this entry. The identification of DHODH defects as the cause of postaxial acrofacial dysostosis (POADS) was obtained via exome sequencing (PubMed:19915526), demonstrating that this method is a powerful tool for identifying genes underlying rare Mendelian disorders. Exome sequencing consists of targeted resequencing of all protein-coding subsequences, which requires around 5% as much sequencing as a whole human genome. Belongs to the dihydroorotate dehydrogenase family. Type 2 subfamily.