ArticleBioscience reports2012
Protein instability and functional defects caused by mutations of dihydro-orotate dehydrogenase in Miller syndrome patients.
Article in Bioscience reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 32 citations in OpenAlex.
- The Phenotypic Spectrum of Miller Syndrome: Insight From a French Cohort.Clinical genetics · 2026Article
- Arzanol Inhibits Human Dihydroorotate Dehydrogenase and Shows Antiviral Activity.Journal of natural products · 2025Article
- PDE7A inhibition suppresses triple-negative breast cancer by attenuating de novo pyrimidine biosynthesis.Cell reports. Medicine · 2025Article
- Expert consensus on classification and diagnosis of congenital orofacial cleft.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2025Article
- Article
- Assessment of a novel variation in DHODH gene causing Miller syndrome: The first report in Chinese population.Molecular genetics & genomic medicine · 2023Article
- Elevated DHODH expression promotes cell proliferation via stabilizing β-catenin in esophageal squamous cell carcinoma.Cell death & disease · 2020Article
- Cross-Cancer Pleiotropic Associations with Lung Cancer Risk in African Americans.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2019Article
- Lipids Shape the Electron Acceptor-Binding Site of the Peripheral Membrane Protein Dihydroorotate Dehydrogenase.Cell chemical biology · 2018Article
- Rare syndromes of the head and face: mandibulofacial and acrofacial dysostoses.Wiley interdisciplinary reviews. Developmental biology · 2017Review
- Pyrimidine Pathway-Dependent and -Independent Functions of the Toxoplasma gondii Mitochondrial Dihydroorotate Dehydrogenase.Infection and immunity · 2016Article
- Facial dysostoses: Etiology, pathogenesis and management.American journal of medical genetics. Part C, Seminars in medical genetics · 2013Review
- Dihydro-orotate dehydrogenase is physically associated with the respiratory complex and its loss leads to mitochondrial dysfunction.Bioscience reports · 2013Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Miller syndrome is a recessive inherited disorder characterized by postaxial acrofacial dysostosis. It is caused by dysfunction of the DHODH (dihydroorotate dehydrogenase) gene, which encodes a key enzyme in the pyrimidine de novo biosynthesis pathway and is localized at mitochondria intermembrane space. We investigated the consequence of three missense mutations, G202A, R346W and R135C of DHODH, which were previously identified in patients with Miller syndrome. First, we established HeLa cell lines stably expressing DHODH with Miller syndrome-causative mutations: G202A, R346W and R135C. These three mutant proteins retained the proper mitochondrial localization based on immunohistochemistry and mitochondrial subfractionation studies. The G202A, R346W DHODH proteins showed reduced protein stability. On the other hand, the third one R135C, in which the mutation lies at the ubiquinone-binding site, was stable but possessed no enzymatic activity. In conclusion, the G202A and R346W mutation causes deficient protein stability, and the R135C mutation does not affect stability but impairs the substrate-induced enzymatic activity, suggesting that impairment of DHODH activity is linked to the Miller syndrome phenotype.
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