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    DHODH dihydroorotate dehydrogenase (quinone) [ Homo sapiens (human) ]

    Gene ID: 1723, updated on 2-Nov-2024

    Summary

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    Official Symbol
    DHODHprovided by HGNC
    Official Full Name
    dihydroorotate dehydrogenase (quinone)provided by HGNC
    Primary source
    HGNC:HGNC:2867
    See related
    Ensembl:ENSG00000102967 MIM:126064; AllianceGenome:HGNC:2867
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    URA1; POADS; DHOdehase
    Summary
    The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in de novo pyrimidine biosynthesis. This protein is a mitochondrial protein located on the outer surface of the inner mitochondrial membrane. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in liver (RPKM 7.8), kidney (RPKM 1.7) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DHODH in Genome Data Viewer
    Location:
    16q22.2
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (72008744..72027659)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (77826803..77845694)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (72042643..72061558)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene polycystin 1 like 3, transient receptor potential channel interacting Neighboring gene ribosomal protein L39 pseudogene 31 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:72042438-72042637 Neighboring gene ATP synthase F1 subunit alpha pseudogene 3 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr16:72057307-72058506 Neighboring gene haptoglobin Neighboring gene haptoglobin-related protein

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. The effect of exon (19C>A) dihydroorotate dehydrogenase gene polymorphism on rheumatoid arthritis treatment with leflunomide. Pawlik A, et al. Pharmacogenomics, 2009 Feb. PMID 19207032
    2. Dihydroorotate dehydrogenase in oxidative phosphorylation and cancer. Boukalova S, et al. Biochim Biophys Acta Mol Basis Dis, 2020 Jun 1. PMID 32151633
    3. Structural Optimization and Structure-Activity Relationship of 4-Thiazolidinone Derivatives as Novel Inhibitors of Human Dihydroorotate Dehydrogenase. Zeng F, et al. Molecules, 2019 Jul 31. PMID 31370178, Free PMC Article
    4. Elevated plasma dihydroorotate in Miller syndrome: Biochemical, diagnostic and clinical implications, and treatment with uridine. Duley JA, et al. Mol Genet Metab, 2016 Sep. PMID 27370710
    5. Conformational changes of the HsDHODH N-terminal Microdomain via DEER Spectroscopy. Vicente EF, et al. J Phys Chem B, 2015 Jul 16. PMID 26086954, Free PMC Article

    See all (61) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Pivotal role of dihydroorotate dehydrogenase as a therapeutic target in adult T-cell leukemia.
      Title: Pivotal role of dihydroorotate dehydrogenase as a therapeutic target in adult T-cell leukemia.
    2. Bioinformatics analysis and experimental verification of the cancer-promoting effect of DHODH in clear cell renal cell carcinoma.
      Title: Bioinformatics analysis and experimental verification of the cancer-promoting effect of DHODH in clear cell renal cell carcinoma.
    3. Exploiting Cancer Vulnerabilities by Blocking of the DHODH and GPX4 Pathways: A Multifunctional Bodipy/PROTAC Nanoplatform for the Efficient Synergistic Ferroptosis Therapy.
      Title: Exploiting Cancer Vulnerabilities by Blocking of the DHODH and GPX4 Pathways: A Multifunctional Bodipy/PROTAC Nanoplatform for the Efficient Synergistic Ferroptosis Therapy.
    4. Screening for DAX1/EWS-FLI1 functional inhibitors identified dihydroorotate dehydrogenase as a therapeutic target for Ewing's sarcoma.
      Title: Screening for DAX1/EWS-FLI1 functional inhibitors identified dihydroorotate dehydrogenase as a therapeutic target for Ewing's sarcoma.
    5. Protein-lipid interactions of human dihydroorotate dehydrogenase and three mutants associated with Miller syndrome.
      Title: Protein-lipid interactions of human dihydroorotate dehydrogenase and three mutants associated with Miller syndrome.
    6. Protein production, kinetic and biophysical characterization of three human dihydroorotate dehydrogenase mutants associated with Miller syndrome.
      Title: Protein production, kinetic and biophysical characterization of three human dihydroorotate dehydrogenase mutants associated with Miller syndrome.
    7. DHODH is an independent prognostic marker and potent therapeutic target in neuroblastoma.
      Title: DHODH is an independent prognostic marker and potent therapeutic target in neuroblastoma.
    8. New Insights into the Interaction of Class II Dihydroorotate Dehydrogenases with Ubiquinone in Lipid Bilayers as a Function of Lipid Composition.
      Title: New Insights into the Interaction of Class II Dihydroorotate Dehydrogenases with Ubiquinone in Lipid Bilayers as a Function of Lipid Composition.
    9. DHODH tangoing with GPX4 on the ferroptotic stage.
      Title: DHODH tangoing with GPX4 on the ferroptotic stage.
    10. DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer.
      Title: DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (33)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Miller syndrome
    MedGen: C0265257 OMIM: 263750 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Conduct disorder and ADHD: evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables dihydroorotase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables dihydroorotate dehydrogenase (quinone) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables dihydroorotate dehydrogenase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in 'de novo' UMP biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in 'de novo' pyrimidine nucleobase biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in UDP biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in pyrimidine ribonucleotide biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in mitochondrial inner membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    dihydroorotate dehydrogenase (quinone), mitochondrial
    Names
    dihydroorotate oxidase
    human complement of yeast URA1
    NP_001352.2
    XP_005255886.1
    XP_047289630.1
    XP_054235689.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016271.1 RefSeqGene

      Range
      5001..21674
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001361.5 → NP_001352.2  dihydroorotate dehydrogenase (quinone), mitochondrial

      See identical proteins and their annotated locations for NP_001352.2

      Status: REVIEWED

      Source sequence(s)
      AC009087, AI499306, AU130529, AU152444, BC065245, BE789211
      Consensus CDS
      CCDS42192.1
      UniProtKB/Swiss-Prot
      A8K8C8, Q02127, Q6P176
      UniProtKB/TrEMBL
      I3NI32
      Related
      ENSP00000219240.4, ENST00000219240.9
      Conserved Domains (1) summary
      cd04738
      Location:45 → 373
      DHOD_2_like; Dihydroorotate dehydrogenase (DHOD) class 2. DHOD catalyzes the oxidation of (S)-dihydroorotate to orotate. This is the fourth step and the only redox reaction in the de novo biosynthesis of UMP, the precursor of all pyrimidine nucleotides. DHOD requires ...

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      72008744..72027659
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047433674.1 → XP_047289630.1  dihydroorotate dehydrogenase (quinone), mitochondrial isoform X1

    2. XM_005255829.5 → XP_005255886.1  dihydroorotate dehydrogenase (quinone), mitochondrial isoform X2

      Conserved Domains (1) summary
      cd04738
      Location:3 → 230
      DHOD_2_like; Dihydroorotate dehydrogenase (DHOD) class 2. DHOD catalyzes the oxidation of (S)-dihydroorotate to orotate. This is the fourth step and the only redox reaction in the de novo biosynthesis of UMP, the precursor of all pyrimidine nucleotides. DHOD requires ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      77826803..77845694
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054379714.1 → XP_054235689.1  dihydroorotate dehydrogenase (quinone), mitochondrial isoform X2

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001025193.1: Suppressed sequence

      Description
      NM_001025193.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q02127.3 GenPept UniProtKB/Swiss-Prot:Q02127

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