This nuclear gene encodes a mitochondrial matrix enzyme. Missense, nonsense, and frameshift mutations in this enzyme lead to ornithine transcarbamylase deficiency, which causes hyperammonemia. Since the gene for this enzyme maps close to that for Duchenne muscular dystrophy, it may play a role in that disease also. [provided by RefSeq, Jul 2008] See more...

Aliases for OTC Gene

Aliases for OTC Gene

  • Ornithine Carbamoyltransferase 2 3 5
  • Ornithine Transcarbamylase 2 3 4
  • OTCase 2 3 4
  • Ornithine Carbamoyltransferase, Mitochondrial 3 4
  • EC 4 51
  • EC 2.1.3 51
  • OCTD 3
  • OTC 5

External Ids for OTC Gene

Previous GeneCards Identifiers for OTC Gene

  • GC0XP036316
  • GC0XP036498
  • GC0XP037053
  • GC0XP037242
  • GC0XP037967
  • GC0XP038096
  • GC0XP038211
  • GC0XP035956

Summaries for OTC Gene

Entrez Gene Summary for OTC Gene

  • This nuclear gene encodes a mitochondrial matrix enzyme. Missense, nonsense, and frameshift mutations in this enzyme lead to ornithine transcarbamylase deficiency, which causes hyperammonemia. Since the gene for this enzyme maps close to that for Duchenne muscular dystrophy, it may play a role in that disease also. [provided by RefSeq, Jul 2008]

GeneCards Summary for OTC Gene

OTC (Ornithine Carbamoyltransferase) is a Protein Coding gene. Diseases associated with OTC include Ornithine Transcarbamylase Deficiency, Hyperammonemia Due To and Disorder Of Ornithine Metabolism. Among its related pathways are Arginine biosynthesis and Viral mRNA Translation. Gene Ontology (GO) annotations related to this gene include phospholipid binding and phosphate ion binding. An important paralog of this gene is CAD.

Gene Wiki entry for OTC Gene

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for OTC Gene

Genomics for OTC Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for OTC Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH0XJ038350 Promoter/Enhancer 1.3 EPDnew Ensembl ENCODE dbSUPER 606.5 +2.5 2538 8.7 ATF7 SP1 ATF3 YY1 ATF2 JUND HNF4A RXRA ZNF664 MAX OTC RPGR SRPX piR-57460-711 TSPAN7
GH0XJ038403 Promoter 0.3 EPDnew 600.2 +51.2 51213 0.1 OTC piR-52079-219 piR-41405-164 TSPAN7
GH0XJ038341 Enhancer 1.1 Ensembl ENCODE dbSUPER 4.6 -9.3 -9273 3.8 GATAD2A RXRB SP1 CEBPA SOX13 TCF7 TCF7L2 FOXA2 OSR2 ZNF580 OTC SRPX RPGR ENSG00000250349
GH0XJ038347 Enhancer 1 FANTOM5 Ensembl ENCODE dbSUPER 4.5 -5.1 -5127 2.4 SOX13 CEBPB MAFF MAFK SPI1 RPGR OTC MID1IP1 ENSG00000250349
GH0XJ038335 Enhancer 0.9 Ensembl ENCODE dbSUPER 0.4 -15.1 -15086 3.9 REST PRDM1 SP1 CTCF ZBTB44 RAD21 USF1 NR2F2 SPI1 HNF4A RPGR OTC ENSG00000250349
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around OTC on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for OTC

Top Transcription factor binding sites by QIAGEN in the OTC gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • COUP
  • COUP-TF1
  • GR
  • GR-alpha
  • HNF-4alpha1
  • HNF-4alpha2

Genomic Locations for OTC Gene

Genomic Locations for OTC Gene
68,919 bases
Plus strand
68,968 bases
Plus strand

Genomic View for OTC Gene

Genes around OTC on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
OTC Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for OTC Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for OTC Gene

Proteins for OTC Gene

  • Protein details for OTC Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Ornithine carbamoyltransferase, mitochondrial
    Protein Accession:
    Secondary Accessions:
    • A8K9P2
    • D3DWB0
    • Q3KNR1
    • Q6B0I1
    • Q9NYJ5

    Protein attributes for OTC Gene

    354 amino acids
    Molecular mass:
    39935 Da
    Quaternary structure:
    • Homotrimer.

    Three dimensional structures from OCA and Proteopedia for OTC Gene

neXtProt entry for OTC Gene

Selected DME Specific Peptides for OTC Gene


Post-translational modifications for OTC Gene

  • Acetylation at Lys-88 negatively regulates ornithine carbamoyltransferase activity in response to nutrient signals.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for OTC Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Santa Cruz Biotechnology (SCBT) Antibodies for OTC

Domains & Families for OTC Gene

Gene Families for OTC Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for OTC Gene

Suggested Antigen Peptide Sequences for OTC Gene

GenScript: Design optimal peptide antigens:
  • Ornithine transcarbamylase (OTC_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the aspartate/ornithine carbamoyltransferase superfamily. OTCase family.
  • Belongs to the aspartate/ornithine carbamoyltransferase superfamily. OTCase family.
genes like me logo Genes that share domains with OTC: view

Function for OTC Gene

Molecular function for OTC Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=carbamoyl phosphate + L-ornithine = H(+) + L-citrulline + phosphate; Xref=Rhea:RHEA:19513, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:46911, ChEBI:CHEBI:57743, ChEBI:CHEBI:58228; EC=;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Negatively regulated by lysine acetylation.
GENATLAS Biochemistry:
ornithine carbamoyltransferase,ornithine metabolism,urea cycle,mitochondrial matrix

Enzyme Numbers (IUBMB) for OTC Gene

Phenotypes From GWAS Catalog for OTC Gene

Gene Ontology (GO) - Molecular Function for OTC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004585 ornithine carbamoyltransferase activity IDA 2556444
GO:0005543 phospholipid binding IEA --
GO:0016597 amino acid binding IEA --
GO:0016740 transferase activity IEA --
GO:0016743 carboxyl- or carbamoyltransferase activity IEA --
genes like me logo Genes that share ontologies with OTC: view
genes like me logo Genes that share phenotypes with OTC: view

Human Phenotype Ontology for OTC Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

miRNA for OTC Gene

miRTarBase miRNAs that target OTC

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for OTC

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for OTC Gene

Localization for OTC Gene

Subcellular locations from UniProtKB/Swiss-Prot for OTC Gene

Mitochondrion matrix.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for OTC gene
Compartment Confidence
mitochondrion 5
cytosol 3
extracellular 2
peroxisome 2
nucleus 2
plasma membrane 1
cytoskeleton 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for OTC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005739 mitochondrion IBA,IDA 3472484
GO:0005743 mitochondrial inner membrane IEA --
GO:0005759 mitochondrial matrix TAS --
GO:0043231 intracellular membrane-bounded organelle IBA 21873635
genes like me logo Genes that share ontologies with OTC: view

Pathways & Interactions for OTC Gene

genes like me logo Genes that share pathways with OTC: view

UniProtKB/Swiss-Prot P00480-OTC_HUMAN

  • Pathway: Nitrogen metabolism; urea cycle; L-citrulline from L-ornithine and carbamoyl phosphate: step 1/1.

SIGNOR curated interactions for OTC Gene

Is activated by:

Gene Ontology (GO) - Biological Process for OTC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000050 urea cycle TAS --
GO:0001889 liver development IEA --
GO:0006520 cellular amino acid metabolic process IEA --
GO:0006526 arginine biosynthetic process IEA --
GO:0006591 ornithine metabolic process IEA --
genes like me logo Genes that share ontologies with OTC: view

Drugs & Compounds for OTC Gene

(48) Drugs for OTC Gene - From: DrugBank, PharmGKB, ClinicalTrials, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Ornithine Approved Nutra Target 84
Citrulline Approved, Investigational Nutra Target 0
Valproic acid Approved, Investigational Pharma HDAC1 inhibitor, Histone deacetylase (HDAC)inhibitors 377
Acetaminophen Approved Pharma 1316
Acetohydroxamic acid Approved Pharma 1

(31) Additional Compounds for OTC Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Carbamoyl phosphate
  • Aminocarbonyl dihydrogen phosphate
  • Carbamic phosphoric monoanhydride
  • Carbamyl phosphate
  • Monocarbamoyl phosphate
  • PHOSPHORIC ACID mono(formamide)ester
  • [po(OH)3]
  • Acide phosphorique
  • Acidum phosphoricum
  • H3PO4
  • Orthophosphoric acid
14066-19-4, 14265-44-2
genes like me logo Genes that share compounds with OTC: view

Transcripts for OTC Gene

mRNA/cDNA for OTC Gene

10 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for OTC

Alternative Splicing Database (ASD) splice patterns (SP) for OTC Gene

No ASD Table

Relevant External Links for OTC Gene

GeneLoc Exon Structure for

Expression for OTC Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for OTC Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for OTC Gene

This gene is overexpressed in Liver (x39.3) and Small Intestine - Terminal Ileum (x6.7).

Protein differential expression in normal tissues from HIPED for OTC Gene

This gene is overexpressed in Liver, secretome (44.7) and Liver (18.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for OTC Gene

Protein tissue co-expression partners for OTC Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for OTC

SOURCE GeneReport for Unigene cluster for OTC Gene:


mRNA Expression by UniProt/SwissProt for OTC Gene:

Tissue specificity: Mainly expressed in liver and intestinal mucosa.

Evidence on tissue expression from TISSUES for OTC Gene

  • Liver(4.7)
  • Nervous system(4.4)
  • Blood(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for OTC Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • endocrine
  • integumentary
  • lymphatic
  • nervous
  • respiratory
  • urinary
Head and neck:
  • brain
  • ear
  • head
  • esophagus
  • heart
  • lung
  • adrenal gland
  • kidney
  • liver
  • spleen
  • stomach
  • blood
  • peripheral nerve
  • peripheral nervous system
  • skin
  • sweat gland
genes like me logo Genes that share expression patterns with OTC: view

Orthologs for OTC Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for OTC Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia OTC 31
  • 99 (a)
(Canis familiaris)
Mammalia OTC 30 31
  • 93.5 (n)
(Bos Taurus)
Mammalia OTC 30 31
  • 92.56 (n)
(Mus musculus)
Mammalia Otc 30 17 31
  • 88.98 (n)
(Rattus norvegicus)
Mammalia Otc 30
  • 88.79 (n)
(Ornithorhynchus anatinus)
Mammalia OTC 31
  • 87 (a)
(Monodelphis domestica)
Mammalia OTC 31
  • 84 (a)
(Gallus gallus)
Aves OTC 30 31
  • 75.05 (n)
(Anolis carolinensis)
Reptilia OTC 31
  • 74 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia otc 30
  • 71.7 (n)
African clawed frog
(Xenopus laevis)
Amphibia otc-A 30
(Danio rerio)
Actinopterygii otc 30 31
  • 68.5 (n)
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8842 30
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ARG3 30 31 33
  • 52.01 (n)
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_AFR098W 30
  • 51.95 (n)
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F14366g 30
  • 51.63 (n)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons OTC 30
  • 50.89 (n)
Bread mold
(Neurospora crassa)
Ascomycetes NCU01667 30
  • 54.3 (n)
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes arg3 30
  • 51.58 (n)
Species where no ortholog for OTC was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for OTC Gene

Gene Tree for OTC (if available)
Gene Tree for OTC (if available)
Evolutionary constrained regions (ECRs) for OTC: view image

Paralogs for OTC Gene

Paralogs for OTC Gene

genes like me logo Genes that share paralogs with OTC: view

Variants for OTC Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for OTC Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
654598 Uncertain Significance: Ornithine carbamoyltransferase deficiency 38,367,329(+) G/A MISSENSE_VARIANT
675568 Benign: not provided 38,413,132(+) A/G INTRON_VARIANT
676164 Benign: not provided 38,403,555(+) G/A INTRON_VARIANT
678890 Likely Benign: not provided 38,410,086(+) G/T INTRON_VARIANT
680700 Benign: not provided 38,352,036(+) C/T

Additional dbSNP identifiers (rs#s) for OTC Gene

Structural Variations from Database of Genomic Variants (DGV) for OTC Gene

Variant ID Type Subtype PubMed ID
dgv2278e212 CNV loss 25503493
dgv2279e212 CNV loss 25503493
esv3573871 CNV loss 25503493
esv3573881 CNV loss 25503493
esv3573885 CNV loss 25503493
nsv6867 CNV insertion 18451855

Variation tolerance for OTC Gene

Residual Variation Intolerance Score: 43.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.28; 76.44% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for OTC Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for OTC Gene

Disorders for OTC Gene

MalaCards: The human disease database

(45) MalaCards diseases for OTC Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
ornithine transcarbamylase deficiency, hyperammonemia due to
  • ornithine carbamoyltransferase deficiency
disorder of ornithine metabolism
  • abnormality of ornithine metabolism
carbonic anhydrase va deficiency, hyperammonemia due to
  • ca5ad
orotic aciduria
  • orotic aciduria i
argininosuccinic aciduria
  • argininosuccinase deficiency
- elite association - COSMIC cancer census association via MalaCards
Search OTC in MalaCards View complete list of genes associated with diseases


  • Ornithine carbamoyltransferase deficiency (OTCD) [MIM:311250]: An X-linked disorder of the urea cycle which causes a form of hyperammonemia. Mutations with no residual enzyme activity are always expressed in hemizygote males by a very severe neonatal hyperammonemic coma that generally proves to be fatal. Heterozygous females are either asymptomatic or express orotic aciduria spontaneously or after protein intake. The disorder is treatable with supplemental dietary arginine and low protein diet. The arbitrary classification of patients into the 'neonatal' group (clinical hyperammonemia in the first few days of life) and 'late' onset (clinical presentation after the neonatal period) has been used to differentiate severe from mild forms. {ECO:0000269 PubMed:10070627, ECO:0000269 PubMed:10502831, ECO:0000269 PubMed:10737985, ECO:0000269 PubMed:11793483, ECO:0000269 PubMed:1480464, ECO:0000269 PubMed:1671317, ECO:0000269 PubMed:1721894, ECO:0000269 PubMed:2347583, ECO:0000269 PubMed:2474822, ECO:0000269 PubMed:2556444, ECO:0000269 PubMed:3170748, ECO:0000269 PubMed:7474905, ECO:0000269 PubMed:7951259, ECO:0000269 PubMed:8019569, ECO:0000269 PubMed:8081373, ECO:0000269 PubMed:8081398, ECO:0000269 PubMed:8099056, ECO:0000269 PubMed:8112735, ECO:0000269 PubMed:8530002, ECO:0000269 PubMed:8807340, ECO:0000269 PubMed:8830175, ECO:0000269 PubMed:8956038, ECO:0000269 PubMed:8956045, ECO:0000269 PubMed:9065786, ECO:0000269 PubMed:9143919, ECO:0000269 PubMed:9266388, ECO:0000269 PubMed:9286441, ECO:0000269 PubMed:9452024, ECO:0000269 PubMed:9452049, ECO:0000269 PubMed:9452065, ECO:0000269 Ref.32, ECO:0000269 Ref.43}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for OTC Gene

neonatal distress and hyperammonemia,including late-onset hyperammonemic coma

Additional Disease Information for OTC

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with OTC: view

Publications for OTC Gene

  1. High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide array CGH. (PMID: 19138872) Shchelochkov OA … Wong LJ (Molecular genetics and metabolism 2009) 3 23 41
  2. Association of ornithine transcarbamylase gene polymorphisms with hypertension and coronary artery vasomotion. (PMID: 19574962) Dumont J … Brousseau T (American journal of hypertension 2009) 3 23 41
  3. Identification of seven novel missense mutations, two splice-site mutations, two microdeletions and a polymorphic amino acid substitution in the gene for ornithine transcarbamylase (OTC) in patients with OTC deficiency. (PMID: 11793483) Climent C … Rubio V (Human mutation 2002) 3 4 23
  4. Crystal structure of human ornithine transcarbamylase complexed with carbamoyl phosphate and L-norvaline at 1.9 A resolution. (PMID: 10813810) Shi D … Allewell NM (Proteins 2000) 3 4 23
  5. Identification of a cytogenetic deletion and of four novel mutations (Q69X, I172F, G188V, G197R) affecting the gene for ornithine transcarbamylase (OTC) in Spanish patients with OTC deficiency. (PMID: 10502831) Climent C … Rubio V (Human mutation 1999) 3 4 23

Products for OTC Gene

Sources for OTC Gene