Affinage

OTC

Ornithine transcarbamylase, mitochondrial · UniProt P00480

Length
354 aa
Mass
39.9 kDa
Annotated
2026-04-29
100 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OTC (ornithine transcarbamylase) is a mitochondrial matrix enzyme that catalyzes the condensation of ornithine and carbamoyl phosphate to form citrulline, constituting the second committed step of the urea cycle. OTC-derived citrulline is essential not only for ureagenesis—where ornithine availability is rate-limiting for cycle flux—but also for de novo arginine synthesis and basal nitric oxide production via the citrulline–arginine–NO pathway (PMID:18697914, PMID:16772445). The OTC precursor is synthesized in the cytoplasm and imported into the mitochondrial matrix, where disease-causing mutations such as P225L/R can impair translocation or folding rather than catalysis per se (PMID:9427144, PMID:10448647). Liver-specific OTC transcription depends on a promoter–enhancer interaction requiring an HNF4α binding site, and the pre-mRNA is subject to species-specific alternative splicing controlled by differential TIA1 recognition of intronic sequences flanking the spf/ash mutation site (PMID:20127982, PMID:35605046, PMID:34906067).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1985 High

    Mapping OTC to Xp11.4–Xp21 and cloning its cDNA established the gene's chromosomal identity and linked it to X-linked ornithine transcarbamylase deficiency.

    Evidence Somatic cell hybrid mapping, Northern blot, and cDNA cloning in human cells

    PMID:3839070

    Open questions at the time
    • Gene structure (intron–exon organization) not yet defined
    • No functional reconstitution of enzyme activity from cloned cDNA
  2. 1991 High

    Demonstration that the OTC precursor must be imported into mitochondria for function—and that liver-specific trans-acting factors are required for OTC transcription—established two distinct regulatory layers: post-translational targeting and tissue-restricted gene expression.

    Evidence Electron microscope immunolocalization after adenoviral gene delivery (mitochondrial import); cell fusion experiments showing OTC reactivation only upon complementation with OTC-positive hepatocytes

    PMID:10448647 PMID:1860901

    Open questions at the time
    • Identity of the liver-specific trans-acting factor(s) not determined
    • Species-specific differences in precursor import (mouse vs. human) unexplained
  3. 1995 Medium

    Transgenic rescue in spf-ash mice revealed that intestinal OTC activity contributes more than hepatic activity to preventing orotic aciduria, establishing tissue-specific functional contributions of OTC beyond the liver.

    Evidence OTC transgene expression in spf-ash mice with quantitation of urinary orotic acid and tissue OTC activity

    PMID:7827141

    Open questions at the time
    • Mechanism of intestinal vs. hepatic OTC contribution to whole-body nitrogen balance not fully dissected
    • Single transgenic line studied
  4. 1997 Medium

    Characterization of disease-causing missense mutations (P225L/R, L148F) separated catalytic defects from import/folding defects, revealing that many pathogenic OTC mutations act by destabilizing the precursor rather than abolishing enzymatic activity.

    Evidence Enzyme kinetics (Km, thermal stability) and immunoblot of mutant OTC in patient liver and COS1 transfection

    PMID:9056557 PMID:9427144

    Open questions at the time
    • No in vitro import assay to directly measure translocation efficiency of mutant precursors
    • Structural basis of folding defects unknown at atomic resolution
  5. 2006 High

    Isotopic flux analyses in spf-ash mice demonstrated that OTC-derived citrulline is rate-limiting for de novo arginine synthesis and whole-body NO production, and that ornithine supply is rate-limiting for OTC-dependent ureagenesis, connecting OTC to systemic nitrogen and NO metabolism.

    Evidence In vivo stable isotope tracer infusion (15N-citrulline→arginine→NO; 13C-urea) in conscious spf-ash mice

    PMID:16772445 PMID:18697914

    Open questions at the time
    • Whether citrulline supplementation can fully restore NO production independent of OTC not tested
    • Contribution of extrahepatic OTC to citrulline-arginine-NO pathway not quantified
  6. 2010 Medium

    Identification of a promoter–enhancer interaction required for full OTC transcription, disrupted by the c.−366A>G variant, defined the cis-regulatory architecture governing liver-specific OTC expression.

    Evidence Dual-luciferase reporter assay with promoter-enhancer constructs and mutagenesis

    PMID:20127982

    Open questions at the time
    • Chromatin-level interaction (e.g. 3C/Hi-C) not confirmed
    • Trans-acting factors mediating the enhancer–promoter loop not identified at this stage
  7. 2015 High

    Dissection of the spf-ash mutation (c.386G>A) revealed that the same nucleotide change causes distinct aberrant splicing events in mouse (partial intron retention) vs. human (exon skipping), explaining species-specific residual OTC activity and complicating preclinical modeling.

    Evidence RT-PCR of liver RNA, minigene splicing assays, and enzyme activity measurement across species

    PMID:25853564

    Open questions at the time
    • Trans-acting factor(s) responsible for species-specific splice-site selection not yet identified
  8. 2021 High

    The species-specific splicing of the spf-ash allele was traced to differential TIA1 binding at intronic positions +10–11 downstream of the cryptic 5′ splice site, and common polymorphic variants (p.Lys46Arg, p.Gln270Arg) were shown to modulate OTC enzymatic activity in cis, refining the genotype–phenotype landscape.

    Evidence RNA pulldown for TIA1, minigene nucleotide-swap mutagenesis, recombinant OTC enzyme activity assays

    PMID:34015158 PMID:34906067

    Open questions at the time
    • Whether TIA1 modulation is therapeutically targetable in patients not established
    • Structural basis for polymorphic modulation of activity not resolved
  9. 2022 Medium

    A promoter variant (c.−106C>A) in a conserved HNF4α binding site was shown to reduce OTC expression >5-fold, mechanistically explaining late-onset hyperammonemia and confirming HNF4α as a key transcriptional regulator of OTC.

    Evidence Dual-luciferase reporter assay with wild-type and mutant promoter ± upstream enhancer

    PMID:35605046

    Open questions at the time
    • Direct HNF4α ChIP at the OTC promoter not shown
    • In vivo validation of this promoter variant's effect on OTC mRNA levels not performed
  10. 2023 High

    A high-throughput functional assay covering 84% of SNV-accessible missense substitutions created a near-complete variant effect map, identifying a 13-amino-acid SMG loop required in human but not yeast cells and enabling clinical variant classification at scale.

    Evidence Yeast-based OTC activity assay for 1,570 individual substitutions, benchmarked against clinical data and protein structure

    PMID:37146589

    Open questions at the time
    • SMG loop function in human cells not mechanistically dissected
    • Yeast assay may not capture all mammalian-specific folding/import defects

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for how disease mutations differentially affect mitochondrial import versus catalytic function, the full complement of trans-acting factors controlling OTC promoter–enhancer looping in vivo, and whether extrahepatic OTC (intestinal, neuronal) can be therapeutically augmented to compensate for hepatic deficiency.
  • No atomic-resolution structure of human OTC with bound precursor signal peptide
  • In vivo chromatin conformation at the OTC locus not mapped
  • Functional significance of neuronal OTC expression not experimentally validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-1430728 Metabolism 3
Partners
HNF4ATIA1

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 The human OTC gene was localized to chromosomal region Xp11.4-Xp21 using somatic cell hybrids, and a frequent RFLP (MspI) was identified; the gene encodes ornithine transcarbamylase, a mitochondrial enzyme of the urea cycle. Somatic cell hybrid mapping, Northern blot, cDNA cloning Nucleic acids research High 3839070
1991 Newly synthesized mouse OTC precursor (pOTC) is efficiently imported into mitochondria following adenovirus-mediated gene delivery in spf(ash) hepatocytes, with mitochondrial localization confirmed by electron microscope immunolocalization; human OTC precursor showed a block in mitochondrial translocation in the same system. Electron microscope immunolocalization, quantitative morphometry, subcellular fractionation after adenoviral OTC gene delivery Molecular medicine High 10448647
1991 Rescue of OTC activity in BWTG3 hepatoma cells (which lack OTC) requires fusion with OTC-positive hepatocytes; the silent OTC gene in hepatoma cells cannot be reactivated by hormones or azacytidine alone, indicating cell-context-dependent transcriptional regulation requiring a liver-specific trans-acting factor. Cell fusion, enzyme activity assay, azacytidine treatment, hormone induction Journal of cell science Medium 1860901
1993 Zinc supplementation increases hepatic OTC enzymatic activity in cirrhotic rats, with OTC activity positively correlated with serum and hepatic zinc content, suggesting zinc as a modulator of OTC catalytic function. In vivo zinc supplementation, radiochemical OTC enzyme activity assay in cirrhotic rat liver Journal of trace elements and electrolytes in health and disease Low 8019156
1995 Small intestinal OTC activity is more important than hepatic OTC activity for preventing urinary orotic acid excretion; in spf-ash mice carrying an OTC transgene, elevated intestinal OTC activity (30% of control) prevents excess orotic aciduria, whereas hepatic activity alone at ~10% is insufficient. OTC transgenic rescue in spf-ash mice, measurement of urinary orotic acid vs. tissue OTC activity Biochimica et biophysica acta Medium 7827141
1997 Mutations P225L and P225R in OTC codon 225 result in undetectable OTC protein antigen in liver despite near-normal residual enzyme properties (normal pH dependence, Km, stability), suggesting the mutations impair efficient import/folding of the precursor into mitochondria rather than catalytic function per se. Immunoblot for OTC antigen, enzyme kinetic assays (Km for ornithine and carbamoyl phosphate, thermal stability, urea stability), sequencing Journal of inherited metabolic disease Medium 9427144
1997 Transfection of COS1 cells with the Leu148Phe mutant OTC cDNA yielded undetectable OTC enzyme activity, confirming this missense mutation abolishes OTC catalytic function. Transient transfection (COS1 cells), enzyme activity assay American journal of medical genetics Medium 9056557
2006 In OTC-deficient spf(ash) mice, reduced citrulline availability (30–50% of wild-type) leads to reduced de novo arginine production and a 50% reduction in whole-body nitric oxide production under basal conditions, demonstrating that OTC-derived citrulline is required to sustain NO synthesis via the citrulline-arginine-NO pathway. Stable isotope tracer infusion (LC-MS measurement of [15N]citrulline→[15N]arginine→NO flux) in vivo in spf(ash) mice American journal of physiology. Endocrinology and metabolism High 18697914
2006 Ornithine supplementation in spf(ash) mice restores ureagenesis, reduces plasma ammonia, and normalizes 15N transfer from glutamine to urea, demonstrating that ornithine availability is rate-limiting for OTC-dependent urea cycle flux under conditions of unbalanced amino acid loads. Multiple stable isotope tracer infusion in vivo ([13C18O]urea, [15N]glutamine tracers) in conscious spf(ash) mice The Journal of nutrition High 16772445
2010 A heterozygous single nucleotide substitution (c.-366A>G) in the OTC promoter disrupts the interaction of the promoter with an upstream enhancer, reducing transcriptional activity; the OTC promoter requires this upstream enhancer for full activity, and the interaction is necessary for liver-specific OTC expression. Dual luciferase reporter assay, transcription start site mapping, promoter-enhancer interaction functional studies Human mutation Medium 20127982
2015 The spf/ash mutation (c.386G>A; p.R129H) causes aberrant splicing via partial use of a cryptic 5' splice site 48 bp into intron 4 of the mouse Otc gene, resulting in partial intron 4 retention. In the equivalent human OTC patient, the same nucleotide change instead causes exon 4 skipping or use of a cryptic splice site at c.386+4. Both result in ~3–6% residual OTC enzyme activity. The divergent splicing outcomes are reproduced in minigene assays. RT-PCR of liver tissue, minigene splicing assay, antisense oligonucleotide experiments, enzyme activity assay PloS one High 25853564
2017 OTC protein is expressed in a small subset of nitrergic (nNOS-positive) neurons in the adult human brain, as shown by double immunolabeling for OTC and nNOS, suggesting that OTC-generated citrulline supports NO production in these neurons by enhancing arginine bioavailability. Double immunofluorescence labeling (OTC + nNOS) in human brain sections Metabolic brain disease Low 28868581
2021 Subtle intronic sequence differences at positions +10-11 downstream of the OTC exon 4 cryptic 5'ss confer preferential binding to the TIA1 splicing factor in the mouse but not human genomic context, explaining species-specific splicing outcomes from the c.386G>A mutation and differential responsiveness to engineered U1snRNA therapeutics. RNA pulldown assay (TIA1 binding), minigene splicing assay with nucleotide swap mutants, U1snRNA co-expression in hepatoma cells Molecular medicine High 34906067
2021 Common polymorphic OTC variants (p.Lys46Arg and p.Gln270Arg) modulate OTC enzymatic activity in cis: the minor allele of p.Gln270Arg significantly enhanced wild-type OTC activity and partially rescued activity of the pathogenic p.Arg40His allele in vitro. In vitro enzymatic activity assay of recombinant OTC variants, structural analysis Human mutation Medium 34015158
2022 An OTC promoter variant (c.-106C>A) in a conserved HNF4α binding site reduces OTC promoter-driven expression >5-fold in a dual-luciferase assay, and this reduction is maintained in the presence of the upstream OTC enhancer, mechanistically explaining late-onset, stress-triggered hyperammonemia in hemizygous males. Dual-luciferase reporter assay with wild-type and mutant OTC promoter constructs, with and without upstream enhancer Journal of inherited metabolic disease Medium 35605046
2023 A high-throughput functional assay measuring OTC activity in yeast for 1,570 individual amino acid substitutions (84% of all SNV-accessible missense mutations) identified a 13 amino acid domain (the SMG loop) whose function is required in human cells but not in yeast, and demonstrated score ranges corresponding to clinically relevant levels of OTC activity impairment. High-throughput yeast-based functional assay for OTC activity, clinical variant benchmarking, protein structure analysis American journal of human genetics High 37146589

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene. Human mutation 138 16786505
2009 AAV2/8-mediated correction of OTC deficiency is robust in adult but not neonatal Spf(ash) mice. Molecular therapy : the journal of the American Society of Gene Therapy 99 19384294
2020 Degradation of tetracycline antibiotics by Arthrobacter nicotianae OTC-16. Journal of hazardous materials 80 33265032
1996 Correction of ornithine transcarbamylase deficiency in adult spf(ash) mice and in OTC-deficient human hepatocytes with recombinant adenoviruses bearing the CAG promoter. Human gene therapy 53 8860834
2012 Changes in the nitrogen removal performance and the properties of granular sludge in an Anammox system under oxytetracycline (OTC) stress. Bioresource technology 52 23232224
1985 Gene for OTC: characterisation and linkage to Duchenne muscular dystrophy. Nucleic acids research 51 3839070
1988 Analysis of linkage relationships of X-linked retinitis pigmentosa with the following Xp loci: L1.28, OTC, 754, XJ-1.1, pERT87, and C7. Human genetics 50 3422211
1999 OTC and AUL1, two convergent and overlapping genes in the nuclear genome of Arabidopsis thaliana. FEBS letters 48 10561504
2009 High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide array CGH. Molecular genetics and metabolism 45 19138872
1993 Four novel gene mutations in five Japanese male patients with neonatal or late onset OTC deficiency: application of PCR-single-strand conformation polymorphisms for all exons and adjacent introns [corrected]. Human genetics 44 8365726
2019 Therapeutic Role of a Cysteine Precursor, OTC, in Ischemic Stroke Is Mediated by Improved Proteostasis in Mice. Translational stroke research 42 31049841
2016 Frequency and Pathophysiology of Acute Liver Failure in Ornithine Transcarbamylase Deficiency (OTCD). PloS one 42 27070778
2017 AAV gene therapy corrects OTC deficiency and prevents liver fibrosis in aged OTC-knock out heterozygous mice. Molecular genetics and metabolism 41 28283349
2011 Preclinical evaluation of a clinical candidate AAV8 vector for ornithine transcarbamylase (OTC) deficiency reveals functional enzyme from each persisting vector genome. Molecular genetics and metabolism 40 22133298
1994 Sequences of the oxytetracycline polyketide synthase-encoding otc genes from Streptomyces rimosus. Gene 40 8163168
2009 Adult-onset ornithine transcarbamylase (OTC) deficiency unmasked by the Atkins' diet. Journal of hepatology 39 20031247
2015 Clinical outcomes and the mutation spectrum of the OTC gene in patients with ornithine transcarbamylase deficiency. Journal of human genetics 38 25994866
2007 Estimation of the total number of disease-causing mutations in ornithine transcarbamylase (OTC) deficiency. Value of the OTC structure in predicting a mutation pathogenic potential. Journal of inherited metabolic disease 37 17334707
2019 Action of oxytetracycline (OTC) degrading bacterium and its application in Moving Bed Biofilm Reactor (MBBR) for aquaculture wastewater pre-treatment. Ecotoxicology and environmental safety 35 30660977
2014 Sudden unexpected fatal encephalopathy in adults with OTC gene mutations-Clues for early diagnosis and timely treatment. Orphanet journal of rare diseases 35 25026867
2011 Sustained correction of OTC deficiency in spf( ash) mice using optimized self-complementary AAV2/8 vectors. Gene therapy 35 21850052
2007 Mutation analysis of the ornithine transcarbamylase (OTC) gene in five Japanese OTC deficiency patients revealed two known and three novel mutations including a deep intronic mutation. The Kobe journal of medical sciences 35 18204299
1990 The risks and benefits of an Rx-to-OTC switch. The case of over-the-counter H2-blockers. Medical care 34 1976142
2008 Analysis of mRNA transcripts improves the success rate of molecular genetic testing in OTC deficiency. Molecular genetics and metabolism 32 18440262
2005 PPI use in the OTC era: who to treat, with what, and for how long? Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 29 15765438
2013 Treatment with the cysteine precursor l-2-oxothiazolidine-4-carboxylate (OTC) implicates taurine deficiency in severity of dystropathology in mdx mice. The international journal of biochemistry & cell biology 28 23892094
1999 The effect of an Rx-to-OTC switch on medication prescribing patterns and utilization of physician services: the case of H2-receptor antagonists. Medical care 27 10213023
2020 The otc gene of Streptococcus suis plays an important role in biofilm formation, adhesion, and virulence in a murine model. Veterinary microbiology 26 33181436
1997 The ornithine transcarbamylase (OTC) gene: mutations in 50 Japanese families with OTC deficiency. American journal of medical genetics 26 9286441
2019 Efficient in vivo editing of OTC-deficient patient-derived primary human hepatocytes. JHEP reports : innovation in hepatology 25 32039406
2015 Functional characterization of the spf/ash splicing variation in OTC deficiency of mice and man. PloS one 22 25853564
1996 Asymptomatic and late-onset ornithine transcarbamylase (OTC) deficiency in males of a five-generation family, caused by an A208T mutation. Clinical genetics 22 9007316
2015 Oculo-facio-cardio-dental (OFCD) syndrome: the first Italian case of BCOR and co-occurring OTC gene deletion. Gene 21 25620158
2013 Multidisciplinary management of ornithine transcarbamylase (OTC) deficiency in pregnancy: essential to prevent hyperammonemic complications. BMJ case reports 21 23283608
2017 A Proposed Physiopathological Pathway to Hyperammonemic Encephalopathy in a Non-Cirrhotic Patient with Fibrolamellar Hepatocellular Carcinoma without Ornithine Transcarbamylase (OTC) Mutation. The American journal of case reports 20 28270654
2023 Simultaneous adsorption of Cd(II) and degradation of OTC by activated biochar with ferrate: Efficiency and mechanism. Journal of hazardous materials 19 36641845
2023 The functional impact of 1,570 individual amino acid substitutions in human OTC. American journal of human genetics 18 37146589
2013 AAV-encoded OTC activity persisting to adulthood following delivery to newborn spf(ash) mice is insufficient to prevent shRNA-induced hyperammonaemia. Gene therapy 18 24108150
2009 Molecular mechanisms underlying large genomic deletions in ornithine transcarbamylase (OTC) gene. Clinical genetics 18 19475717
1997 Familial lethal inheritance of a mutated paternal gene in females causing X-linked ornithine transcarbamylase (OTC) deficiency. American journal of medical genetics 18 9056557
2021 OTC deficiency in females: Phenotype-genotype correlation based on a 130-family cohort. Journal of inherited metabolic disease 17 34014569
2012 Plant growth stimulation in Prunus species plantlets by BTH or OTC treatments under in vitro conditions. Journal of plant physiology 17 22595304
1993 Effects of zinc on hepatic ornithine transcarbamylase (OTC) activity. Journal of trace elements and electrolytes in health and disease 17 8019156
2002 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. Human mutation 16 11793483
2018 Variable X-chromosome inactivation and enlargement of pericentral glutamine synthetase zones in the liver of heterozygous females with OTC deficiency. Virchows Archiv : an international journal of pathology 15 29623395
2008 Postchemotherapy hyperammonemic encephalopathy emulating ornithine transcarbamoylase (OTC) deficiency. Southern medical journal 15 18414167
2008 Reduced citrulline availability by OTC deficiency in mice is related to reduced nitric oxide production. American journal of physiology. Endocrinology and metabolism 15 18697914
2000 Lymphocyte mRNA analysis of the ornithine transcarbamylase gene in Italian OTCD male patients and manifesting carriers: identification of novel mutations. Human mutation 15 10737985
2021 Genomic insights into the antibiotic resistance pattern of the tetracycline-degrading bacterium, Arthrobacter nicotianae OTC-16. Scientific reports 14 34341372
2006 Identification of novel mutations in the human ornithine transcarbamylase (OTC) gene of Korean patients with OTC deficiency and transient expression of the mutant proteins in vitro. Human mutation 14 17041896
2002 Genetic analysis in nine unrelated Italian patients affected by OTC deficiency: detection of novel mutations in the OTC gene. Molecular genetics and metabolism 14 12083811
1976 Propionic acidemia and hyperlysinemia in a case with ornithine transcarbamylase (OTC) deficiency. The Journal of clinical endocrinology and metabolism 14 977722
1998 Selective elevation of glutathione levels in target tissues with L-2-oxothiazolidine-4-carboxylate (OTC) protects against hyperoxia-induced lung damage in protein-energy malnourished rats: implications for a new treatment strategy. The Journal of nutrition 13 9521626
1991 Correction of ornithine transcarbamylase (OTC) deficiency in spf-ash mice by introduction of rat OTC gene. FEBS letters 12 2001730
1986 Clinical application of DNA analysis in a family with OTC deficiency. American journal of medical genetics 12 2878615
2016 Performance and microbial community variations in thermophilic anaerobic digesters treating OTC medicated cow manure under different operational conditions. Bioresource technology 11 26826959
2010 Disruption of OTC promoter-enhancer interaction in a patient with symptoms of ornithine carbamoyltransferase deficiency. Human mutation 11 20127982
2006 Ornithine restores ureagenesis capacity and mitigates hyperammonemia in Otc(spf-ash) mice. The Journal of nutrition 11 16772445
2020 An Exon-Specific Small Nuclear U1 RNA (ExSpeU1) Improves Hepatic OTC Expression in a Splicing-Defective spf/ash Mouse Model of Ornithine Transcarbamylase Deficiency. International journal of molecular sciences 10 33228018
2017 Activity of the liver enzyme ornithine carbamoyltransferase (OTC) in blood: LC-MS/MS assay for non-invasive diagnosis of ornithine carbamoyltransferase deficiency. Clinical chemistry and laboratory medicine 10 28107167
1999 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. Human mutation 10 10502831
1996 Identification of new mutations in the ornithine transcarbamylase (OTC) gene in Korean families. Journal of inherited metabolic disease 10 8830175
2021 Alert to US physicians: DHEA, widely used as an OTC androgen supplement, may exacerbate COVID-19. Endocrine-related cancer 9 33263566
2021 A deep intronic variant is a common cause of OTC deficiency in individuals with previously negative genetic testing. Molecular genetics and metabolism reports 9 33489762
2006 Reduced ornithine transcarbamylase activity does not impair ureagenesis in Otc(spf-ash) mice. The Journal of nutrition 9 16549467
1999 Efficient mitochondrial import of newly synthesized ornithine transcarbamylase (OTC) and correction of secondary metabolic alterations in spf(ash) mice following gene therapy of OTC deficiency. Molecular medicine (Cambridge, Mass.) 9 10448647
1999 Influence of experimentally induced theileriosis (Theileria annulata) on the pharmacokinetics of a long-acting formulation of oxytetracycline (OTC-LA) in calves. Journal of veterinary pharmacology and therapeutics 9 10597536
2024 Are asymptomatic carriers of OTC deficiency always asymptomatic? A multicentric retrospective study of risk using the UCDC longitudinal study database. Molecular genetics & genomic medicine 8 38634223
2020 Late-Onset Ornithine Transcarbamylase Deficiency and Variable Phenotypes in Vietnamese Females With OTC Mutations. Frontiers in pediatrics 8 32793520
2014 OTC gene in ornithine transcarbamylase deficiency: clinical course and mutational spectrum in seven Korean patients. Pediatric neurology 8 25011434
1989 Structure of the ornithine transcarbamylase (OTC) gene and DNA diagnosis of OTC deficiency. Clinica chimica acta; international journal of clinical chemistry 8 2575934
2022 A promoter variant in the OTC gene associated with late and variable age of onset hyperammonemia. Journal of inherited metabolic disease 7 35605046
2021 Common polymorphic OTC variants can act as genetic modifiers of enzymatic activity. Human mutation 7 34015158
1997 Missense mutations in codon 225 of ornithine transcarbamylase (OTC) result in decreased amounts of OTC protein: a hypothesis on the molecular mechanism of the OTC deficiency. Journal of inherited metabolic disease 7 9427144
1996 Prenatal monitoring in a family at high risk for ornithine transcarbamylase (OTC) deficiency: a new mutation of an A-to-C transversion in position +4 of intron 1 of the OTC gene that is likely to abolish enzyme activity. American journal of medical genetics 7 8862622
1988 The pharmacological profile of non-opioid (OTC) analgesics: aspirin, paracetamol (acetaminophen), ibuprofen, and phenazones. Agents and actions. Supplements 7 3066205
2023 Plasma-Polymerised Antibacterial Coating of Ovine Tendon Collagen Type I (OTC) Crosslinked with Genipin (GNP) and Dehydrothermal-Crosslinked (DHT) as a Cutaneous Substitute for Wound Healing. Materials (Basel, Switzerland) 6 37049037
2017 In human brain ornithine transcarbamylase (OTC) immunoreactivity is strongly expressed in a small number of nitrergic neurons. Metabolic brain disease 6 28868581
2006 The efficacy of hydrotalcite compared with OTC famotidine in the on-demand treatment of gastroesophageal reflux disease: a non-inferiority trial. Medical science monitor : international medical journal of experimental and clinical research 6 17179910
1995 Importance of ornithine transcarbamylase (OTC) deficiency in small intestine for urinary orotic acid excretion: analysis of OTC-deficient spf-ash mice with OTC transgene. Biochimica et biophysica acta 6 7827141
1991 X-chromosome inactivation in the liver of female heterozygous OTC-deficient sparse-furash mice. Biochemical medicine and metabolic biology 6 2049185
2023 Monitoring of over-the-counter (OTC) and COVID-19 treatment drugs complement wastewater surveillance of SARS-CoV-2. Journal of exposure science & environmental epidemiology 5 38052940
2021 Generation of a human induced pluripotent stem cell line (SDQLCHi036-A) from a patient with ornithine transcarbamylase deficiency carrying a deletion involving 3-9 exons of OTC gene. Stem cell research 5 33550136
2021 OTC intron 4 variations mediate pathogenic splicing patterns caused by the c.386G>A mutation in humans and spfash mice, and govern susceptibility to RNA-based therapies. Molecular medicine (Cambridge, Mass.) 5 34906067
2009 Mutation screening of the medium-chain acyl-CoA dehydrogenase (MCAD) and the ornithine transcarbamylase (OTC) genes by multiplex PCR amplification and sequencing. Clinical chemistry and laboratory medicine 5 19055470
2006 Mutational spectrum and linkage disequilibrium patterns at the ornithine transcarbamylase gene (OTC). Annals of human genetics 5 17044854
2002 H intragenic polymorphisms and haplotype analysis in the ornithine transcarbamylase (OTC) gene and their relevance for tracking the inheritance of OTC deficiency. Human mutation 5 12402347
1991 BWTG3 hepatoma cells can acquire phenylalanine hydroxylase, cystathionine synthase and CPS-I without genetic manipulation, but activation of the silent OTC gene requires cell fusion with hepatocytes. Journal of cell science 5 1860901
1980 Ornithine transcarbamylase (OTC) in white blood cells. Pediatric research 5 7208155
2022 Effect of Ornithine Transcarbamylase (OTC) Deficiency on Pregnancy and Puerperium. Diagnostics (Basel, Switzerland) 4 35204506
2018 Gene Mutation Analysis and Prenatal Diagnosis of the Ornithine Transcarbamylase (OTC) Gene in Two Families with Ornithine Transcarbamylase Deficiency. Medical science monitor : international medical journal of experimental and clinical research 4 30333473
2017 Urea Cycle Defects: Early-Onset Disease Associated with A208T Mutation in OTC Gene-Expanding the Clinical Phenotype. Case reports in genetics 4 28261508
2016 Toxicity of OTC to Ipomoea aquatica Forsk. and to microorganisms in a long-term sewage-irrigated farmland soil. Environmental science and pollution research international 4 27083912
2014 Hyperammonemic coma in a patient with late-onset OTC deficiency. La Pediatria medica e chirurgica : Medical and surgical pediatrics 4 25573644
2012 Recurrent somnolence in a 17-month-old infant: late-onset ornithine transcarbamylase (OTC) deficiency due to the novel hemizygous mutation c.535C > T (p.Leu179Phe). European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 4 22727265
2018 Mutation Study of Malaysian Patients with Ornithine Transcarbamylase Deficiency: Clinical, Molecular, and Bioinformatics Analyses of Two Novel Missense Mutations of the OTC Gene. BioMed research international 3 30175132
2018 Exonic duplication of the OTC gene by a complex rearrangement that likely occurred via a replication-based mechanism: a case report. BMC medical genetics 3 30541480
2013 [Molecular diagnosis of OTC gene mutation in a Chinese family with ornithine transcarbamylase deficiency]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 3 23568734
2005 Severe, neonatal-onset OTC deficiency in twin sisters with a de novo balanced reciprocal translocation t(X;5)(p21.1;q11). American journal of medical genetics. Part A 3 15578616
1995 OTC pharmaceuticals and genotoxicity testing: the paracetamol, anthraquinone, and griseofulvin cases. Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement 3 7786168