OTC Gene (Ornithine Transcarbamylase)
Genetic and Functional Insights into Ornithine Transcarbamylase Deficiency
Gene Information Card
| Symbol | OTC |
|---|---|
| Full Name | Ornithine transcarbamylase |
| Gene Type | Protein coding |
| Chromosomal Location | Xp11.4 |
| NCBI Gene ID | 5009 ncbi.nlm.nih.gov/gene/5009 |
| Ensembl ID | ENSG00000036473 |
| UniProt ID | P00480 |
| OMIM ID | 300461 |
| HGNC ID | 8512 |
| Aliases | OTCase; MGC126232; MGC126234 |
Description
The OTC gene encodes ornithine transcarbamylase, a mitochondrial enzyme that catalyzes the conversion of ornithine and carbamoyl phosphate to citrulline in the urea cycle. This cycle is essential for detoxifying ammonia in the liver. Mutations in OTC lead to ornithine transcarbamylase deficiency (OTCD), an X-linked inborn error of metabolism characterized by hyperammonemia, which can cause neurological damage and life-threatening episodes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ornithine transcarbamylase deficiency (OTCD) | Loss-of-function mutations reduce enzyme activity, impairing urea cycle and causing ammonia accumulation. | OMIM #311250; ClinVar; multiple publications |
| Hyperammonemia, episodic | Partial enzyme deficiency leads to intermittent hyperammonemia triggered by stress or high protein intake. | OMIM; clinical reports |
| X-linked intellectual disability (in some carriers) | Carrier females may exhibit mild symptoms due to skewed X-inactivation. | Case studies; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High (nTPM ~ 200) | High expression; primary site of urea cycle |
| Small intestine | Moderate (nTPM ~ 50) | Expression in enterocytes |
| Kidney | Low (nTPM ~ 10) | Low expression; minor role |
| Other tissues | Very low or not detected | Restricted expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer cell line) | High | Relevant for urea cycle studies |
| HEK293 (embryonic kidney) | Low | Used for recombinant expression |
| HeLa (cervical cancer) | Not detected | No significant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.119G>A (p.Arg40His) | Missense | Common (~5% of OTCD cases) | Reduced enzyme activity; mild phenotype |
| c.386G>A (p.Arg129His) | Missense | Reported | Severe deficiency; neonatal onset |
| c.583G>A (p.Gly195Arg) | Missense | Reported | Loss of function; severe |
| c.77T>C (p.Leu26Pro) | Missense | Rare | Enzyme instability; late-onset |
Mutation functional classification
Loss of Function (LOF)
Most OTC mutations are loss-of-function, reducing or abolishing enzyme activity, leading to urea cycle impairment.
Gain of Function (GOF)
No gain-of-function mutations reported for OTC.
Dominant Negative (DN)
Not applicable; OTC is X-linked and functions as a trimer; some missense mutations may exert dominant-negative effects in carriers, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • ornithine carbamoyltransferase activity | • amino acid binding |
| • mitochondrion | • urea cycle |
| • arginine biosynthetic process | • response to ammonia |
Pathways
• Urea cycle
• Arginine and proline metabolism
• Metabolic pathways
Protein Summary
Ornithine transcarbamylase is a homotrimeric mitochondrial enzyme. Each subunit binds to carbamoyl phosphate and ornithine to produce citrulline. The enzyme is critical for nitrogen disposal. Defects lead to accumulation of ammonia and orotic acid. The protein is synthesized in the cytoplasm and imported into mitochondria via an N-terminal signal peptide.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NOTCH1 Knockout HEK293 Cell Line | EDJ-KQ435 | Human | 4851 | Details Get a Quote |
| NOTCH2 Knockout HEK293 Cell Line | EDJ-KQ436 | Human | 4853 | Details Get a Quote |
| NOTCH3 Knockout HEK293 Cell Line | EDJ-KQ437 | Human | 4854 | Details Get a Quote |
| NOTCH4 Knockout HEK293 Cell Line | EDJ-KQ439 | Human | 4855 | Details Get a Quote |
| OTC Knockout HEK293 Cell Line | EDJ-KQ5388 | Human | 5009 | Details Get a Quote |
| NOTCH2NLA Knockout HEK293 Cell Line | EDJ-KQ14450 | Human | 388677 | Details Get a Quote |
| NOTCH2NLB Knockout HEK293 Cell Line | EDJ-KQ14451 | Human | 100996763 | Details Get a Quote |
| NOTCH2NLC Knockout HEK293 Cell Line | EDJ-KQ14452 | Human | 100996717 | Details Get a Quote |
| NOTCH2NLR Knockout HEK293 Cell Line | EDJ-KQ14453 | Human | 101929796 | Details Get a Quote |
| NOTCH1 Knockout A-549 Cell Line | EDJ-KQ18001 | Human | 4851 | Details Get a Quote |
| NOTCH3 Knockout HeLa Cell Line | EDJ-KQ18002 | Human | 4854 | Details Get a Quote |
| NOTCH2NLA Knockout A-549 Cell Line | EDJ-KQ44673 | Human | 388677 | Details Get a Quote |
| NOTCH2NLA Knockout HeLa Cell Line | EDJ-KQ44675 | Human | 388677 | Details Get a Quote |
| NOTCH2NLB Knockout A-549 Cell Line | EDJ-KQ44676 | Human | 100996763 | Details Get a Quote |
| NOTCH2NLB Knockout HCT 116 Cell Line | EDJ-KQ44677 | Human | 100996763 | Details Get a Quote |
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