CPS1 Gene - Carbamoyl-Phosphate Synthase 1
A key enzyme in the urea cycle, associated with metabolic disorders and cancer.
Gene Information Card
| Symbol | CPS1 |
|---|---|
| Full Name | Carbamoyl-Phosphate Synthase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q34 |
| NCBI Gene ID | 1373 ncbi.nlm.nih.gov/gene/1373 |
| Ensembl ID | ENSG00000021826 |
| UniProt ID | P31327 |
| OMIM ID | 608307 |
| HGNC ID | 2323 |
| Aliases | CPSASE1, PHN |
Description
CPS1 encodes carbamoyl-phosphate synthase 1, a mitochondrial enzyme that catalyzes the first step of the urea cycle: the conversion of ammonia, bicarbonate, and two ATP molecules to carbamoyl phosphate. This enzyme is critical for ammonia detoxification in the liver. Mutations in CPS1 cause carbamoyl phosphate synthetase I deficiency, a urea cycle disorder leading to hyperammonemia. Altered expression is also observed in certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Carbamoyl phosphate synthetase I deficiency | Loss-of-function mutations impair ammonia detoxification, causing hyperammonemia and encephalopathy. | ClinVar, OMIM |
| Hyperammonemia, type I | Deficient CPS1 activity leads to accumulation of ammonia in blood. | OMIM |
| Hepatocellular carcinoma | CPS1 downregulation is associated with poor prognosis and metabolic reprogramming. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 78.5 | High |
| Small intestine | 12.3 | Medium |
| Kidney | 8.1 | Medium |
| Colon | 4.2 | Low |
| Lung | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 85.2 | Liver cancer cell line; high expression |
| HEK293 | 2.1 | Low expression |
| A549 | 1.8 | Lung cancer cell line; low expression |
| Caco-2 | 6.7 | Colorectal cancer cell line; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1339G>A (p.Gly447Arg) | Missense | Rare | Loss of function; associated with CPS1 deficiency |
| c.2380C>T (p.Arg794Trp) | Missense | Rare | Loss of function; hyperammonemia |
| c.3130C>T (p.Arg1044Trp) | Missense | Rare | Loss of function; neonatal onset |
| c.3650G>A (p.Arg1217His) | Missense | Rare | Loss of function; late-onset phenotype |
Mutation functional classification
Loss of Function (LOF)
Most CPS1 mutations are loss-of-function, reducing or abolishing enzyme activity, leading to urea cycle dysfunction and hyperammonemia.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CPS1.
Dominant Negative (DN)
No dominant-negative mutations have been described; CPS1 deficiency is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • carbamoyl-phosphate synthase (ammonia) activity | • ATP binding |
| • mitochondrion | • urea cycle |
| • ammonia metabolic process | • response to amino acid starvation |
Pathways
• Urea cycle
• Metabolism of amino acids and derivatives
• Arginine and proline metabolism
Protein Summary
CPS1 is a 165 kDa mitochondrial matrix protein that catalyzes the ATP-dependent synthesis of carbamoyl phosphate from ammonia and bicarbonate. It is the rate-limiting enzyme of the urea cycle and is highly expressed in the liver. The protein is regulated by N-acetylglutamate (NAG) as an allosteric activator. Deficiency leads to severe hyperammonemia, often presenting in neonates.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CPS1 Knockout HEK293 Cell Line | EDJ-KQ1984 | Human | 1373 | Details Get a Quote |
| CPS1 Knockout A-549 Cell Line | EDJ-KQ21962 | Human | 1373 | Details Get a Quote |
| CPS1 Knockout HCT 116 Cell Line | EDJ-KQ21963 | Human | 1373 | Details Get a Quote |
| CPS1 Knockout HeLa Cell Line | EDJ-KQ21964 | Human | 1373 | Details Get a Quote |
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