Normal Function
The CPS1 gene provides instructions for making the enzyme carbamoyl phosphate synthetase I. This enzyme participates in the urea cycle, a series of reactions that occurs in liver cells. The urea cycle processes excess nitrogen, generated when protein is used by the body, into a compound called urea that is excreted by the kidneys. Excreting the excess nitrogen prevents it from accumulating in the form of ammonia, which is toxic.
The specific role of carbamoyl phosphate synthetase I is to control the first step of the urea cycle, a reaction in which excess nitrogen compounds are incorporated into the cycle to be processed.
Health Conditions Related to Genetic Changes
Carbamoyl phosphate synthetase I deficiency
Approximately 10 mutations that cause carbamoyl phosphate synthetase I deficiency have been identified in the CPS1 gene. A mutated CPS1 gene may result in a carbamoyl phosphate synthetase I enzyme that is shorter than normal or the wrong shape, or may prevent the enzyme from being produced at all.
The shape of an enzyme affects its ability to control a chemical reaction. If the carbamoyl phosphate synthetase enzyme is misshapen or missing, it cannot fulfill its role in the urea cycle. Excess nitrogen is not converted to urea for excretion, and ammonia accumulates in the body. Ammonia is toxic, especially to the nervous system, so this accumulation causes neurological problems and other signs and symptoms of carbamoyl phosphate synthetase I deficiency.
More About This Health ConditionOther disorders
One common alteration (polymorphism) in the CPS1 gene has been associated with increased risk of circulatory problems in newborns and in individuals who have received bone marrow transplants. This genetic change results in the amino acid (protein building block) asparagine being substituted for the amino acid threonine at position 1405 in the protein sequence (written as Thr1405Asn or T1405N).
Researchers believe that this polymorphism in the CPS1 gene may reduce the production of a compound called nitric oxide (NO). Normally, nitric oxide causes blood vessels to expand (dilate), which reduces blood pressure. A reduced amount of nitric oxide could lead to circulatory problems.
Other Names for This Gene
- carbamoyl phosphate synthase I
- carbamoyl-phosphate synthase 1, mitochondrial
- carbamoyl-phosphate synthase, mitochondrial precursor
- carbamoylphosphate synthetase I
- CPSase I
- CPSM_HUMAN
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Aoshima T, Kajita M, Sekido Y, Mimura S, Itakura A, Yasuda I, Saheki T, Watanabe K, Shimokata K, Niwa T. Carbamoyl phosphate synthetase I deficiency: molecular genetic findings and prenatal diagnosis. Prenat Diagn. 2001 Aug;21(8):634-7. doi: 10.1002/pd.123. Citation on PubMed
- Finckh U, Kohlschutter A, Schafer H, Sperhake K, Colombo JP, Gal A. Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1. Hum Mutat. 1998;12(3):206-11. doi: 10.1002/(SICI)1098-1004(1998)12:33.0.CO;2-E. Citation on PubMed
- Funghini S, Donati MA, Pasquini E, Zammarchi E, Morrone A. Structural organization of the human carbamyl phosphate synthetase I gene (CPS1) and identification of two novel genetic lesions. Hum Mutat. 2003 Oct;22(4):340-1. doi: 10.1002/humu.9184. Citation on PubMed
- Haberle J, Schmidt E, Pauli S, Rapp B, Christensen E, Wermuth B, Koch HG. Gene structure of human carbamylphosphate synthetase 1 and novel mutations in patients with neonatal onset. Hum Mutat. 2003 Apr;21(4):444. doi: 10.1002/humu.9118. Citation on PubMed
- Pearson DL, Dawling S, Walsh WF, Haines JL, Christman BW, Bazyk A, Scott N, Summar ML. Neonatal pulmonary hypertension--urea-cycle intermediates, nitric oxide production, and carbamoyl-phosphate synthetase function. N Engl J Med. 2001 Jun 14;344(24):1832-8. doi: 10.1056/NEJM200106143442404. Citation on PubMed
- Rapp B, Haberle J, Linnebank M, Wermuth B, Marquardt T, Harms E, Koch HG. Genetic analysis of carbamoylphosphate synthetase I and ornithine transcarbamylase deficiency using fibroblasts. Eur J Pediatr. 2001 May;160(5):283-7. doi: 10.1007/s004310100725. Citation on PubMed
- Summar ML, Gainer JV, Pretorius M, Malave H, Harris S, Hall LD, Weisberg A, Vaughan DE, Christman BW, Brown NJ. Relationship between carbamoyl-phosphate synthetase genotype and systemic vascular function. Hypertension. 2004 Feb;43(2):186-91. doi: 10.1161/01.HYP.0000112424.06921.52. Epub 2004 Jan 12. Citation on PubMed
- Summar ML, Hall LD, Eeds AM, Hutcheson HB, Kuo AN, Willis AS, Rubio V, Arvin MK, Schofield JP, Dawson EP. Characterization of genomic structure and polymorphisms in the human carbamyl phosphate synthetase I gene. Gene. 2003 Jun 5;311:51-7. doi: 10.1016/s0378-1119(03)00528-6. Citation on PubMed
- Wakutani Y, Nakayasu H, Takeshima T, Adachi M, Kawataki M, Kihira K, Sawada H, Bonno M, Yamamoto H, Nakashima K. Mutational analysis of carbamoylphosphate synthetase I deficiency in three Japanese patients. J Inherit Metab Dis. 2004;27(6):787-8. doi: 10.1023/b:boli.0000045842.59768.ea. Citation on PubMed
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