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Aliases for CPS1 Gene

Aliases for CPS1 Gene

  • Carbamoyl-Phosphate Synthase 1 2 3 5
  • Carbamoyl-Phosphate Synthase 1, Mitochondrial 2 3
  • Carbamoyl-Phosphate Synthase (Ammonia) 2 3
  • EC 4 63
  • Carbamoyl-Phosphate Synthetase 1, Mitochondrial 2
  • Carbamoyl-Phosphate Synthetase I 4
  • Carbamoylphosphate Synthetase I 3
  • CPSase I 4
  • CPSASE1 3
  • PHN 3

External Ids for CPS1 Gene

Previous GeneCards Identifiers for CPS1 Gene

  • GC02P209696
  • GC02P210145
  • GC02P211385
  • GC02P211623
  • GC02P211246
  • GC02P211050
  • GC02P211129
  • GC02P211342
  • GC02P203189

Summaries for CPS1 Gene

Entrez Gene Summary for CPS1 Gene

  • The mitochondrial enzyme encoded by this gene catalyzes synthesis of carbamoyl phosphate from ammonia and bicarbonate. This reaction is the first committed step of the urea cycle, which is important in the removal of excess urea from cells. The encoded protein may also represent a core mitochondrial nucleoid protein. Three transcript variants encoding different isoforms have been found for this gene. The shortest isoform may not be localized to the mitochondrion. Mutations in this gene have been associated with carbamoyl phosphate synthetase deficiency, susceptibility to persistent pulmonary hypertension, and susceptibility to venoocclusive disease after bone marrow transplantation.[provided by RefSeq, May 2010]

GeneCards Summary for CPS1 Gene

CPS1 (Carbamoyl-Phosphate Synthase 1) is a Protein Coding gene. Diseases associated with CPS1 include Carbamoylphosphate Synthetase I Deficiency and Pulmonary Hypertension, Neonatal. Among its related pathways are Carbon metabolism and CDK-mediated phosphorylation and removal of Cdc6. GO annotations related to this gene include calcium ion binding and phospholipid binding. An important paralog of this gene is CAD.

UniProtKB/Swiss-Prot for CPS1 Gene

  • Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CPS1 Gene

Genomics for CPS1 Gene

Regulatory Elements for CPS1 Gene

Enhancers for CPS1 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around CPS1 on UCSC Golden Path with GeneCards custom track

Promoters for CPS1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around CPS1 on UCSC Golden Path with GeneCards custom track

Genomic Location for CPS1 Gene

210,477,682 bp from pter
210,679,107 bp from pter
201,426 bases
Plus strand

Genomic View for CPS1 Gene

Genes around CPS1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CPS1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CPS1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CPS1 Gene

Proteins for CPS1 Gene

  • Protein details for CPS1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Carbamoyl-phosphate synthase [ammonia], mitochondrial
    Protein Accession:
    Secondary Accessions:
    • B7Z818
    • J3KQL0
    • O43774
    • Q53TL5
    • Q59HF8
    • Q7Z5I5

    Protein attributes for CPS1 Gene

    1500 amino acids
    Molecular mass:
    164939 Da
    Quaternary structure:
    • Can form homooligomers (monomers as predominant form and dimers).
    • Sequence=BAD92037.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for CPS1 Gene

    Alternative splice isoforms for CPS1 Gene


neXtProt entry for CPS1 Gene

Proteomics data for CPS1 Gene at MOPED

Post-translational modifications for CPS1 Gene

  • Glutarylated. Glutarylation levels increase during fasting. Deglutarylated by SIRT5 at Lys-55, Lys-219, Lys-412, Lys-889, Lys-892, Lys-915, Lys-1360 and Lys-1486, leading to activation.
  • Succinylated at Lys-287 and Lys-1291. Desuccinylated at Lys-1291 by SIRT5, leading to activation (By similarity).
  • Undergoes proteolytic cleavage in the C-terminal region corresponding to the loss of approximately 12 AA residues from the C-terminus.
  • Glycosylation at Ser 537, Ser 1331, and Thr 1332
  • Modification sites at PhosphoSitePlus

Domains & Families for CPS1 Gene

Graphical View of Domain Structure for InterPro Entry



  • The type-1 glutamine amidotransferase domain is defective.
  • The type-1 glutamine amidotransferase domain is defective.
  • Contains 2 ATP-grasp domains.
  • Contains 1 glutamine amidotransferase type-1 domain.
genes like me logo Genes that share domains with CPS1: view

No data available for Gene Families for CPS1 Gene

Function for CPS1 Gene

Molecular function for CPS1 Gene

GENATLAS Biochemistry:
carbamoyl phosphate synthetase 1,mitochondrial,urea cycle
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=0.47 mM for ATP {ECO:0000269 PubMed:23649895}; KM=4.0 mM for HCO(3)(-) {ECO:0000269 PubMed:23649895}; KM=1.00 mM for NH(4)(+) {ECO:0000269 PubMed:23649895}; Vmax=1.22 umol/min/mg enzyme for ATP {ECO:0000269 PubMed:23649895}; Vmax=1.23 umol/min/mg enzyme for HCO(3)(-) {ECO:0000269 PubMed:23649895}; Vmax=1.19 umol/min/mg enzyme for NH(4)(+) {ECO:0000269 PubMed:23649895};
UniProtKB/Swiss-Prot CatalyticActivity:
2 ATP + NH(3) + HCO(3)(-) = 2 ADP + phosphate + carbamoyl phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Requires N-acetyl-L-glutamate (NAG) as an allosteric activator. Activated by glycerol in the absence of NAG, whereas in the presence of NAG it is inhibited by increasing concentrations of glycerol.
UniProtKB/Swiss-Prot Function:
Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.

Enzyme Numbers (IUBMB) for CPS1 Gene

Gene Ontology (GO) - Molecular Function for CPS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004070 aspartate carbamoyltransferase activity IBA --
GO:0004088 carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity IEA,IBA --
GO:0016595 glutamate binding IEA --
GO:0072341 modified amino acid binding IDA 20031578
genes like me logo Genes that share ontologies with CPS1: view
genes like me logo Genes that share phenotypes with CPS1: view

Human Phenotype Ontology for CPS1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CPS1 Gene

MGI Knock Outs for CPS1:

miRNA for CPS1 Gene

miRTarBase miRNAs that target CPS1

No data available for Transcription Factor Targets and HOMER Transcription for CPS1 Gene

Localization for CPS1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CPS1 Gene

Mitochondrion. Nucleus, nucleolus.

Subcellular locations from

Jensen Localization Image for CPS1 Gene COMPARTMENTS Subcellular localization image for CPS1 gene
Compartment Confidence
mitochondrion 5
nucleus 5
cytosol 3
endoplasmic reticulum 2

Gene Ontology (GO) - Cellular Components for CPS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005730 nucleolus IEA --
genes like me logo Genes that share ontologies with CPS1: view

Pathways & Interactions for CPS1 Gene

genes like me logo Genes that share pathways with CPS1: view

Gene Ontology (GO) - Biological Process for CPS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001889 liver development IEA --
GO:0006207 de novo pyrimidine nucleobase biosynthetic process IEA,IBA --
GO:0006508 proteolysis IEA --
GO:0006541 glutamine metabolic process IEA --
GO:0006595 polyamine metabolic process TAS --
genes like me logo Genes that share ontologies with CPS1: view

No data available for SIGNOR curated interactions for CPS1 Gene

Drugs & Compounds for CPS1 Gene

(15) Drugs for CPS1 Gene - From: DrugBank, PharmGKB, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Carglumic acid Approved Pharma Target, allosteric modulator 0
Valproic Acid Approved, Investigational Pharma HDAC1 inhibitor, Histone deacetylase (HDAC)inhibitors 312
Adenosine triphosphate Approved Nutra 0
N-Acetylalanine Experimental Pharma 0
N-Acetyl-L-Glutamate Experimental Pharma 0

(12) Additional Compounds for CPS1 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Carbamoyl phosphate
  • Carbamic acid monoanhydride with phosphorate
  • Carbamic acid monoanhydride with phosphoric acid
  • Carbamoyl-P
  • Carbamoyl-phosphate
  • Carbamoylphosphate
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
  • Ammonia anhydrous
  • Ammonia inhalant
  • Ammonia solution strong [usan]
  • Ammonia water
  • Ammoniak
carbon dioxide
  • Carbon oxide
  • Carbon-12 dioxide
  • Carbonic acid anhydride
  • Carbonic acid gas
  • Carbonic anhydride
  • NFB Orthophosphate
  • O-Phosphoric acid
  • Ortho-phosphate
  • Orthophosphate (PO43-)
  • Orthophosphate(3-)
genes like me logo Genes that share compounds with CPS1: view

Transcripts for CPS1 Gene

Unigene Clusters for CPS1 Gene

Carbamoyl-phosphate synthase 1, mitochondrial:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for CPS1 Gene

No ASD Table

Relevant External Links for CPS1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for CPS1 Gene

mRNA expression in normal human tissues for CPS1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CPS1 Gene

This gene is overexpressed in Liver (x45.4).

Protein differential expression in normal tissues from HIPED for CPS1 Gene

This gene is overexpressed in Liver (34.1), Liver, secretome (18.0), and Fetal Liver (12.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for CPS1 Gene

SOURCE GeneReport for Unigene cluster for CPS1 Gene Hs.149252

mRNA Expression by UniProt/SwissProt for CPS1 Gene

Tissue specificity: Primarily in the liver and small intestine.
genes like me logo Genes that share expression patterns with CPS1: view

Protein tissue co-expression partners for CPS1 Gene

Primer Products

Orthologs for CPS1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CPS1 Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia CPS1 35
  • 92.37 (n)
  • 95.06 (a)
CPS1 36
  • 95 (a)
(Canis familiaris)
Mammalia CPS1 35
  • 92.91 (n)
  • 96.27 (a)
CPS1 36
  • 96 (a)
(Mus musculus)
Mammalia Cps1 35
  • 89.24 (n)
  • 95.33 (a)
Cps1 16
Cps1 36
  • 95 (a)
(Pan troglodytes)
Mammalia CPS1 35
  • 99.42 (n)
  • 99.47 (a)
CPS1 36
  • 99 (a)
(Rattus norvegicus)
Mammalia Cps1 35
  • 89.36 (n)
  • 95.53 (a)
(Monodelphis domestica)
Mammalia CPS1 36
  • 93 (a)
(Ornithorhynchus anatinus)
Mammalia CPS1 36
  • 80 (a)
(Gallus gallus)
Aves CPS1 35
  • 76.59 (n)
  • 81.04 (a)
CPS1 36
  • 81 (a)
(Anolis carolinensis)
Reptilia CPS1 36
  • 79 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia cps1 35
  • 73.75 (n)
  • 79.89 (a)
Str.8825 35
African clawed frog
(Xenopus laevis)
Amphibia Xl.24543 35
(Danio rerio)
Actinopterygii cps1 35
  • 69.41 (n)
  • 72.81 (a)
cps1 36
  • 73 (a)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.11701 35
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes URA2 36
  • 34 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons CARB 35
  • 49.03 (n)
  • 40.55 (a)
(Oryza sativa)
Liliopsida Os01g0570700 35
  • 45.19 (n)
  • 30.54 (a)
Species with no ortholog for CPS1:
  • A. gosspyii yeast (Ashbya gossypii)
  • 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)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (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 CPS1 Gene

Gene Tree for CPS1 (if available)
Gene Tree for CPS1 (if available)

Paralogs for CPS1 Gene

Paralogs for CPS1 Gene

(1) SIMAP similar genes for CPS1 Gene using alignment to 10 proteins:

genes like me logo Genes that share paralogs with CPS1: view

Variants for CPS1 Gene

Sequence variations from dbSNP and Humsavar for CPS1 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs1047883 -, - 210,591,913(+) ACAAC(A/G/T)CCCTC upstream-variant-2KB, reference, missense
VAR_006835 Carbamoyl phosphate synthetase 1 deficiency (CPS1D)
rs28940283 Carbamoyl phosphate synthetase 1 deficiency (CPS1D) 210,591,893(+) GAATC(A/G)TGGCT upstream-variant-2KB, reference, missense
VAR_017562 Carbamoyl phosphate synthetase 1 deficiency (CPS1D)
VAR_017563 Carbamoyl phosphate synthetase 1 deficiency (CPS1D)

Structural Variations from Database of Genomic Variants (DGV) for CPS1 Gene

Variant ID Type Subtype PubMed ID
esv2674073 CNV Deletion 23128226
nsv821631 CNV Loss 15273396

Variation tolerance for CPS1 Gene

Residual Variation Intolerance Score: 7.54% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 17.82; 98.35% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CPS1 Gene

Human Gene Mutation Database (HGMD)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CPS1 Gene

Disorders for CPS1 Gene

MalaCards: The human disease database

(9) MalaCards diseases for CPS1 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
carbamoylphosphate synthetase i deficiency
  • carbamoyl phosphate synthetase i deficiency disease
pulmonary hypertension, neonatal
  • postherpetic neuralgia
ornithine transcarbamylase deficiency
  • ornithine carbamoyltransferase deficiency
pulmonary hypertension
  • primary pulmonary hypertension
- elite association - COSMIC cancer census association via MalaCards
Search CPS1 in MalaCards View complete list of genes associated with diseases


  • Carbamoyl phosphate synthetase 1 deficiency (CPS1D) [MIM:237300]: An autosomal recessive disorder of the urea cycle causing hyperammonemia. It can present as a devastating metabolic disease dominated by severe hyperammonemia in neonates or as a more insidious late-onset condition, generally manifesting as life-threatening hyperammonemic crises under catabolic situations. Clinical features include protein intolerance, intermittent ataxia, seizures, lethargy, developmental delay and mental retardation. {ECO:0000269 PubMed:11388595, ECO:0000269 PubMed:11474210, ECO:0000269 PubMed:12655559, ECO:0000269 PubMed:12955727, ECO:0000269 PubMed:15164414, ECO:0000269 PubMed:15617192, ECO:0000269 PubMed:16737834, ECO:0000269 PubMed:17310273, ECO:0000269 PubMed:20578160, ECO:0000269 PubMed:21120950, ECO:0000269 PubMed:23649895, ECO:0000269 PubMed:24813853, ECO:0000269 PubMed:26440671, ECO:0000269 PubMed:9711878}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Pulmonary hypertension, neonatal (PHN) [MIM:615371]: A disease characterized by elevated pulmonary artery pressure. Pulmonary hypertension in the neonate is associated with multiple underlying problems such as respiratory distress syndrome, meconium aspiration syndrome, congenital diaphragmatic hernia, bronchopulmonary dysplasia, sepsis, or congenital heart disease. {ECO:0000269 PubMed:11407344}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. CPS1 variants influence the availability of precursors for nitric oxide (NO) synthesis and play a role in clinical situations where endogenous NO production is critically important, such as neonatal pulmonary hypertension, increased pulmonary artery pressure following surgical repair of congenital heart defects or hepatovenocclusive disease following bone marrow transplantation. Infants with neonatal pulmonary hypertension homozygous for Thr-1406 have lower L-arginine concentrations than neonates homozygous for Asn-1406 (PubMed:11407344). {ECO:0000269 PubMed:11407344}.

Genatlas disease for CPS1 Gene

neonatal distress and hyperammonemia

Relevant External Links for CPS1

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Tumor Gene Database (TGDB):
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with CPS1: view

Publications for CPS1 Gene

  1. The T1405N carbamoyl phosphate synthetase polymorphism does not affect plasma arginine concentrations in preterm infants. (PMID: 20520828) Moonen R.M. … Villamor E. (PLoS ONE 2010) 3 4 23 48 67
  2. N-carbamylglutamate treatment for acute neonatal hyperammonemia in isovaleric acidemia. (PMID: 21207059) Kasapkara C.S. … Hasanoglu A. (Eur. J. Pediatr. 2011) 25 26
  3. Structural insight on the control of urea synthesis: identification of the binding site for N-acetyl-L-glutamate, the essential allosteric activator of mitochondrial carbamoyl phosphate synthetase. (PMID: 19754428) Pekkala S. … Cervera J. (Biochem. J. 2009) 3 23
  4. Highly variable clinical phenotype of carbamylphosphate synthetase 1 deficiency in one family: an effect of allelic variation in gene expression? (PMID: 19793055) Klaus V. … HAoberle J. (Clin. Genet. 2009) 3 23
  5. Loss of carbamoyl phosphate synthetase I in small-intestinal adenocarcinoma. (PMID: 19926579) Cardona D.M. … Liu C. (Am. J. Clin. Pathol. 2009) 3 23

Products for CPS1 Gene

Sources for CPS1 Gene