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CPS1 carbamoyl-phosphate synthase 1 [ Homo sapiens (human) ]

Gene ID: 1373, updated on 29-Mar-2023

Summary

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Official Symbol
CPS1provided by HGNC
Official Full Name
carbamoyl-phosphate synthase 1provided by HGNC
Primary source
HGNC:HGNC:2323
See related
Ensembl:ENSG00000021826 MIM:608307; AllianceGenome:HGNC:2323
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PHN; GATD6; CPSASE1
Summary
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]
Expression
Biased expression in liver (RPKM 281.3), duodenum (RPKM 102.6) and 1 other tissue See more
Orthologs
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Genomic context

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See CPS1 in Genome Data Viewer
Location:
2q34
Exon count:
43
Annotation release Status Assembly Chr Location
RS_2023_03 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (210477685..210679107)
RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (210958482..211159839)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (211342409..211543831)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene LANCL1 antisense RNA 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:211294046-211295245 Neighboring gene NANOG hESC enhancer GRCh37_chr2:211307490-211308075 Neighboring gene NANOG hESC enhancer GRCh37_chr2:211346110-211346611 Neighboring gene LanC like glutathione S-transferase 1 Neighboring gene NANOG hESC enhancer GRCh37_chr2:211405459-211406038 Neighboring gene CPS1 intron CAGE-defined high expression enhancer 1 Neighboring gene CPS1 intron CAGE-defined high expression enhancer 2 Neighboring gene CPS1 intronic transcript 1 Neighboring gene uncharacterized LOC107985978 Neighboring gene 5'-nucleotidase domain containing 2 pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Unfavorable clinical outcomes in patients with carbamoyl phosphate synthetase 1 deficiency. Choi Y, et al. Clin Chim Acta, 2022 Feb 1. PMID 34973183
  2. Discovery of a Carbamoyl Phosphate Synthetase 1-Deficient HCC Subtype With Therapeutic Potential Through Integrative Genomic and Experimental Analysis. Wu T, et al. Hepatology, 2021 Dec. PMID 34343359
  3. Association between genetic variations in carbamoyl-phosphate synthetase gene and persistent neonatal pulmonary hypertension. El-Khazragy N, et al. Eur J Pediatr, 2021 Sep. PMID 33772623
  4. CPS1: Looking at an ancient enzyme in a modern light. Nitzahn M, et al. Mol Genet Metab, 2020 Nov. PMID 33317798, Free PMC Article
  5. Molecular, biochemical, and clinical analyses of five patients with carbamoyl phosphate synthetase 1 deficiency. Fan L, et al. J Clin Lab Anal, 2020 Apr. PMID 31749211, Free PMC Article

See all (148) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Ornithine aminotransferase and carbamoyl phosphate synthetase 1 involved in ammonia metabolism serve as novel targets for early stages of gastric cancer.
    Title: Ornithine aminotransferase and carbamoyl phosphate synthetase 1 involved in ammonia metabolism serve as novel targets for early stages of gastric cancer.
  2. O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis.
    Title: O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis.
  3. The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes.
    Title: The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes.
  4. Unfavorable clinical outcomes in patients with carbamoyl phosphate synthetase 1 deficiency.
    Title: Unfavorable clinical outcomes in patients with carbamoyl phosphate synthetase 1 deficiency.
  5. Discovery of a Carbamoyl Phosphate Synthetase 1-Deficient HCC Subtype With Therapeutic Potential Through Integrative Genomic and Experimental Analysis.
    Title: Discovery of a Carbamoyl Phosphate Synthetase 1-Deficient HCC Subtype With Therapeutic Potential Through Integrative Genomic and Experimental Analysis.
  6. Variants associated with urea cycle disorders in Japanese patients: Nationwide study and literature review.
    Title: Variants associated with urea cycle disorders in Japanese patients: Nationwide study and literature review.
  7. Mitochondrial dysfunction as a mechanistic biomarker in patients with non-alcoholic fatty liver disease (NAFLD).
    Title: Mitochondrial dysfunction as a mechanistic biomarker in patients with non-alcoholic fatty liver disease (NAFLD).
  8. Association between genetic variations in carbamoyl-phosphate synthetase gene and persistent neonatal pulmonary hypertension.
    Title: Association between genetic variations in carbamoyl-phosphate synthetase gene and persistent neonatal pulmonary hypertension.
  9. Suppression of the NTS-CPS1 regulatory axis by AFF1 in lung adenocarcinoma cells.
    Title: Suppression of the NTS-CPS1 regulatory axis by AFF1 in lung adenocarcinoma cells.
  10. CPS1: Looking at an ancient enzyme in a modern light.
    Title: CPS1: Looking at an ancient enzyme in a modern light.
Submit: New GeneRIF Correction See all GeneRIFs (61)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Congenital hyperammonemia, type I
MedGen: C4082171 OMIM: 237300 GeneReviews: Urea Cycle Disorders Overview
Compare labs
Pulmonary hypertension, neonatal, susceptibility to
MedGen: C3714958 OMIM: 615371 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites.
EBI GWAS Catalog
Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.
EBI GWAS Catalog
Discovery and refinement of loci associated with lipid levels.
EBI GWAS Catalog
Genetic determinants influencing human serum metabolome among African Americans.
EBI GWAS Catalog
Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes.
EBI GWAS Catalog
Genome-wide association study of body mass index in 23 000 individuals with and without asthma.
EBI GWAS Catalog
Genome-wide association study of homocysteine levels in Filipinos provides evidence for CPS1 in women and a stronger MTHFR effect in young adults.
EBI GWAS Catalog
Genome-wide meta-analysis of homocysteine and methionine metabolism identifies five one carbon metabolism loci and a novel association of ALDH1L1 with ischemic stroke.
EBI GWAS Catalog
Human metabolic individuality in biomedical and pharmaceutical research.
EBI GWAS Catalog
Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.
EBI GWAS Catalog
New loci associated with kidney function and chronic kidney disease.
EBI GWAS Catalog
Novel loci, including those related to Crohn disease, psoriasis, and inflammation, identified in a genome-wide association study of fibrinogen in 17 686 women: the Women's Genome Health Study.
EBI GWAS Catalog
Prognostic implications of genetic variants in advanced non-small cell lung cancer: a genome-wide association study.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables calcium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables carbamoyl-phosphate synthase (ammonia) activity EXP
Inferred from Experiment
more info
 PubMed 
enables carbamoyl-phosphate synthase (ammonia) activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
contributes_to carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables endopeptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables glutamate binding IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding EXP
Inferred from Experiment
more info
 PubMed 
enables modified amino acid binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables phospholipid binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-containing complex binding IEA
Inferred from Electronic Annotation
more info
  
enables small molecule binding EXP
Inferred from Experiment
more info
 PubMed 
Process Evidence Code Pubs
involved_in 'de novo' pyrimidine nucleobase biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in carbamoyl phosphate biosynthetic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to ammonium ion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to cAMP IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to fibroblast growth factor stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to glucagon stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to oleic acid IEA
Inferred from Electronic Annotation
more info
  
involved_in citrulline biosynthetic process NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in glutamine metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in hepatocyte differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in homocysteine metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in midgut development IEA
Inferred from Electronic Annotation
more info
  
involved_in monoatomic anion homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in nitric oxide metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in response to amine IEA
Inferred from Electronic Annotation
more info
  
involved_in response to amino acid IEA
Inferred from Electronic Annotation
more info
  
involved_in response to dexamethasone IEA
Inferred from Electronic Annotation
more info
  
involved_in response to food IEA
Inferred from Electronic Annotation
more info
  
involved_in response to growth hormone IEA
Inferred from Electronic Annotation
more info
  
involved_in response to lipopolysaccharide IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to starvation IEA
Inferred from Electronic Annotation
more info
  
involved_in response to toxic substance IEA
Inferred from Electronic Annotation
more info
  
involved_in response to xenobiotic stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in response to zinc ion IEA
Inferred from Electronic Annotation
more info
  
involved_in sequestering of metal ion EXP
Inferred from Experiment
more info
 PubMed 
involved_in triglyceride catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in urea cycle NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in urea cycle TAS
Traceable Author Statement
more info
  
involved_in vasodilation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
located_in mitochondrial inner membrane IEA
Inferred from Electronic Annotation
more info
  
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrial nucleoid IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleolus IDA
Inferred from Direct Assay
more info
  
part_of protein-containing complex IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
carbamoyl-phosphate synthase [ammonia], mitochondrial
Names
carbamoyl-phosphate synthase (ammonia)
carbamoyl-phosphate synthase 1, mitochondrial
carbamoylphosphate synthetase I
NP_001116105.2
NP_001356185.1
NP_001356186.1
NP_001866.2

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008285.1 RefSeqGene

    Range
    4998..206423
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_336

mRNA and Protein(s)

  1. NM_001122633.3 → NP_001116105.2  carbamoyl-phosphate synthase [ammonia], mitochondrial isoform b precursor

    Status: REVIEWED

    Source sequence(s)
    AB208800, AC007970, N58033, Y15793
    Consensus CDS
    CCDS2393.1
    UniProtKB/Swiss-Prot
    Q7Z5I5
    UniProtKB/TrEMBL
    A0A024R454
    Related
    ENSP00000501022.1, ENST00000673711.1
    Conserved Domains (2) summary
    TIGR01368
    Location:46 → 400
    CPSaseIIsmall; carbamoyl-phosphate synthase, small subunit
    TIGR01369
    Location:419 → 1477
    CPSaseII_lrg; carbamoyl-phosphate synthase, large subunit

  2. NM_001369256.1 → NP_001356185.1  carbamoyl-phosphate synthase [ammonia], mitochondrial isoform d

    Status: REVIEWED

    Source sequence(s)
    AC007970, AC008172
    Conserved Domains (2) summary
    TIGR01368
    Location:57 → 411
    CPSaseIIsmall; carbamoyl-phosphate synthase, small subunit
    TIGR01369
    Location:430 → 1488
    CPSaseII_lrg; carbamoyl-phosphate synthase, large subunit

  3. NM_001369257.1 → NP_001356186.1  carbamoyl-phosphate synthase [ammonia], mitochondrial isoform b precursor

    Status: REVIEWED

    Source sequence(s)
    AC007970, AC008172
    Consensus CDS
    CCDS2393.1
    UniProtKB/Swiss-Prot
    Q7Z5I5
    UniProtKB/TrEMBL
    A0A024R454
    Related
    ENSP00000500537.1, ENST00000673510.1
    Conserved Domains (2) summary
    TIGR01368
    Location:46 → 400
    CPSaseIIsmall; carbamoyl-phosphate synthase, small subunit
    TIGR01369
    Location:419 → 1477
    CPSaseII_lrg; carbamoyl-phosphate synthase, large subunit

  4. NM_001875.5 → NP_001866.2  carbamoyl-phosphate synthase [ammonia], mitochondrial isoform b precursor

    See identical proteins and their annotated locations for NP_001866.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (b) is shorter at the N-terminus compared to isoform a.
    Source sequence(s)
    BC058010, BC140943, BJ995129
    Consensus CDS
    CCDS2393.1
    UniProtKB/Swiss-Prot
    P31327, Q7Z5I5
    UniProtKB/TrEMBL
    A0A024R454, Q6PEK7
    Related
    ENSP00000233072.5, ENST00000233072.10
    Conserved Domains (2) summary
    TIGR01368
    Location:46 → 400
    CPSaseIIsmall; carbamoyl-phosphate synthase, small subunit
    TIGR01369
    Location:419 → 1477
    CPSaseII_lrg; carbamoyl-phosphate synthase, large subunit

RNA

  1. NR_161225.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC008172

  2. NR_163592.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (c) is shorter at the N-terminus compared to isoform a and may not be localized to the mitochondrion.
    Source sequence(s)
    AB208800, AK302778, AK316425, AY317138, N58033
    Related
    ENST00000451903.3

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_03

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    210477685..210679107
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    210958482..211159839
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001122634.3: Suppressed sequence

    Description
    NM_001122634.3: This RefSeq was removed because currently there is support for the transcript but not for the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P31327.2 GenPept UniProtKB/Swiss-Prot:P31327

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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