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

Summary

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: mouse all
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Genomic context

Location:: 2q34

Exon count:: 43

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (210477685..210679107)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (210958482..211159839)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (211342409..211543831)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Clinical features and CPS1 variants in Chinese patients with carbamoyl phosphate synthetase 1 deficiency.
Title: Clinical features and CPS1 variants in Chinese patients with carbamoyl phosphate synthetase 1 deficiency.
The Role of Carbamoyl Phosphate Synthetase 1 as a Prognostic Biomarker in Patients With Acetaminophen-induced Acute Liver Failure.
Title: The Role of Carbamoyl Phosphate Synthetase 1 as a Prognostic Biomarker in Patients With Acetaminophen-induced Acute Liver Failure.
Variant in the allosteric domain of CPS1 protein associated with effectiveness of N-carbamoyl glutamate therapy in neonatal onset CPS1 deficiency.
Title: Variant in the allosteric domain of CPS1 protein associated with effectiveness of N-carbamoyl glutamate therapy in neonatal onset CPS1 deficiency.
Integrated Proteomics and Metabolomics Analyses of Serum in Chinese Patients with Severe and Active Graves' Orbitopathy: A Cross-sectional Study.
Title: Integrated Proteomics and Metabolomics Analyses of Serum in Chinese Patients with Severe and Active Graves' Orbitopathy: A Cross-sectional Study.
NAGS, CPS1, and SLC25A13 (Citrin) at the Crossroads of Arginine and Pyrimidines Metabolism in Tumor Cells.
Title: NAGS, CPS1, and SLC25A13 (Citrin) at the Crossroads of Arginine and Pyrimidines Metabolism in Tumor Cells.
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.
O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis.
Title: O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis.
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.
Unfavorable clinical outcomes in patients with carbamoyl phosphate synthetase 1 deficiency.
Title: Unfavorable clinical outcomes in patients with carbamoyl phosphate synthetase 1 deficiency.
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.

Submit: New GeneRIF Correction See all GeneRIFs (66)

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 EBI GWAS CatalogPubMed
Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic determinants influencing human serum metabolome among African Americans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of body mass index in 23 000 individuals with and without asthma. EBI GWAS Catalog EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed
Human metabolic individuality in biomedical and pharmaceutical research. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiethnic meta-analysis of genome-wide association studies in &gt;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 EBI GWAS CatalogPubMed
New loci associated with kidney function and chronic kidney disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed
Prognostic implications of genetic variants in advanced non-small cell lung cancer: a genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G32934 (e-PCR)
- UniSTS:117512

RH68320 (e-PCR)
- UniSTS:15119

SHGC-12818 (e-PCR)
- UniSTS:6696

D11S2560 (e-PCR)
- UniSTS:37928

D8S2279 (e-PCR)
- UniSTS:473907

SHGC-33072 (e-PCR)
- UniSTS:577

G32234 (e-PCR)
- UniSTS:116837

D11S2687 (e-PCR)
- UniSTS:151912

RH123929 (e-PCR)
- UniSTS:136304

D15S1477 (e-PCR)
- UniSTS:474482

RH12253 (e-PCR)
- UniSTS:6775

RH36905 (e-PCR)
- UniSTS:87932

RH78779 (e-PCR)
- UniSTS:18577

Cps1 (e-PCR), detects polymorphism
- UniSTS:546708

D2S2818 (e-PCR)
- UniSTS:18839

SHGC-172945 (e-PCR)
- UniSTS:183457

SHGC-146134 (e-PCR)
- UniSTS:175030

SHGC-79694 (e-PCR)
- UniSTS:102073

RH120629 (e-PCR)
- UniSTS:132570

A009X04 (e-PCR)
- UniSTS:16638

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	IBA Inferred from Biological aspect of Ancestor more info
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
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 potassium ion binding	EXP Inferred from Experiment more info	PubMed
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
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 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
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 mitochondrion	HTP more info	PubMed
located_in nucleolus	IDA Inferred from Direct Assay more info
located_in plasma membrane	IEA Inferred from Electronic Annotation 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

EC 6.3.4.16

NP_001356185.1

EC 6.3.4.16

NP_001356186.1

EC 6.3.4.16

NP_001866.2

EC 6.3.4.16

NCBI Reference Sequences (RefSeq)

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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

NG_008285.1 RefSeqGene

Range

4998..206423

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_336

mRNA and Protein(s)

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

B7Z818, J3KQL0, O43774, P31327, Q53TL5, Q59HF8, Q7Z5I5

UniProtKB/TrEMBL

Q5R210

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

Status: REVIEWED

Source sequence(s)

AC007970, AC008172

UniProtKB/TrEMBL

Q5R210

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
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

B7Z818, J3KQL0, O43774, P31327, Q53TL5, Q59HF8, Q7Z5I5

UniProtKB/TrEMBL

Q5R210

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
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

B7Z818, J3KQL0, O43774, P31327, Q53TL5, Q59HF8, Q7Z5I5

UniProtKB/TrEMBL

Q5R210

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

NR_161225.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC008172
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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

210477685..210679107

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

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

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.