CPS1 Gene

Name	carbamoyl-phosphate synthase 1, mitochondrial
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Carbamoyl phosphate synthetase 1 (CPS1) is a mitochondrial, rate‐limiting enzyme of the urea cycle that catalyzes the conversion of ammonia and bicarbonate into carbamoyl phosphate—thereby playing a central role in ammonia detoxification and nitrogen homeostasis. Several studies have highlighted that CPS1 activity is tightly regulated by post‐translational modifications. For example, CPS1 undergoes lysine succinylation, malonylation, and glutarylation that suppress its enzymatic function; these modifications are efficiently reversed by SIRT5‐mediated deacylation, thereby modulating urea cycle flux in response to metabolic cues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its enzymatic role, genetic studies have linked CPS1 to broader aspects of metabolic regulation. Variants in the CPS1 gene have been associated with alterations in plasma glycine and urea cycle metabolite levels, as well as changes in homocysteine metabolism that influence cardiovascular risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " Moreover, perturbations in CPS1 expression and activity—resulting from genetic mutations or altered post‐translational modifications—can lead to hyperammonemia and are central to the pathology of CPS1 deficiency.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its core metabolic function, CPS1 expression is differentially regulated in disease contexts. Its upregulation or loss has been reported in various cancers and liver diseases, suggesting that CPS1 may serve as a potential biomarker for disease progression and tissue damage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": " Furthermore, oxidative modifications such as tyrosine nitration have been shown to impair CPS1 function, linking mitochondrial oxidative stress to defective ammonia clearance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, emerging evidence suggests that CPS1—and the pathways in which it participates—may impact whole‐body metabolic health, including weight loss maintenance, while its dysregulation can contribute to adverse drug effects such as valproate‐induced hyperammonemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifaceted role of CPS1 in metabolic homeostasis, its dynamic regulation by post‐translational modifications and genetic variants, and its clinical relevance as both a marker and mediator of metabolic and liver diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jintang Du, Yeyun Zhou, Xiaoyang Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1207861"}], "href": "https://doi.org/10.1126/science.1207861"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22076378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22076378"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Minjia Tan, Chao Peng, Kristin A Anderson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lysine glutarylation is a protein posttranslational modification regulated by SIRT5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2014.03.014"}], "href": "https://doi.org/10.1016/j.cmet.2014.03.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24703693"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24703693"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jiujiu Yu, Sushabhan Sadhukhan, Lilia G Noriega, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metabolic characterization of a Sirt5 deficient mouse model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep02806"}], "href": "https://doi.org/10.1038/srep02806"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24076663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24076663"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jaana A Hartiala, W H Wilson Tang, Zeneng Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study and targeted metabolomics identifies sex-specific association of CPS1 with coronary artery disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms10558"}], "href": "https://doi.org/10.1038/ncomms10558"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26822151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26822151"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Guillaume Paré, Daniel I Chasman, Alexander N Parker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a healthy population: a genome-wide evaluation of 13 974 participants in the Women's Genome Health Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Cardiovasc Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCGENETICS.108.829804"}], "href": "https://doi.org/10.1161/CIRCGENETICS.108.829804"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20031578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20031578"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Johannes Häberle, Oleg A Shchelochkov, Jing Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21406"}], "href": "https://doi.org/10.1002/humu.21406"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21120950"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21120950"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sen-Lin Ma, Ai-Jun Li, Zhao-Yang Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Co‑expression of the carbamoyl‑phosphate synthase 1 gene and its long non‑coding RNA correlates with poor prognosis of patients with intrahepatic cholangiocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2015.4435"}], "href": "https://doi.org/10.3892/mmr.2015.4435"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26499888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26499888"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Diana M Cardona, Xiaokui Zhang, Chen Liu "}, {"type": "b", "children": [{"type": "t", "text": "Loss of carbamoyl phosphate synthetase I in small-intestinal adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Clin Pathol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1309/AJCP74XGRFWTFLJU"}], "href": "https://doi.org/10.1309/AJCP74XGRFWTFLJU"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19926579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19926579"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Saima Ajaz, Mark J McPhail, Luigi Gnudi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial dysfunction as a mechanistic biomarker in patients with non-alcoholic fatty liver disease (NAFLD)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mitochondrion (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mito.2020.12.010"}], "href": "https://doi.org/10.1016/j.mito.2020.12.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33387664"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33387664"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Hideo Takakusa, Isaac Mohar, Terrance J Kavanagh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein tyrosine nitration of mitochondrial carbamoyl phosphate synthetase 1 and its functional consequences."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2012.02.114"}], "href": "https://doi.org/10.1016/j.bbrc.2012.02.114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22402285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22402285"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Alice Matone, Marie-Pier Scott-Boyer, Jerome Carayol, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Network Analysis of Metabolite GWAS Hits: Implication of CPS1 and the Urea Cycle in Weight Maintenance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0150495"}], "href": "https://doi.org/10.1371/journal.pone.0150495"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26938218"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26938218"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Kazuyuki Inoue, Eri Suzuki, Toshiki Takahashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "4217C>A polymorphism in carbamoyl-phosphate synthase 1 gene may not associate with hyperammonemia development during valproic acid-based therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsy Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.eplepsyres.2014.04.008"}], "href": "https://doi.org/10.1016/j.eplepsyres.2014.04.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24888247"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24888247"}]}]}]}
Synonyms	PHN, CPSASE1
Proteins	CPSM_HUMAN
NCBI Gene ID	1373
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CPS1 has 7,863 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 116 datasets.

Click the + buttons to view associations for CPS1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CPS1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CPS1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CPS1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CPS1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CPS1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CPS1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CPS1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CPS1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CPS1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CPS1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CPS1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CPS1 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CPS1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CPS1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CPS1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CPS1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CPS1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CPS1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CPS1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CPS1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CPS1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CPS1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CPS1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CPS1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CPS1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CPS1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CPS1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CPS1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CPS1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CPS1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CPS1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CPS1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CPS1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CPS1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CPS1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CPS1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CPS1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CPS1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CPS1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CPS1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CPS1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.