CES1 Gene

HGNC Family	Carboxylesterases (CES)
Name	carboxylesterase 1
Description	This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They may participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This enzyme is the major liver enzyme and functions in liver drug clearance. Mutations of this gene cause carboxylesterase 1 deficiency. Three transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Human carboxylesterase 1 (CES1) is a major serine hydrolase highly expressed in the liver that plays a central role in the biotransformation of a wide variety of ester‐containing compounds. Its catalytic versatility is exemplified by its ability to hydrolyze and thereby either inactivate or activate numerous therapeutic agents—including psychostimulants such as methylphenidate, the antiplatelet prodrug clopidogrel, and angiotensin‐converting enzyme inhibitor prodrugs—as well as drugs of abuse like cocaine and heroin analogues [(1,2,3,4)]. Structural studies have revealed that CES1 possesses both rigid and flexible ligand‐binding compartments, which underlie its capacity to interact with chemically diverse substrates and even participate in endogenous processes such as cholesterol metabolism [(2,5)]. Moreover, naturally occurring genetic variants of the CES1 gene have been shown to markedly impair its hydrolytic activity, with clinically relevant consequences for drug disposition and therapeutic response [(1,3,7)]. In addition to its established role in drug metabolism, altered expression of CES1—in particular, its down‐regulation in hepatocellular carcinoma and detection in plasma—suggests that this enzyme may serve as a potential biomarker for liver disease [(6)]. Overall, CES1’s broad substrate specificity, structural promiscuity, and susceptibility to genetic variation underscore its importance in determining both pharmacokinetic outcomes and endogenous metabolic processes.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n (1)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", (2)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", (3)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", (4)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", (5)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", (6)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", (7)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hao-Jie Zhu, Kennerly S Patrick, Hong-Jie Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2008.04.015"}], "href": "https://doi.org/10.1016/j.ajhg.2008.04.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18485328"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18485328"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sompop Bencharit, Christopher L Morton, Yu Xue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsb919"}], "href": "https://doi.org/10.1038/nsb919"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12679808"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12679808"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hao-Jie Zhu, Xinwen Wang, Brian E Gawronski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Carboxylesterase 1 as a determinant of clopidogrel metabolism and activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Exp Ther (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/jpet.112.201640"}], "href": "https://doi.org/10.1124/jpet.112.201640"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23275066"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23275066"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ragnar Thomsen, Henrik B Rasmussen, Kristian Linnet "}, {"type": "b", "children": [{"type": "t", "text": "In vitro drug metabolism by human carboxylesterase 1: focus on angiotensin-converting enzyme inhibitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Dispos (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/dmd.113.053512"}], "href": "https://doi.org/10.1124/dmd.113.053512"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24141856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24141856"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sompop Bencharit, Carol C Edwards, Christopher L Morton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2006.08.025"}], "href": "https://doi.org/10.1016/j.jmb.2006.08.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16962139"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16962139"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Keun Na, Eun-Young Lee, Hyoung-Joo Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proteomics (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pmic.200900105"}], "href": "https://doi.org/10.1002/pmic.200900105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19658107"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19658107"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sharon Marsh, Ming Xiao, Jinsheng Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pharmacogenomic assessment of carboxylesterases 1 and 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygeno.2004.07.008"}], "href": "https://doi.org/10.1016/j.ygeno.2004.07.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15475243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15475243"}]}]}]}
Synonyms	CEH, TGH, CE-1, PCE-1, CES2, HMSE1, HMSE, HCE-1, REH
Proteins	EST1_HUMAN
NCBI Gene ID	1066
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CES1 has 22,511 functional associations with biological entities spanning 9 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, sequence feature) extracted from 123 datasets.

Click the + buttons to view associations for CES1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CES1 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CES1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CES1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CES1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CES1 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 CES1 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 CES1 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 CES1 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 CES1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CES1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CES1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CES1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CES1 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 CES1 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 CES1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CES1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CES1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CES1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CES1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CES1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CES1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CES1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CES1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CES1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CES1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CES1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CES1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CES1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CES1 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 CES1 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 CES1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CES1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CES1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CES1 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 CES1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CES1 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 CES1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CES1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CES1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CES1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CES1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.