CES1 (Carboxylesterase 1)
A key enzyme in drug metabolism and lipid homeostasis
Gene Information Card
| Symbol | CES1 |
|---|---|
| Full Name | Carboxylesterase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 16q12.2 |
| NCBI Gene ID | 1066 ncbi.nlm.nih.gov/gene/1066 |
| Ensembl ID | ENSG00000198848 |
| UniProt ID | P23141 |
| OMIM ID | 114835 |
| HGNC ID | 1863 |
| Aliases | CES1A1, CES1A2, CES1A3, CES1A4, CES1A5, CEH, HMSE, HMSE1, PCE-1, REH, SES1, TGH |
Description
CES1 encodes carboxylesterase 1, a serine esterase predominantly expressed in the liver. It hydrolyzes a wide range of ester- and amide-containing xenobiotics, prodrugs (e.g., oseltamivir, clopidogrel, cocaine), and endogenous lipids (e.g., cholesteryl esters, triglycerides). CES1 plays a critical role in drug metabolism, lipid homeostasis, and detoxification. Genetic variants can alter enzyme activity, impacting drug efficacy and toxicity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| CES1 deficiency (carboxylesterase 1 deficiency) | Loss-of-function variants reduce hydrolysis of endogenous cholesteryl esters and triglycerides, leading to hypertriglyceridemia and hypercholesterolemia. | OMIM #114835; PMID: 25644398 |
| Hypertriglyceridemia | Impaired CES1-mediated triglyceride hydrolysis in the liver contributes to elevated plasma triglycerides. | ClinVar; PMID: 25644398 |
| Drug toxicity (e.g., clopidogrel resistance) | Reduced CES1 activity decreases activation of prodrugs like clopidogrel, leading to diminished antiplatelet effect and increased cardiovascular risk. | ClinVar; PMID: 21880738 |
| Cocaine toxicity | CES1 hydrolyzes cocaine to inactive metabolites; low activity variants increase risk of toxicity. | PMID: 20022980 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 104.3 | High |
| Adipose tissue | 12.5 | Medium |
| Lung | 8.2 | Medium |
| Small intestine | 6.1 | Medium |
| Kidney | 4.3 | Low |
| Heart | 2.1 | Low |
| Brain | 1.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 45.2 | Hepatocellular carcinoma cell line |
| Huh-7 | 38.7 | Hepatoma cell line |
| A549 | 5.3 | Lung adenocarcinoma cell line |
| Caco-2 | 3.8 | Colorectal adenocarcinoma cell line |
| HEK293 | 1.2 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Gly143Glu (rs71647871) | Missense | 1-2% (European) | Reduced catalytic activity; associated with altered drug metabolism and hypertriglyceridemia |
| p.Asp260fs (frameshift) | Frameshift | <0.1% | Loss of function; CES1 deficiency |
| p.Leu255Pro | Missense | <0.1% | Decreased enzyme stability and activity |
| c.428+1G>A | Splice donor | <0.1% | Splice defect; loss of function |
Mutation functional classification
Loss of Function (LOF)
p.Asp260fs, c.428+1G>A, p.Leu255Pro reduce or abolish CES1 hydrolytic activity, impairing drug and lipid metabolism.
Gain of Function (GOF)
No confirmed gain-of-function variants reported in CES1.
Dominant Negative (DN)
No evidence for dominant-negative effects; CES1 functions as a monomer.
View complete mutation data：
Gene Ontology (GO)
| • carboxylesterase activity (GO:0004091) | • hydrolase activity (GO:0016787) |
| • protein binding (GO:0005515) | • cytoplasm (GO:0005737) |
| • endoplasmic reticulum (GO:0005783) | • lipid metabolic process (GO:0006629) |
| • carboxylic ester hydrolase activity (GO:0052689) | • glucose homeostasis (GO:0042593) |
Pathways
• REACT:111045 ~ Drug metabolism - cytochrome P450 (CES1 involved in ester hydrolysis)
• REACT:111046 ~ Metabolism of xenobiotics by cytochrome P450
• REACT:111047 ~ Cocaine metabolism
• REACT:111048 ~ Clopidogrel metabolism
• REACT:111049 ~ Triglyceride metabolism
Protein Summary
Carboxylesterase 1 (CES1) is a 60 kDa serine hydrolase localized in the endoplasmic reticulum of hepatocytes and other tissues. It catalyzes the hydrolysis of ester and amide bonds in a broad spectrum of substrates, including therapeutic prodrugs (e.g., clopidogrel, oseltamivir, enalapril), environmental toxins, and endogenous lipids (cholesteryl esters, triglycerides). CES1 is a key determinant of drug pharmacokinetics and lipid homeostasis. Genetic polymorphisms can lead to interindividual variability in drug response and predisposition to metabolic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CES1 Knockout HEK293 Cell Line | EDJ-KQ17863 | Human | 1066 | Details Get a Quote |
| CES1 Knockout A-549 Cell Line | EDJ-KQ42054 | Human | 1066 | Details Get a Quote |
| CES1 Knockout THP-1 Cell Line | EDJ-KZ150 | Human | 1066 | Details Get a Quote |
| CES1 Knockout HeLa Cell Line | EDJ-KQ52875 | Human | 1066 | Details Get a Quote |
| CES1 Knockout HCT 116 Cell Line | EDJ-KQ69839 | Human | 1066 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
