CES3
protein-codingcarboxylesterase 3, the group of Carboxylesterases
Gene summary
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 gene is expressed in several tissues, particularly in colon, trachea and in brain, and the protein participates in colon and neural drug metabolism. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported, but the biological validity and/or full-length nature of some variants have not been determined.[provided by RefSeq, Jun 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CES3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024922.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 82 | 10 | 92 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 86 | 10 | 0 | 96 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_079198.2 | 13 | MANE Select | |
| Ensembl | ENSP00000304782.4 | 13 | MANE Select | |
| RefSeq | NP_001172105.1 | 5 | Standard | |
| RefSeq | NP_001172106.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ces3 | Danio rerio | Structure: otolith Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Aryl Hydrocarbon Receptor Pathway
- Nuclear Receptors Meta-Pathway
- NRF2 pathway
- Phase I - Functionalization of compounds
- Biological oxidations
Biological Process
- xenobiotic metabolic process
- lipid catabolic process
- low-density lipoprotein particle clearance
Molecular Function
- sterol esterase activity
- triglyceride lipase activity
- carboxylic ester hydrolase activity
Cellular Component
- extracellular space
- endoplasmic reticulum lumen
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000303334
- Coding exons
- 13
- Length
- 13912
- Individuals with no LoFs
- 125550
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 197
- Defined
- 125748
- p
- 0.000788
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.526 | 319 | 347 | 0.920 | 0.0000200 | 3726 |
| Missense (PolyPhen) | 124 | 125.29 | 0.98973 | 1522 | ||
| Synonymous | 0.0188 | 138 | 138 | 0.998 | 0.00000881 | 1136 |
| Loss of Function | 0.973 | 21 | 26.4 | 0.796 | 0.00000132 | 272 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0042 | 0.0041 | notable |
| Latino/Admixed American | 0.00046 | 0.00046 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0026 | 0.0026 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00043 | 0.00043 | rare |
| South Asian | 0.00056 | 0.00052 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows low catalytic efficiency for hydrolysis of CPT-11 (7-ethyl-10-[4-(1-piperidino)- 1-piperidino]-carbonyloxycamptothecin), a prodrug for camptothecin used in cancer therapeutics.;
Intolerance Scores
- LoFtool
- 0.935
- RVIS EVS
- 0.23
- RVIS percentile EVS
- 68.52
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.672
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |