CES4A
protein-codingcarboxylesterase 4A, 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 also participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This gene, also called CES6, encodes a secreted enzyme, and may play a role in the detoxification of drugs and xenobiotics in neural and other tissues of the body and in the cerebrospinal fluid. Multiple transcript variants encoding different isoforms have been reported, but the full-length nature and/or biological validity of some variants have not been determined. [provided by RefSeq, Jun 2010]
- CES8
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.8 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 CES4A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001364782.1. 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 | 1 | 1 | ||||
| missense | 71 | 15 | 86 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 74 | 15 | 0 | 89 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001351711.1 | 14 | MANE Select | |
| Ensembl | ENSP00000497868.2 | 14 | MANE Select | |
| RefSeq | NP_001177130.1 | 12 | Standard | |
| RefSeq | NP_001177131.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Nuclear Receptors Meta-Pathway
- NRF2 pathway
- retinol biosynthesis
- E2F transcription factor network
Biological Process
- lipid catabolic process
Molecular Function
- sterol esterase activity
- triglyceride lipase activity
- carboxylic ester hydrolase activity
Cellular Component
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000540947
- Coding exons
- 12
- Length
- 21170
- Individuals with no LoFs
- 124747
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 66
- Defined
- 124813
- p
- 0.000264
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.08 | 226 | 277 | 0.817 | 0.0000144 | 3033 |
| Missense (PolyPhen) | 56 | 75.541 | 0.74132 | 906 | ||
| Synonymous | -0.00735 | 112 | 112 | 1.00 | 0.00000623 | 926 |
| Loss of Function | 1.97 | 14 | 24.5 | 0.571 | 0.00000115 | 264 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000064 | rare |
| Latino/Admixed American | 0.00067 | 0.00067 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00061 | 0.00061 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00027 | 0.00024 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable carboxylesterase. {ECO:0000250}.;
Intolerance Scores
- RVIS EVS
- -0.31
- RVIS percentile EVS
- 31.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |