CES2

protein-coding

carboxylesterase 2, 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. The protein encoded by this gene is the major intestinal enzyme and functions in intestine drug clearance. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2010]

MANE transcript

NM_001365405.1

Inheritance

—

ClinVar variants

U:63B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.92

Max pathogenic AF

—

Genomic locus

chr16:66,934,444-66,945,096

External References & Databases

Ensembl (ENSG00000172831)

Transcript & Mutation Effects

hg38 • Region Span ~10.7 kb

Loading mutation effect viewer...

GenCC 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 CES2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001365405.1. 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			4 clinvar	3 clinvar	1 clinvar	8
missense			58 clinvar	3 clinvar		61
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	63	6	1	70

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 79 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001365405.1	RefSeq	NP_001352334.1	12	MANE Select
ENST00000317091.10	Ensembl	ENSP00000317842.5	12	MANE Select
NM_001365406.1	RefSeq	NP_001352335.1	11	Standard
NM_001365407.1	RefSeq	NP_001352336.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Drug metabolism - other enzymes - Homo sapiens (human)
Fluoropyrimidine Pathway, Pharmacokinetics
Mycophenolic acid Pathway, Pharmacokinetics
Mycophenolic acid Pathway, Pharmacokinetics/Pharmacodynamics
Irinotecan Pathway, Pharmacokinetics

Biological Process

prostaglandin metabolic process
xenobiotic metabolic process
catabolic process

Molecular Function

methylumbelliferyl-acetate deacetylase activity
carboxylic ester hydrolase activity

Cellular Component

extracellular space
endoplasmic reticulum
endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000317091
Coding exons: 12
Length: 10653
Individuals with no LoFs: 125568
Homozygous LoFs: 0
Heterozygous LoFs: 180
Defined: 125748
p: 0.000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.372	351	371	0.946	0.0000220	4068
Missense (PolyPhen)		93	120.47	0.772		1445
Synonymous	0.514	150	158	0.948	0.0000104	1272
Loss of Function	0.374	25	27.1	0.922	0.00000129	279

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00080	0.00080	rare
Latino/Admixed American	0.0019	0.0019	notable
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00049	0.00049	rare
Finnish	0.00055	0.00055	rare
European (Non-Finnish)	0.00054	0.00054	rare
South Asian	0.00056	0.00056	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:9169443). Shows high catalytic efficiency for hydrolysis of cocaine, 4- methylumbelliferyl acetate, heroin and 6-monoacetylmorphine (PubMed:9169443). Hydrolyzes aspirin, substrates with large alcohol group and small acyl group and endogenous lipids such as triacylglycerol (PubMed:28677105). {ECO:0000269|PubMed:9169443, ECO:0000303|PubMed:28677105}.;

Recessive Scores

pRec: 0.141

Intolerance Scores

LoFtool: 0.930
RVIS EVS: -0.86
RVIS percentile EVS: 10.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.297

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium