CES1

protein-coding

carboxylesterase 1, 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 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]

MANE transcript

NM_001025195.2

Inheritance

AD, AR

ClinVar variants

P:2U:102B:15

Top phenotype

Drug metabolism, altered, CES1-related (Carboxylesterase 1 deficiency)

gnomAD constraint

pLI —, LoF o/e 1.02

Max pathogenic AF

—

Genomic locus

chr16:55,802,851-55,833,337

External References & Databases

Ensembl (ENSG00000198848)

Transcript & Mutation Effects

hg38 • Region Span ~30.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Drug metabolism, altered, CES1-related (Carboxylesterase 1 deficiency)AD/AR

Manifestation: Biochemical

Intervention: Pharmacogenomic

Rationale: Selection and dosing of certain medications may be affected by the presence of variants

Refs: 18485328; 23111421; 26817948; 27614009; 28087982

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CES1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 109

DRUG METABOLISM, ALTERED, CES1-RELATEDTotal: 4

not providedTotal: 3

CES1-related conditionTotal: 2

clopidogrel response - EfficacyTotal: 1

clopidogrel response - Metabolism/PKTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001025195.2. 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 clinvar	5 clinvar		6
missense	1 clinvar		96 clinvar	10 clinvar		107
nonsense						0
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	2	0	102	15	0	119

Highest pathogenic variant AF is 0.000037756698

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 139 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001025195.2	RefSeq	NP_001020366.1	14	MANE Select
ENST00000360526.8	Ensembl	ENSP00000353720.4	14	MANE Select
NM_001025194.2	RefSeq	NP_001020365.1	14	Standard
NM_001266.5	RefSeq	NP_001257.4	14	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
Clopidogrel Pathway, Pharmacokinetics
Mycophenolic acid Pathway, Pharmacokinetics
Mycophenolic acid Pathway, Pharmacokinetics/Pharmacodynamics

Biological Process

cholesterol biosynthetic process
xenobiotic metabolic process
response to toxic substance
lipid catabolic process
epithelial cell differentiation

Molecular Function

sterol esterase activity
triglyceride lipase activity
methylumbelliferyl-acetate deacetylase activity
carboxylic ester hydrolase activity

Cellular Component

extracellular space
endoplasmic reticulum
endoplasmic reticulum lumen
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360526
Coding exons: 14
Length: 30487
Individuals with no LoFs: 118876
Homozygous LoFs: 6
Heterozygous LoFs: 6866
Defined: 125748
p: 0.0277

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.00	307	223	1.38	0.0000124	3604
Missense (PolyPhen)		98	72.254	1.3563		1185
Synonymous	-3.37	130	89.4	1.45	0.00000543	1103
Loss of Function	-0.0859	22	21.6	1.02	0.00000112	319

Population LoF Frequency

Population	CAF	p-value	Status
African	0.015	0.015	notable
Latino/Admixed American	0.047	0.047	notable
Ashkenazi Jewish	0.022	0.023	notable
East Asian	0.063	0.064	notable
Finnish	0.011	0.011	notable
European (Non-Finnish)	0.017	0.017	notable
South Asian	0.043	0.043	notable
Other	0.029	0.029	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate. {ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443}.;

Recessive Scores

pRec: 0.333

Intolerance Scores

LoFtool: 0.954
RVIS EVS: 1.91
RVIS percentile EVS: 97.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.988

Gene Damage Prediction

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