CES1

Chr 16AD

carboxylesterase 1

Also known as: ACAT, CE-1, CEH, CES2, HMSE, HMSE1, PCE-1, REH

NCBI Gene: 1066ENSG00000198848UniProt: P02795

The protein functions as the major liver carboxylesterase enzyme responsible for hydrolysis of various drugs and xenobiotics including cocaine and heroin, serving a critical role in hepatic drug clearance. Mutations cause CES1-related altered drug metabolism through an autosomal dominant inheritance pattern. The pathogenic mechanism involves dominant-negative effects where mutant proteins interfere with normal enzyme function.

Summary from RefSeq, OMIM, UniProt, Mechanism

Primary Disease Associations & Inheritance

Drug metabolism, altered, CES1-relatedMIM #618057
AD
3
Active trials
68
Pubs (1 yr)
19
P/LP submissions
5%
P/LP missense
1.46
LOEUF
DN
Mechanism· predicted
Clinical Summary— CES1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 101 VUS of 145 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.46LOEUF
pLI 0.000
Z-score -0.09
OE 1.02 (0.73–1.46)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.00Z-score
OE missense 1.38 (1.25–1.51)
307 obs / 223.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.02 (0.73–1.46)
0≤0.351.4
Missense OE1.38 (1.25–1.51)
0≤0.61.4
Synonymous OE1.45
0≤1.21.6
LoF obs/exp: 22 / 21.6Missense obs/exp: 307 / 223.1Syn Z: -3.37
DN
0.6937th %ile
GOF
0.6051th %ile
LOF
0.2581th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

145 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic2
VUS101
Likely Benign6
Conflicting1
17
Pathogenic
2
Likely Pathogenic
101
VUS
6
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
15
0
17
Likely Pathogenic
0
0
2
0
2
VUS
1
92
8
0
101
Likely Benign
0
6
0
0
6
Benign
0
0
0
0
0
Conflicting
—1
Total299250127

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CES1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients