CES1

carboxylesterase 1, the group of Carboxylesterases

Basic information

Region (hg38): 16:55802851-55833337

Links

ENSG00000198848 ∙ NCBI:1066 ∙ OMIM:114835 ∙ HGNC:1863 ∙ Uniprot:P23141 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Drug metabolism, altered, CES1-related (Carboxylesterase 1 deficiency)	AD/AR	Pharmacogenomic	Selection and dosing of certain medications may be affected by the presence of variants	Biochemical	18485328; 23111421; 26817948; 27614009; 28087982

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CES1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CES1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			42	2		44
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	42	2	0

Variants in CES1

This is a list of pathogenic ClinVar variants found in the CES1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-55810528-C-T		not specified	Uncertain significance (Jul 26, 2021)
16-55810529-G-C		not specified	Uncertain significance (Mar 21, 2024)
16-55810597-T-C		not specified	Uncertain significance (Dec 14, 2023)
16-55810604-T-C		not specified	Uncertain significance (Aug 22, 2023)
16-55810627-T-A		not specified	Uncertain significance (Nov 25, 2024)
16-55810937-T-C		not specified	Uncertain significance (Aug 11, 2024)
16-55810965-T-A		not specified	Uncertain significance (Apr 06, 2024)
16-55810997-T-C		not specified	Conflicting classifications of pathogenicity (Jun 01, 2024)
16-55811002-C-T		not specified	Uncertain significance (Sep 26, 2024)
16-55812941-C-T		not specified	Uncertain significance (Feb 03, 2022)
16-55812956-C-A		not specified	Uncertain significance (Jun 22, 2021)
16-55812976-G-C		not specified	Uncertain significance (Dec 04, 2024)
16-55816928-C-T		not specified	Uncertain significance (Jan 26, 2023)
16-55816931-G-T		not specified	Uncertain significance (Oct 01, 2024)
16-55819548-G-A		not specified	Uncertain significance (Aug 01, 2022)
16-55819602-G-A		not specified	Uncertain significance (Jul 14, 2024)
16-55819609-T-C		not specified	Uncertain significance (Aug 10, 2024)
16-55819630-T-C		not specified	Likely benign (Mar 25, 2024)
16-55820389-CA-C		DRUG METABOLISM, ALTERED, CES1-RELATED	Pathogenic (Jun 01, 2008)
16-55821400-C-T		not specified	Uncertain significance (Feb 21, 2024)
16-55821502-G-A		not specified	Uncertain significance (Jan 24, 2024)
16-55821517-C-G		not specified	Uncertain significance (May 24, 2024)
16-55823593-C-T		not specified	Uncertain significance (Dec 18, 2023)
16-55823599-C-T		not specified	Uncertain significance (Sep 30, 2024)
16-55823611-C-T		not specified	Uncertain significance (Dec 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CES1	protein_coding	protein_coding	ENST00000360526	14	30487

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.32e-15	0.0106	118876	6	6866	125748	0.0277

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.00	307	223	1.38	0.0000124	3604
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0624	0.0619
Ashkenazi Jewish	0.0225	0.0227
East Asian	0.0628	0.0637
Finnish	0.0110	0.0110
European (Non-Finnish)	0.0173	0.0174
Middle Eastern	0.0628	0.0637
South Asian	0.0429	0.0433
Other	0.0290	0.0291

dbNSFP

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}.
• Pathway: Drug metabolism - other enzymes - Homo sapiens (human);Fluoropyrimidine Pathway, Pharmacokinetics;Clopidogrel Pathway, Pharmacokinetics;Mycophenolic acid Pathway, Pharmacokinetics;Mycophenolic acid Pathway, Pharmacokinetics/Pharmacodynamics;Irinotecan Pathway, Pharmacokinetics;Irinotecan Pathway, Pharmacodynamics;Mycophenolic Acid Metabolism Pathway;Capecitabine Action Pathway;Heroin Metabolism Pathway;Irinotecan Action Pathway;Capecitabine Metabolism Pathway;Heroin Action Pathway;Irinotecan Metabolism Pathway;Phase I biotransformations, non P450;Fluoropyrimidine Activity;Irinotecan Pathway;Heroin metabolism;Nuclear Receptors Meta-Pathway;NRF2 pathway;Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling;Phase I - Functionalization of compounds;Biological oxidations;Metabolism;retinol biosynthesis;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.333

Intolerance Scores

• loftool: 0.954
• rvis_EVS: 1.91
• rvis_percentile_EVS: 97.43

Haploinsufficiency Scores

• pHI: 0.472
• hipred: N
• hipred_score: 0.153

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ces1h

Gene ontology

• Biological process: cholesterol biosynthetic process;xenobiotic metabolic process;response to toxic substance;lipid catabolic process;epithelial cell differentiation;medium-chain fatty acid metabolic process;cholesterol ester hydrolysis involved in cholesterol transport
• Cellular component: extracellular space;endoplasmic reticulum;endoplasmic reticulum lumen;cytosol
• Molecular function: sterol esterase activity;triglyceride lipase activity;methylumbelliferyl-acetate deacetylase activity;carboxylic ester hydrolase activity