CEL

Chr 9AD

carboxyl ester lipase

Also known as: BAL, BSDL, BSSL, CELL, CEase, FAP, FAPP, MODY8

NCBI Gene: 1056 ENSG00000170835 UniProt: P19835

The protein encoded by this gene is a glycoprotein secreted from the pancreas into the digestive tract and from the lactating mammary gland into human milk. The physiological role of this protein is in cholesterol and lipid-soluble vitamin ester hydrolysis and absorption. This encoded protein promotes large chylomicron production in the intestine. Also its presence in plasma suggests its interactions with cholesterol and oxidized lipoproteins to modulate the progression of atherosclerosis. In pancreatic tumoral cells, this encoded protein is thought to be sequestrated within the Golgi compartment and is probably not secreted. This gene contains a variable number of tandem repeat (VNTR) polymorphism in the coding region that may influence the function of the encoded protein. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Maturity-onset diabetes of the young, type VIIIMIM #609812

Active trials

Pathogenic / LP

100

ClinVar variants

Pubs (1 yr)

0.1

Missense Z

0.89

LOEUF

Clinical Summary— CEL

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Gene-Disease Validity (ClinGen)

maturity-onset diabetes of the young type 8 · ADModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

7 Pathogenic / Likely Pathogenic· 46 VUS of 100 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

📖

GeneReview available — CEL

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.89LOEUF

pLI 0.000

Z-score 1.96

OE 0.56 (0.36–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.11Z-score

OE missense 0.98 (0.91–1.07)

415 obs / 421.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.36–0.89)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.91–1.07)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.20

0≤1.21.6

LoF obs/exp: 13 / 23.2Missense obs/exp: 415 / 421.5Syn Z: -2.22

0.74top 25%

GOF

0.87top 5%

LOF

0.2289th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median · 1 literature citation

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.

Literature Evidence

GOFWe tested the hypothesis that a deletion and frameshift mutation (C563fsX673) in the CEL VNTR causes CP through proteotoxic gain-of-function activation of maladaptive cell signaling pathways including cell death pathways. Our results demonstrate that disorders of protein homeostasis can lead to CP aPMID:27650499

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

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic1

VUS46

Likely Benign36

Benign5

Conflicting6

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	6	0	6
Likely Pathogenic	1	0	0	0	1
VUS	1	39	5	1	46
Likely Benign	0	2	1	33	36
Benign	0	2	2	1	5
Conflicting	—				6
Total	2	43	14	35	100

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

View in ClinVar →

Protein Context — Lollipop Plot

CEL · protein map & ClinVar variants

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

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

📖

GeneReview available — CEL

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Neoplasms

Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Solid Tumors

ACTIVE NOT RECRUITING

NCT03967223Phase PHASE2USWM CT, LLCStarted 2019-12-31

Letetresgene autoleucel (lete-cel, GSK3377794)FludarabineCyclophosphamide

RASopathy

Study of the Thyroid Function and Echostructural Morphology in Patients Affected With Rasopathies (ECORAS2023)

RECRUITING

NCT06489067University of Bari Aldo MoroStarted 2024-01-15

HealthyHealthy Nutrition

The BEGIN Study Bifidobacterium Infantis to Newborns: Effects of Modulating the Gut Microbial Composition on Growth, Immune Function and Inflammatory Conditions - a Randomized Placebo-controlled Double-blinded Intervention Trial

RECRUITING

NCT06452199Phase NAUniversity of AarhusStarted 2024-06-10

B. infantisPlacebo

Carpal Tunnel SyndromeNeurodynamic TreatmentNerve Mobilisation

Mechanisms of Neurodynamic Treatments

RECRUITING

NCT05859412Phase NAUniversity of OxfordStarted 2023-05-17

Neurodynamic exercisesSteroid injection (Depomedrone 40mg)Advice

Beta-Thalassemia

A Study of Participants with Β-Thalassemia Treated with Betibeglogene Autotemcel

RECRUITING

NCT06271512Genetix Biotherapeutics Inc.Started 2024-01-23