CEL

Chr 9AD

carboxyl ester lipase

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

The protein functions as a pancreatic lipase that catalyzes hydrolysis of cholesteryl esters, phospholipids, and other lipid substrates, playing an essential role in dietary lipid digestion and fat-soluble vitamin absorption. Mutations cause maturity-onset diabetes of the young type VIII (MODY8), inherited in an autosomal dominant pattern. This gene shows very low constraint against loss-of-function variants (pLI near 0), suggesting haploinsufficiency may not be the primary disease mechanism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.891 OMIM phenotype
Clinical SummaryCEL
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Gene-Disease Validity (ClinGen)
maturity-onset diabetes of the young type 8 · ADModerate

Moderate evidence — consider for supplementary testing

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

Tolerant — LoF & missense variants common in population
LoF Constraint
0.89LOEUF
pLI 0.000
Z-score 1.96
OE 0.56 (0.360.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.11Z-score
OE missense 0.98 (0.911.07)
415 obs / 421.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.360.89)
00.351.4
Missense OE0.98 (0.911.07)
00.61.4
Synonymous OE1.20
01.21.6
LoF obs/exp: 13 / 23.2Missense obs/exp: 415 / 421.5Syn Z: -2.22
DN
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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Sickle Cell Disease

Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease

RECRUITING
NCT04819841Phase PHASE1, PHASE2Kamau TherapeuticsStarted 2021-11-15
nula-cel Drug Product
Primary MyelofibrosisPolycythemia VeraEssential Thrombocythemia

Myeloproliferative Neoplasms (MPNs) Patient Registry

RECRUITING
NCT02760238University Health Network, TorontoStarted 2015-04
Observational
Spinal Muscular Atrophy (SMA)

Long-term Follow-up of Patients With Spinal Muscular Atrophy Treated With OAV101 in Clinical Trials

RECRUITING
NCT05335876Phase PHASE3Novartis PharmaceuticalsStarted 2022-12-19
onasemnogene abeparvovec
Neoplasms, Breast

Efficacy and Safety Comparison of Niraparib to Placebo in Participants With Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer Susceptibility Gene Mutation (BRCAmut) or Triple-Negative Breast Cancer (TNBC) With Molecular Disease

ACTIVE NOT RECRUITING
NCT04915755Phase PHASE3GlaxoSmithKlineStarted 2021-06-28
NiraparibPlacebo
Neoplasms

Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Treated Advanced (Metastatic or Unresectable) Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

ACTIVE NOT RECRUITING
NCT06703346Phase PHASE2USWM CT, LLCStarted 2019-12-31
Letetresgene autoleucel (Lete-Cel (GSK3377794))CyclophosphamideFludarabine
Schizophrenia

A Study of ANAVEX3-71 in Adults With Schizophrenia

ACTIVE NOT RECRUITING
NCT06245213Phase PHASE2Anavex Life Sciences Corp.Started 2024-03-15
ANAVEX3-71 oral capsulesPlacebo oral capsules
Sickle Cell Disease

A Study Evaluating Gene Therapy With BB305 Lentiviral Vector in Sickle Cell Disease

ACTIVE NOT RECRUITING
NCT04293185Phase PHASE3Genetix Biotherapeutics Inc.Started 2020-02-14
bb1111
Recurrent Transformed Chronic Lymphocytic LeukemiaRefractory Transformed Chronic Lymphocytic LeukemiaTransformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell Lymphoma

Zanubrutinib and Lisocabtagene Maraleucel for the Treatment of Richter's Syndrome

RECRUITING
NCT05873712Phase PHASE2Aseel AlsouqiStarted 2023-07-28
Biospecimen CollectionBone Marrow BiopsyComputed Tomography
Breast Cancer Female

A Prospective Evaluation of the Peri-operative Hypoxia in Breast Cancer

RECRUITING
NCT03797482Tata Memorial HospitalStarted 2017-11-27
Intra-operative Tumor Tissue Biopsy
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
Vestibular DiseasesDFNA9

Genotype-phenotype Correlation Study of Presymptomatic and Symptomatic DFNA9 Patients

RECRUITING
NCT03716908Jessa HospitalStarted 2018-06-01
Alzheimer DiseaseInactivityPreventive Therapy

The Link Between Physical Activity and Brain Health in Healthy Adults

RECRUITING
NCT07025070Technical University of MadridStarted 2024-11-25
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
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