CEL

Summary

CEL (carboxyl ester lipase, HGNC:1848) is a protein-coding gene on chromosome 9q34.13, encoding Bile salt-activated lipase (P19835). Catalyzes the hydrolysis of a wide range of substrates including cholesteryl esters, phospholipids, lysophospholipids, di- and tri-acylglycerols, and fatty acid esters of hydroxy fatty acids (FAHFAs).

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.

Source: NCBI Gene 1056 — RefSeq curated summary.

At a glance

• Gene–disease (curated): maturity-onset diabetes of the young type 8 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 428 total — 2 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 31
• Druggable target: yes
• MANE Select transcript: NM_001807

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1848
Approved symbol	CEL
Name	carboxyl ester lipase
Location	9q34.13
Locus type	gene with protein product
Status	Approved
Aliases	BSSL, MODY8
Ensembl gene	ENSG00000170835
Ensembl biotype	protein_coding
OMIM	114840
Entrez	1056

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000372080

RefSeq mRNA: 1 — MANE Select: NM_001807 NM_001807

CCDS: CCDS43896

Canonical transcript exons

ENST00000372080 — 11 exons

Exon	Start	End
ENSE00000000356	133061981	133062068
ENSE00001136798	133067088	133067205
ENSE00001136804	133066838	133066945
ENSE00001136809	133066530	133066660
ENSE00001136814	133065040	133065237
ENSE00001136821	133064640	133064762
ENSE00001136823	133064404	133064554
ENSE00001240014	133070461	133070658
ENSE00001456865	133070987	133071861
ENSE00001593673	133069056	133069259
ENSE00001679789	133068672	133068858

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 99.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.4399 / max 1810.7302, expressed in 16 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99205	0.5254	8
99200	0.2390	6
99198	0.1402	3
99203	0.1391	4
99225	0.1005	3
99199	0.0694	3
99201	0.0654	3
99202	0.0457	5
99224	0.0456	3
99204	0.0383	3

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.96	gold quality
type B pancreatic cell	CL:0000169	99.00	gold quality
pancreas	UBERON:0001264	98.80	gold quality
islet of Langerhans	UBERON:0000006	97.71	gold quality
pituitary gland	UBERON:0000007	95.57	gold quality
adenohypophysis	UBERON:0002196	94.17	gold quality
corpus epididymis	UBERON:0004359	93.81	gold quality
epithelial cell of pancreas	CL:0000083	90.65	gold quality
caput epididymis	UBERON:0004358	85.12	gold quality
duodenum	UBERON:0002114	78.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.63	gold quality
right uterine tube	UBERON:0001302	77.88	gold quality
lower esophagus mucosa	UBERON:0035834	77.86	gold quality
frontal pole	UBERON:0002795	77.52	gold quality
cerebellar hemisphere	UBERON:0002245	77.21	gold quality
paraflocculus	UBERON:0005351	77.18	silver quality
cerebellar cortex	UBERON:0002129	76.96	gold quality
middle frontal gyrus	UBERON:0002702	76.70	gold quality
esophagus mucosa	UBERON:0002469	76.34	gold quality
cerebellum	UBERON:0002037	76.20	gold quality
right lobe of liver	UBERON:0001114	76.12	gold quality
ectocervix	UBERON:0012249	75.90	gold quality
left ovary	UBERON:0002119	75.87	gold quality
right ovary	UBERON:0002118	75.45	gold quality
adult mammalian kidney	UBERON:0000082	75.42	gold quality
right coronary artery	UBERON:0001625	75.18	gold quality
nasal cavity epithelium	UBERON:0005384	75.06	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	75.04	gold quality
body of stomach	UBERON:0001161	74.05	gold quality
metanephros cortex	UBERON:0010533	73.83	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	5095.50
E-MTAB-9841	yes	3937.24
E-MTAB-10855	yes	2564.77
E-ANND-3	yes	32.16
E-MTAB-5061	yes	18.06
E-CURD-114	yes	11.56
E-ENAD-27	yes	7.34
E-GEOD-75367	no	102.89
E-HCAD-31	no	3.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, ARX, ASCL1, ATF4, BACH2, BCL11B, BCL3, BCL6, CDX1, CDX2, CEBPA, CEBPB, CEBPG, CREB1, CUX1, DLX2, EBF1, EGR2, ELF1, ELF2, ESR1, ESRRA, ETS1, ETV6, EWSR1, FOS, FOXA1, FOXA2, FOXC1, FOXJ1, FOXM1, FOXN1, FOXP1, FOXP3, GATA1, GATA3, GLI1, HNF1A, HNF4A

Literature-anchored findings (GeneRIF, showing 40)

• protein conformation of active site (PMID:11563913)
• transcriptional regulation in monocytes (PMID:11945176)
• determination of functional signifcance of N-terminal cluster (PMID:12110666)
• BSDL was found to be associated with vascular smooth muscle cells [SMCs] but not with macrophages. BSDL was significantly mitogenic for cultured rabbit SMCs (PMID:12821548)
• Liver receptor homolog 1 controls the expression of this enzyme in pancreas. (PMID:12853459)
• The CEL gene polymorphism, especially an increase in the frequency of the L allele, was found to be associated with alcohol-induced pancreatitis. (PMID:15841033)
• Analysis of the ability of human milk to inhibit the attachment of rNV VLPs (recombinant NV-like particles) to their carbohydrate ligands and to characterize potential inhibitors found in milk is presented. (PMID:16266293)
• binds DC-SIGN and inhibits transfer of HIV-1 to CD4+ T lymphocytes. (PMID:17005819)
• BSDL plays a role in optimal platelet activation and thrombus formation by interacting with CXCR4 on platelets. (PMID:18037996)
• Pancreatic enzyme substitution alleviated symptoms and malabsorption and normalized vitamin E levels. The CEL syndrome seems associated with a demyelinating neuropathology. (PMID:18544793)
• Carboxyl ester lipase modulates apo B-lipoprotein in vivo, which results in reduced very-low-density lipoprotein clearance and elevated plasma cholesterol levels. (PMID:18803939)
• Data show that the CEL gene is highly polymorphic, but mutations in CEL are likely to be a rare cause of monogenic diabetes. (PMID:19760265)
• Atypical interactions of pBSDL-J28, expressed on tumoral pancreatic tissue, with dendritic cells may lead to adequate antigen trafficking and processing and result in T cell activation. (PMID:21346236)
• Binding of human milk to pathogen receptor DC-SIGN varies with bile salt-stimulated lipase (BSSL) gene polymorphism. (PMID:21386960)
• CEL-MUT protein has a high propensity to form aggregates found intracellularly and extracellularly; CEL-MODY is a protein misfolding disease (PMID:21784842)
• BSSL and PLRP2 hydrolyzed triglycerides (TG) to free FA and glycerol. (PMID:21865348)
• We identify BSSL as a marker for HIV-1 disease progression and emergence of X4 variants. Additionally, we identified a relation between BSSL genotype and CD4 cell counts prior to infection. (PMID:22412885)
• Monoclonal antibody 16D10 inhibits the proliferation of human pancreatic tumor cells expressing 16D10 plasma membrane antigen. (PMID:22956586)
• This study did not find evidence that supported an association between the common length variations of the CEL VNTR and chronic pancreatitis. (PMID:23395566)
• CEL-MODY patients with a mutation in the variable number of tandem repeat region in exon 11 of the CEL gene displayed severely reduced acinar function and moderately reduced ductal function of the pancreas compared with control subjects. (PMID:23770712)
• subjects with CEL-maturity-onset diabetes of the young develop multiple pancreatic cysts by the time they develop diabetes. upregulated MAPK signaling in the pancreas may reflect the pathophysiological development of pancreatic cysts and diabetes. (PMID:24062244)
• secreted carboxyl ester lipase has a role in a syndrome of diabetes and pancreatic exocrine dysfunction (PMID:25160620)
• Expression of CEL-HYB in originating from a crossover between CEL and its neighboring pseudogene, CELP is associated with chronic pancreatitis. (PMID:25774637)
• Data show that the c.1719C > T transition (single nucleotide polymorphism rs488087) present in bile salt-dependent lipase (BSDL) VNTR may be a useful marker for defining a population at risk of developing pancreatic cancer (PC) (PMID:26498142)
• Data suggest that anti-PRAAHG antibodies were uniquely reactive with a short isoform of BSDL specifically expressed in pre-neoplastic lesions of the pancreas. The detection of truncated BSDL reactive to antibodies against the PRAAHG C-terminal sequence in pancreatic juice or in pancreatic biopsies may be a new tool in the early diagnosis of PDAC. (PMID:27602750)
• CEL deletion mutation increased endoplasmic reticulum stress, activated the unfolded protein response, and caused cell death by apoptosis in chronic pancreatitis. (PMID:27650499)
• We could not demonstrate an association between CEL copy number variants and pancreatic cancer. An association is also unlikely for CEL variable number of tandem repeat lengths (VNTR), although analyses in larger materials are necessary to completely exclude an effect of rare VNTR alleles. (PMID:27773618)
• The CEL gene harbours a variable number of tandem repeats (VNTR) region in exon 11. These results suggest that CEL VNTR lengths might associate with Alcoholic Liver Cirrhosis. (PMID:27802312)
• mucinous domain of pancreatic carboxyl-ester lipase (CEL) contains core 1/core 2 O-glycans that can be modified by ABO blood group determinants (PMID:30315106)
• BAL has inverted stereoselectivity for the surrogates of nerve agent compared to human cholinesterases (PMID:30359675)
• This study found no statistically significant association between CEL-HYB1 and chronic pancreatitis in a cohort of Polish pediatric chronic pancreatitis patients (PMID:31036489)
• Studied association between carboxyl ester lipase (CEL) expression in breast cancer (BC) tissues and the survival of BC patients by analyzing The Cancer Genome Atlas Breast Carcinoma level 3 database. Found high CEL expression was associated with the poor overall survival of breast cancer. (PMID:31561066)
• No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the Bile-salt stimulate lipase (BSSL) gene is observed when comparing homosexual male cohort composed of Hepatitis C (HCV) multiple exposed uninfected and multiple exposed HCV infected individuals. The exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility. (PMID:31622635)
• Pathogenic Carboxyl Ester Lipase (CEL) Variants Interact with the Normal CEL Protein in Pancreatic Cells. (PMID:31963687)
• Characterization of CEL-DUP2: Complete duplication of the carboxyl ester lipase gene is unlikely to influence risk of chronic pancreatitis. (PMID:32007358)
• Single nucleotide polymorphisms in CEL-HYB1 increase risk for chronic pancreatitis through proteotoxic misfolding. (PMID:32906201)
• Protein misfolding in combination with other risk factors in CEL-HYB1-mediated chronic pancreatitis. (PMID:33079780)
• Generation of beta Cells from iPSC of a MODY8 Patient with a Novel Mutation in the Carboxyl Ester Lipase (CEL) Gene. (PMID:33417713)
• Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis: How to Correctly Identify MODY8 Cases. (PMID:34850019)
• Triacylglycerols containing branched palmitic acid ester of hydroxystearic acid (PAHSA) are present in the breast milk and hydrolyzed by carboxyl ester lipase. (PMID:35486985)

Cross-species orthologs

46 orthologs

Organism	Symbol	Gene ID
danio_rerio	cel.1	ENSDARG00000017490
danio_rerio	cel.2	ENSDARG00000029822
mus_musculus	Cel	ENSMUSG00000026818
rattus_norvegicus	Cel	ENSRNOG00000010406
drosophila_melanogaster	Est-6	FBGN0000592
drosophila_melanogaster	Est-P	FBGN0000594
drosophila_melanogaster	Glt	FBGN0001114
drosophila_melanogaster	Jhe	FBGN0010052
drosophila_melanogaster	alpha-Est1	FBGN0015568
drosophila_melanogaster	alpha-Est10	FBGN0015569
drosophila_melanogaster	alpha-Est2	FBGN0015570
drosophila_melanogaster	alpha-Est3	FBGN0015571
drosophila_melanogaster	alpha-Est4	FBGN0015572
drosophila_melanogaster	alpha-Est6	FBGN0015574
drosophila_melanogaster	alpha-Est7	FBGN0015575
drosophila_melanogaster	alpha-Est8	FBGN0015576
drosophila_melanogaster	alpha-Est9	FBGN0015577
drosophila_melanogaster	CG4757	FBGN0027584
drosophila_melanogaster	CG9287	FBGN0032057
drosophila_melanogaster	CG9289	FBGN0032058
drosophila_melanogaster	CG3841	FBGN0032131
drosophila_melanogaster	CG4382	FBGN0032132
drosophila_melanogaster	Jhedup	FBGN0034076
drosophila_melanogaster	gas	FBGN0034736
drosophila_melanogaster	alpha-Est5	FBGN0261393
caenorhabditis_elegans		WBGENE00000037
caenorhabditis_elegans		WBGENE00000038
caenorhabditis_elegans		WBGENE00007691
caenorhabditis_elegans		WBGENE00007692
caenorhabditis_elegans		WBGENE00007693
caenorhabditis_elegans		WBGENE00007695
caenorhabditis_elegans		WBGENE00008451
caenorhabditis_elegans		WBGENE00011362
caenorhabditis_elegans		WBGENE00011364
caenorhabditis_elegans		WBGENE00013873
caenorhabditis_elegans		WBGENE00013874
caenorhabditis_elegans		WBGENE00013875
caenorhabditis_elegans		WBGENE00015067
caenorhabditis_elegans		WBGENE00015071
caenorhabditis_elegans		WBGENE00015279
caenorhabditis_elegans		WBGENE00015284
caenorhabditis_elegans		WBGENE00016595
caenorhabditis_elegans		WBGENE00016862
caenorhabditis_elegans		WBGENE00016863
caenorhabditis_elegans	cest-27	WBGENE00018958
caenorhabditis_elegans		WBGENE00020688

Paralogs (13): TG (ENSG00000042832), ACHE (ENSG00000087085), BCHE (ENSG00000114200), NLGN4X (ENSG00000146938), CES5A (ENSG00000159398), NLGN4Y (ENSG00000165246), NLGN1 (ENSG00000169760), NLGN2 (ENSG00000169992), CES4A (ENSG00000172824), CES3 (ENSG00000172828), CES2 (ENSG00000172831), NLGN3 (ENSG00000196338), CES1 (ENSG00000198848)

Protein

Protein identifiers

Bile salt-activated lipase — P19835 (reviewed: P19835)

Alternative names: Bile salt-stimulated lipase, Bucelipase, Carboxyl ester lipase, Cholesterol esterase, Pancreatic lysophospholipase, Sterol esterase

All UniProt accessions (1): P19835

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of a wide range of substrates including cholesteryl esters, phospholipids, lysophospholipids, di- and tri-acylglycerols, and fatty acid esters of hydroxy fatty acids (FAHFAs). Preferentially hydrolyzes FAHFAs with the ester bond further away from the carboxylate. Unsaturated FAHFAs are hydrolyzed more quickly than saturated FAHFAs. Has an essential role in the complete digestion of dietary lipids and their intestinal absorption, along with the absorption of fat-soluble vitamins.

Subunit / interactions. Interacts with CLC.

Subcellular location. Secreted.

Tissue specificity. Mammary gland and pancreas. Detected in pancreatic and duodenal juice (at protein level). Expressed by eosinophils.

Post-translational modifications. N- and O-glycosylated.

Disease relevance. Maturity-onset diabetes of the young 8 with exocrine dysfunction (MODY8) [MIM:609812] An autosomal dominant form of diabetes characterized by a primary defect in insulin secretion, exocrine pancreatic dysfunction, altered pancreatic morphology, recurrent abdominal pain, and fecal elastase deficiency. Disease onset is at less than 25 years of age. The disease is caused by variants affecting the gene represented in this entry. Single base deletions in the VNTR-region, that result in frame shift and protein truncation, have been identified as disease causing variants in MODY8 families.

Activity regulation. Activated by bile salts such as sodium taurocholate.

Polymorphism. The variable number of tandem repeats (VNTR)-region in exon 11 is highly polymorphic, and VNTR number varies between 3 and 23. The most common allele contains 16 repeats. Some alleles contain common single base insertions in the VNTR region that are predicted to lead to protein truncation and may be associated with an increased risk of exocrine pancreatic dysfunction in autoimmune diabetes.

Similarity. Belongs to the type-B carboxylesterase/lipase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P19835-1	Long	yes
P19835-2	Short

RefSeq proteins (1): NP_001798* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002018	CarbesteraseB	Domain
IPR019819	Carboxylesterase_B_CS	Conserved_site
IPR019826	Carboxylesterase_B_AS	Active_site
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR032059	Mucin-like	Domain
IPR051093	Neuroligin/BSAL	Family

Pfam: PF00135, PF16058

Enzyme classification (BRENDA):

• EC 3.1.1.13 — sterol esterase (BRENDA: 26 organisms, 244 substrates, 524 inhibitors, 68 Km, 38 kcat entries)

Substrate kinetics (BRENDA)

27 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CHOLESTERYL OLEATE	0.002–1	13
4-NITROPHENYL BUTYRATE	0.061–0.73	7
CHOLESTERYL LINOLEATE	0.09–0.99	5
P-NITROPHENYL OCTANOATE	0.144–1.782	4
4-NITROPHENYL PALMITATE	0.33–1	3
CHOLESTERYL MYRISTATE	0.34–0.49	3
CHOLESTERYL PALMITATE	0.87–6.8	3
CHOLESTERYL STEARATE	1.1–7	3
P-NITROPHENYL HEXANOATE	0.0122–0.0384	3
4-NITROPHENYL LAURATE	0.53–0.63	2
4-NITROPHENYL MYRISTATE	0.77–0.8	2
LIPOYL 4-AMINOBENZOATE	0.011–0.024	2
P-NITROPHENYL BUTYRATE	0.052–0.073	2
P-NITROPHENYL CAPROATE	0.046–0.074	2
TRIOLEIN	0.05–0.98	2

Catalyzed reactions (Rhea), 12 shown:

• a sterol ester + H2O = a sterol + a fatty acid + H(+) (RHEA:10100)
• a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+) (RHEA:12044)
• an acetyl ester + H2O = an aliphatic alcohol + acetate + H(+) (RHEA:12957)
• cholesteryl (9Z-octadecenoate) + H2O = cholesterol + (9Z)-octadecenoate + H(+) (RHEA:33875)
• 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = di-(9Z)-octadecenoylglycerol + (9Z)-octadecenoate + H(+) (RHEA:38575)
• 1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = sn-glycerol 3-phosphocholine + hexadecanoate + H(+) (RHEA:40435)
• a butanoate ester + H2O = an aliphatic alcohol + butanoate + H(+) (RHEA:47348)
• 1,2,3-trioctanoylglycerol + H2O = dioctanoylglycerol + octanoate + H(+) (RHEA:47864)
• 9-(9Z-octadecenoyloxy)-octadecanoate + H2O = 9-hydroxy-octadecanoate + (9Z)-octadecenoate + H(+) (RHEA:52048)
• 9-hexadecanoyloxy-octadecanoate + H2O = 9-hydroxy-octadecanoate + hexadecanoate + H(+) (RHEA:52052)
• 12-hexadecanoyloxy-octadecanoate + H2O = 12-hydroxyoctadecanoate + hexadecanoate + H(+) (RHEA:52056)
• 12-(9Z-octadecenoyloxy)-octadecanoate + H2O = 12-hydroxyoctadecanoate + (9Z)-octadecenoate + H(+) (RHEA:52060)

UniProt features (106 total): helix 26, strand 25, repeat 17, glycosylation site 11, turn 7, sequence conflict 7, region of interest 3, active site 3, disulfide bond 2, signal peptide 1, chain 1, compositionally biased region 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6H1A	X-RAY DIFFRACTION	1.75
6H18	X-RAY DIFFRACTION	1.85
6H19	X-RAY DIFFRACTION	1.89
6H0T	X-RAY DIFFRACTION	1.9
6H0V	X-RAY DIFFRACTION	2.2
1F6W	X-RAY DIFFRACTION	2.3
1JMY	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19835-F1	84.10	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 214 (acyl-ester intermediate); 340 (charge relay system); 455 (charge relay system)

Disulfide bonds (2): 84–100, 266–277

Glycosylation sites (11): 207, 558, 569, 579, 607, 618, 629, 640, 651, 662, 673

Mutagenesis-validated functional residues (1):

Position	Phenotype
455	abolishes lipase activity. decreases vmax for esterase activity by 2.5-fold.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-192456	Digestion of dietary lipid
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells
R-HSA-1266738	Developmental Biology
R-HSA-8935690	Digestion
R-HSA-8963743	Digestion and absorption
R-HSA-9734767	Developmental Cell Lineages

MSigDB gene sets: 205 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_DIGESTION, AREB6_03, GOBP_REGULATION_OF_HORMONE_LEVELS, AREB6_01, TGACCTY_ERR1_Q2, GOBP_RETINOL_METABOLIC_PROCESS, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, GOBP_LIPID_DIGESTION, MODULE_66, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_SECRETION

GO Biological Process (6): lipid metabolic process (GO:0006629), pancreatic juice secretion (GO:0030157), intestinal cholesterol absorption (GO:0030299), ceramide catabolic process (GO:0046514), lipid catabolic process (GO:0016042), retinol metabolic process (GO:0042572)

GO Molecular Function (9): catalytic activity (GO:0003824), sterol ester esterase activity (GO:0004771), triacylglycerol lipase activity (GO:0004806), acetylesterase activity (GO:0008126), heparin binding (GO:0008201), hydrolase activity (GO:0016787), retinyl-palmitate esterase activity (GO:0050253), protein binding (GO:0005515), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Digestion	1
Developmental Cell Lineages of the Exocrine Pancreas	1
Digestion and absorption	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
carboxylic ester hydrolase activity	3
cellular anatomical structure	3
lipase activity	2
primary metabolic process	1
body fluid secretion	1
digestive system process	1
secretion by tissue	1
lipid digestion	1
intestinal lipid absorption	1
ceramide metabolic process	1
sphingolipid catabolic process	1
lipid metabolic process	1
catabolic process	1
retinoid metabolic process	1
primary alcohol metabolic process	1
hormone metabolic process	1
olefinic compound metabolic process	1
molecular_function	1
short-chain carboxylesterase activity	1
glycosaminoglycan binding	1
sulfur compound binding	1
catalytic activity	1
retinol metabolic process	1
binding	1
hydrolase activity, acting on ester bonds	1
intracellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1231 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEL	PLEKHA3	Q9HB20	902
CEL	PLEKHA8	Q96JA3	891
CEL	PRKCD	Q05655	801
CEL	PNLIP	P16233	778
CEL	PXDN	Q92626	748
CEL	PXDNL	A1KZ92	748
CEL	CLPS	P04118	740
CEL	ARF1	P10947	703
CEL	PNLIPRP1	P54315	696
CEL	GLTP	Q9NZD2	638
CEL	LIPF	P07098	619
CEL	GK	P32189	609
CEL	GK2	Q14410	600
CEL	CD209	Q9NNX6	580
CEL	HMGCR	P04035	574

IntAct

2 interactions, top by confidence:

A	B	Type	Score
BPGM	CEL	psi-mi:“MI:0915”(physical association)	0.370

ESM2 similar proteins: A0A6P8HC43, A4QNR3, A5A3E0, A8MQ14, B4DH59, B5DUH6, E9Q0N2, O75290, O95744, O96790, P00738, P0CG38, P0CG39, P19835, P23253, P30205, P48960, P52742, P60883, Q08DG8, Q4A3R3, Q6S8J3, Q80Z71, Q8BZE1, Q8CIZ5, Q8HXZ7, Q8HXZ8, Q8HY00, Q8HY01, Q8HY02, Q8HY03, Q8HY04, Q8HY06, Q8HY10, Q8HY11, Q8HY12, Q8HYC0, Q8RXK2, Q923X1, Q95218

Diamond homologs: A0A075TXZ3, A0A0E4AET8, A0A0G3FWY4, A0A8B0RBM2, A1CFK9, A7YN26, D2D3B6, D4B1N9, D6WMZ8, F1RRV3, I1RIF1, P07882, P19835, P23654, P30122, P32750, P32751, P32752, P32753, P32947, P33438, P35501, P35502, P36196, P86325, P9WK86, P9WK87, Q3T930, Q47M62, Q64285, Q64419, Q92035, Q95000, Q95001, Q99156, Q9NDG8, Q9UKY3, A0A060S684, B0F2B4, G3V7J5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

428 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	5
Uncertain significance	224
Likely benign	126
Benign	26

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
17600	NM_001807.6(CEL):c.1677del (p.Val560fs)	Pathogenic
3383345	NC_000009.11:g.(135939771_135947171)del	Pathogenic
1676818	NM_001807.6(CEL):c.615_618delinsAAA (p.Asn206fs)	Likely pathogenic
2438974	NM_001807.6(CEL):c.1875del (p.Val626fs)	Likely pathogenic
35815	NM_001807.6(CEL):c.1776del (p.Val593fs)	Likely pathogenic
3596587	NM_001807.6(CEL):c.2139dup (p.Val714fs)	Likely pathogenic
828119	NM_001807.6(CEL):c.703C>T (p.Arg235Ter)	Likely pathogenic

SpliceAI

1573 predictions. Top by Δscore:

Variant	Effect	Δscore
9:133064399:C:A	acceptor_gain	1.0000
9:133064401:CA:C	acceptor_loss	1.0000
9:133064402:A:AG	acceptor_gain	1.0000
9:133064402:A:T	acceptor_loss	1.0000
9:133064402:AGCT:A	acceptor_gain	1.0000
9:133064402:AGCTG:A	acceptor_gain	1.0000
9:133064403:G:GC	acceptor_gain	1.0000
9:133064403:GC:G	acceptor_gain	1.0000
9:133064403:GCT:G	acceptor_gain	1.0000
9:133064403:GCTG:G	acceptor_gain	1.0000
9:133064403:GCTGG:G	acceptor_gain	1.0000
9:133064635:TGCAG:T	acceptor_loss	1.0000
9:133064636:GCAGG:G	acceptor_loss	1.0000
9:133064637:CAGG:C	acceptor_loss	1.0000
9:133064638:A:AG	acceptor_gain	1.0000
9:133064638:AG:A	acceptor_gain	1.0000
9:133064638:AGG:A	acceptor_gain	1.0000
9:133064639:G:GG	acceptor_gain	1.0000
9:133064639:GG:G	acceptor_gain	1.0000
9:133064639:GGG:G	acceptor_gain	1.0000
9:133064639:GGGA:G	acceptor_gain	1.0000
9:133064639:GGGAC:G	acceptor_gain	1.0000
9:133064755:G:GT	donor_gain	1.0000
9:133064759:CAAGG:C	donor_loss	1.0000
9:133064760:AAG:A	donor_loss	1.0000
9:133064761:AGGTC:A	donor_loss	1.0000
9:133064762:GG:G	donor_loss	1.0000
9:133064763:G:GA	donor_loss	1.0000
9:133064764:T:G	donor_loss	1.0000
9:133065038:A:AG	acceptor_gain	1.0000

AlphaMissense

4910 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000646720 (9:133060301 G>A), RS1000707129 (9:133071488 G>A,T), RS1000714804 (9:133065780 A>T), RS1000759172 (9:133060683 A>C), RS1001018569 (9:133066053 A>G), RS1001223035 (9:133063330 G>A), RS1001277329 (9:133067916 AC>A), RS1001377346 (9:133067681 A>G), RS1001719816 (9:133063040 G>A), RS1002221102 (9:133061503 G>A), RS1002291875 (9:133066856 A>G), RS1003013190 (9:133068766 C>G,T), RS1003042607 (9:133069319 C>G,T), RS1004022396 (9:133061270 C>A,G,T), RS1004115432 (9:133061049 C>A,T)

Disease associations

OMIM: gene MIM:114840 | disease phenotypes: MIM:609812, MIM:125850, MIM:606391, MIM:125853, MIM:191100

GenCC curated gene-disease

Disease	Classification	Inheritance
maturity-onset diabetes of the young type 8	Strong	Autosomal dominant
maturity-onset diabetes of the young	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
maturity-onset diabetes of the young type 8	Moderate	AD

Mondo (6): maturity-onset diabetes of the young type 8 (MONDO:0012348), monogenic diabetes (MONDO:0015967), maturity-onset diabetes of the young (MONDO:0018911), type 2 diabetes mellitus (MONDO:0005148), tuberous sclerosis 1 (MONDO:0008612), transient neonatal diabetes mellitus (MONDO:0020525)

Orphanet (3): MODY (Orphanet:552), Rare genetic diabetes mellitus (Orphanet:183625), Tuberous sclerosis complex (Orphanet:805)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000077	Abnormality of the kidney
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000119	Abnormality of the genitourinary system
HP:0000488	Retinopathy
HP:0000825	Hyperinsulinemic hypoglycemia
HP:0000831	Insulin-resistant diabetes mellitus
HP:0000956	Acanthosis nigricans
HP:0001511	Intrauterine growth retardation
HP:0001513	Obesity
HP:0001520	Large for gestational age
HP:0001738	Exocrine pancreatic insufficiency
HP:0001952	Glucose intolerance
HP:0001953	Diabetic ketoacidosis
HP:0001998	Neonatal hypoglycemia
HP:0002027	Abdominal pain
HP:0002594	Pancreatic hypoplasia
HP:0003074	Hyperglycemia
HP:0003076	Glycosuria
HP:0004904	Maturity-onset diabetes of the young
HP:0004924	Abnormal oral glucose tolerance
HP:0008255	Transient neonatal diabetes mellitus
HP:0011462	Young adult onset
HP:0012028	Hepatocellular adenoma
HP:0025502	Overweight
HP:0030057	Autoimmune antibody positivity
HP:0030794	Abnormal circulating C-peptide concentration
HP:0040214	Abnormal circulating insulin concentration
HP:0040216	Hypoinsulinemia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004138_13	Early-onset Parkinson’s disease	1.000000e-14
GCST006585_966	Blood protein levels	7.000000e-27
GCST90014023_28	Type 1 diabetes	4.000000e-17

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
C562772	Mason-Type Diabetes (supp.)
C565225	Maturity-Onset Diabetes of the Young, Type 8, with Exocrine Dysfunction (supp.)
C565346	Tuberous Sclerosis 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3219 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 3.1.1.- Carboxylic Ester Hydrolases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 10f [PMID: 24556381]	Inhibition	5.88	pIC50
compound 10l [PMID: 24556381]	Inhibition	5.7	pIC50

ChEMBL bioactivities

7 potent at pChembl≥5 of 8 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.60	Ki	25	nM	CHEMBL134339
7.40	Ki	40	nM	CHEMBL133091
7.24	Ki	58	nM	CHEMBL135891
7.22	Ki	60	nM	CHEMBL336175
6.24	Ki	580	nM	CHEMBL135278
5.66	Ki	2200	nM	CHEMBL441090
5.64	Ki	2300	nM	CHEMBL134790

PubChem BioAssay actives

7 with measured affinity, of 33 total; 7 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
6-chloro-3-(2-cyclohexylethyl)pyran-2-one	51770: Inhibition of the Pancreatic Cholesterol Esterase from porcine	ki	0.0250	uM
6-chloro-3-cyclopentylpyran-2-one	51770: Inhibition of the Pancreatic Cholesterol Esterase from porcine	ki	0.0400	uM
6-chloro-5-(2-cyclohexylethyl)pyran-2-one	51770: Inhibition of the Pancreatic Cholesterol Esterase from porcine	ki	0.0580	uM
6-chloro-3-(3-cyclohexylpropyl)pyran-2-one	51770: Inhibition of the Pancreatic Cholesterol Esterase from porcine	ki	0.0600	uM
6-chloro-3-(4-cyclohexylbutyl)pyran-2-one	51770: Inhibition of the Pancreatic Cholesterol Esterase from porcine	ki	0.5800	uM
6-chloro-3-(cyclohexylmethyl)pyran-2-one	51770: Inhibition of the Pancreatic Cholesterol Esterase from porcine	ki	2.2000	uM
6-chloro-3-cyclohexylpyran-2-one	51770: Inhibition of the Pancreatic Cholesterol Esterase from porcine	ki	2.3000	uM

CTD chemical–gene interactions

64 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, increases expression, increases methylation	6
Benzo(a)pyrene	decreases methylation, increases expression	4
Valproic Acid	affects methylation, increases methylation, affects cotreatment, increases expression	3
Orlistat	decreases activity	2
Estradiol	decreases expression, affects cotreatment	2
Methyl Methanesulfonate	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Rotenone	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
lasiocarpine	increases expression	1
bisphenol A	decreases expression	1
4-nitrophenyl acetate	affects metabolic processing	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
deguelin	decreases expression	1
2-palmitoylglycerol	increases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
pyrimidifen	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pyrachlostrobin	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2174359	Binding	Inhibition of human pancreatic CEH assessed as residual activity at 40 molar excess after 30 mins by mass spectrophotometric analysis	Analysis of the discriminative inhibition of mammalian digestive lipases by 3-phenyl substituted 1,3,4-oxadiazol-2(3H)-ones. — Eur J Med Chem

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
NCT00192803	PHASE4	UNKNOWN	Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs
NCT00202033	PHASE4	COMPLETED	Impact of Self-Monitoring Blood Glucose Frequency on Glycemic Control in Patients With Type 2 Diabetes
NCT00205660	PHASE4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00212290	PHASE4	COMPLETED	Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
NCT00212303	PHASE4	COMPLETED	Exercise Training in Type 2 Diabetes and Hypertension
NCT00225342	PHASE4	WITHDRAWN	Study Protocol for Rosiglitazone Versus Gliclazide in Diabetics With Angina
NCT00238472	PHASE4	COMPLETED	A Pilot Study to Evaluate the Effects of Nateglinide vs. Glibenclamide on Renal Hemodynamics and Albumin Excretion
NCT00239538	PHASE4	COMPLETED	SMOOTH - Blood Pressure Control in Diabetic/Obese Patients
NCT00240253	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Safety of Adding Symlin® to Lantus® (Insulin Glargine) in Subjects With Type 2 Diabetes
NCT00240422	PHASE4	COMPLETED	Trial to Compare the Effects of Either Telmisartan (40-80 mg PO Once Daily) or Ramipril (5-10 mg PO Once Daily) on Renal Endothelial Dysfunction in Hypertensive Patients With Type 2 Diabetes
NCT00241085	PHASE4	COMPLETED	Effect of Valsartan on Proteinuria in Patients With Hypertension and Diabetes Mellitus