CELA3B

Summary

CELA3B (chymotrypsin like elastase 3B, HGNC:15945) is a protein-coding gene on chromosome 1p36.12, encoding Chymotrypsin-like elastase family member 3B (P08861). Efficient protease with alanine specificity but only little elastolytic activity.

Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes which encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, and 3B. Unlike other elastases, elastase 3B has little elastolytic activity. Like most of the human elastases, elastase 3B is secreted from the pancreas as a zymogen and, like other serine proteases such as trypsin, chymotrypsin and kallikrein, it has a digestive function in the intestine. Elastase 3B preferentially cleaves proteins after alanine residues. Elastase 3B may also function in the intestinal transport and metabolism of cholesterol. Both elastase 3A and elastase 3B have been referred to as protease E and as elastase 1, and excretion of this protein in fecal material is frequently used as a measure of pancreatic function in clinical assays.

Source: NCBI Gene 23436 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_007352

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15945
Approved symbol	CELA3B
Name	chymotrypsin like elastase 3B
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	CBPP
Ensembl gene	ENSG00000219073
Ensembl biotype	protein_coding
OMIM	618694
Entrez	23436

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000337107, ENST00000374666, ENST00000400277, ENST00000473526

RefSeq mRNA: 1 — MANE Select: NM_007352 NM_007352

CCDS: CCDS219

Canonical transcript exons

ENST00000337107 — 8 exons

Exon	Start	End
ENSE00000956426	21981038	21981172
ENSE00000956429	21984189	21984331
ENSE00001464211	21977022	21977082
ENSE00001613142	21983694	21983830
ENSE00001724987	21980824	21980921
ENSE00001761732	21978369	21978454
ENSE00001890098	21989262	21989354
ENSE00003659503	21986531	21986683

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 99.93.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 30.5644 / max 52552.5631, expressed in 14 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1244	30.5644	14
1243	0.3149	3
1245	0.3107	4
1248	0.1702	4
1242	0.0903	3
1249	0.0890	4
1246	0.0660	3
1251	0.0563	3
1241	0.0444	3
1252	0.0421	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.93	gold quality
pancreas	UBERON:0001264	97.29	gold quality
islet of Langerhans	UBERON:0000006	91.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.69	silver quality
body of stomach	UBERON:0001161	78.57	gold quality
fundus of stomach	UBERON:0001160	77.60	gold quality
duodenum	UBERON:0002114	75.58	gold quality
ectocervix	UBERON:0012249	73.84	gold quality
stomach	UBERON:0000945	73.78	gold quality
right coronary artery	UBERON:0001625	73.32	gold quality
right lobe of liver	UBERON:0001114	71.17	gold quality
placenta	UBERON:0001987	70.98	gold quality
left uterine tube	UBERON:0001303	70.75	gold quality
endocervix	UBERON:0000458	70.09	gold quality
descending thoracic aorta	UBERON:0002345	69.83	gold quality
right adrenal gland	UBERON:0001233	68.57	gold quality
right uterine tube	UBERON:0001302	67.95	gold quality
uterine cervix	UBERON:0000002	67.83	gold quality
lower esophagus mucosa	UBERON:0035834	67.52	gold quality
right adrenal gland cortex	UBERON:0035827	67.39	gold quality
left adrenal gland cortex	UBERON:0035825	67.27	gold quality
thoracic aorta	UBERON:0001515	66.99	gold quality
left adrenal gland	UBERON:0001234	66.89	gold quality
ascending aorta	UBERON:0001496	66.85	gold quality
transverse colon	UBERON:0001157	66.66	gold quality
apex of heart	UBERON:0002098	65.98	gold quality
lower esophagus	UBERON:0013473	65.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	65.26	gold quality
body of uterus	UBERON:0009853	65.09	gold quality
metanephros cortex	UBERON:0010533	64.91	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	10856.99
E-GEOD-81547	yes	31.34
E-MTAB-5061	yes	18.91
E-GEOD-111727	no	44.33
E-HCAD-31	no	3.26
E-GEOD-83139	no	3.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 20)

• As an independent variable, correlated with C-peptide and HBA1c levels in type 1 diabetes. (PMID:15277440)
• pancreatic elastase induced proinflammatory effects are mediated by TLR4 and NF-kappaB in human myeloid cells (PMID:15351720)
• Patients with type 1 diabetes and low fecal elastase 1 concentrations were succesfully treatted with pancretin. (PMID:17103488)
• Fecal fat excretion is increased in patients with type 2 diabetes with fecal elastase deficiency. (PMID:17989309)
• Neither low fecal elastase 1 nor raised fecal fat levels reliably indicate exocrine pancreatic insufficiency in type-1 diabetes. (PMID:18362841)
• Reduced fecal elastase 1 connected with lowered serum levels of vitamin D3 is associated with osteoporotic bone fractures. (PMID:18424365)
• Parathormone levels and Vitamin D metabolism in female patients with various grades of fecal ELA1 deficiency are reported. (PMID:19073396)
• Hypermethylation of ELA3B gene promoter were associated with pancreatic cancer. (PMID:20428826)
• FE-1 is a poor surrogate for diagnosing impaired fat absorption. (PMID:22094930)
• A low value of faecal elastase-1, indicating reduced exocrine pancrease secretion, is strongly correlated with a poor survival in advanced pancreatic cancer. (PMID:22749648)
• Recombinant type I pancreatic elastase improves unassisted arteriovenous fistula maturation in hemodialysis patients. (PMID:24684771)
• The results of the study suggest that the levels of apelin, TNF-alpha and elastase-1 are important diagnostic markers of CP in patients with type 2 diabetes mellitus. (PMID:26817104)
• this study demonstrated a strong association of diabetes with low pancreatic elastase levels in feces (PMID:27069032)
• Complex Formation of Human Proelastases with Procarboxypeptidases A1 and A2. (PMID:27358403)
• variants affecting amino-acid position 241 in CELA3A and CELA3B are not associated with chronic pancreatitis, indicating that changes in complex formation between proelastases and procarboxypeptidases do not alter pancreatitis risk. (PMID:27999401)
• The aim of this study was to examine the frequency of exocrine dysfunctions of the pancreas according to the level of fecal elastase-1 (FE-1) in patients with diabetes mellitus, type 1 and diabetes mellitus, type 2. (PMID:30106003)
• Elastase 3B mutation links to familial pancreatitis with diabetes and pancreatic adenocarcinoma. (PMID:31369399)
• The reversion variant (p.Arg90Leu) at the evolutionarily adaptive p.Arg90 site in CELA3B predisposes to chronic pancreatitis. (PMID:33565216)
• Utility of Fecal Elastase-1 to diagnose severe exocrine insufficiency in chronic pancreatitis: Real world experience. (PMID:36610873)
• Does the Complex of CELA3B Variants With Other Pancreatitis-Related Genes Affect Developing Childhood Pancreatitis? (PMID:37307306)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cela3b	ENSMUSG00000023433
mus_musculus	Cela3a	ENSMUSG00000078520
rattus_norvegicus	Cela3b	ENSRNOG00000021619

Paralogs (6): CELA1 (ENSG00000139610), CELA2A (ENSG00000142615), CELA3A (ENSG00000142789), PRTN3 (ENSG00000196415), ELANE (ENSG00000197561), CELA2B (ENSG00000215704)

Protein

Protein identifiers

Chymotrypsin-like elastase family member 3B — P08861 (reviewed: P08861)

Alternative names: Elastase IIIB, Elastase-3B, Protease E

All UniProt accessions (2): P08861, A0A0A0MSA6

UniProt curated annotations — full annotation on UniProt →

Function. Efficient protease with alanine specificity but only little elastolytic activity.

Tissue specificity. Pancreas. Not detectable in keratinocytes.

Similarity. Belongs to the peptidase S1 family. Elastase subfamily.

RefSeq proteins (1): NP_031378* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504
IPR050850	Peptidase_S1_Elastase_sf	Family

Pfam: PF00089

UniProt features (18 total): disulfide bond 5, sequence conflict 4, active site 3, signal peptide 1, propeptide 1, sequence variant 1, chain 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08861-F1	91.13	0.85

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): 73 (charge relay system); 123 (charge relay system); 217 (charge relay system)

Disulfide bonds (5): 157–223, 188–204, 213–244, 58–74, 117–120

Glycosylation sites (1): 114

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells
R-HSA-1266738	Developmental Biology
R-HSA-9734767	Developmental Cell Lineages

MSigDB gene sets: 53 (showing top): YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, MYOD_01, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GATA1_04, TAL1BETAE47_01, SANSOM_APC_TARGETS, GOBP_PROTEOLYSIS, E2A_Q2, GOMF_PEPTIDASE_ACTIVITY, chr1p36, BIOCARTA_PEPI_PATHWAY, SERVITJA_LIVER_HNF1A_TARGETS_UP, GATA1_05, FOXN3_TARGET_GENES, ZNF436_TARGET_GENES

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (4): serine-type endopeptidase activity (GO:0004252), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (1): obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Cell Lineages of the Exocrine Pancreas	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
endopeptidase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1

Protein interactions and networks

STRING

826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CELA3B	SCT	P09683	644
CELA3B	CPA1	P15085	627
CELA3B	SPINK1	P00995	546
CELA3B	CPA2	P48052	542
CELA3B	PNLIP	P16233	542
CELA3B	PNLIPRP1	P54315	507
CELA3B	CPB1	P15086	501
CELA3B	ENPEP	Q07075	480
CELA3B	CFTR	P13569	477
CELA3B	SYCN	Q0VAF6	468
CELA3B	INS	P01308	421
CELA3B	PTF1A	Q7RTS3	399
CELA3B	CEL	P19835	393
CELA3B	GRN	P23781	385
CELA3B	GCG	P01275	385

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CELA3B	BCAT2	psi-mi:“MI:0914”(association)	0.350
CELA3B	HBD	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): CELA3B (PCA), TIMP3 (Affinity Capture-MS), NME2 (Affinity Capture-MS), GRN (Affinity Capture-MS), UBR7 (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS), BCAT2 (Affinity Capture-MS), ADAMTS1 (Affinity Capture-MS), CELA3A (Affinity Capture-MS), UBR2 (Affinity Capture-MS), GDF15 (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), HBD (Affinity Capture-MS), CELA3B (Positive Genetic)

ESM2 similar proteins: A0A126GUP6, A0A1S4H5M5, A0A6J1W8N1, B5U2W0, F5HKX0, O19023, O46644, O97366, P00772, P00773, P00774, P05208, P05805, P06871, P06872, P07477, P07478, P08217, P08218, P08419, P08861, P09093, P13582, P16049, P21902, P47796, P55091, P80009, P80010, Q29461, Q2VG86, Q3SYP2, Q49QW1, Q5R1M5, Q7M3E1, Q7M4I3, Q7PEV7, Q7QBP4, Q867B0, Q8I6K0

Diamond homologs: A1KXI1, C0HKF7, C0HKF8, O19023, O60235, O97370, O97398, P00760, P00761, P00762, P00763, P00764, P00765, P00766, P00767, P00768, P00769, P00771, P00774, P03951, P03952, P04813, P04814, P05208, P05805, P06871, P06872, P07146, P07338, P07477, P07478, P08217, P08218, P08419, P08426, P08861, P08897, P09093, P12788, P15947

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1010 predictions. Top by Δscore:

Variant	Effect	Δscore
1:21978367:A:AG	acceptor_gain	1.0000
1:21978368:G:GA	acceptor_gain	1.0000
1:21978368:GCCT:G	acceptor_gain	1.0000
1:21980814:G:A	acceptor_gain	1.0000
1:21980922:G:GG	donor_gain	1.0000
1:21981033:CGCA:C	acceptor_loss	1.0000
1:21981035:CAG:C	acceptor_loss	1.0000
1:21981036:A:AG	acceptor_gain	1.0000
1:21981036:A:G	acceptor_loss	1.0000
1:21981036:AG:A	acceptor_gain	1.0000
1:21981037:G:GT	acceptor_gain	1.0000
1:21981037:GG:G	acceptor_gain	1.0000
1:21981037:GGA:G	acceptor_gain	1.0000
1:21981037:GGAGC:G	acceptor_gain	1.0000
1:21981169:GTGG:G	donor_gain	1.0000
1:21981171:GG:G	donor_gain	1.0000
1:21981172:GG:G	donor_gain	1.0000
1:21981172:GGTG:G	donor_loss	1.0000
1:21981173:G:C	donor_loss	1.0000
1:21981173:G:GG	donor_gain	1.0000
1:21981174:TGA:T	donor_loss	1.0000
1:21981175:GAGT:G	donor_loss	1.0000
1:21981176:AGTG:A	donor_loss	1.0000
1:21981177:G:C	donor_loss	1.0000
1:21983831:G:GG	donor_gain	1.0000
1:21984184:T:A	acceptor_gain	1.0000
1:21984184:TGCA:T	acceptor_loss	1.0000
1:21984186:CA:C	acceptor_loss	1.0000
1:21984187:A:AG	acceptor_gain	1.0000
1:21984188:G:GA	acceptor_gain	1.0000

AlphaMissense

1747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:21983817:G:C	W162C	1.000
1:21983817:G:T	W162C	1.000
1:21983699:A:C	D123A	0.999
1:21983699:A:T	D123V	0.999
1:21984299:T:A	C204S	0.999
1:21984300:G:C	C204S	0.999
1:21984326:T:A	C213S	0.999
1:21984327:G:C	C213S	0.999
1:21986535:A:T	D216V	0.999
1:21980867:G:A	C58Y	0.998
1:21980915:G:A	C74Y	0.998
1:21980916:C:G	C74W	0.998
1:21983698:G:C	D123H	0.998
1:21983699:A:G	D123G	0.998
1:21983802:C:G	C157W	0.998
1:21983815:T:A	W162R	0.998
1:21983815:T:C	W162R	0.998
1:21983818:G:T	G163C	0.998
1:21984251:T:A	C188S	0.998
1:21984252:G:C	C188S	0.998
1:21984327:G:A	C213Y	0.998
1:21986535:A:C	D216A	0.998
1:21986541:G:T	G218V	0.998
1:21986597:A:C	S237R	0.998
1:21986599:C:A	S237R	0.998
1:21986599:C:G	S237R	0.998
1:21986618:T:A	C244S	0.998
1:21986619:G:C	C244S	0.998
1:21986645:T:C	F253L	0.998
1:21986647:C:A	F253L	0.998

dbSNP variants (sampled 300 via entrez): RS1000509788 (1:21977652 C>T), RS1000637248 (1:21982931 T>C), RS1000898902 (1:21996096 C>A), RS1000950544 (1:21995790 G>A), RS1001079154 (1:21987513 G>T), RS1001353295 (1:21981340 G>A,T), RS1001533503 (1:21987193 G>A), RS1001568076 (1:21992847 C>T), RS1001620607 (1:21992660 G>A), RS1001855907 (1:21975813 T>G), RS1002205922 (1:21985125 T>A,G), RS1002307005 (1:21981950 C>A,T), RS1002472601 (1:21998981 G>A), RS1002685986 (1:21996599 C>T), RS1002892608 (1:21975301 A>G)

Disease associations

OMIM: gene MIM:618694 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002394_127	Monocyte percentage of white cells	5.000000e-18
GCST90002407_388	White blood cell count	1.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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