CELA3A

Summary

CELA3A (chymotrypsin like elastase 3A, HGNC:15944) is a protein-coding gene on chromosome 1p36.12, encoding Chymotrypsin-like elastase family member 3A (P09093). 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 3A has little elastolytic activity. Like most of the human elastases, elastase 3A 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 3A preferentially cleaves proteins after alanine residues. Elastase 3A 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.

Source: NCBI Gene 10136 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_005747

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15944
Approved symbol	CELA3A
Name	chymotrypsin like elastase 3A
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	ELA3
Ensembl gene	ENSG00000142789
Ensembl biotype	protein_coding
OMIM	618693
Entrez	10136

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000290122, ENST00000374663, ENST00000400271

RefSeq mRNA: 1 — MANE Select: NM_005747 NM_005747

CCDS: CCDS220

Canonical transcript exons

ENST00000290122 — 8 exons

Exon	Start	End
ENSE00000956439	22005662	22005796
ENSE00001066275	22001657	22001717
ENSE00001609388	22005447	22005544
ENSE00001669949	22009705	22009857
ENSE00001673840	22007373	22007515
ENSE00001690412	22003003	22003088
ENSE00001867297	22012450	22012542
ENSE00002180576	22006878	22007014

Expression profiles

Bgee: expression breadth ubiquitous, 118 present calls, max score 99.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 25.7149 / max 43324.8940, expressed in 15 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1244	30.5644	14
1254	24.9842	15
1262	0.5490	3
1243	0.3149	3
1242	0.0903	3
1265	0.0598	3
1253	0.0539	3
1241	0.0444	3
201404	0.0250	2
1263	0.0244	3

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	99.98	gold quality
pancreas	UBERON:0001264	99.53	gold quality
islet of Langerhans	UBERON:0000006	98.63	gold quality
duodenum	UBERON:0002114	86.54	gold quality
body of stomach	UBERON:0001161	85.40	gold quality
fundus of stomach	UBERON:0001160	84.58	gold quality
right coronary artery	UBERON:0001625	83.21	gold quality
ectocervix	UBERON:0012249	81.19	gold quality
stomach	UBERON:0000945	80.14	gold quality
right uterine tube	UBERON:0001302	80.09	gold quality
endocervix	UBERON:0000458	79.15	gold quality
right adrenal gland	UBERON:0001233	78.16	gold quality
right lobe of liver	UBERON:0001114	77.97	gold quality
lower esophagus mucosa	UBERON:0035834	77.08	gold quality
left uterine tube	UBERON:0001303	77.07	gold quality
descending thoracic aorta	UBERON:0002345	77.05	gold quality
right adrenal gland cortex	UBERON:0035827	76.17	gold quality
placenta	UBERON:0001987	73.83	gold quality
metanephros cortex	UBERON:0010533	73.33	gold quality
transverse colon	UBERON:0001157	72.38	gold quality
left adrenal gland	UBERON:0001234	72.07	gold quality
right ovary	UBERON:0002118	71.78	gold quality
uterine cervix	UBERON:0000002	71.36	gold quality
esophagus mucosa	UBERON:0002469	70.42	gold quality
left adrenal gland cortex	UBERON:0035825	70.39	gold quality
spleen	UBERON:0002106	69.86	gold quality
thoracic aorta	UBERON:0001515	69.27	gold quality
body of uterus	UBERON:0009853	69.16	gold quality
small intestine	UBERON:0002108	69.14	gold quality
left ovary	UBERON:0002119	68.98	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	50407.68
E-ENAD-27	yes	26044.60
E-MTAB-5061	yes	9072.33
E-HCAD-31	yes	4.47
E-GEOD-83139	no	3.10
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• expression of PE IIIA and its splicing variants in pancreatic carcinoma cells (PMID:12373299)
• 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)

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), PRTN3 (ENSG00000196415), ELANE (ENSG00000197561), CELA2B (ENSG00000215704), CELA3B (ENSG00000219073)

Protein

Protein identifiers

Chymotrypsin-like elastase family member 3A — P09093 (reviewed: P09093)

Alternative names: Elastase IIIA, Elastase-3A, Protease E

All UniProt accessions (2): P09093, B1AQ55

UniProt curated annotations — full annotation on UniProt →

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

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

RefSeq proteins (1): NP_005738* (*=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 (20 total): disulfide bond 5, sequence variant 4, sequence conflict 3, active site 3, signal peptide 1, propeptide 1, chain 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09093-F1	91.09	0.88

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

0 pathways

MSigDB gene sets: 53 (showing top): MODULE_172, AP4_Q6, CAGCTG_AP4_Q5, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, WEI_MYCN_TARGETS_WITH_E_BOX, MYOD_01, MODULE_109, OUELLET_CULTURED_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, GATA1_04, MODULE_236, MODULE_48, MODULE_209, MEF2_Q6_01, MODULE_95, TTTNNANAGCYR_UNKNOWN

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

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

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

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
binding	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

814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CELA3A	CPA2	P48052	640
CELA3A	CPA1	P15085	599
CELA3A	CPB1	P15086	528
CELA3A	PNLIP	P16233	480
CELA3A	PNLIPRP1	P54315	420
CELA3A	AMY2A	P04746	384
CELA3A	CUZD1	Q86UP6	384
CELA3A	CLPS	P04118	355
CELA3A	PLA2G1B	P04054	350
CELA3A	IQCC	Q4KMZ1	339
CELA3A	MS4A10	Q96PG2	322
CELA3A	PROSER3	Q2NL68	313
CELA3A	RNPEP	Q9H4A4	307
CELA3A	CEL	P19835	296
CELA3A	PDIA2	Q13087	292

IntAct

14 interactions, top by confidence:

A	B	Type	Score
CELA3A	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
CELA3A	POTEF	psi-mi:“MI:0914”(association)	0.530
CELA3A	CREB3	psi-mi:“MI:0915”(physical association)	0.370
CELA3B	BCAT2	psi-mi:“MI:0914”(association)	0.350
BTBD1	IGHA2	psi-mi:“MI:0914”(association)	0.350
CELA3B	HBD	psi-mi:“MI:0914”(association)	0.350
ZNF843	AMY2A	psi-mi:“MI:0914”(association)	0.350
CELA3A	IGF1R	psi-mi:“MI:0914”(association)	0.350
CELA3A	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
MIS18A	CCDC85C	psi-mi:“MI:0914”(association)	0.350
CELA3A	AGTRAP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): CREB3 (Two-hybrid), POTEF (Affinity Capture-MS), TROAP (Affinity Capture-MS), PPP2R5D (Affinity Capture-MS), HELZ (Affinity Capture-MS), CNTNAP3 (Affinity Capture-MS), PPIP5K2 (Affinity Capture-MS), PCSK5 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), FBXO7 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TMEM132A (Affinity Capture-MS), AGTRAP (Two-hybrid), CELA3A (Affinity Capture-MS), HELZ (Affinity Capture-MS)

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: A1L453, A6H6T1, B8V7S0, B8VIV4, C0HKA2, C0HKA3, C0HKA4, F2YMG0, O15393, O18783, O46644, P00740, P00741, P00747, P00766, P00774, P03951, P03952, P03953, P06867, P06868, P08217, P08218, P08419, P08426, P08519, P08709, P09093, P0CW18, P12545, P14272, P14417, P15944, P16291, P16292, P16293, P16295, P16296, P19236, P19540

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1042 predictions. Top by Δscore:

Variant	Effect	Δscore
1:22003001:A:AG	acceptor_gain	1.0000
1:22003002:G:GG	acceptor_gain	1.0000
1:22005436:T:TA	acceptor_gain	1.0000
1:22005541:TCTC:T	donor_gain	1.0000
1:22005545:G:GG	donor_gain	1.0000
1:22005658:GCA:G	acceptor_loss	1.0000
1:22005659:CA:C	acceptor_loss	1.0000
1:22005660:A:AC	acceptor_loss	1.0000
1:22005660:A:AG	acceptor_gain	1.0000
1:22005660:AG:A	acceptor_gain	1.0000
1:22005660:AGGAG:A	acceptor_gain	1.0000
1:22005661:G:GA	acceptor_gain	1.0000
1:22005661:GG:G	acceptor_gain	1.0000
1:22005661:GGA:G	acceptor_gain	1.0000
1:22005661:GGAGG:G	acceptor_gain	1.0000
1:22005793:GTGG:G	donor_gain	1.0000
1:22005794:TGGG:T	donor_loss	1.0000
1:22005795:GG:G	donor_gain	1.0000
1:22005795:GGGT:G	donor_loss	1.0000
1:22005796:GG:G	donor_gain	1.0000
1:22005797:G:GG	donor_gain	1.0000
1:22005797:GT:G	donor_loss	1.0000
1:22005798:T:A	donor_loss	1.0000
1:22005799:G:GG	donor_loss	1.0000
1:22007015:G:GG	donor_gain	1.0000
1:22007371:A:AG	acceptor_gain	1.0000
1:22007372:G:GG	acceptor_gain	1.0000
1:22007372:GC:G	acceptor_gain	1.0000
1:22007372:GCC:G	acceptor_gain	1.0000
1:22007372:GCCA:G	acceptor_gain	1.0000

AlphaMissense

1750 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:22007001:G:C	W162C	0.999
1:22007001:G:T	W162C	0.999
1:22006883:A:C	D123A	0.997
1:22006883:A:T	D123V	0.997
1:22009848:G:C	W262C	0.997
1:22009848:G:T	W262C	0.997
1:22007483:T:A	C204S	0.996
1:22007484:G:C	C204S	0.996
1:22009709:A:T	D216V	0.996
1:22009771:A:C	S237R	0.995
1:22009773:C:A	S237R	0.995
1:22009773:C:G	S237R	0.995
1:22006882:G:C	D123H	0.994
1:22006888:G:C	A125P	0.994
1:22006986:C:G	C157W	0.994
1:22006999:T:A	W162R	0.994
1:22006999:T:C	W162R	0.994
1:22007435:T:A	C188S	0.994
1:22007436:G:C	C188S	0.994
1:22007510:T:A	C213S	0.994
1:22007511:G:C	C213S	0.994
1:22009709:A:C	D216A	0.994
1:22009819:T:C	F253L	0.994
1:22009821:C:A	F253L	0.994
1:22009821:C:G	F253L	0.994
1:22005537:T:A	C74S	0.993
1:22005538:G:A	C74Y	0.993
1:22005538:G:C	C74S	0.993
1:22006883:A:G	D123G	0.993
1:22007002:G:T	G163C	0.993

dbSNP variants (sampled 300 via entrez): RS1000114694 (1:22007138 A>T), RS1000737194 (1:22000618 C>T), RS1000886678 (1:22000159 C>A,G,T), RS1001785290 (1:22010097 A>G,T), RS1001786832 (1:22005739 T>A), RS1002402197 (1:22012927 G>A), RS1002513036 (1:22001787 G>A,T), RS1002614220 (1:22009220 C>G,T), RS1003459208 (1:22003645 C>A,T), RS1003511467 (1:22003462 T>C), RS1004016239 (1:22010644 T>A,C), RS1004691331 (1:22007790 G>C), RS1005352688 (1:22004088 T>C), RS1005506140 (1:22010741 C>A,T), RS1005808162 (1:21999741 C>T)

Disease associations

OMIM: gene MIM:618693 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004899_8	Gestational age at birth (maternal effect)	3.000000e-14
GCST012191_2	Body mass index and systolic blood pressure (bivariate analysis)	7.000000e-06
GCST90002398_42	Neutrophil count	7.000000e-18
GCST90002399_28	Neutrophil percentage of white cells	7.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005112	gestational age
EFO:0005939	parental genotype effect measurement
EFO:0004340	body mass index
EFO:0006335	systolic blood pressure
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Catechin	increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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