CPA1

Summary

CPA1 (carboxypeptidase A1, HGNC:2296) is a protein-coding gene on chromosome 7q32.2, encoding Carboxypeptidase A1 (P15085). Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.

This gene encodes a member of the carboxypeptidase A family of zinc metalloproteases. This enzyme is produced in the pancreas and preferentially cleaves C-terminal branched-chain and aromatic amino acids from dietary proteins. This gene and several family members are present in a gene cluster on chromosome 7. Mutations in this gene may be linked to chronic pancreatitis, while elevated protein levels may be associated with pancreatic cancer.

Source: NCBI Gene 1357 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary chronic pancreatitis (Strong, GenCC)
• GWAS associations: 17
• Clinical variants (ClinVar): 1,070 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes
• MANE Select transcript: NM_001868

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2296
Approved symbol	CPA1
Name	carboxypeptidase A1
Location	7q32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000091704
Ensembl biotype	protein_coding
OMIM	114850
Entrez	1357

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 retained_intron

ENST00000011292, ENST00000470838, ENST00000476062, ENST00000478096, ENST00000479106, ENST00000481342, ENST00000484324, ENST00000491460, ENST00000604896

RefSeq mRNA: 1 — MANE Select: NM_001868 NM_001868

CCDS: CCDS5820

Canonical transcript exons

ENST00000011292 — 10 exons

Exon	Start	End
ENSE00000723253	130383684	130383794
ENSE00000723256	130384536	130384626
ENSE00000882293	130387824	130388108
ENSE00000977674	130385146	130385345
ENSE00003591799	130381630	130381863
ENSE00003602568	130382108	130382209
ENSE00003627625	130380494	130380585
ENSE00003663546	130381098	130381179
ENSE00003674925	130383391	130383492
ENSE00003787632	130385839	130385923

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 99.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 163.9401 / max 264510.5229, expressed in 47 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81082	159.7213	44
81094	1.1789	4
81101	0.6924	4
81095	0.6712	5
81096	0.5703	6
81083	0.2698	3
81098	0.2478	5
81102	0.1855	4
81097	0.1420	3
81103	0.1390	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.99	gold quality
islet of Langerhans	UBERON:0000006	99.60	gold quality
pancreas	UBERON:0001264	99.31	gold quality
type B pancreatic cell	CL:0000169	97.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.05	gold quality
epithelial cell of pancreas	CL:0000083	84.31	gold quality
ectocervix	UBERON:0012249	83.25	gold quality
right coronary artery	UBERON:0001625	82.02	gold quality
right lobe of liver	UBERON:0001114	80.65	gold quality
left uterine tube	UBERON:0001303	80.58	gold quality
endocervix	UBERON:0000458	80.24	gold quality
right uterine tube	UBERON:0001302	79.48	gold quality
right adrenal gland	UBERON:0001233	79.44	gold quality
descending thoracic aorta	UBERON:0002345	78.73	gold quality
oocyte	CL:0000023	78.07	silver quality
body of stomach	UBERON:0001161	77.60	gold quality
spleen	UBERON:0002106	77.15	gold quality
right adrenal gland cortex	UBERON:0035827	77.14	gold quality
omental fat pad	UBERON:0010414	76.75	gold quality
peritoneum	UBERON:0002358	76.65	gold quality
lower esophagus mucosa	UBERON:0035834	76.10	gold quality
metanephros cortex	UBERON:0010533	75.96	gold quality
right ovary	UBERON:0002118	75.87	gold quality
left adrenal gland cortex	UBERON:0035825	75.39	gold quality
adipose tissue of abdominal region	UBERON:0007808	74.85	gold quality
left adrenal gland	UBERON:0001234	74.79	gold quality
body of uterus	UBERON:0009853	74.36	gold quality
thoracic aorta	UBERON:0001515	74.08	gold quality
tibial artery	UBERON:0007610	74.06	gold quality
popliteal artery	UBERON:0002250	74.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	31.60
E-MTAB-5061	yes	21.06
E-ENAD-27	yes	7.66
E-HCAD-31	yes	4.48
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NEUROG3, PTF1A

Literature-anchored findings (GeneRIF, showing 14)

• Data show that the level of CAM1 and CAM5 gene mRNAs were consistently greater in response to heat stress in both root and shoot. (PMID:20554213)
• TIC32, was also shown to be dependent on its calmodulin-binding site for retention in the cytosol. Complementary approaches (bimolecular fluorescence complementation and reverse genetics) demonstrated that the calmodulin isoform CAM5 is specifically involved in the retention of ceQORH in the cytosol. (PMID:31578278)
• A description of the ternary complex hCPA1-Zn2+-poly(acrylic acid) is included as a model of the interaction of mucoadhesive polymers with proteases in the gastrointestinal tract. (PMID:18566513)
• Serum pro-CPA and CPA levels were increased in either pancreatitis or pancreatic malignancy (PMID:21502183)
• mechanism by which CPA1 variants confer increased pancreatitis risk may involve misfolding-induced endoplasmic reticulum stress rather than elevated trypsin activity (PMID:23955596)
• Complex Formation of Human Proelastases with Procarboxypeptidases A1 and A2. (PMID:27358403)
• Gene mutations were present in PRSS1 in 26 patients with acute recurrent and chronic pancreatitis, SPINK1 in 23, CTRC in 3, and CPA1 in 5. In the 31 patients with mutations in SPINK1, CTRC, or CPA1, 16 (51.6%) had homozygous or heterozygous mutations with other mutations. (PMID:27409067)
• Data found no significant enrichment of rare functionally defective CPA1 variants in a large Chinese idiopathic chronic pancreatitis cohort (PMID:28497564)
• study indicates ER stress-inducing variants in CPB1 and CPA1 are associated with pancreatic cancer susceptibility and implicate ER stress in pancreatic acinar cells in pancreatic cancer development. (PMID:29669919)
• Carboxypeptidase A1 and regenerating islet-derived 1alpha as new markers for pancreatic acinar cell carcinoma. (PMID:32702400)
• Enhanced carboxypeptidase efficacies and differentiation of peptide epimers. (PMID:34774536)
• Endoplasmic stress-inducing variants in CPB1 and CPA1 and risk of pancreatic cancer: A case-control study and meta-analysis. (PMID:34817877)
• Carboxypeptidase A1 (CPA1) Immunohistochemistry Is Highly Sensitive and Specific for Acinar Cell Carcinoma (ACC) of the Pancreas. (PMID:34889867)
• Novel p.G250A Mutation Associated with Chronic Pancreatitis Highlights Misfolding-Prone Region in Carboxypeptidase A1 (CPA1). (PMID:36555104)

Cross-species orthologs

25 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpa5	ENSDARG00000021339
danio_rerio	cpa1	ENSDARG00000030915
mus_musculus	Cpa1	ENSMUSG00000054446
rattus_norvegicus	Cpa1	ENSRNOG00000010725
drosophila_melanogaster	CG3097	FBGN0029804
drosophila_melanogaster	CG3108	FBGN0029807
drosophila_melanogaster	CG18585	FBGN0031929
drosophila_melanogaster	CG7025	FBGN0031930
drosophila_melanogaster	CG4017	FBGN0032143
drosophila_melanogaster	CG17633	FBGN0032144
drosophila_melanogaster	CG2915	FBGN0033241
drosophila_melanogaster	CG12374	FBGN0033774
drosophila_melanogaster	CG14820	FBGN0035718
drosophila_melanogaster	CG8563	FBGN0035777
drosophila_melanogaster	CG8562	FBGN0035779
drosophila_melanogaster	CG18417	FBGN0035780
drosophila_melanogaster	CG8560	FBGN0035781
drosophila_melanogaster	CG8539	FBGN0035791
drosophila_melanogaster	CG4408	FBGN0039073
drosophila_melanogaster	CG32379	FBGN0052379
drosophila_melanogaster	CG42264	FBGN0259149
caenorhabditis_elegans		WBGENE00004747
caenorhabditis_elegans	T06A4.1	WBGENE00020281
caenorhabditis_elegans	Y47G6A.19	WBGENE00021645
caenorhabditis_elegans		WBGENE00021984

Paralogs (8): CPB2 (ENSG00000080618), CPA4 (ENSG00000128510), CPO (ENSG00000144410), CPB1 (ENSG00000153002), CPA2 (ENSG00000158516), CPA5 (ENSG00000158525), CPA3 (ENSG00000163751), CPA6 (ENSG00000165078)

Protein

Protein identifiers

Carboxypeptidase A1 — P15085 (reviewed: P15085)

All UniProt accessions (5): C9JQ63, C9JUF9, C9JUZ4, P15085, S4R433

UniProt curated annotations — full annotation on UniProt →

Function. Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro. Catalyzes the conversion of leukotriene C4 to leukotriene F4 via the hydrolysis of an amide bond.

Subunit / interactions. Monomer. May form a complex with proelastase 2.

Subcellular location. Secreted.

Activity regulation. Inhibited by interaction with the S.magnifica carboxypeptidase inhibitor SmCI.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M14 family.

RefSeq proteins (1): NP_001859* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000834	Peptidase_M14	Domain
IPR003146	M14A_act_pep	Domain
IPR034248	CPA_M14_CPD	Domain
IPR036990	M14A-like_propep	Homologous_superfamily
IPR057246	CARBOXYPEPT_ZN_1	Binding_site
IPR057247	CARBOXYPEPT_ZN_2	Binding_site

Pfam: PF00246, PF02244

Enzyme classification (BRENDA):

• EC 3.4.17.1 — carboxypeptidase A (BRENDA: 32 organisms, 224 substrates, 281 inhibitors, 110 Km, 101 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
HIPPURYL-L-PHENYLALANINE	0.075–1.5	11
HIPPURYL-L-PHE	0.33–60	8
CARBOBENZOXY-GLY-L-PHE	0.21–16.1	5
BENZOYL-GLY-L-PHE	0.23–10	3
HIPPURYL-L-PHENYLLACTATE	0.062–0.11	3
N-[3-(2-FURYL)ACRYLOYL]-PHE-PHE	27–340	3
O-(TRANS-P-CHLOROCINNAMOYL)-L-BETA-PHENYLLACTATE	0.49–120	3
ANGIOTENSIN I	0.227–0.78	2
CARBOBENZOXY-GLY-L-LEU	0.16–33	2
HIPPURYL-DL-BETA-PHENYLLACTATE	780–1300	2
N-(3-[2-FURYL]ACRYLOYL)-PHE-PHE	0.024–0.034	2
N-CARBOBENZOXY-GLY-GLY-L-LEU	0.74–6.53	2
N-CARBOBENZOXY-GLY-GLY-L-PHE	0.0346–0.314	2
N-CARBOBENZOXY-GLY-L-PHE	0.0449–0.985	2
N-CARBOBENZOXY-GLY-L-TYR	0.143–0.145	2

Catalyzed reactions (Rhea), 1 shown:

• leukotriene C4 + H2O = leukotriene F4 + glycine (RHEA:50740)

UniProt features (53 total): strand 16, helix 16, binding site 8, turn 4, sequence variant 2, signal peptide 1, propeptide 1, disulfide bond 1, sequence conflict 1, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3FJU	X-RAY DIFFRACTION	1.6
2V77	X-RAY DIFFRACTION	1.6
6I6Z	X-RAY DIFFRACTION	1.72
5OM9	X-RAY DIFFRACTION	1.8
4UEE	X-RAY DIFFRACTION	2.27
4UEZ	X-RAY DIFFRACTION	2.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15085-F1	95.41	0.93

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 (1): 380 (proton donor/acceptor)

Ligand- & substrate-binding residues (8): 306; 307–308; 358; 179–182; 179; 182; 237; 254–255

Disulfide bonds (1): 248–271

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: 111 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_METAL_ION, MODULE_492, GATA6_01, chr7q32, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, MODULE_165, MODULE_48, GOBP_RESPONSE_TO_CADMIUM_ION, MODULE_95, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_LEUKOTRIENE_METABOLIC_PROCESS, GATA_Q6

GO Biological Process (4): proteolysis (GO:0006508), leukotriene metabolic process (GO:0006691), response to cadmium ion (GO:0046686), obsolete proteolysis involved in protein catabolic process (GO:0051603)

GO Molecular Function (9): metallocarboxypeptidase activity (GO:0004181), zinc ion binding (GO:0008270), carboxypeptidase activity (GO:0004180), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), exopeptidase activity (GO:0008238), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

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
peptidase activity	2
protein metabolic process	1
icosanoid metabolic process	1
response to metal ion	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
transition metal ion binding	1
exopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

878 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPA1	CTRC	Q99895	810
CPA1	CELA2A	P08217	766
CPA1	PRSS1	P07477	726
CPA1	PTF1A	Q7RTS3	719
CPA1	SPINK1	P00995	697
CPA1	LXN	Q9BS40	669
CPA1	PRSS58	Q8IYP2	630
CPA1	CELA3B	P08861	627
CPA1	PRSS2	P07478	602
CPA1	CELA3A	P09093	599
CPA1	CELA1	Q9UNI1	590
CPA1	RBPJL	Q9UBG7	589
CPA1	NEUROG3	Q9Y4Z2	587
CPA1	PRSS3	P15951	559
CPA1	CTRB1	P17538	557

IntAct

5 interactions, top by confidence:

A	B	Type	Score
	CPA1	psi-mi:“MI:0407”(direct interaction)	0.560
	CPA1	psi-mi:“MI:0407”(direct interaction)	0.440
ARRB1		psi-mi:“MI:0914”(association)	0.350

BioGRID (2): CPA1 (Positive Genetic), CPA1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1S4F020, A6XGK3, B6V865, B8JLQ9, B8XGR3, C5FH26, C5FVN6, D4AS12, D4B5N0, D4D675, D4DL57, O02350, O17754, O97397, P00730, P00731, P00732, P09954, P09955, P15085, P15086, P15088, P15089, P16406, P19222, P19223, P21961, P37892, P38836, P42787, P48052, P54969, P55261, Q0II73, Q29NC4, Q2KIG3, Q2KJ83, Q3T905, Q4R7R2, Q504N0

Diamond homologs: A0A1S4F020, A6XGK3, B6H233, B6Q972, B6V865, B8JLQ9, B8XGR3, C5FH26, C5FVN6, D4AS12, D4DL57, O02350, P00730, P00731, P00732, P04069, P09954, P09955, P15085, P15086, P18143, P19222, P19223, P29068, P38836, P42788, P48052, P55261, Q0C9B4, Q0II73, Q29NC4, Q3T905, Q504N0, Q5U901, Q7TPZ8, Q8IVL8, Q8N4T0, Q9VL86, A1CSU3, A1DGH9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1070 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	618
Likely benign	370
Benign	23

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2136614	NM_001868.4(CPA1):c.844T>C (p.Ser282Pro)	Pathogenic
1701535	NM_001868.4(CPA1):c.1085G>A (p.Gly362Glu)	Likely pathogenic
871495	NM_001868.4(CPA1):c.768C>G (p.Asn256Lys)	Likely pathogenic

SpliceAI

1607 predictions. Top by Δscore:

Variant	Effect	Δscore
7:130381860:GGAG:G	donor_gain	1.0000
7:130381861:GAGG:G	donor_gain	1.0000
7:130381862:AGGTG:A	donor_loss	1.0000
7:130381863:GGT:G	donor_loss	1.0000
7:130381864:G:A	donor_loss	1.0000
7:130381865:T:A	donor_loss	1.0000
7:130382099:A:AG	acceptor_gain	1.0000
7:130382100:C:G	acceptor_gain	1.0000
7:130382101:A:AG	acceptor_gain	1.0000
7:130382102:C:G	acceptor_gain	1.0000
7:130382102:CCTCA:C	acceptor_loss	1.0000
7:130382103:CTCAG:C	acceptor_loss	1.0000
7:130382105:CAG:C	acceptor_loss	1.0000
7:130382106:A:AG	acceptor_gain	1.0000
7:130382107:G:GG	acceptor_gain	1.0000
7:130382107:GA:G	acceptor_gain	1.0000
7:130382107:GAT:G	acceptor_gain	1.0000
7:130382107:GATC:G	acceptor_gain	1.0000
7:130382107:GATCT:G	acceptor_gain	1.0000
7:130382205:TGAAG:T	donor_loss	1.0000
7:130382207:AAGGT:A	donor_loss	1.0000
7:130382210:G:GA	donor_loss	1.0000
7:130383387:CCA:C	acceptor_loss	1.0000
7:130383388:CA:C	acceptor_loss	1.0000
7:130383389:A:AG	acceptor_gain	1.0000
7:130383389:AG:A	acceptor_loss	1.0000
7:130383390:G:GA	acceptor_gain	1.0000
7:130383390:GTTC:G	acceptor_gain	1.0000
7:130383390:GTTCA:G	acceptor_gain	1.0000
7:130383790:GCACG:G	donor_gain	1.0000

AlphaMissense

2768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:130384603:G:T	R255M	0.998
7:130384607:C:A	N256K	0.997
7:130384607:C:G	N256K	0.997
7:130384620:T:C	F261L	0.997
7:130384622:T:A	F261L	0.997
7:130384622:T:G	F261L	0.997
7:130387916:T:C	F389L	0.997
7:130387918:C:A	F389L	0.997
7:130387918:C:G	F389L	0.997
7:130383449:G:C	R181P	0.996
7:130384594:A:G	D252G	0.996
7:130384603:G:C	R255T	0.996
7:130384604:G:C	R255S	0.996
7:130384604:G:T	R255S	0.996
7:130384608:T:A	W257R	0.996
7:130384608:T:C	W257R	0.996
7:130384547:G:C	W236C	0.995
7:130384547:G:T	W236C	0.995
7:130384549:G:C	R237P	0.995
7:130383456:G:C	W183C	0.994
7:130383456:G:T	W183C	0.994
7:130383764:C:A	N222K	0.994
7:130383764:C:G	N222K	0.994
7:130384548:C:A	R237S	0.994
7:130384594:A:T	D252V	0.994
7:130385188:G:T	G277V	0.994
7:130383452:A:T	E182V	0.993
7:130384545:T:A	W236R	0.993
7:130384545:T:C	W236R	0.993
7:130384593:G:C	D252H	0.993

dbSNP variants (sampled 300 via entrez): RS1000876682 (7:130382934 C>T), RS1001268032 (7:130382673 G>C), RS1001544246 (7:130385569 A>G), RS1001690074 (7:130379622 G>A), RS1001868170 (7:130383975 C>T), RS1005097251 (7:130379228 G>A), RS1005497058 (7:130379007 G>T), RS1005617045 (7:130388211 C>A,G,T), RS1006058009 (7:130380255 C>A,T), RS1006524376 (7:130380647 C>A,T), RS1006725974 (7:130383263 G>A), RS1008263153 (7:130379898 C>A,T), RS1008627133 (7:130379663 G>A), RS1009079470 (7:130384615 C>T), RS1010853854 (7:130385613 G>A)

Disease associations

OMIM: gene MIM:114850 | disease phenotypes: MIM:167800

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary chronic pancreatitis	Strong	Autosomal dominant

Mondo (1): hereditary chronic pancreatitis (MONDO:0008185)

Orphanet (1): Autosomal dominant hereditary chronic pancreatitis (Orphanet:676)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000819	Diabetes mellitus
HP:0000952	Jaundice
HP:0001974	Increased total leukocyte count
HP:0002027	Abdominal pain
HP:0005213	Pancreatic calcification
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0012379	Abnormal circulating enzyme concentration or activity
HP:0030247	Splanchnic vein thrombosis
HP:0100027	Recurrent pancreatitis

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST005958_14	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-07
GCST005962_34	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-07
GCST012228_317	Waist-hip index	2.000000e-08
GCST012228_318	Waist-hip index	3.000000e-08
GCST012230_479	Waist-to-hip ratio adjusted for BMI	3.000000e-08
GCST012230_480	Waist-to-hip ratio adjusted for BMI	4.000000e-08
GCST90020024_115	A body shape index	3.000000e-13
GCST90020024_118	A body shape index	4.000000e-14
GCST90020024_119	A body shape index	1.000000e-10
GCST90020024_120	A body shape index	4.000000e-08
GCST90020026_599	Hip index	2.000000e-19
GCST90020026_601	Hip index	4.000000e-17
GCST90020028_277	Hip circumference adjusted for BMI	4.000000e-13
GCST90020028_475	Hip circumference adjusted for BMI	5.000000e-15
GCST90020029_890	Waist circumference adjusted for body mass index	1.000000e-11
GCST90020029_893	Waist circumference adjusted for body mass index	3.000000e-13
GCST90020029_894	Waist circumference adjusted for body mass index	1.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537262	Hereditary pancreatitis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2088 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M14: Carboxypeptidase A

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

Ligand	Action	Affinity	Parameter
S-BMPA	Inhibition	8.11	pKi
compound 1b [PMID: 18078750]	Inhibition	6.51	pKi

ChEMBL bioactivities

65 potent at pChembl≥5 of 89 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	Ki	0.04	nM	CHEMBL4460840
10.15	Ki	0.07	nM	CHEMBL4445882
10.10	Ki	0.08	nM	CHEMBL4436298
10.06	Ki	0.087	nM	CHEMBL4528407
10.05	Ki	0.089	nM	CHEMBL4445882
9.97	Ki	0.107	nM	CHEMBL4483485
9.89	Ki	0.1287	nM	CHEMBL4454162
9.85	Ki	0.14	nM	CHEMBL4528407
9.80	Ki	0.16	nM	CHEMBL4454162
9.80	Ki	0.16	nM	CHEMBL4483485
9.62	Ki	0.24	nM	CHEMBL4445882
9.52	Ki	0.3	nM	CHEMBL4513310
9.33	Ki	0.47	nM	CHEMBL4528407
9.28	Ki	0.53	nM	CHEMBL4454162
9.28	Ki	0.53	nM	CHEMBL4483485
8.92	Ki	1.2	nM	CHEMBL4532731
8.77	Ki	1.7	nM	CHEMBL4453900
8.70	IC50	2	nM	ANABAENOPEPTIN G
8.51	Ki	3.1	nM	CHEMBL4448096
8.23	Ki	5.9	nM	CHEMBL4440735
6.82	Ki	150	nM	CHEMBL407567
6.80	Ki	160	nM	CHEMBL571509
6.70	Ki	200	nM	CHEMBL565957
6.51	Ki	310	nM	CHEMBL163454
6.50	Ki	320	nM	CHEMBL161702
6.46	Ki	350	nM	CHEMBL253224
6.40	IC50	400	nM	CHEMBL151284
6.37	Ki	430	nM	CHEMBL571291
6.35	Ki	450	nM	CHEMBL259621
6.28	Ki	530	nM	CHEMBL400526
6.25	Ki	560	nM	CHEMBL161819
6.10	Ki	790	nM	CHEMBL261331
6.01	Ki	980	nM	CHEMBL161705
5.96	IC50	1100	nM	ANABAENOPEPTIN F
5.94	Ki	1160	nM	CHEMBL159616
5.92	Ki	1200	nM	CHEMBL350414
5.92	Ki	1200	nM	CHEMBL161863
5.85	IC50	1400	nM	CHEMBL68399
5.80	Ki	1600	nM	CHEMBL254493
5.77	IC50	1700	nM	CHEMBL33352
5.77	Ki	1700	nM	CHEMBL258333
5.72	Ki	1900	nM	CHEMBL398771
5.68	Ki	2080	nM	CHEMBL407566
5.66	IC50	2200	nM	CHEMBL68399
5.64	Ki	2300	nM	CHEMBL251804
5.48	Ki	3300	nM	CHEMBL251808
5.44	Ki	3600	nM	CHEMBL400527
5.43	IC50	3700	nM	ANABAENOPEPTIN H
5.41	IC50	3900	nM	ANABAENOPEPTIN B
5.34	Ki	4600	nM	CHEMBL251809

PubChem BioAssay actives

65 with measured affinity, of 157 total; 50 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
(2S)-2-[[[(1R)-1-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-2-phenylethyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1614545: Inhibition of human CPA1 using AAFP as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	ki	<0.0001	uM
(2S)-2-[[[(1R)-1-[[(2S)-2-acetamido-4-methylpentanoyl]amino]ethyl]-hydroxyphosphoryl]methyl]-4-phenylbutanoic acid	1614545: Inhibition of human CPA1 using AAFP as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	ki	0.0001	uM
(2S)-2-[[[(1R)-1-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]ethyl]-hydroxyphosphoryl]methyl]-4-phenylbutanoic acid	1614545: Inhibition of human CPA1 using AAFP as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	ki	0.0001	uM
(2S)-2-[[[(1R)-1-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-2-phenylethyl]-hydroxyphosphoryl]methyl]-4-phenylbutanoic acid	1614545: Inhibition of human CPA1 using AAFP as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	ki	0.0001	uM
(2E)-2-[(2Z,4E)-3-[4-[3-[2-[2-[2-[3-[2-[2-[2-[[(2S)-1-[[(1R)-1-[[(2S)-2-carboxy-4-phenylbutyl]-hydroxyphosphoryl]ethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethoxy]ethoxy]ethylamino]-3-oxopropoxy]ethoxy]ethoxy]ethylamino]-3-oxopropyl]phenyl]-5-[1,1-dimethyl-6,8-disulfo-3-(4-sulfobutyl)benzo[e]indol-3-ium-2-yl]penta-2,4-dienylidene]-1,1-dimethyl-8-sulfo-3-(4-sulfobutyl)benzo[e]indole-6-sulfonate	1614545: Inhibition of human CPA1 using AAFP as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	ki	0.0001	uM
(2S)-2-[[[(1R)-1-[[(2S)-2-[[2-[2-(2-acetamidoethoxy)ethoxy]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]ethyl]-hydroxyphosphoryl]methyl]-4-phenylbutanoic acid	1614545: Inhibition of human CPA1 using AAFP as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	ki	0.0001	uM
(2S)-2-[[[(1R)-1-[[(2S)-2-[[2-[2-(2-aminoethoxy)ethoxy]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]ethyl]-hydroxyphosphoryl]methyl]-4-phenylbutanoic acid	1614545: Inhibition of human CPA1 using AAFP as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	ki	0.0003	uM
(2S)-2-[[[(1R)-1-[[(2S)-2-acetamido-6-aminohexanoyl]amino]ethyl]-hydroxyphosphoryl]methyl]-4-phenylbutanoic acid	1614545: Inhibition of human CPA1 using AAFP as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	ki	0.0012	uM
(2S)-2-[[[(1R)-1-[[(2S)-1-acetylpyrrolidine-2-carbonyl]amino]ethyl]-hydroxyphosphoryl]methyl]-4-phenylbutanoic acid	1614545: Inhibition of human CPA1 using AAFP as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	ki	0.0017	uM
(2S)-2-[[(3S,6S,9S,12S,15R)-3,12-bis[(2S)-butan-2-yl]-6,9-bis[2-(4-hydroxyphenyl)ethyl]-7-methyl-2,5,8,11,14-pentaoxo-1,4,7,10,13-pentazacyclononadec-15-yl]carbamoylamino]-3-(4-hydroxyphenyl)propanoic acid	1713519: Inhibition of carboxypeptidase A (unknown origin) assessed as reduction in hydrolysis of hippuryl-L-phenylalanine using hippuryl-L-phenylalanine as substrate	ic50	0.0020	uM
(4S)-4-acetamido-5-[[(1R)-1-[[(2S)-2-carboxy-4-phenylbutyl]-hydroxyphosphoryl]ethyl]amino]-5-oxopentanoic acid	1614545: Inhibition of human CPA1 using AAFP as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	ki	0.0031	uM
(2S)-2-[[[(1R)-1-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]ethyl]-hydroxyphosphoryl]methyl]-4-phenylbutanoic acid	1614545: Inhibition of human CPA1 using AAFP as substrate preincubated for 45 mins to 2 hrs measured at 30 sec intervals for 15 mins by UV/vis-spectrophotometry	ki	0.0059	uM
(2R)-2-benzyl-3-nitropropanoic acid	318340: Inhibition of CPA	ki	0.1500	uM
(2R)-2-benzyl-5-nitro-4-oxopentanoic acid	448095: Inhibition of Carboxypeptidase A assessed as amount of Cl-CPL consumed by UV spectrometer	ki	0.1600	uM
2-benzyl-5,5,5-trifluoro-4-oxopentanoic acid	448095: Inhibition of Carboxypeptidase A assessed as amount of Cl-CPL consumed by UV spectrometer	ki	0.2000	uM
(2S)-3-(4-phenylphenyl)-2-[[(2R)-3-phenyl-2-sulfanylpropanoyl]amino]propanoic acid	317221: Inhibition of human recombinant carboxy peptidase A1 by fluorescence assay	ki	0.3100	uM
2-benzyl-3-[hydroxy-(2-phenylacetyl)amino]propanoic acid	48479: Compound was tested for its inhibitory activity against carboxypeptidase A (CPA)	ki	0.3200	uM
(2S)-3-(4-hydroxyphenyl)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]propanoic acid	314427: Inhibition of human recombinant CpA by fluorescence assay	ki	0.3500	uM
2-benzylbutanedioic acid	48477: In vitro inhibition of Carboxypeptidase A (CPA) was determined by clot lysis assay using human plasma	ic50	0.4000	uM
2-benzyl-5-nitro-4-oxopentanoic acid	448095: Inhibition of Carboxypeptidase A assessed as amount of Cl-CPL consumed by UV spectrometer	ki	0.4300	uM
(2R)-2-benzylbutanedioic acid	318340: Inhibition of CPA	ki	0.4500	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-phenylpropanoic acid	314427: Inhibition of human recombinant CpA by fluorescence assay	ki	0.5300	uM
(2R)-2-benzyl-3-[formyl(hydroxy)amino]propanoic acid	48479: Compound was tested for its inhibitory activity against carboxypeptidase A (CPA)	ki	0.5600	uM
2-benzyl-3-nitropropanoic acid	318340: Inhibition of CPA	ki	0.7900	uM
2-benzyl-3-[formyl(hydroxy)amino]propanoic acid	48479: Compound was tested for its inhibitory activity against carboxypeptidase A (CPA)	ki	0.9800	uM
(2S)-2-[[(3S,6S,9S,12S,15R)-3-benzyl-12-[(2S)-butan-2-yl]-9-[2-(4-hydroxyphenyl)ethyl]-6,7-dimethyl-2,5,8,11,14-pentaoxo-1,4,7,10,13-pentazacyclononadec-15-yl]carbamoylamino]-5-(diaminomethylideneamino)pentanoic acid	1227128: Inhibition of CPA (unknown origin)	ic50	1.1000	uM
2-benzyl-3-[hydroxy(4-phenylbutanoyl)amino]propanoic acid	48479: Compound was tested for its inhibitory activity against carboxypeptidase A (CPA)	ki	1.1600	uM
2-benzyl-3-[hydroxy(3-phenylpropanoyl)amino]propanoic acid	48479: Compound was tested for its inhibitory activity against carboxypeptidase A (CPA)	ki	1.2000	uM
(2S)-3-(4-phenylphenyl)-2-[[(2S)-3-phenyl-2-sulfanylpropanoyl]amino]propanoic acid	317221: Inhibition of human recombinant carboxy peptidase A1 by fluorescence assay	ki	1.2000	uM
3-(6-amino-3-pyridinyl)-2-[1-(3-methylbutyl)imidazol-4-yl]propanoic acid	48477: In vitro inhibition of Carboxypeptidase A (CPA) was determined by clot lysis assay using human plasma	ic50	1.4000	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-(2-phenylmethoxyphenyl)propanoic acid	314427: Inhibition of human recombinant CpA by fluorescence assay	ki	1.6000	uM
2-(1H-imidazol-5-yl)-3-phenylpropanoic acid	48477: In vitro inhibition of Carboxypeptidase A (CPA) was determined by clot lysis assay using human plasma	ic50	1.7000	uM
(2S)-3-(4-phenylphenyl)-2-[(2-sulfanylacetyl)amino]propanoic acid	317221: Inhibition of human recombinant carboxy peptidase A1 by fluorescence assay	ki	1.7000	uM
(2S)-3-[4-[(2,4-difluorophenyl)methoxy]phenyl]-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]propanoic acid	314427: Inhibition of human recombinant CpA by fluorescence assay	ki	1.9000	uM
4-methyl-2-(nitromethyl)pentanoic acid	318340: Inhibition of CPA	ki	2.0800	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-(2-phenoxyphenyl)propanoic acid	314427: Inhibition of human recombinant CpA by fluorescence assay	ki	2.3000	uM
(2S)-3-[4-[(3,4-difluorophenyl)methoxy]phenyl]-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]propanoic acid	314427: Inhibition of human recombinant CpA by fluorescence assay	ki	3.3000	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-naphthalen-1-ylpropanoic acid	314427: Inhibition of human recombinant CpA by fluorescence assay	ki	3.6000	uM
(2S)-2-[[(3S,6S,9S,12S,15R)-3,12-bis[(2S)-butan-2-yl]-6,9-bis[2-(4-hydroxyphenyl)ethyl]-7-methyl-2,5,8,11,14-pentaoxo-1,4,7,10,13-pentazacyclononadec-15-yl]carbamoylamino]-5-(diaminomethylideneamino)pentanoic acid	1713519: Inhibition of carboxypeptidase A (unknown origin) assessed as reduction in hydrolysis of hippuryl-L-phenylalanine using hippuryl-L-phenylalanine as substrate	ic50	3.7000	uM
(2S)-2-[[(3S,6S,9S,12S,15R)-3-benzyl-9-[2-(4-hydroxyphenyl)ethyl]-6,7-dimethyl-2,5,8,11,14-pentaoxo-12-propan-2-yl-1,4,7,10,13-pentazacyclononadec-15-yl]carbamoylamino]-5-(diaminomethylideneamino)pentanoic acid	1227128: Inhibition of CPA (unknown origin)	ic50	3.9000	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-(4-phenylmethoxyphenyl)propanoic acid	314427: Inhibition of human recombinant CpA by fluorescence assay	ki	4.6000	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-[4-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]propanoic acid	314427: Inhibition of human recombinant CpA by fluorescence assay	ki	4.6000	uM
(2S)-2-benzyl-3-[formyl(hydroxy)amino]propanoic acid	48479: Compound was tested for its inhibitory activity against carboxypeptidase A (CPA)	ki	4.9500	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-(3-phenylphenyl)propanoic acid	314427: Inhibition of human recombinant CpA by fluorescence assay	ki	5.0000	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-(3-phenylmethoxyphenyl)propanoic acid	314427: Inhibition of human recombinant CpA by fluorescence assay	ki	5.0000	uM
(2S)-3-(4-phenylphenyl)-2-[[(2S)-4-phenyl-2-sulfanylbutanoyl]amino]propanoic acid	317221: Inhibition of human recombinant carboxy peptidase A1 by fluorescence assay	ki	5.0000	uM
2-benzyl-3-[hydroxy(propanoyl)amino]propanoic acid	48479: Compound was tested for its inhibitory activity against carboxypeptidase A (CPA)	ki	5.8200	uM
2-[[acetyl(hydroxy)amino]methyl]-3-phenylpropanoic acid	48479: Compound was tested for its inhibitory activity against carboxypeptidase A (CPA)	ki	5.9000	uM
3-(6-amino-3-pyridinyl)-2-(1-propan-2-ylimidazol-4-yl)propanoic acid	48477: In vitro inhibition of Carboxypeptidase A (CPA) was determined by clot lysis assay using human plasma	ic50	6.4000	uM
2-[[benzoyl(hydroxy)amino]methyl]-3-phenylpropanoic acid	48479: Compound was tested for its inhibitory activity against carboxypeptidase A (CPA)	ki	6.5000	uM

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
aflatoxin B2	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Triclosan	increases expression	1
Genistein	decreases expression	1

ChEMBL screening assays

30 unique, capped per target: 26 binding, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1027877	Binding	Inhibition of carboxypeptidase A up to 20 ug/ml	Homotyrosine-containing cyanopeptolins 880 and 960 and anabaenopeptins 908 and 915 from Planktothrix agardhii CYA 126/8. — J Nat Prod
CHEMBL3755112	ADMET	Stability of the compound in Tris buffer assessed as carboxypeptidase A (unknown origin)-mediated compound degradation at pH 7.5 at 37 degC after 4 hrs by UPLC analysis	Cysteine-Rich Peptide Family with Unusual Disulfide Connectivity from Jasminum sambac. — J Nat Prod

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00830557	Not specified	RECRUITING	Collecting Medical Information and Tissue Samples From Patients With Pancreatic Cancer or Other Pancreatic Disorders
NCT02078245	Not specified	UNKNOWN	Quality Control Study of MR Based Screening of Individual With Increased Risk for Pancreas Cancer.
NCT02206360	Not specified	ACTIVE_NOT_RECRUITING	Pancreatic Cancer Early Detection Program
NCT02309632	Not specified	WITHDRAWN	Pancreatic Cancer Screening of High-Risk Individuals in Arkansas
NCT04095195	Not specified	RECRUITING	Registry of Subjects at Risk of Pancreatic Cancer
NCT04743479	Not specified	RECRUITING	Artificial Intelligence-based Early Screening of Pancreatic Cancer and High Risk Tracing (ESPRIT-AI)
NCT07413029	Not specified	RECRUITING	French National Cohort of Patients With PRSS1 Mutations