PRCP

Summary

PRCP (prolylcarboxypeptidase, HGNC:9344) is a protein-coding gene on chromosome 11q14, encoding Lysosomal Pro-X carboxypeptidase (P42785). Cleaves C-terminal amino acids linked to proline in peptides such as angiotensin II, III and des-Arg9-bradykinin.

This gene encodes a member of the peptidase S28 family of serine exopeptidases. The encoded preproprotein is proteolytically processed to generate the mature lysosomal prolylcarboxypeptidase. This enzyme cleaves C-terminal amino acids linked to proline in peptides such as angiotension II, III and des-Arg9-bradykinin. The cleavage occurs at acidic pH, but the enzyme activity is retained with some substrates at neutral pH. This enzyme has been shown to be an activator of the cell matrix-associated prekallikrein. The importance of angiotension II, one of the substrates of this enzyme, in regulating blood pressure and electrolyte balance suggests that this gene may be related to essential hypertension. A pseudogene of this gene has been identified on chromosome 2. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 5547 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 85 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005040

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9344
Approved symbol	PRCP
Name	prolylcarboxypeptidase
Location	11q14
Locus type	gene with protein product
Status	Approved
Aliases	PCP, HUMPCP
Ensembl gene	ENSG00000137509
Ensembl biotype	protein_coding
OMIM	176785
Entrez	5547

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 24 protein_coding, 8 retained_intron, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 TEC

ENST00000313010, ENST00000393399, ENST00000524642, ENST00000525772, ENST00000526918, ENST00000527444, ENST00000528082, ENST00000529671, ENST00000531128, ENST00000531283, ENST00000531801, ENST00000532709, ENST00000532809, ENST00000533126, ENST00000534264, ENST00000534396, ENST00000534631, ENST00000623464, ENST00000679387, ENST00000679623, ENST00000679809, ENST00000680040, ENST00000680186, ENST00000680341, ENST00000680437, ENST00000680524, ENST00000680566, ENST00000681126, ENST00000681155, ENST00000681322, ENST00000681432, ENST00000681508, ENST00000681592, ENST00000681637, ENST00000681781, ENST00000681826, ENST00000681883, ENST00000913715, ENST00000949391

RefSeq mRNA: 3 — MANE Select: NM_005040 NM_001319214, NM_005040, NM_199418

CCDS: CCDS41695, CCDS8262, CCDS91553

Canonical transcript exons

ENST00000313010 — 9 exons

Exon	Start	End
ENSE00000927712	82849049	82849218
ENSE00000927714	82850324	82850505
ENSE00002149928	82822936	82825122
ENSE00002150116	82900235	82900430
ENSE00003487282	82838387	82838574
ENSE00003534552	82839261	82839425
ENSE00003554074	82859977	82860117
ENSE00003642450	82853177	82853278
ENSE00003787376	82849914	82850071

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 88.5378 / max 588.2413, expressed in 1823 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121571	87.6287	1823
121573	0.3473	122
121569	0.1473	61
121574	0.1350	39
121572	0.0943	30
121575	0.0928	41
121570	0.0613	35
121577	0.0166	10
121576	0.0145	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.35	gold quality
lymph node	UBERON:0000029	97.46	gold quality
monocyte	CL:0000576	97.29	gold quality
right adrenal gland cortex	UBERON:0035827	97.27	gold quality
mononuclear cell	CL:0000842	97.18	gold quality
right adrenal gland	UBERON:0001233	97.18	gold quality
leukocyte	CL:0000738	97.17	gold quality
gall bladder	UBERON:0002110	97.13	gold quality
periodontal ligament	UBERON:0008266	97.13	gold quality
synovial joint	UBERON:0002217	97.08	gold quality
left adrenal gland	UBERON:0001234	96.91	gold quality
adrenal cortex	UBERON:0001235	96.91	gold quality
urethra	UBERON:0000057	96.89	gold quality
left adrenal gland cortex	UBERON:0035825	96.88	gold quality
adrenal gland	UBERON:0002369	96.87	gold quality
smooth muscle tissue	UBERON:0001135	96.84	gold quality
adrenal tissue	UBERON:0018303	96.82	gold quality
metanephros cortex	UBERON:0010533	96.60	gold quality
decidua	UBERON:0002450	96.57	gold quality
tibia	UBERON:0000979	96.53	gold quality
penis	UBERON:0000989	96.22	gold quality
skin of hip	UBERON:0001554	96.21	gold quality
endocervix	UBERON:0000458	96.19	gold quality
bone marrow cell	CL:0002092	96.16	gold quality
ectocervix	UBERON:0012249	96.14	gold quality
renal medulla	UBERON:0000362	96.11	gold quality
colonic epithelium	UBERON:0000397	96.07	gold quality
right atrium auricular region	UBERON:0006631	96.03	gold quality
upper leg skin	UBERON:0004262	96.01	gold quality
medial globus pallidus	UBERON:0002477	96.00	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-10137	yes	2116.53
E-CURD-112	yes	1731.68
E-MTAB-10553	yes	1353.24
E-HCAD-10	yes	1290.84
E-GEOD-124472	yes	1264.52
E-MTAB-8271	yes	797.03
E-GEOD-135922	yes	372.57
E-HCAD-1	yes	30.42
E-MTAB-8410	yes	24.29
E-HCAD-9	yes	19.97
E-MTAB-6701	yes	15.44
E-HCAD-13	yes	12.37
E-MTAB-9067	yes	8.03
E-MTAB-10042	yes	7.90
E-MTAB-9801	yes	7.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

124 targeting PRCP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 21)

• PRCP appears to be a HUVEC-associated prekallikrein activator. (PMID:11830581)
• Identification of prolylcarboxypeptidase as the cell matrix-associated prekallikrein activator. (PMID:12123826)
• recombinant protein, identical to enzyme from human umbilical vein endothelial cells, is a prekallikrein activator. (PMID:14996700)
• Prolylcarboxypepdiase E112D (rs2298668)D allele alone and jointly with chronic hypertension were associated with a significantly increased risk of preeclampsia (PMID:16681991)
• role in regulation cardiovascular tone; proinflammatory agent (PMID:18396440)
• These investigations showed that the C-terminal region of the rPRCP(40) contributes to PRCP’s catalytic function, and provided additional experimental evidence for this suggestion. (PMID:18656443)
• Data suggest that the E112D polymorphism in the PRCP gene may be a useful genetic marker to predict the antihypertensive effect of short-term benazepril treatment in hypertensive patients. (PMID:20079160)
• Purified PrCP yielded crystals belonging to space group R32, with unit-cell parameters a = b = 181.14, c = 240.13 A, that diffracted to better than 2.8 A resolution. (PMID:20516604)
• A single peptide, with the sequence YPRPIHPA, as a novel substrate for PRCP in human cerebrospinal fluid. (PMID:20517885)
• A structure-based alignment with the previously undescribed structure of DPP7 illuminates the mechanism of orthogonal substrate specificity of PRCP and DPP7. (PMID:20540760)
• PRCP as a resistance factor for 4OHTAM resistance in estrogen receptor-positive breast cancer cells. (PMID:21087932)
• analysis of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors (PMID:22079761)
• The present results indicated PRCP rs7104980 can be considered as a marker for EH and Hap3 GAGCACTAACA (PRCP) and Hap16 TTTA (CMA1) might be associated with essential hypertension in Chinese Han population. (PMID:22679278)
• PRCP regulates cell growth, angiogenesis, and the response to vascular injury (PMID:23744584)
• PRCP1 interacts with plasma kallikrein (PK) at multiple sites for PK activation. (PMID:25324000)
• The decrease in PRCP levels in the first 24 h after stroke onset is associated with stroke severity and an unfavourable short-term stroke outcome (PMID:25370794)
• For the first time, PRCP is identified as an apelin-cleaving enzyme. (PMID:27449720)
• Using multiple -omics approach, study validated key molecules, such as CAP1, SHC1 and PRCP, that might play a significant role in IgA nephropathy pathogenesis. (PMID:28831120)
• Fast oxidation of alpha-melanocyte-stimulating hormone and derived peptides under laboratory conditions causes irreproducible results-Insights from studies of prolylcarboxypeptidase in human cell types. (PMID:31837203)
• Genetic association study of prolylcarboxypeptidase polymorphisms with susceptibility to essential hypertension in the Yi minority of China: A case-control study based on an isolated population. (PMID:32448049)
• Haplotype-based association study between PRCP gene polymorphisms and essential hypertension in Hani minority group from a remote region of China. (PMID:33319614)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prcp	ENSDARG00000037883
mus_musculus	Prcp	ENSMUSG00000061119
rattus_norvegicus	Prcp	ENSRNOG00000010630
drosophila_melanogaster	CG2493	FBGN0032864
caenorhabditis_elegans		WBGENE00022801

Paralogs (2): PRSS16 (ENSG00000112812), DPP7 (ENSG00000176978)

Protein

Protein identifiers

Lysosomal Pro-X carboxypeptidase — P42785 (reviewed: P42785)

Alternative names: Angiotensinase C, Lysosomal carboxypeptidase C, Proline carboxypeptidase, Prolylcarboxypeptidase

All UniProt accessions (12): A0A7P0TB23, A0A7P0Z451, B3KR26, B7Z7Q6, E9PKN6, E9PL49, E9PL85, E9PLY4, P42785, E9PNF7, E9PNJ1, E9PQB5

UniProt curated annotations — full annotation on UniProt →

Function. Cleaves C-terminal amino acids linked to proline in peptides such as angiotensin II, III and des-Arg9-bradykinin. This cleavage occurs at acidic pH, but enzymatic activity is retained with some substrates at neutral pH.

Subunit / interactions. Homodimer.

Subcellular location. Lysosome.

Tissue specificity. Highest levels in placenta, lung and liver. Also present in heart, brain, pancreas and kidney.

Similarity. Belongs to the peptidase S28 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P42785-1	1	yes
P42785-2	2

RefSeq proteins (3): NP_001306143, NP_005031, NP_955450 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008758	Peptidase_S28	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR042269	Ser_carbopepase_S28_SKS	Homologous_superfamily

Pfam: PF05577

Enzyme classification (BRENDA):

• EC 3.4.16.2 — lysosomal Pro-Xaa carboxypeptidase (BRENDA: 8 organisms, 43 substrates, 60 inhibitors, 20 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ALA-PRO-4-NITROANILIDE	1.5–3.1	3
ANGIOTENSIN II	0.34–1	2
MYOGLOBIN	0.1–0.13	2
N-BENZYLOXYCARBONYL-PRO-PHE	0.77–1.3	2
PREKALLIKREIN	—	2
ANGIOTENSIN III	2	1
GLY-PRO-4-NITROANILIDE	4	1
L-ALA-L-PRO 4-NITROANILIDE	0.157	1
N-BENZYLOXYCARBONYL-GLY-L-PRO 4-NITROANILIDE	0.147	1
N-BENZYLOXYCARBONYL-L-ALA-L-ALA-L-PRO 4-NITROANI	0.34	1
N-BENZYLOXYCARBONYL-L-ALA-L-PRO 4-NITROANILIDE	0.095	1
N-BENZYLOXYCARBONYL-L-PRO 4-NITROANILIDE	0.17	1
N-BENZYLOXYCARBONYL-L-PRO-L-ALA	4.7	1
N-BENZYLOXYCARBONYL-L-PRO-LEU	0.26	1

UniProt features (56 total): helix 18, strand 12, glycosylation site 6, disulfide bond 4, sequence conflict 3, turn 3, active site 3, sequence variant 2, signal peptide 1, propeptide 1, splice variant 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3N2Z	X-RAY DIFFRACTION	2.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42785-F1	90.99	0.87

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): 179 (charge relay system); 430 (charge relay system); 455 (charge relay system)

Disulfide bonds (4): 215–372, 233–310, 264–343, 364–394

Glycosylation sites (6): 336, 345, 415, 47, 101, 317

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-9970672	FXIIa activates plasma kallikrein-kinin system
R-HSA-140837

MSigDB gene sets: 342 (showing top): GOBP_PROTEIN_ACTIVATION_CASCADE, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE_BY_CIRCULATORY_RENIN_ANGIOTENSIN, GOBP_REGULATION_OF_BLOOD_PRESSURE, CCAWYNNGAAR_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_INFLAMMATORY_RESPONSE, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_REGULATION_OF_HORMONE_LEVELS

GO Biological Process (10): angiotensin maturation (GO:0002003), regulation of thyroid hormone receptor signaling pathway (GO:0002155), plasma kallikrein-kinin cascade (GO:0002353), negative regulation of systemic arterial blood pressure (GO:0003085), glucose homeostasis (GO:0042593), regulation of blood vessel endothelial cell migration (GO:0043535), angiogenesis involved in wound healing (GO:0060055), energy homeostasis (GO:0097009), regulation of reactive oxygen species metabolic process (GO:2000377), proteolysis (GO:0006508)

GO Molecular Function (8): metallocarboxypeptidase activity (GO:0004181), serine-type carboxypeptidase activity (GO:0004185), dipeptidyl-peptidase activity (GO:0008239), carboxypeptidase activity (GO:0004180), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), serine-type exopeptidase activity (GO:0070008)

GO Cellular Component (7): plasma membrane (GO:0005886), azurophil granule membrane (GO:0035577), basal part of cell (GO:0045178), extracellular exosome (GO:0070062), ficolin-1-rich granule membrane (GO:0101003), extracellular region (GO:0005576), lysosome (GO:0005764)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
exopeptidase activity	3
carboxypeptidase activity	2
secretory granule membrane	2
cellular anatomical structure	2
regulation of angiotensin levels in blood	1
peptide hormone processing	1
thyroid hormone receptor signaling pathway	1
regulation of intracellular signal transduction	1
kinin cascade	1
regulation of systemic arterial blood pressure	1
negative regulation of blood pressure	1
carbohydrate homeostasis	1
regulation of endothelial cell migration	1
blood vessel endothelial cell migration	1
angiogenesis	1
wound healing	1
multicellular organismal-level homeostasis	1
regulation of metabolic process	1
reactive oxygen species metabolic process	1
protein metabolic process	1
metalloexopeptidase activity	1
serine-type exopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
serine-type peptidase activity	1
membrane	1
cell periphery	1
lysosomal membrane	1
azurophil granule	1
extracellular vesicle	1
tertiary granule	1
ficolin-1-rich granule	1
lytic vacuole	1

Protein interactions and networks

STRING

992 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRCP	PREP	P48147	897
PRCP	KNG1	P01042	757
PRCP	ACE2	Q9BYF1	736
PRCP	DPP4	P27487	693
PRCP	REN	P00797	669
PRCP	KLKB1	P03952	648
PRCP	GBE1	Q04446	628
PRCP	KLK4	Q9Y5K2	600
PRCP	AGT	P01019	599
PRCP	THOP1	P52888	594
PRCP	MME	P08473	545
PRCP	ACE	P12821	540
PRCP	MMEL1	Q495T6	538
PRCP	LRPAP1	P30533	522
PRCP	MEP1A	Q16819	521

IntAct

41 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
CARNMT1	NUP42	psi-mi:“MI:0914”(association)	0.640
GPR37L1	PRCP	psi-mi:“MI:0570”(protein cleavage)	0.560
PRCP	GPR37L1	psi-mi:“MI:0407”(direct interaction)	0.560
HNRNPH2	PLOD2	psi-mi:“MI:0914”(association)	0.530
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
FAM81A	PCCA	psi-mi:“MI:0914”(association)	0.530
AGT	PRCP	psi-mi:“MI:0570”(protein cleavage)	0.440
VDR	PRCP	psi-mi:“MI:0915”(physical association)	0.370
Ppp2r1a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Smad3		psi-mi:“MI:0914”(association)	0.350
Fus	DDX3X	psi-mi:“MI:0914”(association)	0.350
POC5	PDHX	psi-mi:“MI:0914”(association)	0.350
CCP110	A2ML1	psi-mi:“MI:0914”(association)	0.350
FAM133A	C1orf226	psi-mi:“MI:0914”(association)	0.350
IGF2R	MANBA	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
FAM133A	DNM1L	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
BRICD5	PODXL	psi-mi:“MI:0914”(association)	0.350

BioGRID (70): PRCP (Affinity Capture-MS), PRCP (Affinity Capture-MS), PRCP (Affinity Capture-MS), PRCP (Co-fractionation), PRCP (Co-fractionation), PRCP (Co-fractionation), PRCP (Co-fractionation), PRCP (Co-fractionation), PRCP (Co-fractionation), PRCP (Co-fractionation), PRCP (Affinity Capture-MS), PRCP (Affinity Capture-MS), PRCP (Affinity Capture-MS), PRCP (Affinity Capture-MS), PRCP (Affinity Capture-MS)

ESM2 similar proteins: A0A0C3VJP4, A0A0D3QS97, A8QCV4, B9DFR3, C0HLA0, E7F0Z8, F4I107, F4I839, O04084, O23364, O80731, P42785, P45582, P48980, Q0INM3, Q0IZZ8, Q0WRX3, Q2TA14, Q4PSY2, Q5RBU7, Q66GM8, Q6DBP4, Q7TMR0, Q84JS1, Q84LR6, Q84W27, Q84WF0, Q8L9Y0, Q8S8K6, Q93Z24, Q940J8, Q949Q7, Q9FH06, Q9FH82, Q9FZI8, Q9LEY1, Q9LJX8, Q9LSM9, Q9LZV3, Q9MAR8

Diamond homologs: D4AYS6, P34610, P34676, P42785, Q1PF50, Q2TA14, Q5RBU7, Q7TMR0, Q9EPB1, Q9ET22, Q9NQE7, Q9QXE5, Q9UHL4, W7DQR8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRCP	“down-regulates activity”	POMC

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2752 predictions. Top by Δscore:

Variant	Effect	Δscore
11:82825118:CATTG:C	acceptor_gain	1.0000
11:82825119:ATTG:A	acceptor_gain	1.0000
11:82825120:TTG:T	acceptor_gain	1.0000
11:82825121:TG:T	acceptor_gain	1.0000
11:82825123:C:CA	acceptor_loss	1.0000
11:82825123:C:CC	acceptor_gain	1.0000
11:82825124:T:A	acceptor_loss	1.0000
11:82825126:CAAG:C	acceptor_gain	1.0000
11:82825129:G:C	acceptor_gain	1.0000
11:82825129:G:GC	acceptor_gain	1.0000
11:82839434:T:TC	acceptor_gain	1.0000
11:82849908:GCTTA:G	donor_loss	1.0000
11:82849909:CTTA:C	donor_loss	1.0000
11:82849910:TTAC:T	donor_loss	1.0000
11:82849911:TACC:T	donor_loss	1.0000
11:82849912:A:AC	donor_gain	1.0000
11:82849912:A:AG	donor_loss	1.0000
11:82849913:C:A	donor_loss	1.0000
11:82849913:C:CC	donor_gain	1.0000
11:82850070:CT:C	acceptor_gain	1.0000
11:82850318:ACTT:A	donor_loss	1.0000
11:82850321:T:TG	donor_loss	1.0000
11:82850322:A:AC	donor_gain	1.0000
11:82850322:A:C	donor_loss	1.0000
11:82850322:AC:A	donor_gain	1.0000
11:82850323:C:CC	donor_gain	1.0000
11:82850323:CC:C	donor_gain	1.0000
11:82850323:CCCAA:C	donor_gain	1.0000
11:82850504:TC:T	acceptor_gain	1.0000
11:82850505:CC:C	acceptor_gain	1.0000

AlphaMissense

3254 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:82824976:C:G	R474P	0.992
11:82825122:G:C	S425R	0.992
11:82825122:G:T	S425R	0.992
11:82838388:T:G	S425R	0.992
11:82850382:A:G	S179P	0.991
11:82860082:A:C	F68L	0.991
11:82860082:A:T	F68L	0.991
11:82860084:A:G	F68L	0.991
11:82839417:G:C	C310W	0.990
11:82839418:C:G	C310S	0.990
11:82839418:C:T	C310Y	0.990
11:82839419:A:T	C310S	0.990
11:82849123:A:G	W283R	0.990
11:82849123:A:T	W283R	0.990
11:82853231:A:C	F119L	0.990
11:82853231:A:T	F119L	0.990
11:82853233:A:G	F119L	0.990
11:82839419:A:G	C310R	0.989
11:82850460:C:G	D153H	0.989
11:82850465:A:G	L151P	0.989
11:82850070:C:G	A199P	0.988
11:82850350:C:A	R189S	0.988
11:82850350:C:G	R189S	0.988
11:82850463:C:G	A152P	0.987
11:82853229:G:T	A120D	0.986
11:82860068:A:G	L73P	0.986
11:82824977:G:T	R474S	0.985
11:82825018:C:G	R460P	0.985
11:82825021:A:G	L459P	0.985
11:82838390:A:G	F424S	0.985

dbSNP variants (sampled 300 via entrez): RS1000074086 (11:82893324 C>A), RS1000087398 (11:82869428 G>A,T), RS1000099422 (11:82830767 T>C), RS1000222440 (11:82834226 A>G), RS1000224229 (11:82869095 C>G), RS1000257899 (11:82827537 G>C), RS1000303364 (11:82833937 GC>G), RS1000304860 (11:82870073 T>A), RS1000358588 (11:82870256 G>T), RS1000445075 (11:82881554 G>A), RS1000472822 (11:82863668 T>G), RS1000497240 (11:82847133 T>C), RS1000509350 (11:82847203 A>G), RS1000513362 (11:82851777 G>A), RS1000530005 (11:82840319 A>C)

Disease associations

OMIM: gene MIM:176785 | 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
GCST002826_16	Urate levels (BMI interaction)	1.000000e-06
GCST003209_13	Colorectal or endometrial cancer	2.000000e-06
GCST006585_2250	Blood protein levels	2.000000e-09
GCST009391_1836	Metabolite levels	7.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0004230	endometrial neoplasm
EFO:0010412	triacylglycerol 50:5 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2335 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 42,377 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL73234	CARBETAPENTANE	4	7,316
CHEMBL275528	PHENCYCLIDINE	2	25,537
CHEMBL279676	TENOCYCLIDINE	2	612
CHEMBL284237	DIZOCILPINE	2	5,015
CHEMBL61946	CARAMIPHEN	2	3,897

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2229437	Efficacy	3	benazepril	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2229437	PRCP	3	3.50	1	benazepril

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S28: Lysosomal Pro-Xaa carboxypeptidase

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 35 [PMID: 24157366]	Inhibition	10.1	pIC50

Binding affinities (BindingDB)

76 measured of 87 human assays (87 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
methyl 3-[4-[3-(4-fluorophenyl)-1-pyrimidin-2-ylpyrazol-5-yl]piperidin-1-yl]-2-phenylpropanoate	IC50	0.035 nM	US-9365539: Prolylcarboxypeptidase inhibitors
2-[3-(4-chlorophenyl)-5-[1-(2-phenylethyl)piperidin-4-yl]pyrazol-1-yl]pyrimidine	IC50	0.051 nM	US-9365539: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-(2-fluoro-4-pyridinyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	0.16 nM	US-8669252: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-fluorophenyl)-(2-fluoro-4-pyridinyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	0.18 nM	US-8669252: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-pyridin-4-ylmethyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	0.18 nM	US-8669252: Prolylcarboxypeptidase inhibitors
2-[4-[3-(4-chlorophenyl)-1-pyrimidin-2-ylpyrazol-5-yl]piperidin-1-yl]-1-phenylethanol	IC50	0.31 nM	US-9365539: Prolylcarboxypeptidase inhibitors
5-(4-chloro-2-pyridinyl)-1’-[2-[4-(trifluoromethoxy)phenyl]propan-2-yl]spiro[5H-furo[3,4-b]pyridine-7,4’-piperidine]	IC50	0.49 nM	US-8785634: Spiropiperidine prolylcarboxypeptidase inhibitors
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(3-chloro-4-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	IC50	0.5 nM	US-8569299: Prolylcarboxypeptidase inhibitors
3-[4-[3-(4-fluorophenyl)-1-pyrimidin-2-ylpyrazol-5-yl]piperidin-1-yl]-2-phenylpropanoic acid	IC50	0.51 nM	US-9365539: Prolylcarboxypeptidase inhibitors
1-(4-chloro-2-pyridinyl)-1’-[[4-(trifluoromethoxy)phenyl]methyl]spiro[1H-2-benzofuran-3,4’-piperidine]	IC50	0.66 nM	US-8785634: Spiropiperidine prolylcarboxypeptidase inhibitors
2-[2-(4-chlorophenyl)-5-[1-(2-phenylethyl)piperidin-4-yl]-1H-imidazol-4-yl]pyrimidine	IC50	0.7 nM	US-9006268: Prolylcarboxypeptidase inhibitors
2-(4-fluorophenyl)-5-[1-(2-phenylethyl)piperidin-4-yl]-4-pyrimidin-2-yl-1,3-oxazole	IC50	0.78 nM	US-9006268: Prolylcarboxypeptidase inhibitors
[4-[2-(3,4-dichlorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	IC50	0.8 nM	US-8569299: Prolylcarboxypeptidase inhibitors
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chloro-3-methylphenyl)-5-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]methanone	IC50	0.9 nM	US-8569299: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-(5-fluoro-2-pyridinyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	0.95 nM	US-8669252: Prolylcarboxypeptidase inhibitors
1-[4-[3-(4-fluorophenyl)-1-pyrimidin-2-ylpyrazol-5-yl]piperidin-1-yl]-2-[2-(trifluoromethyl)phenyl]ethanone	IC50	1.28 nM	US-9365539: Prolylcarboxypeptidase inhibitors
1-(4-chloro-1-oxidopyridin-1-ium-2-yl)-1’-[[4-(trifluoromethoxy)phenyl]methyl]spiro[1H-2-benzofuran-3,4’-piperidine]	IC50	1.3 nM	US-8785634: Spiropiperidine prolylcarboxypeptidase inhibitors
(1R,2R,4R)-N-[(4-fluorophenyl)-pyridin-4-ylmethyl]-4-morpholin-4-yl-2-phenylcyclohexane-1-carboxamide	IC50	1.4 nM	US-8669252: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-N-[bis(4-fluorophenyl)methyl]-2-(4-bromophenyl)-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	1.4 nM	US-8669252: Prolylcarboxypeptidase inhibitors
5-(3,5-dichlorophenyl)-1’-[4-(trifluoromethoxy)phenyl]sulfonylspiro[5H-furo[3,4-b]pyridine-7,4’-piperidine]	IC50	1.6 nM	US-8785634: Spiropiperidine prolylcarboxypeptidase inhibitors
(1R,2R,4R)-N-[bis(4-fluorophenyl)methyl]-2-(2-fluorophenyl)-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	1.7 nM	US-8669252: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-2-(4-bromophenyl)-N-[1-(4-chlorophenyl)-2,2,2-trifluoroethyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	2.1 nM	US-8669252: Prolylcarboxypeptidase inhibitors
2-(4-fluorophenyl)-5-[1-(2-phenylethyl)piperidin-4-yl]-4-pyridin-2-yl-1,3-thiazole	IC50	2.4 nM	US-9006268: Prolylcarboxypeptidase inhibitors
2-[3-(4-fluorophenyl)-5-[1-[(2R)-2-methoxy-2-phenylethyl]piperidin-4-yl]-1,2,4-triazol-1-yl]pyrimidine	IC50	2.58 nM	US-9365539: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-N-[bis(4-chlorophenyl)methyl]-2-(4-bromophenyl)-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	2.6 nM	US-8669252: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-(3-chloro-4-pyridinyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	2.7 nM	US-8669252: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-N-[bis(4-fluorophenyl)methyl]-2-(4-cyanophenyl)-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	2.9 nM	US-8669252: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-(2-methyl-4-pyridinyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	3.1 nM	US-8669252: Prolylcarboxypeptidase inhibitors
2-[2-phenyl-5-[(3R,6S)-6-phenyl-1-(2-phenylethyl)piperidin-3-yl]-1H-imidazol-4-yl]pyridine	IC50	4.4 nM	US-9006268: Prolylcarboxypeptidase inhibitors
5-(3,5-dichlorophenyl)-1’-[[4-(trifluoromethoxy)phenyl]methyl]spiro[5H-furo[3,4-b]pyridine-7,4’-piperidine]	IC50	5.2 nM	US-8785634: Spiropiperidine prolylcarboxypeptidase inhibitors
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-(4-cyanophenyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	IC50	5.4 nM	US-8669252: Prolylcarboxypeptidase inhibitors
[4-[2-(4-chloro-3-methylphenyl)-5-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-[methyl(3,3,3-trifluoropropyl)amino]cyclopentyl]methanone	IC50	5.9 nM	US-8569299: Prolylcarboxypeptidase inhibitors
[4-[2-(3-chloro-4-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-methyl-4-morpholin-4-ylcyclopentyl]methanone	IC50	6.3 nM	US-8569299: Prolylcarboxypeptidase inhibitors
1-pyridin-2-yl-1’-[4-(trifluoromethoxy)phenyl]sulfonylspiro[1H-2-benzofuran-3,4’-piperidine]	IC50	7.8 nM	US-8785634: Spiropiperidine prolylcarboxypeptidase inhibitors
2-[2-(4-chlorophenyl)-5-[(3R,6R)-6-phenylpiperidin-3-yl]-1H-imidazol-4-yl]pyrimidine	IC50	8 nM	US-9006268: Prolylcarboxypeptidase inhibitors
[(1R,2R,4S)-4-amino-2-(2,4-difluorophenyl)-4-methylcyclopentyl]-[4-[2-(3-chloro-4-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	IC50	8.1 nM	US-8569299: Prolylcarboxypeptidase inhibitors
[4-[2-(4-chloro-3-methylphenyl)-5-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]-[(1R,2R)-2-(2,4-difluorophenyl)-4-(3,3-difluoropyrrolidin-1-yl)cyclopentyl]methanone	IC50	9.8 nM	US-8569299: Prolylcarboxypeptidase inhibitors
[4-[2-(3-chloro-4-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]-[(3S,4R)-4-(2,4-difluorophenyl)pyrrolidin-3-yl]methanone	IC50	10.7 nM	US-8569299: Prolylcarboxypeptidase inhibitors
2-phenyl-5-[(3S,6R)-6-phenylpiperidin-3-yl]-4-pyridin-4-yl-1,3-oxazole	IC50	12 nM	US-9006268: Prolylcarboxypeptidase inhibitors
[4-[2-(4-chloro-3-methylphenyl)-5-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(methylamino)cyclopentyl]methanone	IC50	13.9 nM	US-8569299: Prolylcarboxypeptidase inhibitors
(1R,2R,4R)-N-[bis(4-fluorophenyl)methyl]-2-(4-bromophenyl)-4-[[2-(diethylamino)acetyl]amino]cyclohexane-1-carboxamide	IC50	17 nM	US-8669252: Prolylcarboxypeptidase inhibitors
[(1S,2S,4S)-4-amino-2-(2,4-difluorophenyl)-4-methylcyclopentyl]-[4-[2-(3-chloro-4-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	IC50	18 nM	US-8569299: Prolylcarboxypeptidase inhibitors
4-[3-(4-chlorophenyl)-1-phenylpyrazol-5-yl]-1-(1-methylsulfonylpyrrolidin-3-yl)piperidine	IC50	21.1 nM	US-9365539: Prolylcarboxypeptidase inhibitors
6-[5-(4-fluorophenyl)-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]-3-(2-phenylethyl)-3-azabicyclo[3.1.0]hexane	IC50	28.6 nM	US-9365539: Prolylcarboxypeptidase inhibitors
4-[3-(4-chlorophenyl)-1-ethylpyrazol-5-yl]-1-(2-phenylethyl)piperidine	IC50	31.8 nM	US-9365539: Prolylcarboxypeptidase inhibitors
2-(4-chlorophenyl)-5-[1-(2-phenylethyl)piperidin-4-yl]-4-pyridin-2-yl-1,3-thiazole	IC50	32 nM	US-9006268: Prolylcarboxypeptidase inhibitors
2,4-diphenyl-5-[1-(2-phenylethyl)piperidin-4-yl]-1,3-thiazole	IC50	35 nM	US-9006268: Prolylcarboxypeptidase inhibitors
4-[5-(4-chlorophenyl)-3-[1-(2-phenylethyl)piperidin-4-yl]pyrazol-1-yl]pyrimidine	IC50	38.4 nM	US-9365539: Prolylcarboxypeptidase inhibitors
2-[5-(3,5-dichlorophenyl)spiro[5H-furo[3,4-b]pyridine-7,4’-piperidine]-1’-yl]-2-[4-(trifluoromethoxy)phenyl]acetic acid	IC50	65 nM	US-8785634: Spiropiperidine prolylcarboxypeptidase inhibitors
4-[[6-[4-[3-(4-chlorophenyl)-1-pyrimidin-2-ylpyrazol-5-yl]piperidin-1-yl]-3-pyridinyl]sulfonyl]morpholine	IC50	80.2 nM	US-9365539: Prolylcarboxypeptidase inhibitors

ChEMBL bioactivities

418 potent at pChembl≥5 of 450 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.46	IC50	0.035	nM	CHEMBL3910523
10.29	IC50	0.051	nM	CHEMBL3919329
10.10	IC50	0.079	nM	CHEMBL3086040
9.80	IC50	0.16	nM	CHEMBL3086040
9.77	IC50	0.17	nM	CHEMBL1950440
9.74	IC50	0.18	nM	CHEMBL3086037
9.74	IC50	0.18	nM	CHEMBL3652599
9.70	IC50	0.2	nM	CHEMBL2022787
9.70	IC50	0.2	nM	CHEMBL2022793
9.70	IC50	0.2	nM	CHEMBL2023210
9.52	IC50	0.3	nM	CHEMBL2023202
9.52	IC50	0.3	nM	CHEMBL1938522
9.51	IC50	0.31	nM	CHEMBL3901469
9.43	IC50	0.37	nM	CHEMBL1950444
9.40	IC50	0.4	nM	CHEMBL2022794
9.40	IC50	0.4	nM	CHEMBL2031595
9.36	IC50	0.44	nM	CHEMBL1951465
9.31	IC50	0.49	nM	CHEMBL1951476
9.30	IC50	0.5	nM	CHEMBL2023207
9.30	IC50	0.5	nM	CHEMBL2023209
9.29	IC50	0.51	nM	CHEMBL3932961
9.22	IC50	0.6	nM	CHEMBL3085780
9.22	IC50	0.6	nM	CHEMBL1938510
9.18	IC50	0.66	nM	CHEMBL3086036
9.18	IC50	0.66	nM	CHEMBL1951465
9.15	IC50	0.7	nM	CHEMBL2022786
9.15	IC50	0.7	nM	CHEMBL3677679
9.14	IC50	0.73	nM	CHEMBL1951474
9.13	IC50	0.74	nM	CHEMBL1950439
9.11	IC50	0.78	nM	CHEMBL3677678
9.11	IC50	0.78	nM	CHEMBL1951478
9.10	IC50	0.8	nM	CHEMBL2031596
9.10	IC50	0.8	nM	CHEMBL3655577
9.05	IC50	0.9	nM	CHEMBL2024198
9.05	IC50	0.9	nM	CHEMBL2031590
9.05	IC50	0.9	nM	CHEMBL2031588
9.05	IC50	0.9	nM	CHEMBL1938502
9.02	IC50	0.95	nM	CHEMBL3086041
9.00	IC50	1	nM	CHEMBL2022785
9.00	IC50	1	nM	CHEMBL2022789
9.00	IC50	1	nM	CHEMBL2023211
9.00	IC50	1	nM	CHEMBL1259194
9.00	IC50	1	nM	CHEMBL1950443
9.00	IC50	1	nM	CHEMBL1951470
8.96	IC50	1.1	nM	CHEMBL2031580
8.96	IC50	1.1	nM	CHEMBL1684306
8.92	IC50	1.2	nM	CHEMBL3086029
8.92	IC50	1.2	nM	CHEMBL1938523
8.92	IC50	1.2	nM	CHEMBL1951468
8.89	IC50	1.3	nM	CHEMBL1951468

PubChem BioAssay actives

362 with measured affinity, of 453 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
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-(2-fluoro-4-pyridinyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	1055050: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by fluorescence assay	ic50	0.0001	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(3-chloro-4-fluorophenyl)pyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0002	uM
(2S,3S)-2-[(2-amino-2-methylpropanoyl)amino]-N-[(1S)-1-(5,6-dichloro-1H-benzimidazol-2-yl)ethyl]-3-[4-(2,2,2-trifluoroethoxy)phenyl]butanamide	647767: Inhibition of human recombinant PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate for 30 mins by continuous fluorimetric assay	ic50	0.0002	uM
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-pyridin-4-ylmethyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	1055050: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by fluorescence assay	ic50	0.0002	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(3,4-dichlorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0002	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(3-chloro-4-methylphenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0002	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(2,5-dichlorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0003	uM
N-[(4-chlorophenyl)-pyridin-4-ylmethyl]-3-(4-phenylpiperidin-1-yl)propanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0003	uM
1-(4-chloro-2-pyridinyl)-1’-[[4-(trifluoromethoxy)phenyl]methyl]spiro[1H-2-benzofuran-3,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0004	uM
(2S,3S)-2-[(2-amino-2-methylpropanoyl)amino]-N-[(1S)-1-(5,6-dichloro-1H-benzimidazol-2-yl)ethyl]-3-(4-phenylphenyl)butanamide	647767: Inhibition of human recombinant PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate for 30 mins by continuous fluorimetric assay	ic50	0.0004	uM
[4-[2-(3-chloro-4-fluorophenyl)pyrazol-3-yl]piperidin-1-yl]-[(1S,2S,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	661170: Inhibition of human PrCP	ic50	0.0004	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(2,4-dichlorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0004	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(3-chloro-4-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0005	uM
5-(4-chloro-2-pyridinyl)-1’-[2-[4-(trifluoromethoxy)phenyl]propan-2-yl]spiro[5H-furo[3,4-b]pyridine-7,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0005	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chloro-2-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0005	uM
(2S,3S)-2-[(2-amino-2-methylpropanoyl)amino]-N-[(4-chlorophenyl)-pyridin-4-ylmethyl]-3-(4-phenylphenyl)butanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0006	uM
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-fluorophenyl)-pyridin-4-ylmethyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	1055050: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by fluorescence assay	ic50	0.0006	uM
(1R,2R,4R)-N-[bis(4-fluorophenyl)methyl]-2-(4-bromophenyl)-4-morpholin-4-ylcyclohexane-1-carboxamide	1055050: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by fluorescence assay	ic50	0.0007	uM
(2S,3S)-N-[(1S)-1-(5,6-dichloro-1H-benzimidazol-2-yl)ethyl]-2-[(2-hydroxy-2-methylpropanoyl)amino]-3-[4-(2,2,2-trifluoroethoxy)phenyl]butanamide	647767: Inhibition of human recombinant PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate for 30 mins by continuous fluorimetric assay	ic50	0.0007	uM
1-(3,5-dichlorophenyl)-1’-[1-(5-fluoro-2-pyridinyl)ethyl]spiro[1H-2-benzofuran-3,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0007	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chloro-2-methylphenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0007	uM
1-(4-chloro-1-oxidopyridin-1-ium-2-yl)-1’-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]spiro[1H-2-benzofuran-3,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0008	uM
[4-[2-(3-chloro-4-fluorophenyl)pyrazol-3-yl]piperidin-1-yl]-[(1S,2S,4R)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	661170: Inhibition of human PrCP	ic50	0.0008	uM
(2S,3S)-2-[(2-amino-2-methylpropanoyl)amino]-N-[(1S)-1-(4-chlorophenyl)ethyl]-3-(4-phenylphenyl)butanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0009	uM
(1R,2R,4R)-2-(4-bromophenyl)-N-[(4-chlorophenyl)-(5-fluoro-2-pyridinyl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide	1055050: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by fluorescence assay	ic50	0.0009	uM
[4-[2-(2,5-dichlorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	661170: Inhibition of human PrCP	ic50	0.0009	uM
[4-[2-(3-chloro-4-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	661170: Inhibition of human PrCP	ic50	0.0009	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chloro-3-methylphenyl)-5-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0009	uM
2-amino-N-[(2S,3S)-1-[(2S)-2-(5,6-dichloro-1H-benzimidazol-2-yl)pyrrolidin-1-yl]-1-oxo-3-(4-phenylphenyl)butan-2-yl]-2-methylpropanamide	517810: Inhibition of human PrCP by FRET	ic50	0.0010	uM
(2S)-2-[(2-amino-2-methylpropyl)amino]-N-[(1S)-1-(5,6-dichloro-1H-benzimidazol-2-yl)ethyl]-3-(4-phenylphenyl)propanamide	647767: Inhibition of human recombinant PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate for 30 mins by continuous fluorimetric assay	ic50	0.0010	uM
1-(4-chloro-2-pyridinyl)-1’-[1-(5-fluoro-2-pyridinyl)ethyl]spiro[1H-2-benzofuran-3,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0010	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(5-chloro-2-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0010	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chloro-3-methylphenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0010	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chlorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0010	uM
1-[(2S)-2-(5,6-dichloro-1H-benzimidazol-2-yl)pyrrolidin-1-yl]-3-[4-(1-methyl-5-pyridin-4-ylpyrazol-3-yl)piperidin-1-yl]propan-1-one	647242: Inhibition of human recombinant PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate after 30 mins by fluorescence analysis	ic50	0.0011	uM
[4-[2-(4-chloro-3-methylphenyl)-5-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	661170: Inhibition of human PrCP	ic50	0.0011	uM
1-(4-chloro-1-oxidopyridin-1-ium-2-yl)-1’-[[4-(trifluoromethoxy)phenyl]methyl]spiro[1H-2-benzofuran-3,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0012	uM
N-[1-(4-chlorophenyl)-1-pyridin-4-ylethyl]-3-(4-phenylpiperidin-1-yl)propanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0012	uM
[(1R,2R,4R)-2-(4-bromophenyl)-4-morpholin-4-ylcyclohexyl]-(3,3-diphenylazetidin-1-yl)methanone	1055050: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by fluorescence assay	ic50	0.0012	uM
N-[1-(4-chlorophenyl)-2,2,2-trifluoroethyl]-3-(4-phenylpiperidin-1-yl)propanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0014	uM
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]-[4-[2-(4-chloro-3-fluorophenyl)-5-methylpyrazol-3-yl]piperidin-1-yl]methanone	658207: Inhibition of human PrCP	ic50	0.0014	uM
N-[(1S)-1-(4-chlorophenyl)-2-methylpropyl]-3-(4-phenylpiperidin-1-yl)propanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0015	uM
5-(3,5-dichlorophenyl)-1’-[4-(trifluoromethoxy)phenyl]sulfonylspiro[5H-furo[3,4-b]pyridine-7,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0016	uM
[4-[2-(2,5-dichlorophenyl)-5-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]-[(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone	661170: Inhibition of human PrCP	ic50	0.0016	uM
1-[(2S)-2-(5,6-dichloro-1H-benzimidazol-2-yl)pyrrolidin-1-yl]-3-[4-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]propan-1-one	578622: Inhibition of human PrCP	ic50	0.0017	uM
(2S,3S)-2-[(2-amino-2-methylpropanoyl)amino]-N-[1-(4-chlorophenyl)-2,2,2-trifluoroethyl]-3-(4-phenylphenyl)butanamide	642001: Inhibition of recombinant human PrCP using Mca-Ala-Pro-Lys(Dnp)-OH as substrate measured for 30 mins by continuous fluorometric assay	ic50	0.0017	uM
5-(3,5-dichlorophenyl)-1’-[1-(5-fluoro-2-pyridinyl)ethyl]spiro[5H-furo[3,4-b]pyridine-7,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0019	uM
1-(3,5-dichlorophenyl)-1’-[[4-(trifluoromethoxy)phenyl]methyl]spiro[1H-2-benzofuran-3,4’-piperidine]	645433: Inhibition of human PrCP	ic50	0.0019	uM
2-amino-N-[(2S)-1-[(2S)-2-(5-tert-butyl-1H-imidazol-2-yl)pyrrolidin-1-yl]-1-oxo-3-(4-phenylphenyl)propan-2-yl]-2-methylpropanamide	517812: Inhibition of human PrCP by FRET in presence of 1% mouse serum albumin	ic50	0.0020	uM
N-[(2S,3S)-1-[(2S)-2-(5,6-dichloro-1H-benzimidazol-2-yl)pyrrolidin-1-yl]-3-[4-(4-fluorophenyl)phenyl]-1-oxobutan-2-yl]-2-hydroxy-2-methylpropanamide	517810: Inhibition of human PrCP by FRET	ic50	0.0020	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases methylation, decreases expression	3
trichostatin A	affects cotreatment, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
afimoxifene	decreases response to substance	1
sodium arsenite	decreases expression, increases abundance	1
tetrabromobisphenol A	decreases expression	1
ochratoxin A	increases expression	1
benazepril	affects response to substance	1
arsenic disulfide	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Arsenic	increases abundance, decreases expression	1
Cisplatin	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Ozone	increases abundance, increases expression	1

ChEMBL screening assays

46 unique, capped per target: 46 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1110131	Binding	Inhibition of carboxypeptidase P	Inhibitors of prolyl oligopeptidases for the therapy of human diseases: defining diseases and inhibitors. — J Med Chem

Clinical trials (associated diseases)

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