DPEP1

Summary

DPEP1 (dipeptidase 1, HGNC:3002) is a protein-coding gene on chromosome 16q24.3, encoding Dipeptidase 1 (P16444). Hydrolyzes a wide range of dipeptides including the conversion of leukotriene D4 to leukotriene E4.

The protein encoded by this gene is a kidney membrane enzyme involved in the metabolism of glutathione and other similar proteins by dipeptide hydrolysis. The encoded protein is known to regulate leukotriene activity by catalyzing the conversion of leukotriene D4 to leukotriene E4. This protein uses zinc as a cofactor and acts as a disulfide-linked homodimer.

Source: NCBI Gene 1800 — RefSeq curated summary.

At a glance

• GWAS associations: 40
• Clinical variants (ClinVar): 56 total
• Druggable target: yes
• MANE Select transcript: NM_001389466

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3002
Approved symbol	DPEP1
Name	dipeptidase 1
Location	16q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000015413
Ensembl biotype	protein_coding
OMIM	179780
Entrez	1800

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 4 retained_intron

ENST00000261615, ENST00000393092, ENST00000421184, ENST00000561484, ENST00000564281, ENST00000564645, ENST00000565249, ENST00000568281, ENST00000570029, ENST00000690203, ENST00000876490, ENST00000876491, ENST00000876492, ENST00000876493, ENST00000936228, ENST00000936229, ENST00000936230, ENST00000936231, ENST00000936232, ENST00000936233, ENST00000936234, ENST00000946841

RefSeq mRNA: 8 — MANE Select: NM_001389466 NM_001128141, NM_001389466, NM_001389467, NM_001389468, NM_001389469, NM_001389470, NM_001389471, NM_004413

CCDS: CCDS10982

Canonical transcript exons

ENST00000690203 — 11 exons

Exon	Start	End
ENSE00001292673	89637468	89637552
ENSE00001305962	89637632	89637707
ENSE00003461661	89630305	89630514
ENSE00003489016	89637836	89637971
ENSE00003493384	89636866	89636935
ENSE00003559127	89636533	89636683
ENSE00003576057	89637204	89637380
ENSE00003587007	89636264	89636396
ENSE00003639751	89635908	89636040
ENSE00003928060	89638052	89638433
ENSE00003937322	89613642	89613719

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 99.05.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3569 / max 918.2773, expressed in 218 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155619	0.9078	148
155627	0.8778	22
155624	0.1815	38
155618	0.1316	56
155622	0.0862	25
208012	0.0555	24
155623	0.0456	16
155616	0.0252	12
155617	0.0234	12
155628	0.0224	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.05	gold quality
body of pancreas	UBERON:0001150	98.82	gold quality
adult mammalian kidney	UBERON:0000082	96.41	gold quality
nephron tubule	UBERON:0001231	94.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.82	gold quality
left testis	UBERON:0004533	94.44	gold quality
right testis	UBERON:0004534	93.90	gold quality
kidney epithelium	UBERON:0004819	93.84	gold quality
duodenum	UBERON:0002114	93.81	gold quality
jejunal mucosa	UBERON:0000399	93.46	gold quality
small intestine	UBERON:0002108	93.14	gold quality
testis	UBERON:0000473	92.00	gold quality
renal glomerulus	UBERON:0000074	91.94	gold quality
metanephric glomerulus	UBERON:0004736	91.89	gold quality
adult organism	UBERON:0007023	91.32	gold quality
kidney	UBERON:0002113	91.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.30	gold quality
pancreas	UBERON:0001264	89.40	gold quality
cortex of kidney	UBERON:0001225	86.80	gold quality
metanephros	UBERON:0000081	85.21	gold quality
metanephros cortex	UBERON:0010533	84.07	gold quality
renal medulla	UBERON:0000362	83.65	gold quality
jejunum	UBERON:0002115	82.51	gold quality
oocyte	CL:0000023	82.21	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.78	gold quality
type B pancreatic cell	CL:0000169	76.68	gold quality
olfactory bulb	UBERON:0002264	76.55	gold quality
ganglionic eminence	UBERON:0004023	75.18	gold quality
gall bladder	UBERON:0002110	74.98	gold quality
vena cava	UBERON:0004087	73.78	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	3279.11
E-GEOD-134144	yes	1744.97
E-GEOD-124263	yes	1369.88
E-MTAB-8410	yes	280.91
E-MTAB-5061	yes	274.17
E-CURD-119	yes	49.01
E-GEOD-81547	yes	24.00
E-ANND-3	yes	21.20
E-CURD-135	no	541.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, CTNNB1, DNMT1, MBD2, NR6A1, TFCP2

miRNA regulators (miRDB)

7 targeting DPEP1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-6841-3P	98.08	66.54	604
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-6749-5P	89.28	58.87	75

Literature-anchored findings (GeneRIF, showing 15)

• Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis (PMID:12144777)
• DPEP1 has a role in colorectal carcinoma (PMID:15145522)
• CPS1, MUT, NOX4, and DPEP1 is associated with plasma homocysteine in healthy Women. (PMID:20031578)
• DPEP1 is expressed in the early stages of colon carcinogenesis and affects cancer cell invasiveness. (PMID:20824289)
• we identified a novel immunohistochemical marker, dipeptidase 1, to distinguish primary mucinous ovarian cancers from ovarian metastasis of colorectal cancers. (PMID:21076463)
• DPEP1 plays a role in pancreatic cancer aggressiveness. (PMID:22363658)
• Dipeptidase 1 has been identified as an excellent marker of high-grade IEN and CRC, and may thus be applied for screening of early neoplastic lesions and for prognostic stratification. (PMID:23839495)
• In this study, we present an analysis of Neanderthal introgression at the dipeptidase 1 gene, DPEP1. (PMID:26392408)
• The results suggest that DPEP1 promotes cancer metastasis by regulating E-cadherin plasticity and that it might be a potential therapeutic target for preventing the progression of colon cancer. (PMID:26824987)
• DPEP1 is a direct target of miR-193a-5p and promotes hepatoblastoma progression by PI3K/Akt/mTOR pathway. (PMID:31541079)
• DPEP1 expression promotes proliferation and survival of leukaemia cells and correlates with relapse in adults with common B cell acute lymphoblastic leukaemia. (PMID:32068254)
• The relationship between common variants in the DPEP1 gene and the susceptibility and clinical severity of osteoarthritis. (PMID:34291562)
• A single genetic locus controls both expression of DPEP1/CHMP1A and kidney disease development via ferroptosis. (PMID:34426578)
• DPEP1 promotes drug resistance in colon cancer cells by forming a positive feedback loop with ASCL2. (PMID:35670012)
• Dipeptidase 1 promotes ferroptosis in renal tubular epithelial cells in diabetic nephropathy via inhibition of the GSH/GPX4 axis. (PMID:38626544)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dpep1	ENSDARG00000068181
mus_musculus	Dpep1	ENSMUSG00000019278
rattus_norvegicus	Dpep1	ENSRNOG00000015880
drosophila_melanogaster	CG6154	FBGN0039420
drosophila_melanogaster	CG44837	FBGN0266100

Paralogs (2): DPEP3 (ENSG00000141096), DPEP2 (ENSG00000167261)

Protein

Protein identifiers

Dipeptidase 1 — P16444 (reviewed: P16444)

Alternative names: Beta-lactamase, Dehydropeptidase-I, Microsomal dipeptidase, Renal dipeptidase

All UniProt accessions (4): P16444, A0A140VJI3, H3BP43, H3BQS5

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes a wide range of dipeptides including the conversion of leukotriene D4 to leukotriene E4. Hydrolyzes cystinyl-bis-glycine (cys-bis-gly) formed during glutathione degradation. Also possesses beta lactamase activity and can hydrolyze the beta-lactam antibiotic imipenem. Independently of its dipeptidase activity, acts as an adhesion receptor for neutrophil recruitment from bloodstream into inflamed lungs and liver.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Apical cell membrane. Cell projection. Microvillus membrane.

Tissue specificity. Expressed in lung and kidneys.

Activity regulation. Inhibited by L-penicillamine. Beta-lactamase activity is inhibited by cilastatin.

Cofactor. Binds 2 Zn(2+) ion per monomer.

Induction. Up-regulated in n colorectal cancers.

Similarity. Belongs to the metallo-dependent hydrolases superfamily. Peptidase M19 family.

RefSeq proteins (8): NP_001121613, NP_001376395, NP_001376396, NP_001376397, NP_001376398, NP_001376399, NP_001376400, NP_004404 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000180	Dipep_AS	Active_site
IPR008257	Pept_M19	Family
IPR032466	Metal_Hydrolase	Homologous_superfamily

Pfam: PF01244

Enzyme classification (BRENDA):

• EC 3.4.13.19 — membrane dipeptidase (BRENDA: 12 organisms, 121 substrates, 55 inhibitors, 49 Km, 24 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
GLY-D-PHE	0.77–12.5	4
L-ARG-L-ASP	1.8–8.8	4
L-CYSTINYL-BIS-GLY	0.45–2.5	3
L-LEU-L-LEU	0.056–1.4	3
GLYCYLDEHYDROPHENYLALANINE	0.102–1	2
LEUKOTRIENE D4	0.005–0.01	2
BETA-LACTAM	0.111	1
GLY-L-LEU	1.22	1
GLY-L-PHE	0.99	1
GLY-L-TRP	2.03	1
GLY-L-VAL	11	1
GLY-LEU	0.79	1
L-ALA-D-ALA	4.4	1
L-ALA-GLY	0.8	1
L-ALA-L-ASP	13.8	1

Catalyzed reactions (Rhea), 5 shown:

• a beta-lactam + H2O = a substituted beta-amino acid (RHEA:20401)
• leukotriene D4 + H2O = leukotriene E4 + glycine (RHEA:48616)
• an L-aminoacyl-L-amino acid + H2O = 2 an L-alpha-amino acid (RHEA:48940)
• L-cystine-bis-glycine + 2 H2O = L-cystine + 2 glycine (RHEA:60520)
• glycyldehydrophenylalanine + H2O = 2,3-didehydrophenylalanine + glycine (RHEA:62704)

UniProt features (74 total): helix 20, strand 16, binding site 9, turn 7, mutagenesis site 5, glycosylation site 4, disulfide bond 3, sequence variant 3, sequence conflict 3, signal peptide 1, chain 1, lipid moiety-binding region 1, propeptide 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1ITU	X-RAY DIFFRACTION	2
1ITQ	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16444-F1	93.34	0.89

Functional residue map

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

Ligand- & substrate-binding residues (9): 246; 304; 36; 38; 141; 141; 168; 214; 235

Post-translational modifications (1): 385

Disulfide bonds (3): 87–170, 242–274, 377

Glycosylation sites (4): 57, 279, 332, 358

Mutagenesis-validated functional residues (5):

Position	Phenotype
141	loss of zinc binding.
141	complete loss of activity.
141	abolished dipeptidase activity. does not affect ability to bind neutrophils.
141	partial loss of activity.
304	loss of ability to hydrolyze cystinyl-bis-glycine.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2142691	Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-HSA-5423646	Aflatoxin activation and detoxification
R-HSA-9664535	LTC4-CYSLTR mediated IL4 production

MSigDB gene sets: 176 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_BIOLOGICAL_OXIDATIONS, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_INFLAMMATORY_RESPONSE, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_MODIFIED_AMINO_ACID_CATABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_RESPONSE_TO_METAL_ION, GOBP_HOMOCYSTEINE_METABOLIC_PROCESS, GOBP_TAXIS, YOKOE_CANCER_TESTIS_ANTIGENS

GO Biological Process (14): proteolysis (GO:0006508), glutathione metabolic process (GO:0006749), glutathione catabolic process (GO:0006751), inflammatory response (GO:0006954), antibiotic metabolic process (GO:0016999), negative regulation of cell migration (GO:0030336), neutrophil chemotaxis (GO:0030593), homocysteine metabolic process (GO:0050667), cellular response to calcium ion (GO:0071277), cellular response to nitric oxide (GO:0071732), lactam catabolic process (GO:0072340), leukotriene D4 catabolic process (GO:1901749), lipid metabolic process (GO:0006629), leukotriene metabolic process (GO:0006691)

GO Molecular Function (12): metalloexopeptidase activity (GO:0008235), zinc ion binding (GO:0008270), beta-lactamase activity (GO:0008800), dipeptidase activity (GO:0016805), GPI anchor binding (GO:0034235), metallodipeptidase activity (GO:0070573), modified amino acid binding (GO:0072341), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (11): obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), cell junction (GO:0030054), microvillus membrane (GO:0031528), apical part of cell (GO:0045177), extracellular exosome (GO:0070062), side of membrane (GO:0098552), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Arachidonate metabolism	1
Biological oxidations	1
Anti-inflammatory response favouring Leishmania parasite infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
sulfur compound catabolic process	2
exopeptidase activity	2
binding	2
membrane	2
protein metabolic process	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
glutathione metabolic process	1
modified amino acid catabolic process	1
defense response	1
metabolic process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
granulocyte chemotaxis	1
neutrophil migration	1
sulfur amino acid metabolic process	1
non-proteinogenic amino acid metabolic process	1
response to calcium ion	1
cellular response to metal ion	1
response to nitric oxide	1
cellular response to oxygen-containing compound	1
cellular response to reactive nitrogen species	1
catabolic process	1
lactam metabolic process	1
leukotriene catabolic process	1
icosanoid catabolic process	1
primary metabolic process	1
icosanoid metabolic process	1
metallopeptidase activity	1
transition metal ion binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides	1
phospholipid binding	1
glycolipid binding	1
metalloexopeptidase activity	1
dipeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1

Protein interactions and networks

STRING

1114 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPEP1	DERPC	P0CG12	507
DPEP1	ABR	Q12979	506
DPEP1	CNDP2	Q96KP4	495
DPEP1	DNASE1L2	Q92874	447
DPEP1	ADAMDEC1	O15204	411
DPEP1	BSG	P35613	410
DPEP1	ABTB1	Q969K4	407
DPEP1	OGDHL	Q9ULD0	398
DPEP1	CTSZ	Q9UBR2	394
DPEP1	CA9	Q16790	389
DPEP1	SPATA33	Q96N06	385
DPEP1	A0A2R8YEI5	A0A2R8YEI5	383
DPEP1	DRC4	O95995	382
DPEP1	CHN2	P52757	373
DPEP1	CTSC	P53634	372
DPEP1	XPNPEP2	O43895	372

IntAct

15 interactions, top by confidence:

A	B	Type	Score
ACADS	DPEP1	psi-mi:“MI:0915”(physical association)	0.590
DPEP1	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
APPBP2	DPEP1	psi-mi:“MI:0915”(physical association)	0.560
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
DPEP1	KIFBP	psi-mi:“MI:0915”(physical association)	0.510
FKBP15	DPEP1	psi-mi:“MI:0915”(physical association)	0.400
DPEP1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TEX101	PSMD12	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
MRPL12	GTPBP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (109): APPBP2 (Two-hybrid), KIAA1279 (Two-hybrid), KIAA1279 (Affinity Capture-Western), TMUB2 (Affinity Capture-MS), FANCG (Affinity Capture-MS), ORC5 (Affinity Capture-MS), SUN1 (Affinity Capture-MS), FLCN (Affinity Capture-MS), STEAP3 (Affinity Capture-MS), NCAPD2 (Affinity Capture-MS), PIGA (Affinity Capture-MS), NCAPG (Affinity Capture-MS), C1GALT1 (Affinity Capture-MS), PICK1 (Affinity Capture-MS), ILVBL (Affinity Capture-MS)

ESM2 similar proteins: A0A7N9VSG0, A0JNU3, D3ZBP4, D3ZX08, F1MH07, O43542, O55137, O55171, O88202, O88267, P15575, P16444, P22412, P31429, P41226, P43477, Q08DH8, Q0P5I5, Q14CH7, Q2KHY1, Q2V057, Q32Q92, Q3SZM7, Q3UQ84, Q5E9L5, Q5JTZ9, Q5M876, Q5RCH4, Q66KF6, Q68FW7, Q6P3H4, Q6PAY6, Q86U10, Q8K4F6, Q8K4V2, Q8R123, Q8TDZ2, Q8VCZ9, Q8VDG5, Q8VDP3

Diamond homologs: A0A1U9YI27, B8LWT1, C4JQN7, C5FK77, C5PCN6, C5PCZ0, C7ZIE1, D4B2N2, D4DEJ7, E5R2Q7, E9CV02, E9D269, M1VV65, O14124, O59832, P16444, P22412, P31428, P31429, P31430, P43477, Q0CS61, Q2UPB0, Q3SZM7, Q4R7M2, Q4WMJ8, Q5M872, Q5U2X4, Q6Q886, Q8C255, Q9DA79, Q9H4A9, Q9H4B8, P27509

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2218 predictions. Top by Δscore:

Variant	Effect	Δscore
16:89635895:C:CA	acceptor_gain	1.0000
16:89635899:A:AG	acceptor_gain	1.0000
16:89636014:C:G	donor_gain	1.0000
16:89636262:A:AG	acceptor_gain	1.0000
16:89636263:G:GG	acceptor_gain	1.0000
16:89636356:G:GT	donor_gain	1.0000
16:89636377:G:GG	donor_gain	1.0000
16:89636861:TCCA:T	acceptor_loss	1.0000
16:89636862:CCAGG:C	acceptor_loss	1.0000
16:89636864:A:AC	acceptor_loss	1.0000
16:89636864:A:AG	acceptor_gain	1.0000
16:89636865:G:GA	acceptor_loss	1.0000
16:89636865:G:GG	acceptor_gain	1.0000
16:89637363:G:GT	donor_gain	1.0000
16:89637378:GTG:G	donor_gain	1.0000
16:89637461:T:A	acceptor_gain	1.0000
16:89637466:A:AC	acceptor_loss	1.0000
16:89637466:A:AG	acceptor_gain	1.0000
16:89637467:G:GT	acceptor_gain	1.0000
16:89637467:GA:G	acceptor_gain	1.0000
16:89637467:GAA:G	acceptor_gain	1.0000
16:89637467:GAAA:G	acceptor_gain	1.0000
16:89637467:GAAAC:G	acceptor_gain	1.0000
16:89637540:TCCC:T	donor_gain	1.0000
16:89637551:CGGTA:C	donor_loss	1.0000
16:89637553:GTA:G	donor_loss	1.0000
16:89637554:T:G	donor_loss	1.0000
16:89637832:ACAG:A	acceptor_gain	1.0000
16:89637834:AG:A	acceptor_gain	1.0000
16:89637835:GG:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000025790 (16:89631314 C>T), RS1000124588 (16:89633856 C>G,T), RS1000132061 (16:89632208 C>A,G,T), RS1000177967 (16:89631799 G>A), RS1000178733 (16:89633964 G>C), RS1000277575 (16:89639376 A>C,T), RS1000329889 (16:89630225 A>C,G), RS1000366412 (16:89621000 G>A,T), RS1000411991 (16:89632408 G>A), RS1000488543 (16:89616380 G>A), RS1000632914 (16:89638989 A>C,G,T), RS1000695668 (16:89612063 C>T), RS1000762076 (16:89615289 G>C), RS1000936616 (16:89615147 A>G), RS1000958642 (16:89614510 T>C)

Disease associations

OMIM: gene MIM:179780 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

40 associations (top):

Study	Trait	p-value
GCST002087_17	Homocysteine levels	8.000000e-11
GCST002087_6	Homocysteine levels	2.000000e-43
GCST003401_11	Glomerular filtration rate in non diabetics (creatinine)	2.000000e-08
GCST003790_29	Glomerular filtration rate	8.000000e-06
GCST004292_56	Glomerular filtration rate (creatinine)	3.000000e-07
GCST006020_29	Diastolic blood pressure	6.000000e-15
GCST006021_14	Systolic blood pressure	8.000000e-06
GCST006023_7	Hypertension	3.000000e-07
GCST006227_13	Diastolic blood pressure	2.000000e-13
GCST006585_2063	Blood protein levels	5.000000e-39
GCST006986_15	Red vs. brown/black hair color	1.000000e-13
GCST007094_214	Diastolic blood pressure	4.000000e-12
GCST007095_118	Systolic blood pressure	7.000000e-07
GCST007098_19	Diastolic blood pressure	9.000000e-10
GCST007098_20	Diastolic blood pressure	5.000000e-08
GCST007344_43	Estimated glomerular filtration rate	4.000000e-09
GCST007916_10	Hyperuricemia	2.000000e-16
GCST007917_13	Estimated glomerular filtration rate	2.000000e-16
GCST007918_23	Serum uric acid levels	2.000000e-16
GCST007919_2	Creatinine levels	2.000000e-16
GCST007920_12	Chronic kidney disease	2.000000e-16
GCST008747_62	Estimated glomerular filtration rate	9.000000e-13
GCST008790_52	Urinary albumin-to-creatinine ratio	4.000000e-08
GCST008839_166	Height	5.000000e-47
GCST009733_125	Urinary metabolite levels in chronic kidney disease	9.000000e-25
GCST009733_195	Urinary metabolite levels in chronic kidney disease	4.000000e-34
GCST009733_96	Urinary metabolite levels in chronic kidney disease	4.000000e-20
GCST009733_99	Urinary metabolite levels in chronic kidney disease	1.000000e-99
GCST010083_322	Hemoglobin levels	3.000000e-22
GCST010703_280	Brain morphology (MOSTest)	2.000000e-15

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004578	homocysteine measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0003924	hair color
EFO:0009104	hyperuricemia
EFO:0004761	uric acid measurement
EFO:0007778	urinary albumin to creatinine ratio
EFO:0005116	urinary metabolite measurement
EFO:0004509	hemoglobin measurement
EFO:0004346	neuroimaging measurement
EFO:0004348	hematocrit
EFO:0010701	mean reticulocyte volume
EFO:0004533	alkaline phosphatase measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1989 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Leukotriene and lipoxin metabolism

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

Ligand	Action	Affinity	Parameter
cilastatin	Inhibition	5.96	pKi

ChEMBL bioactivities

20 potent at pChembl≥5 of 20 total, top 20 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.30	IC50	5	nM	CHEMBL119723
8.22	IC50	6	nM	CHEMBL117337
8.10	IC50	8	nM	CHEMBL326292
8.00	IC50	10	nM	CHEMBL333841
7.82	IC50	15	nM	CHEMBL119055
7.70	IC50	20	nM	CHEMBL332970
7.60	IC50	25	nM	CHEMBL334279
7.52	IC50	30	nM	CHEMBL120600
7.52	IC50	30	nM	CHEMBL334143
7.40	IC50	40	nM	CHEMBL332290
7.35	IC50	45	nM	CHEMBL122415
7.16	IC50	70	nM	CHEMBL119261
7.00	IC50	100	nM	CHEMBL325021
6.82	IC50	150	nM	CHEMBL120198
6.70	IC50	200	nM	CHEMBL119118
6.70	IC50	200	nM	CHEMBL420537
6.60	IC50	250	nM	CHEMBL118190
6.46	IC50	350	nM	CHEMBL119392
6.00	IC50	1000	nM	CHEMBL331554
5.52	IC50	3000	nM	CHEMBL118275

PubChem BioAssay actives

20 with measured affinity, of 65 total; 20 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
(Z)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(4-fluorophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.0050	uM
(Z)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(4-bromophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.0060	uM
(Z)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(4-iodophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.0080	uM
(Z)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-[4-(trifluoromethyl)phenyl]prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.0100	uM
(E)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(4-fluorophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.0150	uM
(Z)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(3,4-dichlorophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.0200	uM
(E)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(4-iodophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.0250	uM
(E)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(4-bromophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.0300	uM
(Z)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(3-chloro-4-fluorophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.0300	uM
(Z)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(3-bromo-4-fluorophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.0400	uM
(Z)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(3-iodophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.0450	uM
(Z)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(4-aminophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.0700	uM
(Z)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(2-iodophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.1000	uM
(E)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(4-aminophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.1500	uM
(E)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(3,4-dichlorophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.2000	uM
(E)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-[4-(trifluoromethyl)phenyl]prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.2000	uM
(E)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(3-iodophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.2500	uM
(E)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(3-chloro-4-fluorophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	0.3500	uM
(E)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(2-iodophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	1.0000	uM
(E)-2-[[(1-amino-2-cyclohexylethyl)-hydroxyphosphoryl]methyl]-3-(3-bromo-4-fluorophenyl)prop-2-enoic acid	195429: Concentration required to inhibit renal dipeptidase (RDP) by 50% in crude lysates prepared from human colon cancer	ic50	3.0000	uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	4
Silicon Dioxide	decreases expression, increases expression	2
bufotalin	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects expression	1
deoxynivalenol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases expression	1
K 7174	decreases expression	1
Smoke	increases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Cilastatin	decreases activity	1
Cyclosporine	decreases expression	1
beta-Naphthoflavone	decreases expression	1
Copper Sulfate	decreases expression	1
S-Nitrosoglutathione	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 4 functional, 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL661434	Functional	Compound stability against human renal DHP-1 relative to imipenem (IMP)	Synthesis and antibacterial evaluation of novel 2-[N-Imidoylpyrrolidinyl] carbapenems. — Bioorg Med Chem Lett
CHEMBL664506	Binding	Susceptibility to mammalian dehydropeptidase DHP-1 relative to thienamycin	Structure-activity relationships in the 2-arylcarbapenem series: synthesis of 1-methyl-2-arylcarbapenems. — J Med Chem

Clinical trials (associated diseases)

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