TMPRSS15

Summary

TMPRSS15 (transmembrane serine protease 15, HGNC:9490) is a protein-coding gene on chromosome 21q21.1, encoding Enteropeptidase (P98073). Responsible for initiating activation of pancreatic proteolytic proenzymes (trypsin, chymotrypsin and carboxypeptidase A).

This gene encodes an enzyme that converts the pancreatic proenzyme trypsinogen to trypsin, which activates other proenzymes including chymotrypsinogen and procarboxypeptidases. The precursor protein is cleaved into two chains that form a heterodimer linked by a disulfide bond. This protein is a member of the trypsin family of peptidases. Mutations in this gene cause enterokinase deficiency, a malabsorption disorder characterized by diarrhea and failure to thrive.

Source: NCBI Gene 5651 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital enteropathy due to enteropeptidase deficiency (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 679 total — 50 pathogenic, 27 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes
• MANE Select transcript: NM_002772

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9490
Approved symbol	TMPRSS15
Name	transmembrane serine protease 15
Location	21q21.1
Locus type	gene with protein product
Status	Approved
Aliases	ENTK, MGC133046
Ensembl gene	ENSG00000154646
Ensembl biotype	protein_coding
OMIM	606635
Entrez	5651

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000284885, ENST00000422787, ENST00000474775

RefSeq mRNA: 3 — MANE Select: NM_002772 NM_001428056, NM_001428057, NM_002772

CCDS: CCDS13571

Canonical transcript exons

ENST00000284885 — 25 exons

Exon	Start	End
ENSE00001016995	18352903	18353052
ENSE00001016996	18297734	18297829
ENSE00001016997	18341413	18341548
ENSE00001016998	18278964	18279059
ENSE00001016999	18343506	18343656
ENSE00001017000	18379283	18379318
ENSE00001017001	18359757	18359863
ENSE00001017002	18326432	18326572
ENSE00001017003	18275197	18275336
ENSE00001017004	18281040	18281221
ENSE00001017005	18294603	18294652
ENSE00001017006	18315146	18315256
ENSE00001017008	18269116	18270124
ENSE00001017009	18353723	18353863
ENSE00001017011	18329169	18329294
ENSE00001017012	18343955	18344060
ENSE00001017014	18312945	18313077
ENSE00001017015	18332084	18332173
ENSE00001017016	18397879	18397946
ENSE00001017017	18398199	18398329
ENSE00001017018	18294270	18294444
ENSE00001017019	18403478	18403785
ENSE00003606729	18383627	18383778
ENSE00003669261	18372193	18372324
ENSE00003787340	18365140	18365248

Expression profiles

Bgee: expression breadth broad, 57 present calls, max score 98.66.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4907 / max 217.0164, expressed in 30 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189864	0.3495	4
189867	0.1262	20
189866	0.0084	6
189865	0.0066	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.66	gold quality
duodenum	UBERON:0002114	97.40	gold quality
olfactory bulb	UBERON:0002264	88.11	silver quality
type B pancreatic cell	CL:0000169	88.04	silver quality
cervix squamous epithelium	UBERON:0006922	85.33	silver quality
pancreatic ductal cell	CL:0002079	84.16	silver quality
diaphragm	UBERON:0001103	82.70	silver quality
buccal mucosa cell	CL:0002336	81.79	silver quality
epithelial cell of pancreas	CL:0000083	80.82	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.69	gold quality
mucosa of urinary bladder	UBERON:0001259	80.01	silver quality
ileal mucosa	UBERON:0000331	79.42	gold quality
tibialis anterior	UBERON:0001385	79.10	gold quality
jejunum	UBERON:0002115	77.63	gold quality
quadriceps femoris	UBERON:0001377	74.76	gold quality
vastus lateralis	UBERON:0001379	74.61	gold quality
decidua	UBERON:0002450	74.04	silver quality
oocyte	CL:0000023	73.24	gold quality
deltoid	UBERON:0001476	73.05	silver quality
endothelial cell	CL:0000115	72.97	silver quality
male germ cell	CL:0000015	72.69	gold quality
triceps brachii	UBERON:0001509	72.31	gold quality
gluteal muscle	UBERON:0002000	72.21	silver quality
choroid plexus epithelium	UBERON:0003911	71.29	silver quality
sperm	CL:0000019	70.99	gold quality
tongue squamous epithelium	UBERON:0006919	70.73	gold quality
thymus	UBERON:0002370	68.43	gold quality
squamous epithelium	UBERON:0006914	68.37	gold quality
epithelium of esophagus	UBERON:0001976	68.31	gold quality
CA1 field of hippocampus	UBERON:0003881	67.16	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.56
E-GEOD-110499	no	6.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting TMPRSS15, 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-9-5P	100.00	72.28	2361
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641

Literature-anchored findings (GeneRIF, showing 9)

• Engineered recombinant enteropeptidase catalytic subunit: effect of N-terminal modification (PMID:11913964)
• Produced in enterocytes and goblet cells. Localization on brush border of cells for physiological activation of digestive enzymes. In duodenal polyps and adenocarcinoma at duodenum but not in Brunner’s gland adenoma. (PMID:12907431)
• Enterokinase directly cleaved proMMP-9 at the Lys65-Ser66 site. (PMID:18062964)
• Because mesotrypsin is resistant to naturally occurring trypsin inhibitors, confined expression of the isoforms of mesotrypsinogens and enteropeptidase may indicate that mesotrypsin is involved in keratinocyte terminal differentiation (PMID:19924134)
• Human enteropeptidase shows 10x faster kinetics compared to other animal sources but low solubility under low salt conditions. A supercharged variant of enteropeptidase light chain with increased solubility was used for crystallization. (PMID:22488687)
• Characterization of the different catalytic activity of human and bovine enteropeptidase light chains toward hydrolysis of peptides and proteins lacking tetraaspartate sequence. (PMID:22571433)
• Enteropeptidase is a gene associated with a starvation human phenotype and a novel target for obesity treatment (PMID:23185382)
• The Y174R variant showed improved specificities for substrates containing the sequences DDDDK (kcat/KM = 6.83 x 106 M-1 sec-1) and DDDDR (kcat/KM = 1.89 x 107 M-1 sec-1) relative to all other enteropeptidase variants reported to date. (PMID:23436726)
• Enterokinases was able to enhance the proliferation of H1N1 virus in 293T human kidney cells, but the proliferation was reduced by knocking down the endogenous enterokinase in A549 cells. (PMID:29629340)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmprss15	ENSMUSG00000022857
rattus_norvegicus	Tmprss15	ENSRNOG00000001916
drosophila_melanogaster	Sb	FBGN0003319
drosophila_melanogaster	CG1632	FBGN0030027
drosophila_melanogaster	CG17242	FBGN0250841

Paralogs (17): PRSS22 (ENSG00000005001), PRSS21 (ENSG00000007038), TMPRSS11E (ENSG00000087128), HPN (ENSG00000105707), TMPRSS13 (ENSG00000137747), ST14 (ENSG00000149418), TMPRSS11D (ENSG00000153802), TMPRSS3 (ENSG00000160183), TMPRSS5 (ENSG00000166682), TMPRSS7 (ENSG00000176040), TMPRSS9 (ENSG00000178297), TMPRSS2 (ENSG00000184012), TMPRSS11B (ENSG00000185873), TMPRSS6 (ENSG00000187045), TMPRSS11A (ENSG00000187054), TMPRSS11F (ENSG00000198092), PRSS41 (ENSG00000215148)

Protein

Protein identifiers

Enteropeptidase — P98073 (reviewed: P98073)

Alternative names: Enterokinase, Serine protease 7, Transmembrane protease serine 15

All UniProt accessions (2): P98073, E9PG70

UniProt curated annotations — full annotation on UniProt →

Function. Responsible for initiating activation of pancreatic proteolytic proenzymes (trypsin, chymotrypsin and carboxypeptidase A). It catalyzes the conversion of trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases.

Subunit / interactions. Heterodimer of a catalytic (light) chain and a multidomain (heavy) chain linked by a disulfide bond.

Subcellular location. Membrane.

Tissue specificity. Intestinal brush border.

Post-translational modifications. The chains are derived from a single precursor that is cleaved by a trypsin-like protease.

Disease relevance. Enterokinase deficiency (ENTKD) [MIM:226200] Life-threatening intestinal malabsorption disorder characterized by diarrhea and failure to thrive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (3): NP_001414985, NP_001414986, NP_002763* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000082	SEA_dom	Domain
IPR000859	CUB_dom	Domain
IPR000998	MAM_dom	Domain
IPR001190	SRCR	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR011163	Pept_S1A_enterop	Family
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR023415	LDLR_class-A_CS	Conserved_site
IPR033116	TRYPSIN_SER	Active_site
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR036364	SEA_dom_sf	Homologous_superfamily
IPR036772	SRCR-like_dom_sf	Homologous_superfamily
IPR043504

Pfam: PF00057, PF00089, PF00431, PF00629, PF01390, PF15494

Enzyme classification (BRENDA):

• EC 3.4.21.9 — enteropeptidase (BRENDA: 7 organisms, 179 substrates, 44 inhibitors, 139 Km, 110 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
GLY-ASP-ASP-ASP-ASP-LYS-2-NAPHTHYLAMIDE	0.034–1.25	16
TRYPSINOGEN	0.001–1.2	9
GDDDDK-2-NAPHTHYLAMIDE	0.019–0.6	7
APFDDDDKIVGG	0.0647–1.41	5
BENZYLOXYCARBONYL-PHE-ARG-7-AMIDO-4-METHYLCOUMAR	0.5–1.6	5
BOC-GLU(OBZL)-ALA-ARG-MCA	0.2–1.3	5
PRO-PHE-ARG-4-METHYLCOUMARYL-7-AMIDE	1–10	5
T-BUTYLOXYCARBONYL-E(BENZYL ESTER)-ALA-ARG-7-AMI	0.2–1.5	5
THIOBENZYL BENZYLOXYCARBONYL-L-LYSINATE	0.05–0.14	5
Z-PHE-ARG-4-METHYLCOUMARYL-7-AMIDE	0.1–0.4	5
GLY-ASP-ASP-ASP-ASP-LYS-NAPHTHYLAMIDE	0.034–0.332	4
GD4R-4-NITROANILIDE	0.0026–0.018	3
GDDDDK-4-NITROANILIDE	0.0179–0.276	3
HUMAN CATIONIC TRYPSINOGEN	0.0014–1.5	3
THIOBENZYL BENZYLOXY-CARBONYL-L-LYSINATE	0.12–0.14	3

UniProt features (104 total): strand 36, glycosylation site 18, disulfide bond 14, domain 8, sequence variant 8, helix 7, active site 3, turn 3, chain 2, topological domain 2, initiator methionine 1, lipid moiety-binding region 1, transmembrane region 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
4DGJ	X-RAY DIFFRACTION	1.9
6ZOV	X-RAY DIFFRACTION	2.19
8ZIY	ELECTRON MICROSCOPY	2.64
8ZJ4	ELECTRON MICROSCOPY	2.67
7WQX	ELECTRON MICROSCOPY	2.7
8ZIZ	ELECTRON MICROSCOPY	2.89
8ZIW	ELECTRON MICROSCOPY	2.92
8ZI4	ELECTRON MICROSCOPY	2.95
8ZIV	ELECTRON MICROSCOPY	2.95
7WR7	ELECTRON MICROSCOPY	3.1
7WQW	ELECTRON MICROSCOPY	3.2
7WQZ	ELECTRON MICROSCOPY	3.7
8H3U	ELECTRON MICROSCOPY	4.7
8H3S	ELECTRON MICROSCOPY	4.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P98073-F1	82.03	0.30

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): 825 (charge relay system); 876 (charge relay system); 971 (charge relay system)

Post-translational modifications (1): 2

Disulfide bonds (14): 184–197, 191–210, 204–221, 225–253, 524–552, 643–655, 650–668, 662–677, 757–767, 772–896, 810–826, 910–977, 941–956, 967–995

Glycosylation sites (18): 116, 147, 179, 328, 335, 388, 440, 470, 503, 534, 630, 682, 706, 725, 848, 887, 909, 949

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 95 (showing top): ZHAN_MULTIPLE_MYELOMA_MF_UP, CROONQUIST_NRAS_SIGNALING_UP, HNF1_Q6, GOBP_PROTEIN_MATURATION, MODULE_99, HNF1_C, VECCHI_GASTRIC_CANCER_EARLY_DN, FOXO4_02, SHEN_SMARCA2_TARGETS_DN, GOCC_APICAL_PART_OF_CELL, GOCC_CLUSTER_OF_ACTIN_BASED_CELL_PROJECTIONS, GOBP_PROTEOLYSIS, GARY_CD5_TARGETS_UP, GOMF_PEPTIDASE_ACTIVITY, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_DN

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

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

GO Cellular Component (2): brush border (GO:0005903), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
endopeptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
microvillus	1
apical part of cell	1
cluster of actin-based cell projections	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1044 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMPRSS15	AGRN	O00468	845
TMPRSS15	SPINK1	P00995	810
TMPRSS15	TXN	P10599	703
TMPRSS15	MUC1	P13931	653
TMPRSS15	MUC20	Q8N307	597
TMPRSS15	MUC7	Q8TAX7	568
TMPRSS15	MUC12	Q9UKN1	554
TMPRSS15	MUC17	Q685J3	540
TMPRSS15	MUC13	Q9H3R2	496
TMPRSS15	MUC21	Q5SSG8	479
TMPRSS15	MUC16	Q8WXI7	479
TMPRSS15	MUC3A	Q02505	477
TMPRSS15	MSR1	P21757	472
TMPRSS15	MUC4	Q99102	472
TMPRSS15	MUC5B	Q9HC84	463

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TMPRSS15	Tnfrsf11a	psi-mi:“MI:0194”(cleavage reaction)	0.440
TMPRSS15	TNFRSF11A	psi-mi:“MI:0194”(cleavage reaction)	0.440
PYCARD	MYO1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): TMPRSS15 (Affinity Capture-MS), TMPRSS15 (Affinity Capture-MS), TMPRSS15 (Affinity Capture-MS)

ESM2 similar proteins: A0A182C2Z2, A0A1S4GMJ4, A6MFK8, B5G6G5, O15393, O60235, O70244, O96900, P00750, P05156, P11214, P19637, P25723, P29598, P79953, P81428, P82807, P83370, P86091, P97435, P98072, P98073, P98074, P98119, P98121, Q05589, Q14C59, Q17800, Q20176, Q4QXT9, Q58L93, Q58L94, Q5QSK2, Q5R5A4, Q5R8J0, Q61129, Q66TN7, Q6DIV5, Q6IE14, Q6ZMR5

Diamond homologs: A0A126GUP6, A0A182C2Z2, A0A1S4H5M5, A8JUP7, B5U2W0, B7YZU2, F5HKX0, O15393, O35453, O60235, O60259, O97366, P00774, P03951, P03952, P05049, P05981, P08419, P09871, P10323, P13582, P14272, P21902, P23578, P25155, P26262, P28175, P29293, P31394, P33587, P35035, P35036, P35037, P35039, P35041, P35045, P35046, P35047, P40313, P48038

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	50
Likely pathogenic	27
Uncertain significance	265
Likely benign	270
Benign	37

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1028048	NM_002772.3(TMPRSS15):c.1512del (p.Ser505fs)	Pathogenic
1251988	NM_002772.3(TMPRSS15):c.2808_2809insATCA (p.Ser937fs)	Pathogenic
1935335	NM_002772.3(TMPRSS15):c.1312dup (p.Ser438fs)	Pathogenic
1997513	NM_002772.3(TMPRSS15):c.2441_2442dup (p.Val815fs)	Pathogenic
2004823	NM_002772.3(TMPRSS15):c.1929C>A (p.Cys643Ter)	Pathogenic
2028638	NM_002772.3(TMPRSS15):c.622_626del (p.Val208fs)	Pathogenic
2030242	NM_002772.3(TMPRSS15):c.2514del (p.Ala839fs)	Pathogenic
2034097	NM_002772.3(TMPRSS15):c.1012G>T (p.Glu338Ter)	Pathogenic
2090917	NM_002772.3(TMPRSS15):c.1320dup (p.Ile441fs)	Pathogenic
2106466	NM_002772.3(TMPRSS15):c.1638C>G (p.Tyr546Ter)	Pathogenic
2114207	NM_002772.3(TMPRSS15):c.661del (p.Cys221fs)	Pathogenic
2117016	NM_002772.3(TMPRSS15):c.1485del (p.Ser496fs)	Pathogenic
2119439	NM_002772.3(TMPRSS15):c.1492del (p.Thr498fs)	Pathogenic
2130735	NM_002772.3(TMPRSS15):c.1741G>T (p.Glu581Ter)	Pathogenic
2132186	NM_002772.3(TMPRSS15):c.1093G>T (p.Glu365Ter)	Pathogenic
2161655	NM_002772.3(TMPRSS15):c.1957G>T (p.Gly653Ter)	Pathogenic
2181643	NM_002772.3(TMPRSS15):c.2599_2600insGATTAATAGATGAAATTGTC (p.His867fs)	Pathogenic
2186565	NM_002772.3(TMPRSS15):c.390G>A (p.Trp130Ter)	Pathogenic
2420761	NM_002772.3(TMPRSS15):c.2827C>T (p.Gln943Ter)	Pathogenic
2424536	NC_000021.8:g.(?19775775)(19775939_?)del	Pathogenic
2692830	NM_002772.3(TMPRSS15):c.2744G>A (p.Trp915Ter)	Pathogenic
2707446	NM_002772.3(TMPRSS15):c.1675C>T (p.Gln559Ter)	Pathogenic
2798112	NM_002772.3(TMPRSS15):c.2128C>T (p.Gln710Ter)	Pathogenic
2814681	NM_002772.3(TMPRSS15):c.2785C>T (p.Gln929Ter)	Pathogenic
2818632	NM_002772.3(TMPRSS15):c.552C>A (p.Cys184Ter)	Pathogenic
2869535	NM_002772.3(TMPRSS15):c.1216C>T (p.Arg406Ter)	Pathogenic
2876930	NM_002772.3(TMPRSS15):c.142C>T (p.Arg48Ter)	Pathogenic
2878602	NM_002772.3(TMPRSS15):c.2388G>A (p.Trp796Ter)	Pathogenic
3645090	NM_002772.3(TMPRSS15):c.296C>G (p.Ser99Ter)	Pathogenic
3647491	NM_002772.3(TMPRSS15):c.2275C>T (p.Gln759Ter)	Pathogenic

SpliceAI

3556 predictions. Top by Δscore:

Variant	Effect	Δscore
21:18294441:CAAG:C	acceptor_gain	1.0000
21:18294653:C:CC	acceptor_gain	1.0000
21:18295036:TGA:T	donor_gain	1.0000
21:18297000:AAAT:A	donor_gain	1.0000
21:18297825:CACTC:C	acceptor_gain	1.0000
21:18297827:CTC:C	acceptor_gain	1.0000
21:18297828:TC:T	acceptor_gain	1.0000
21:18297828:TCC:T	acceptor_loss	1.0000
21:18297829:CC:C	acceptor_gain	1.0000
21:18297829:CCTAG:C	acceptor_loss	1.0000
21:18297830:C:CC	acceptor_gain	1.0000
21:18312943:AC:A	donor_gain	1.0000
21:18312944:CC:C	donor_gain	1.0000
21:18313074:CGCA:C	acceptor_gain	1.0000
21:18313076:CA:C	acceptor_gain	1.0000
21:18313078:C:CC	acceptor_gain	1.0000
21:18315255:CT:C	acceptor_gain	1.0000
21:18329164:CTTA:C	donor_loss	1.0000
21:18329166:TACCT:T	donor_loss	1.0000
21:18329167:A:AC	donor_gain	1.0000
21:18329167:AC:A	donor_gain	1.0000
21:18329167:ACCT:A	donor_loss	1.0000
21:18329168:C:CT	donor_gain	1.0000
21:18329168:CC:C	donor_gain	1.0000
21:18329168:CCT:C	donor_gain	1.0000
21:18329168:CCTA:C	donor_gain	1.0000
21:18329168:CCTAA:C	donor_gain	1.0000
21:18329292:CAC:C	acceptor_gain	1.0000
21:18329295:C:CA	acceptor_loss	1.0000
21:18329295:C:CC	acceptor_gain	1.0000

AlphaMissense

6747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:18343548:C:A	W462C	0.995
21:18343548:C:G	W462C	0.995
21:18352978:A:G	W366R	0.995
21:18352978:A:T	W366R	0.995
21:18278983:C:A	W915C	0.994
21:18278983:C:G	W915C	0.994
21:18352976:C:A	W366C	0.994
21:18352976:C:G	W366C	0.994
21:18343550:A:G	W462R	0.993
21:18343550:A:T	W462R	0.993
21:18281199:A:G	W837R	0.992
21:18281199:A:T	W837R	0.992
21:18312989:C:A	W707C	0.992
21:18312989:C:G	W707C	0.992
21:18365150:A:G	W255R	0.992
21:18365150:A:T	W255R	0.992
21:18281197:C:A	W837C	0.991
21:18281197:C:G	W837C	0.991
21:18294362:C:A	W798C	0.991
21:18294362:C:G	W798C	0.991
21:18343999:G:C	S411R	0.991
21:18343999:G:T	S411R	0.991
21:18344001:T:G	S411R	0.991
21:18365148:C:A	W255C	0.991
21:18365148:C:G	W255C	0.991
21:18353008:A:G	W356R	0.990
21:18353008:A:T	W356R	0.990
21:18278985:A:G	W915R	0.989
21:18278985:A:T	W915R	0.989
21:18294364:A:G	W798R	0.988

dbSNP variants (sampled 300 via entrez): RS1000004651 (21:18448585 T>C), RS1000007374 (21:18343771 T>G), RS1000042691 (21:18385009 T>C), RS1000049562 (21:18426757 A>C), RS1000050308 (21:18347229 T>A), RS1000096048 (21:18314605 T>C), RS1000101519 (21:18427059 A>C,G), RS1000112173 (21:18390640 C>T), RS1000142297 (21:18407337 G>A), RS1000152707 (21:18344398 G>C), RS1000164899 (21:18314365 G>A), RS1000195217 (21:18407624 C>A,T), RS1000195368 (21:18311227 G>C), RS1000205784 (21:18358685 T>C,G), RS1000219468 (21:18441808 A>C,G)

Disease associations

OMIM: gene MIM:606635 | disease phenotypes: MIM:226200

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital enteropathy due to enteropeptidase deficiency	Strong	Autosomal recessive

Mondo (1): congenital enteropathy due to enteropeptidase deficiency (MONDO:0009173)

Orphanet (1): Congenital enteropathy due to enteropeptidase deficiency (Orphanet:168601)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001508	Failure to thrive
HP:0002014	Diarrhea
HP:0003075	Hypoproteinemia
HP:0007609	Hypoproteinemic edema

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001958_21	Bulimia nervosa	1.000000e-06
GCST005212_11	Asthma	6.000000e-06
GCST005241_2	Nucleus accumbens volume in trauma-exposed individuals	3.000000e-07
GCST010724_27	HOMA-B (corrected for HOMA-IR)	2.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008483	response to trauma exposure
EFO:0004469	HOMA-B

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562649	Enterokinase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741195 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

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

Ligand	Action	Affinity	Parameter
sucunamostat	Inhibition	8.27	pIC50

Binding affinities (BindingDB)

313 measured of 313 human assays (313 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S)-2-[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonyl-3-methylthiophen-2-yl]propanoylamino]butanedioic acid	KI	0.13 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]amino]butanedioic acid	KI	0.14 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[1-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]cyclobutanecarbonyl]amino]butanedioic acid	KI	0.14 nM	US-9024044: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[(4R)-3-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-1,3-thiazolidine-4-carbonyl]amino]butanedioic acid	KI	0.15 nM	US-9346821: Heterocyclic carboxylic acid ester derivative
(2S)-2-[[2-(4-carbamimidoyl-2-fluorophenoxy)carbonyl-5,7-dihydro-4H-thieno[2,3-c]pyridine-6-carbonyl]amino]butanedioic acid	KI	0.2 nM	US-9346821: Heterocyclic carboxylic acid ester derivative
(2R)-2-[[3-[5-(4-carbamimidoyl-2-chlorophenoxy)carbonylthiophen-2-yl]-2-methylpropanoyl]amino]-3-sulfopropanoic acid	KI	0.21 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]-prop-2-enylamino]acetic acid	KI	0.24 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
4-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]amino]phthalic acid	KI	0.24 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]-3-(2H-tetrazol-5-yl)propanoic acid	KI	0.24 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
(2R)-2-[[(2S)-1-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]pyrrolidine-2-carbonyl]amino]-3-sulfopropanoic acid	KI	0.24 nM	US-9346821: Heterocyclic carboxylic acid ester derivative
(2R)-2-[[(2R)-1-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]pyrrolidine-2-carbonyl]amino]-3-sulfopropanoic acid	KI	0.24 nM	US-9346821: Heterocyclic carboxylic acid ester derivative
(2S)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]-3-(2H-tetrazol-5-yl)propanoic acid	KI	0.24 nM	US-9655879: Heteroarylcarboxylic acid ester derivative
(2R)-2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylfuran-2-yl]-2-methylpropanoyl]amino]butanedioic acid	KI	0.25 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2R)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]butanedioic acid	KI	0.26 nM	US-9024044: Heteroarylcarboxylic acid ester derivative
(2R)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]butanedioic acid	KI	0.26 nM	US-9655879: Heteroarylcarboxylic acid ester derivative
(2R)-2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2-methylpropanoyl]amino]-3-sulfopropanoic acid	KI	0.27 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]pentanedioic acid	KI	0.27 nM	US-9024044: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]pentanedioic acid	KI	0.27 nM	US-9655879: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2-methylpropanoyl]amino]butanedioic acid	KI	0.28 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
3-[5-(2-bromo-4-carbamimidoylphenoxy)carbonylthiophen-2-yl]-2-methylpropanoic acid	KI	0.29 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]amino]acetic acid	KI	0.29 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]amino]acetic acid	KI	0.29 nM	US-9655879: Heteroarylcarboxylic acid ester derivative
(2S,4R)-1-[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]-4-hydroxypyrrolidine-2-carboxylic acid	KI	0.3 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
(2S,4R)-1-[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]-4-hydroxypyrrolidine-2-carboxylic acid	KI	0.3 nM	US-9655879: Heteroarylcarboxylic acid ester derivative
2-[[5-(4-carbamimidoylphenoxy)carbonylfuran-2-yl]methyl]pentanedioic acid	KI	0.31 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]propanoylamino]butanedioic acid	KI	0.31 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
5-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]amino]benzene-1,3-dicarboxylic acid	KI	0.31 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[3-[4-(4-carbamimidoyl-2-fluorophenoxy)carbonylfuran-2-yl]-2-methylpropanoyl]amino]butanedioic acid	KI	0.32 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[(2R)-3-[5-(4-carbamimidoylphenoxy)carbonylfuran-2-yl]-2-methylpropanoyl]amino]butanedioic acid	KI	0.33 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[3-[5-(4-carbamimidoyl-2-chlorophenoxy)carbonylthiophen-2-yl]-2-methylpropanoyl]amino]butanedioic acid	KI	0.33 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]butanedioic acid	KI	0.33 nM	US-9024044: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl-propan-2-ylcarbamoyl]amino]butanedioic acid	KI	0.33 nM	US-9346821: Heterocyclic carboxylic acid ester derivative
(2S)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]butanedioic acid	KI	0.33 nM	US-9655879: Heteroarylcarboxylic acid ester derivative
(2R)-2-[[(2R)-3-[5-(4-carbamimidoylphenoxy)carbonylfuran-2-yl]-2-methylpropanoyl]amino]butanedioic acid	KI	0.35 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[5-[5-(4-carbamimidoylphenoxy)carbonylfuran-2-yl]-4-methylpentanoyl]amino]butanedioic acid	KI	0.35 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2-methylpropanoyl]amino]methylphosphonic acid	KI	0.37 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]propanoylamino]methylphosphonic acid	KI	0.38 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[[5-(4-carbamimidoylphenoxy)carbonylfuran-2-yl]methyl-propan-2-ylcarbamoyl]amino]butanedioic acid	KI	0.38 nM	US-9346821: Heterocyclic carboxylic acid ester derivative
(2S)-2-[[(2S)-2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl-methylamino]-3-phenylpropanoyl]amino]pentanedioic acid	KI	0.38 nM	US-9346821: Heterocyclic carboxylic acid ester derivative
(2S)-2-[[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl-methylcarbamoyl]amino]butanedioic acid	KI	0.38 nM	US-9346821: Heterocyclic carboxylic acid ester derivative
(2R)-2-[[3-[5-(4-carbamimidoylphenoxy)carbonylfuran-2-yl]-2-methylpropanoyl]amino]-3-sulfopropanoic acid	KI	0.39 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[3-[4-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2-methylpropanoyl]amino]butanedioic acid	KI	0.39 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]amino]terephthalic acid	KI	0.39 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoic acid	KI	0.39 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[(2S)-3-[5-(4-carbamimidoylphenoxy)carbonylfuran-2-yl]-2-methylpropanoyl]amino]butanedioic acid	KI	0.4 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2-methylpropanoyl]amino]-3-hydroxypropanoic acid	KI	0.4 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[5-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-4-methylpentanoyl]amino]butanedioic acid	KI	0.41 nM	US-8609715: Heteroarylcarboxylic acid ester derivative
2-[[3-[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]-2,2-dimethylpropanoyl]-methylamino]acetic acid	KI	0.41 nM	US-9227949: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]-3-hydroxypropanoic acid	KI	0.41 nM	US-9024044: Heteroarylcarboxylic acid ester derivative
(2S)-2-[[2-[[5-(4-carbamimidoyl-2-fluorophenoxy)carbonylthiophen-2-yl]methyl]-2-ethylbutanoyl]amino]-3-hydroxypropanoic acid	KI	0.41 nM	US-9655879: Heteroarylcarboxylic acid ester derivative

ChEMBL bioactivities

565 potent at pChembl≥5 of 565 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.89	Ki	0.13	nM	CHEMBL3639418
9.85	Ki	0.14	nM	CHEMBL3642979
9.85	Ki	0.14	nM	CHEMBL5914411
9.82	Ki	0.15	nM	CHEMBL3921980
9.80	Ki	0.16	nM	CHEMBL5927122
9.70	Ki	0.2	nM	CHEMBL3915122
9.68	Ki	0.21	nM	CHEMBL3642960
9.62	Ki	0.24	nM	CHEMBL3667883
9.62	Ki	0.24	nM	CHEMBL3672880
9.62	Ki	0.24	nM	CHEMBL3977688
9.62	Ki	0.24	nM	CHEMBL3900248
9.62	Ki	0.24	nM	CHEMBL3914629
9.62	Ki	0.24	nM	CHEMBL5886404
9.60	Ki	0.25	nM	CHEMBL3642886
9.59	Ki	0.26	nM	CHEMBL3667897
9.59	Ki	0.26	nM	CHEMBL3667903
9.59	Ki	0.26	nM	CHEMBL5925594
9.57	Ki	0.27	nM	CHEMBL3642957
9.57	Ki	0.27	nM	CHEMBL3667902
9.57	Ki	0.27	nM	CHEMBL6031861
9.55	Ki	0.28	nM	CHEMBL3642902
9.54	Ki	0.29	nM	CHEMBL3642898
9.54	Ki	0.29	nM	CHEMBL3667881
9.54	Ki	0.29	nM	CHEMBL5956828
9.52	Ki	0.3	nM	CHEMBL4109414
9.52	Ki	0.3	nM	CHEMBL5974605
9.51	Ki	0.31	nM	CHEMBL3642925
9.51	Ki	0.31	nM	CHEMBL3642948
9.51	Ki	0.31	nM	CHEMBL3672872
9.49	Ki	0.32	nM	CHEMBL3642931
9.48	Ki	0.33	nM	CHEMBL3642910
9.48	Ki	0.33	nM	CHEMBL3642947
9.48	Ki	0.33	nM	CHEMBL3667897
9.48	Ki	0.33	nM	CHEMBL3951843
9.48	Ki	0.33	nM	CHEMBL6033391
9.46	Ki	0.35	nM	CHEMBL3642912
9.46	Ki	0.35	nM	CHEMBL3642924
9.43	Ki	0.37	nM	CHEMBL3642958
9.42	Ki	0.38	nM	CHEMBL3642962
9.42	Ki	0.38	nM	CHEMBL3967865
9.42	Ki	0.38	nM	CHEMBL3965069
9.42	Ki	0.38	nM	CHEMBL3920627
9.41	Ki	0.39	nM	CHEMBL3642922
9.41	Ki	0.39	nM	CHEMBL3642968
9.41	Ki	0.39	nM	CHEMBL3672887
9.41	Ki	0.39	nM	CHEMBL3897603
9.40	Ki	0.4	nM	CHEMBL3642909
9.40	Ki	0.4	nM	CHEMBL3642951
9.39	Ki	0.41	nM	CHEMBL3642965
9.39	Ki	0.41	nM	CHEMBL3667885

PubChem BioAssay actives

50 with measured affinity, of 203 total; 26 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-[[10-(diaminomethylideneamino)-13-oxo-7,8-dihydro-6H-benzo[e][1,8]benzodioxecine-4-carbonyl]amino]butanedioic acid	2014317: Inhibition of human recombinant enteropeptidase using 5FAM-Abu-Gly-Asp-Asp-Asp-Lys-Ile-Val-Gly-Gly-Lys(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence plate reader analysis	ic50	0.0004	uM
(2S)-2-[[3-(diaminomethylideneamino)-14-oxo-7,8-dihydro-6H-benzo[e][1,7]benzodioxecine-9-carbonyl]amino]butanedioic acid	2014317: Inhibition of human recombinant enteropeptidase using 5FAM-Abu-Gly-Asp-Asp-Asp-Lys-Ile-Val-Gly-Gly-Lys(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence plate reader analysis	ic50	0.0007	uM
(2S)-2-[[2-[4-[4-(diaminomethylideneamino)-2-fluorobenzoyl]oxyphenyl]acetyl]amino]butanedioic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0008	uM
(2S)-2-[[3-[4-(diaminomethylideneamino)benzoyl]oxybenzoyl]amino]butanedioic acid;2,2,2-trifluoroacetic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0008	uM
(5R)-5-(carboxymethyl)-3-[3-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]-4H-1,2-oxazole-5-carboxylic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0012	uM
(2S)-2-[[2-[3-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]butanedioic acid;2,2,2-trifluoroacetic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0016	uM
(2S)-2-[[7-(diaminomethylideneamino)-3-oxo-2,14-dioxatricyclo[13.4.0.04,9]nonadeca-1(19),4(9),5,7,15,17-hexaene-16-carbonyl]amino]butanedioic acid	2014317: Inhibition of human recombinant enteropeptidase using 5FAM-Abu-Gly-Asp-Asp-Asp-Lys-Ile-Val-Gly-Gly-Lys(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence plate reader analysis	ic50	0.0017	uM
(5S)-5-(carboxymethyl)-3-[3-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]-4H-1,2-oxazole-5-carboxylic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0018	uM
(2S)-2-[[7-(diaminomethylideneamino)-3-oxo-2-oxatricyclo[13.4.0.04,9]nonadeca-1(19),4(9),5,7,15,17-hexaene-16-carbonyl]amino]butanedioic acid	2014317: Inhibition of human recombinant enteropeptidase using 5FAM-Abu-Gly-Asp-Asp-Asp-Lys-Ile-Val-Gly-Gly-Lys(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence plate reader analysis	ic50	0.0029	uM
(2S)-2-[[3-(diaminomethylideneamino)-14-oxo-5,6,7,8-tetrahydrobenzo[c][1]benzoxecine-9-carbonyl]amino]butanedioic acid	2014317: Inhibition of human recombinant enteropeptidase using 5FAM-Abu-Gly-Asp-Asp-Asp-Lys-Ile-Val-Gly-Gly-Lys(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence plate reader analysis	ic50	0.0032	uM
(2S)-2-[[4-[4-(diaminomethylideneamino)benzoyl]oxybenzoyl]amino]butanedioic acid;2,2,2-trifluoroacetic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0032	uM
(2S)-2-[[3-[4-(diaminomethylideneamino)benzoyl]oxy-2-methylbenzoyl]amino]butanedioic acid;2,2,2-trifluoroacetic acid	2014317: Inhibition of human recombinant enteropeptidase using 5FAM-Abu-Gly-Asp-Asp-Asp-Lys-Ile-Val-Gly-Gly-Lys(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence plate reader analysis	ic50	0.0044	uM
(2S)-2-[[2-[4-[2-chloro-4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]butanedioic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0056	uM
(2S)-2-[[2-[4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]butanedioic acid;hydrochloride	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0059	uM
(2S)-2-[[2-[(3R)-6-[4-(diaminomethylideneamino)benzoyl]oxy-2,3-dihydro-1-benzofuran-3-yl]acetyl]amino]butanedioic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0077	uM
(2S)-2-[[2-[4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]pentanedioic acid;2,2,2-trifluoroacetic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0079	uM
(2S)-2-[[2-[6-[4-(diaminomethylideneamino)benzoyl]oxy-2,3-dihydro-1-benzofuran-2-yl]acetyl]amino]butanedioic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0140	uM
(2S)-2-[[9-(diaminomethylideneamino)-6-oxo-12,13-dihydro-11H-benzo[c][1]benzoxonine-1-carbonyl]amino]butanedioic acid	2014317: Inhibition of human recombinant enteropeptidase using 5FAM-Abu-Gly-Asp-Asp-Asp-Lys-Ile-Val-Gly-Gly-Lys(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence plate reader analysis	ic50	0.0220	uM
(2S)-4-amino-2-[[2-[4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]-4-oxobutanoic acid;2,2,2-trifluoroacetic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0230	uM
2-[[2-[4-[4-(diaminomethylideneamino)benzoyl]oxyphenyl]acetyl]amino]acetic acid;2,2,2-trifluoroacetic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0300	uM
(2S)-2-[[2-[4-[4-(diaminomethylideneamino)-2-methylbenzoyl]oxyphenyl]acetyl]amino]butanedioic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.0540	uM
(2S)-2-[[7-(diaminomethylideneamino)-3-oxo-2-oxatricyclo[14.4.0.04,9]icosa-1(20),4(9),5,7,16,18-hexaene-17-carbonyl]amino]butanedioic acid	2014317: Inhibition of human recombinant enteropeptidase using 5FAM-Abu-Gly-Asp-Asp-Asp-Lys-Ile-Val-Gly-Gly-Lys(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence plate reader analysis	ic50	0.0810	uM
(5-methyl-1,2-oxazol-3-yl) 4-(diaminomethylideneamino)benzoate;hydrochloride	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.1400	uM
methanesulfonic acid;phenyl 4-(diaminomethylideneamino)benzoate	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.4000	uM
(2S)-2-[[2-[4-[4-(diaminomethylideneamino)-3-methylbenzoyl]oxyphenyl]acetyl]amino]butanedioic acid	1873992: Inhibition of human recombinant Enteropeptidase assessed as inhibition based on steady state using 5FAM-Abu-Gly-Asp -Asp-Asp -Lys-Ile-Val-Gly-Gly-Lys-(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence based plate reader method	ic50	0.6800	uM
(2S)-2-[[3-[4-(diaminomethylideneamino)benzoyl]oxy-4-methylbenzoyl]amino]butanedioic acid;2,2,2-trifluoroacetic acid	2014317: Inhibition of human recombinant enteropeptidase using 5FAM-Abu-Gly-Asp-Asp-Asp-Lys-Ile-Val-Gly-Gly-Lys(CPQ2)-Lys-Lys-NH2 as substrate incubated for 120 mins by fluorescence plate reader analysis	ic50	0.7100	uM

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Temozolomide	decreases expression, affects response to substance	2
tobacco tar	decreases reaction, increases expression	1
diallyl disulfide	increases expression, decreases reaction	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
Biotin	increases expression	1
Carmustine	affects response to substance	1
Lipopolysaccharides	increases expression, affects cotreatment, affects response to substance	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Vanadates	increases expression	1
Asbestos, Serpentine	affects expression	1
Asbestos, Crocidolite	affects expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

18 unique, capped per target: 17 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1738398	Functional	PUBCHEM_BIOASSAY: CHOP2 Reporter Counterscreen Assay for Inhibitors of Ubiquitin-specific Protease USP2a. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2281, AID463106, AID463254]	PubChem BioAssay data set
CHEMBL3705370	Binding	Inhibition Assay: Using a 96 well plate (#3915, Costar), a test compound (25 μL), 400 mM Tris-HCl buffer (pH 8.0, 25 μL) and 0.5 mg/mL fluorescence enzyme substrate (Gly-Asp-Asp-Asp-Asp-Lys-β-Naphtylamide, 25 μL) were mixed, and recombinant	Heteroarylcarboxylic acid ester derivative

Clinical trials (associated diseases)

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