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): 683 total — 50 pathogenic, 29 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 1 tissue, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 5
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.12 (unconstrained)
• 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

MANE Select: ENST00000284885

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 5: 2

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.

Highest expression (Bgee): jejunal mucosa, duodenum, olfactory bulb, type B pancreatic cell, cervix squamous epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TMPRSS15 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 1 tissue and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

1 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	4.2e-10	+0.52	21:18262502:C:G

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

showing 100 of 212 tissues 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
esophagus squamous epithelium	UBERON:0006920	65.79	gold quality
superficial temporal artery	UBERON:0001614	65.44	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	65.31	gold quality
lower lobe of lung	UBERON:0008949	65.23	silver quality
small intestine	UBERON:0002108	64.79	gold quality
blood vessel layer	UBERON:0004797	64.34	silver quality
vena cava	UBERON:0004087	63.85	silver quality
oral cavity	UBERON:0000167	63.70	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	63.41	gold quality
periodontal ligament	UBERON:0008266	61.71	gold quality
Brodmann (1909) area 46	UBERON:0006483	61.66	gold quality
secondary oocyte	CL:0000655	61.37	silver quality
epithelium of bronchus	UBERON:0002031	61.04	gold quality
bronchus	UBERON:0002185	60.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	60.83	gold quality
biceps brachii	UBERON:0001507	60.76	gold quality
subthalamic nucleus	UBERON:0001906	60.50	silver quality
cranial nerve II	UBERON:0000941	60.31	gold quality
inferior vagus X ganglion	UBERON:0005363	60.30	silver quality
pericardium	UBERON:0002407	59.87	silver quality
gingival epithelium	UBERON:0001949	59.81	gold quality
calcaneal tendon	UBERON:0003701	59.62	gold quality
ventral tegmental area	UBERON:0002691	59.50	silver quality
mammary duct	UBERON:0001765	59.47	gold quality
body of tongue	UBERON:0011876	59.25	gold quality
cartilage tissue	UBERON:0002418	58.87	gold quality
superior vestibular nucleus	UBERON:0007227	58.66	silver quality
dorsal root ganglion	UBERON:0000044	58.63	silver quality
trigeminal ganglion	UBERON:0001675	58.61	silver quality
synovial joint	UBERON:0002217	58.48	silver quality
pharyngeal mucosa	UBERON:0000355	58.36	silver quality
nipple	UBERON:0002030	58.25	silver quality
cerebellar vermis	UBERON:0004720	58.01	gold quality
pons	UBERON:0000988	57.92	silver quality
pylorus	UBERON:0001166	57.85	silver quality
penis	UBERON:0000989	57.81	gold quality
cardia of stomach	UBERON:0001162	57.81	silver quality
epithelium of nasopharynx	UBERON:0001951	57.80	gold quality
renal medulla	UBERON:0000362	57.76	silver quality
gingiva	UBERON:0001828	57.32	gold quality
tibia	UBERON:0000979	57.30	gold quality
amniotic fluid	UBERON:0000173	57.19	gold quality
lateral nuclear group of thalamus	UBERON:0002736	56.97	gold quality
substantia nigra pars compacta	UBERON:0001965	56.67	gold quality
parotid gland	UBERON:0001831	56.08	gold quality
bone marrow	UBERON:0002371	55.94	gold quality
mucosa of paranasal sinus	UBERON:0005030	55.87	gold quality
bronchial epithelial cell	CL:0002328	54.75	gold quality
colonic mucosa	UBERON:0000317	54.60	gold quality
germinal epithelium of ovary	UBERON:0001304	54.49	gold quality
upper leg skin	UBERON:0004262	53.45	silver quality
mucosa of sigmoid colon	UBERON:0004993	53.43	gold quality
pleura	UBERON:0000977	53.38	gold quality
tendon	UBERON:0000043	53.25	gold quality
skin of hip	UBERON:0001554	53.22	silver quality
trabecular bone tissue	UBERON:0002483	52.97	gold quality
bone marrow cell	CL:0002092	52.60	gold quality
caecum	UBERON:0001153	51.76	gold quality
parietal pleura	UBERON:0002400	51.70	gold quality
visceral pleura	UBERON:0002401	51.40	gold quality
heart right ventricle	UBERON:0002080	50.78	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
inferior olivary complex	UBERON:0002127	50.26	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
lymph node	UBERON:0000029	49.67	gold quality
placenta	UBERON:0001987	49.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	49.26	silver quality
vermiform appendix	UBERON:0001154	49.24	gold 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

HPA expression

RNA tissue specificity: Tissue enriched

46 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Duodenum	tissue	921.9	high
Small intestine	tissue	20.6	high
Postcentral gyrus	tissue	7.9
Olfactory bulb	tissue	7.2
Hippocampus	tissue	6.0	not detected
Nucleus accumbens	tissue	4.4
Locus coeruleus	tissue	4.2
Choroid plexus	tissue	3.0
Spinal cord	tissue	2.6
Corpus callosum	tissue	1.0
Testis	tissue	0.9	not detected
Putamen	tissue	0.8
Lymph node	tissue	0.6	not detected
Hypothalamus	tissue	0.6
Septum	tissue	0.6
Medulla oblongata	tissue	0.5
Hippocampal formation	tissue	0.5
Periaqueductal gray	tissue	0.5
Prefrontal cortex	tissue	0.4
Cerebral cortex	tissue	0.4	not detected
Pons	tissue	0.4
Motor cortex	tissue	0.4
Basal ganglia	tissue	0.4	not detected
Amygdala	tissue	0.4
Midbrain	tissue	0.4
Thalamus	tissue	0.4
Substantia nigra	tissue	0.4
Entorhinal cortex	tissue	0.4
Ventral forebrain	tissue	0.4
Retrosplenial and cingulate cortex	tissue	0.4
Retrosplenial cortex	tissue	0.4
Insular cortex	tissue	0.4
Stomach 1	tissue	0.3	not detected
Somatosensory cortex	tissue	0.3
Temporal cortex	tissue	0.3
Occipital cortex	tissue	0.3
Endometrium 1	tissue	0.2	not detected
Superior colliculi	tissue	0.2
Thyroid gland	tissue	0.2	not detected
Appendix	tissue	0.2	not detected
Skin 1	tissue	0.1	not detected
Heart muscle	tissue	0.1	not detected
Retina	tissue	0.1
Esophagus	tissue	0.1	not detected
Salivary gland	tissue	0.1	not detected
Gallbladder	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Vermis (8.3), Flocculonodular lobe (8.1), Cerebellar cortex (8.0), Somatosensory cortex, postcentral gyrus, ventral (white matter) (7.4), Somatomor cortex, precentral gyrus (white matter) (6.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting TMPRSS15 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 80 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 2.51e-34, LOEUF 1.12, missense Z -0.0398 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000284885 — one region, missense o/e 1.06.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1197523) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 12 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating HDL cholesterol level	1
increased leukocyte cell number	1
decreased body length	1
decreased body weight	1
decreased circulating alanine transaminase level	1
increased circulating chloride level	1
decreased circulating cholesterol level	1
increased mean corpuscular hemoglobin	1
increased blood urea nitrogen level	1
increased circulating sodium level	1
increased circulating amylase level	1
decreased total body fat amount	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Phytophthora sojae	Q945T8	100.0%	Diamond
Pongo abelii	Q5R5E8	99.3%	Diamond
Pan troglodytes	Q5G271	99.2%	Diamond
Macaca fascicularis	Q9BE74	99.0%	Diamond
Pan paniscus	Q2F9P4	98.7%	Diamond
Nomascus leucogenys	Q5G268	98.5%	Diamond
Gorilla gorilla gorilla	Q5G270	98.5%	Diamond
Trachypithecus phayrei	Q5G266	98.3%	Diamond
Macaca mulatta	Q5G267	98.3%	Diamond
Canis lupus familiaris	Q867B7	97.7%	Diamond
Felis catus	Q9BH09	97.7%	Diamond
Bos taurus	Q76BS1	97.4%	Diamond
Tachypleus tridentatus	P28175	97.2%	Diamond
Carcinoscorpius rotundicauda	Q26422	97.2%	Diamond
Pongo pygmaeus	Q5G269	96.7%	Diamond
Manduca sexta	P35045	96.1%	Diamond
Saguinus labiatus	Q5G265	95.5%	Diamond
Rhinella arenarum	Q66TN7	90.6%	Diamond
Bufo japonicus	Q90WD8	90.6%	Diamond
Acropora millepora	B8V7S0	87.4%	Diamond
Sus scrofa	P16293	86.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR548XHG	ncRNA	101927797
CHODL	protein-coding	140578
MIR548X	ncRNA	100422920
LINC03147	ncRNA	54075
C21orf91-OT1	ncRNA	246312
C21orf91	protein-coding	54149

Protein

Protein identifiers

Enteropeptidase — P98073 (reviewed: P98073)

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

All UniProt accessions (2): E9PG70, P98073

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 (108 total): strand 36, glycosylation site 18, disulfide bond 14, helix 11, domain 8, sequence variant 8, 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 by resolution:

PDB	Title	Method	Resolution (Å)
4DGJ	Structure of a human enteropeptidase light chain variant	X-RAY DIFFRACTION	1.9
6ZOV	ENTEROPEPTIDASE IN COMPLEX WITH COMPOUND 6	X-RAY DIFFRACTION	2.19
8ZIY	trypsinogen-EP-E574A	ELECTRON MICROSCOPY	2.64
8ZJ4	trypsinogen-EP-N619A	ELECTRON MICROSCOPY	2.67
7WQX	Structure of Inactive-EP	ELECTRON MICROSCOPY	2.7
8ZIZ	enteropeptidase with N619A	ELECTRON MICROSCOPY	2.89
8ZIW	enteropeptidase with E574A	ELECTRON MICROSCOPY	2.92
8ZI4	Cryo-EM structure of wtEP-trypsinogen	ELECTRON MICROSCOPY	2.95
8ZIV	wtEP-trypsinogen in Tryp-1	ELECTRON MICROSCOPY	2.95
7WR7	Structure of Inhibited-EP	ELECTRON MICROSCOPY	3.1
7WQW	Structure of Active-EP	ELECTRON MICROSCOPY	3.2
7WQZ	Structure of Active-mutEP	ELECTRON MICROSCOPY	3.7
8H3U	Inhibitor-bound EP, polyA model	ELECTRON MICROSCOPY	4.7
8H3S	Substrate-bound EP, polyA model	ELECTRON MICROSCOPY	4.9

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Serine-type peptidases, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Other congenital disorders of metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH enhanced · IF approved

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)

Position	Role
825	charge relay system
876	charge relay system
971	charge relay system

Post-translational modifications (1)

Type	Positions
N-myristoyl glycine	2

Disulfide bonds (14)

Type	Positions
Disulfide bond	184–197, 191–210, 204–221, 225–253, 524–552, 643–655, 650–668, 662–677, 757–767, 810–826, 910–977, 941–956, 967–995
Interchain (between heavy and light chains)	772–896

Glycosylation sites (18)

Type	Positions
N-linked (glcnac…) asparagine	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 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 (2): protein processing (GO:0016485), 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

15 GO namespaces:

Category	Terms
proteolysis	1
protein maturation	1
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

showing 15 of 844 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMPRSS15	AGRN	O00468	839
TMPRSS15	SPINK1	P00995	801
TMPRSS15	MUC1	P13931	667
TMPRSS15	TXN	P10599	622
TMPRSS15	MUC20	Q8N307	599
TMPRSS15	MUC7	Q8TAX7	586
TMPRSS15	MUC21	Q5SSG8	574
TMPRSS15	MUC13	Q9H3R2	568
TMPRSS15	MUC12	Q9UKN1	514
TMPRSS15	MUC17	Q685J3	507
TMPRSS15	NCAM2	O15394	491
TMPRSS15	MUC5B	Q9HC84	490
TMPRSS15	MSR1	P21757	486
TMPRSS15	MUC6	Q6W4X9	479
TMPRSS15	LDLR	P01130	468

IntAct

Human interaction partners of TMPRSS15 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
TNFRSF11A	cleavage reaction	0.440	1

BioGRID (3 interactions; top human partners by supporting records): NR2C2 (Affinity Capture-MS), PYCARD (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for TMPRSS15: 683 ClinVar records (79 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	50
Likely pathogenic	29
Uncertain significance	267
Likely benign	270
Benign	26

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 79 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4164	NM_002772.3(TMPRSS15):c.2135C>G (p.Ser712Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
2628751	NM_002772.3(TMPRSS15):c.2486+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1325205	NM_002772.3(TMPRSS15):c.1922-1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2049508	NM_002772.3(TMPRSS15):c.2033-1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
4165	NM_002772.3(TMPRSS15):c.2569C>T (p.Arg857Ter)	Pathogenic	criteria provided, single submitter	2
4166	NM_002772.3(TMPRSS15):c.781C>T (p.Gln261Ter)	Pathogenic	criteria provided, single submitter	2
4167	NM_002772.3(TMPRSS15):c.2707_2708del (p.Val903fs)	Pathogenic	criteria provided, single submitter	2
1028048	NM_002772.3(TMPRSS15):c.1512del (p.Ser505fs)	Pathogenic	criteria provided, single submitter	1
1935335	NM_002772.3(TMPRSS15):c.1312dup (p.Ser438fs)	Pathogenic	criteria provided, single submitter	1
1997513	NM_002772.3(TMPRSS15):c.2441_2442dup (p.Val815fs)	Pathogenic	criteria provided, single submitter	1
2004823	NM_002772.3(TMPRSS15):c.1929C>A (p.Cys643Ter)	Pathogenic	criteria provided, single submitter	1
2028638	NM_002772.3(TMPRSS15):c.622_626del (p.Val208fs)	Pathogenic	criteria provided, single submitter	1
2030242	NM_002772.3(TMPRSS15):c.2514del (p.Ala839fs)	Pathogenic	criteria provided, single submitter	1
2034097	NM_002772.3(TMPRSS15):c.1012G>T (p.Glu338Ter)	Pathogenic	criteria provided, single submitter	1
2090917	NM_002772.3(TMPRSS15):c.1320dup (p.Ile441fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore TMPRSS15’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 2,124):

Position(s)	Effect	Δscore	Sites
21:18297830–18297831	acceptor_loss	1.0000	5
21:18329167–18329168	donor_loss	1.0000	4
21:18329295–18329296	acceptor_loss	1.0000	2
21:18352962	donor_gain	1.0000
21:18353721–18353722	donor_loss	1.0000	4
21:18353864–18353865	acceptor_loss	1.0000	2
21:18383625–18383626	donor_loss	1.0000	5
21:18396105	donor_gain	1.0000
21:18275195–18275196	donor_loss	0.9900	6
21:18278962–18278963	donor_loss	0.9900	5

AlphaMissense

1,449 missense substitutions predicted likely pathogenic (of 6,747 scored), across 407 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D876	8	0.945	0.978
D578	8	0.925	0.958
D493	8	0.918	0.959
F627	8	0.905	0.987
F349	8	0.900	0.970
F568	8	0.893	0.975
D383	8	0.890	0.926
F537	8	0.863	0.978
F425	8	0.862	0.973
D970	8	0.857	0.936
D965	8	0.817	0.908
H384	8	0.793	0.949
H825	8	0.773	0.860
D215	8	0.747	0.870
W462	7	0.978	0.995
C826	7	0.973	0.983
C967	7	0.969	0.981
C810	7	0.963	0.981
C956	7	0.963	0.980
W366	7	0.962	0.995

HPA cancer prognostics

RNA cancer specificity: Group enriched (Liver Hepatocellular Carcinoma, Pancreatic Adenocarcinoma, Stomach Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000149

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital enteropathy due to enteropeptidase deficiency	Strong	Autosomal recessive	4

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Intestinal failure or congenital diarrhoea	green

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

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

HPO phenotypes

5 phenotypes (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:

Study	Trait	p-value
GCST010724_2	HOMA-B (corrected for HOMA-IR)	2e-7
GCST005241_2	Nucleus accumbens volume in trauma-exposed individuals	3e-7
GCST001958_14	Bulimia nervosa	1e-6
GCST005212_11	Asthma	6e-6

EFO canonical traits (from GWAS)

2 canonical traits:

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

MeSH disease descriptors

1 disease descriptors:

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 (CPIC guideline: no)

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)

422 measured of 422 human assays (422 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
(Z)-3-((6-((4-Carbamimidoyl-2-fluorophenoxy)carbonyl)-3-ethylbenzo[d]thiazole-2(3H)-ylidine)amino)-2,2-dimethylpropanoic Acid	KI	0.16 nM	US-11447480: Compound exhibiting enteropeptidase inhibitory activity
(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

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	decreases reaction, increases expression	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	affects response to substance, increases expression, affects cotreatment	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TMPRSS15 across ~30M SureChEMBL compounds — explore on Sugi Predict.