TPSD1

Summary

TPSD1 (tryptase delta 1, HGNC:14118) is a protein-coding gene on chromosome 16p13.3, encoding Tryptase delta (Q9BZJ3). Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type.

Tryptases comprise a family of trypsin-like serine proteases, the peptidase family S1. Tryptases are enzymatically active only as heparin-stabilized tetramers, and they are resistant to all known endogenous proteinase inhibitors. Several tryptase genes are clustered on chromosome 16p13.3. These genes are characterized by several distinct features. They have a highly conserved 3’ UTR and contain tandem repeat sequences at the 5’ flank and 3’ UTR which are thought to play a role in regulation of the mRNA stability. Although this gene may be an exception, most of the tryptase genes have an intron immediately upstream of the initiator Met codon, which separates the site of transcription initiation from protein coding sequence. This feature is characteristic of tryptases but is unusual in other genes. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders. This gene was once considered to be a pseudogene, although it is now believed to be a functional gene that encodes a protein.

Source: NCBI Gene 23430 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 76 total
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency dosage sensitivity unlikely, triplosensitivity no evidence
• MANE Select transcript: NM_012217

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14118
Approved symbol	TPSD1
Name	tryptase delta 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000095917
Ensembl biotype	protein_coding
OMIM	609272
Entrez	23430

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000211076, ENST00000397534, ENST00000711393

RefSeq mRNA: 1 — MANE Select: NM_012217 NM_012217

CCDS: CCDS10432

Canonical transcript exons

ENST00000211076 — 5 exons

Exon	Start	End
ENSE00000615327	1258059	1258222
ENSE00001649278	1256797	1257062
ENSE00001693239	1256069	1256362
ENSE00001741135	1256516	1256687
ENSE00003745645	1258332	1259008

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 84.34.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 6.1911 / max 2406.5168, expressed in 83 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152067	2.1294	52
152076	1.8193	18
152069	0.8314	22
152075	0.6806	17
152068	0.2496	20
152074	0.1879	13
152073	0.1185	12
152071	0.0733	9
152070	0.0701	8
152072	0.0311	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	84.34	gold quality
right lung	UBERON:0002167	80.37	gold quality
lower esophagus muscularis layer	UBERON:0035833	79.25	gold quality
lower esophagus	UBERON:0013473	78.86	gold quality
fundus of stomach	UBERON:0001160	78.21	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	77.37	gold quality
urinary bladder	UBERON:0001255	77.33	gold quality
body of stomach	UBERON:0001161	77.09	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.29	gold quality
skin of leg	UBERON:0001511	75.88	gold quality
small intestine	UBERON:0002108	75.42	gold quality
upper lobe of left lung	UBERON:0008952	75.36	gold quality
right coronary artery	UBERON:0001625	75.11	gold quality
esophagus	UBERON:0001043	74.52	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.89	gold quality
ectocervix	UBERON:0012249	73.69	gold quality
zone of skin	UBERON:0000014	73.61	gold quality
smooth muscle tissue	UBERON:0001135	72.82	gold quality
stomach	UBERON:0000945	72.40	gold quality
transverse colon	UBERON:0001157	72.05	gold quality
skin of abdomen	UBERON:0001416	71.16	gold quality
duodenum	UBERON:0002114	71.16	gold quality
esophagus mucosa	UBERON:0002469	71.11	gold quality
body of uterus	UBERON:0009853	71.02	gold quality
gall bladder	UBERON:0002110	70.58	gold quality
adipose tissue	UBERON:0001013	70.47	gold quality
vagina	UBERON:0000996	70.34	gold quality
intestine	UBERON:0000160	69.57	gold quality
lung	UBERON:0002048	69.40	gold quality
colon	UBERON:0001155	68.88	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	8549.98
E-MTAB-9801	yes	3857.58
E-ANND-3	yes	26.06
E-CURD-122	yes	17.29
E-MTAB-10042	yes	9.68
E-GEOD-130148	yes	9.32
E-MTAB-9543	no	2380.13
E-MTAB-6678	no	3.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, FOS, JUN, MITF, SMAD3, SMAD4

miRNA regulators (miRDB)

7 targeting TPSD1, 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-6772-5P	99.94	67.01	577
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-4652-5P	96.46	64.22	553
HSA-MIR-3165	96.18	66.22	473

Functional genomics

ClinGen dosage: haploinsufficiency 40 (dosage sensitivity unlikely), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 2)

• Delta tryptase transcripts have been detected in a wide variety of tissues including lung, heart, stomach, spleen, skin, and colon, and a recombinant form is proteolytically active. (PMID:12391231)
• Increase in TPSB2 and TPSD1 Expression in Synovium of Hip Osteoarthritis Patients Who Are Overweight. (PMID:37511292)

Cross-species orthologs

55 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-16l2.17	ENSDARG00000027196
danio_rerio	gzmk	ENSDARG00000028780
danio_rerio	zgc:92313	ENSDARG00000040513
danio_rerio	zgc:112038	ENSDARG00000046140
danio_rerio	si:dkeyp-93a5.2	ENSDARG00000052064
danio_rerio	zgc:165423	ENSDARG00000052905
danio_rerio	prss60.2	ENSDARG00000055644
danio_rerio	zgc:123295	ENSDARG00000056324
danio_rerio	zgc:163079	ENSDARG00000056773
danio_rerio	zgc:153968	ENSDARG00000061858
danio_rerio	si:dkey-32n7.7	ENSDARG00000063444
danio_rerio	prss60.3	ENSDARG00000070710
danio_rerio	prss60.1	ENSDARG00000070713
danio_rerio	si:dkey-32n7.9	ENSDARG00000071841
danio_rerio	gzma	ENSDARG00000090380
danio_rerio	si:dkey-9p24.5	ENSDARG00000094330
danio_rerio		ENSDARG00000101956
danio_rerio		ENSDARG00000101990
drosophila_melanogaster	ea	FBGN0000533
drosophila_melanogaster	Ser6	FBGN0011834
drosophila_melanogaster	CG4793	FBGN0028514
drosophila_melanogaster	CG18478	FBGN0028517
drosophila_melanogaster	CG18477	FBGN0028864
drosophila_melanogaster	CG9676	FBGN0030773
drosophila_melanogaster	CG4653	FBGN0030776
drosophila_melanogaster	CG1304	FBGN0031141
drosophila_melanogaster	CG4259	FBGN0031389
drosophila_melanogaster	CG18557	FBGN0031470
drosophila_melanogaster	CG3117	FBGN0031471
drosophila_melanogaster	CG3355	FBGN0031619
drosophila_melanogaster	CG5390	FBGN0032213
drosophila_melanogaster	SPH93	FBGN0032638
drosophila_melanogaster	CG18563	FBGN0032639
drosophila_melanogaster	CG8586	FBGN0033320
drosophila_melanogaster	CG8738	FBGN0033321
drosophila_melanogaster	CG8172	FBGN0033362
drosophila_melanogaster	tpr	FBGN0034661
drosophila_melanogaster	CG9294	FBGN0034666
drosophila_melanogaster	CG14990	FBGN0035496
drosophila_melanogaster	CG6462	FBGN0035663
drosophila_melanogaster	CG4613	FBGN0036427
drosophila_melanogaster	CG9372	FBGN0036891
drosophila_melanogaster	Sp7	FBGN0037515
drosophila_melanogaster	CG11836	FBGN0039272
drosophila_melanogaster	CG9737	FBGN0039758
drosophila_melanogaster	CG9733	FBGN0039759
drosophila_melanogaster	CG11313	FBGN0039798
drosophila_melanogaster	CG18735	FBGN0042098
drosophila_melanogaster	CG31780	FBGN0051780
drosophila_melanogaster	CG31827	FBGN0051827
drosophila_melanogaster	CG32376	FBGN0052376
drosophila_melanogaster	CG32523	FBGN0052523
drosophila_melanogaster	CG40160	FBGN0058160
drosophila_melanogaster	flz	FBGN0286782
caenorhabditis_elegans		WBGENE00006619

Paralogs (3): TPSG1 (ENSG00000116176), TPSAB1 (ENSG00000172236), TPSB2 (ENSG00000197253)

Protein

Protein identifiers

Tryptase delta — Q9BZJ3 (reviewed: Q9BZJ3)

Alternative names: Delta-tryptase, HmMCP-3-like tryptase III, Mast cell mMCP-7-like, Tryptase-3

All UniProt accessions (2): Q9BZJ3, A0A0C4DFZ7

UniProt curated annotations — full annotation on UniProt →

Function. Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type.

Subunit / interactions. Homotetramer.

Subcellular location. Secreted.

Tissue specificity. Expressed in colon, lung, heart and synovial tissue. May be specific to mast cells.

Similarity. Belongs to the peptidase S1 family. Tryptase subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BZJ3-1	1	yes
Q9BZJ3-2	2

RefSeq proteins (1): NP_036349* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00089

UniProt features (17 total): disulfide bond 3, sequence variant 3, active site 3, sequence conflict 2, signal peptide 1, propeptide 1, splice variant 1, chain 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZJ3-F1	85.89	0.71

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): 81 (charge relay system); 128 (charge relay system); 231 (charge relay system)

Disulfide bonds (3): 195–218, 66–82, 162–237

Glycosylation sites (1): 139

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, MARTINEZ_RB1_TARGETS_UP, MARTINEZ_RB1_AND_TP53_TARGETS_UP, LEIN_CHOROID_PLEXUS_MARKERS, GOBP_PROTEOLYSIS, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, GOMF_PEPTIDASE_ACTIVITY, VILIMAS_NOTCH1_TARGETS_DN, YOSHIMURA_MAPK8_TARGETS_UP, SCHRAETS_MLL_TARGETS_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, PRC1_BMI_UP.V1_DN, PDGF_UP.V1_DN, ZNF329_TARGET_GENES, MIR6810_5P

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

GO Molecular Function (4): serine-type endopeptidase activity (GO:0004252), serine-type peptidase activity (GO:0008236), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

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

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
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPSD1	CPA3	P15088	459
TPSD1	CPA4	Q9UI42	444
TPSD1	CCDC9	Q9Y3X0	314
TPSD1	ZNF98	A6NK75	311
TPSD1	ZNF141	Q15928	305
TPSD1	FAM234A	Q9H0X4	278
TPSD1	CDH26	Q8IXH8	277
TPSD1	SRGN	P10124	272
TPSD1	CTSC	P53634	272
TPSD1	CPAMD8	Q8IZJ3	270
TPSD1	Q5T8A5	Q5T8A5	269
TPSD1	PGAP6	Q9HCN3	247
TPSD1	CAPN14	A8MX76	235
TPSD1	HLA-DOA	P06340	225
TPSD1	TESPA1	A2RU30	224

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A1L453, A6NIE9, O43240, P07288, P15944, P20151, P20231, P33619, P49862, P51124, P51779, P83748, Q03238, Q14B24, Q15661, Q16651, Q2L4Q9, Q2UVH8, Q571E5, Q5K2P8, Q5K2P9, Q61096, Q6BEA2, Q6DT45, Q6IE59, Q6IE62, Q6UWY2, Q76B45, Q7JIG6, Q7RTY9, Q7Z5A4, Q80WM7, Q8K4I7, Q920S2, Q92876, Q9BQR3, Q9BZJ3, Q9ER04, Q9ES87, Q9ESD1

Diamond homologs: A0A1B0GVH4, A1L453, A2VE36, E5RG02, F2YMG0, O35205, O35453, O60235, O97370, P03952, P05981, P06868, P08001, P08709, P10323, P14272, P19236, P20231, P22457, P23578, P26262, P29293, P29786, P35035, P35036, P35038, P35039, P35040, P35041, P39675, P49275, P49864, P50342, P69526, P70375, P83748, P98139, Q05511, Q14B25, Q14BX2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

926 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1256363:GTGA:G	donor_loss	1.0000
16:1256364:T:G	donor_loss	1.0000
16:1256363:G:GG	donor_gain	0.9900
16:1256365:GAG:G	donor_loss	0.9900
16:1256982:TC:T	donor_gain	0.9900
16:1257061:TGG:T	donor_loss	0.9900
16:1257062:GGT:G	donor_loss	0.9900
16:1257063:G:A	donor_loss	0.9900
16:1257064:T:A	donor_loss	0.9900
16:1258057:A:AG	acceptor_gain	0.9900
16:1258058:G:GG	acceptor_gain	0.9900
16:1256983:C:A	donor_gain	0.9800
16:1257998:A:G	acceptor_gain	0.9800
16:1256360:CTG:C	donor_gain	0.9700
16:1256361:TG:T	donor_gain	0.9700
16:1256362:GG:G	donor_gain	0.9700
16:1256793:CCA:C	acceptor_loss	0.9700
16:1256794:CA:C	acceptor_loss	0.9700
16:1256795:A:AG	acceptor_gain	0.9700
16:1256796:G:GG	acceptor_gain	0.9700
16:1256822:AG:A	acceptor_gain	0.9700
16:1256823:GG:G	acceptor_gain	0.9700
16:1257019:G:T	donor_gain	0.9700
16:1258218:GCCAG:G	donor_loss	0.9700
16:1258219:CCAGG:C	donor_loss	0.9700
16:1258220:CAGGT:C	donor_loss	0.9700
16:1258221:AG:A	donor_loss	0.9700
16:1258222:GG:G	donor_loss	0.9700
16:1258223:GTGGG:G	donor_loss	0.9700
16:1258224:T:A	donor_loss	0.9700

AlphaMissense

1575 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1257043:G:C	W167C	0.997
16:1257043:G:T	W167C	0.997
16:1258121:T:A	C195S	0.996
16:1258122:G:C	C195S	0.996
16:1258190:T:A	C218S	0.995
16:1258191:G:C	C218S	0.995
16:1256658:G:C	W75C	0.993
16:1256658:G:T	W75C	0.993
16:1257028:C:G	C162W	0.992
16:1258336:A:C	D230A	0.992
16:1258336:A:T	D230V	0.992
16:1256580:G:C	W49C	0.991
16:1256580:G:T	W49C	0.991
16:1256630:G:A	C66Y	0.991
16:1256930:G:C	A130P	0.991
16:1256934:T:C	L131P	0.991
16:1257027:G:A	C162Y	0.991
16:1258122:G:A	C195Y	0.991
16:1256586:G:C	W51C	0.990
16:1256586:G:T	W51C	0.990
16:1256900:T:C	F120L	0.990
16:1256902:C:A	F120L	0.990
16:1256902:C:G	F120L	0.990
16:1256925:A:T	D128V	0.990
16:1257026:T:A	C162S	0.990
16:1257027:G:C	C162S	0.990
16:1257041:T:A	W167R	0.990
16:1257041:T:C	W167R	0.990
16:1258337:C:A	D230E	0.990
16:1258337:C:G	D230E	0.990

dbSNP variants (sampled 300 via entrez): RS1000439247 (16:1255546 C>T), RS1000620971 (16:1259222 G>A), RS1000893300 (16:1256158 T>G), RS1002173952 (16:1257233 G>A,C,T), RS1002615816 (16:1259009 G>A), RS1002835161 (16:1258989 A>G), RS1003040370 (16:1259130 G>A), RS1003954688 (16:1254640 C>G), RS1004409676 (16:1255422 T>A), RS1005199427 (16:1258519 G>A,C), RS1006039215 (16:1259161 G>A), RS1007020538 (16:1258439 C>T), RS1010371515 (16:1256189 G>A), RS1011093264 (16:1258044 C>T), RS1011383894 (16:1257263 C>A,G)

Disease associations

OMIM: gene MIM:609272 | disease phenotypes: MIM:600057

GenCC curated gene-disease

Mondo (1): bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039)

Orphanet (1): Classic bladder exstrophy (Orphanet:93930)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005588_7	Idiopathic dilated cardiomyopathy	3.000000e-06
GCST010002_107	Refractive error	6.000000e-18

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009094	idiopathic dilated cardiomyopathy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2095193 (PROTEIN FAMILY)

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

ChEMBL bioactivities

230 potent at pChembl≥5 of 245 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.72	Ki	0.019	nM	CHEMBL113452
10.55	Ki	0.028	nM	CHEMBL112240
10.54	Ki	0.029	nM	CHEMBL324622
10.34	Ki	0.046	nM	CHEMBL112197
10.24	Ki	0.057	nM	CHEMBL322345
10.15	Ki	0.07	nM	CHEMBL46809
10.00	Ki	0.1	nM	CHEMBL431969
10.00	Ki	0.1	nM	CHEMBL311655
9.92	Ki	0.12	nM	CHEMBL112049
9.70	Ki	0.2	nM	CHEMBL311482
9.40	IC50	0.4	nM	CHEMBL322526
9.40	Ki	0.4	nM	CHEMBL448786
9.40	Ki	0.4	nM	CHEMBL75750
9.40	Ki	0.4	nM	CHEMBL432172
9.40	Ki	0.4	nM	CHEMBL297220
9.30	Ki	0.5	nM	CHEMBL42900
9.30	Ki	0.5	nM	CHEMBL309830
9.30	Ki	0.5	nM	CHEMBL75972
9.22	Ki	0.6	nM	CHEMBL310290
9.15	IC50	0.7	nM	CHEMBL322538
9.15	IC50	0.7	nM	CHEMBL110061
9.15	Ki	0.7	nM	CHEMBL76883
9.07	Ki	0.85	nM	CHEMBL43938
9.04	Ki	0.91	nM	CHEMBL40491
9.00	IC50	1	nM	CHEMBL111250
9.00	IC50	1	nM	CHEMBL443539
9.00	IC50	1	nM	CHEMBL109888
9.00	IC50	1	nM	CHEMBL72532
9.00	IC50	1	nM	CHEMBL72708
9.00	IC50	1	nM	CHEMBL70350
9.00	IC50	1	nM	CHEMBL304359
9.00	IC50	1	nM	CHEMBL69394
9.00	Ki	1	nM	CHEMBL308763
8.96	Ki	1.1	nM	CHEMBL111643
8.95	Ki	1.12	nM	CHEMBL42898
8.77	IC50	1.7	nM	CHEMBL303437
8.74	IC50	1.8	nM	CHEMBL306448
8.72	IC50	1.9	nM	CHEMBL109504
8.70	Ki	2	nM	CHEMBL75679
8.70	Ki	2	nM	CHEMBL76424
8.52	IC50	3	nM	CHEMBL107493
8.52	Ki	3	nM	CHEMBL308632
8.52	Ki	3	nM	CHEMBL311043
8.40	IC50	4	nM	CHEMBL71037
8.40	IC50	4	nM	CHEMBL302058
8.40	IC50	4	nM	CHEMBL321622
8.40	IC50	4	nM	CHEMBL70813
8.40	Ki	4	nM	CHEMBL80930
8.40	Ki	4	nM	CHEMBL76796
8.40	Ki	4	nM	CHEMBL308630

PubChem BioAssay actives

239 with measured affinity, of 330 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[4-[9-[4-(5-carbamimidoyl-1-benzofuran-2-carbonyl)piperazin-1-yl]-9-oxononanoyl]piperazine-1-carbonyl]-1-benzofuran-5-carboximidamide	213504: Inhibition of tryptase activity	ki	<0.0001	uM
2-[4-[2-[4-[2-[4-(5-carbamimidoyl-1-benzothiophene-2-carbonyl)piperazin-1-yl]-2-oxoethoxy]phenoxy]acetyl]piperazine-1-carbonyl]-1-benzothiophene-5-carboximidamide	213504: Inhibition of tryptase activity	ki	<0.0001	uM
2-[4-[2-[4-[2-[4-(5-carbamimidoyl-6,7-dihydro-4H-thieno[3,2-c]pyridine-2-carbonyl)piperazin-1-yl]-2-oxoethoxy]phenoxy]acetyl]piperazine-1-carbonyl]-6,7-dihydro-4H-thieno[3,2-c]pyridine-5-carboximidamide	213504: Inhibition of tryptase activity	ki	<0.0001	uM
2-[4-[2-[5-[2-[4-(5-carbamimidoyl-1-benzofuran-2-carbonyl)piperazin-1-yl]-2-oxoethoxy]cyclooctyl]oxyacetyl]piperazine-1-carbonyl]-1-benzofuran-5-carboximidamide	213504: Inhibition of tryptase activity	ki	<0.0001	uM
[5-[4-[[4-(aminomethyl)phenyl]methylcarbamoyl]piperazine-1-carbonyl]oxycyclooctyl] 4-[[4-(aminomethyl)phenyl]methylcarbamoyl]piperazine-1-carboxylate	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0001	uM
2-[4-[2-[4-[2-[4-(5-carbamimidoyl-1-benzofuran-2-carbonyl)piperazin-1-yl]-2-oxoethoxy]phenoxy]acetyl]piperazine-1-carbonyl]-1-benzofuran-5-carboximidamide	213504: Inhibition of tryptase activity	ki	0.0001	uM
2-[4-[8-[4-(5-carbamimidoyl-1-benzofuran-2-carbonyl)piperazin-1-yl]-8-oxooctanoyl]piperazine-1-carbonyl]-1-benzofuran-5-carboximidamide	213504: Inhibition of tryptase activity	ki	0.0001	uM
N-[[4-(diaminomethylideneamino)phenyl]methyl]-4-[8-[4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazin-1-yl]-8-oxooctanoyl]piperazine-1-carboxamide	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0001	uM
[5-[4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carbonyl]oxycyclooctyl] 4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carboxylate	213377: Inhibition of Tryptase in human mast cells	ki	0.0001	uM
[5-[4-[2-(4-carbamimidoylphenyl)acetyl]piperazine-1-carbonyl]oxycyclooctyl] 4-[2-(4-carbamimidoylphenyl)acetyl]piperazine-1-carboxylate	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0002	uM
[4-[[4-[[(4-carbamimidoylbenzoyl)amino]methyl]piperidine-1-carbonyl]oxymethyl]phenyl]methyl 4-[[(4-carbamimidoylbenzoyl)amino]methyl]piperidine-1-carboxylate	213377: Inhibition of Tryptase in human mast cells	ki	0.0004	uM
[5-[4-[3-(4-carbamimidoylphenyl)propanoyl]piperazine-1-carbonyl]oxycyclooctyl] 4-[3-(4-carbamimidoylphenyl)propanoyl]piperazine-1-carboxylate	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0004	uM
[4-[[4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carbonyl]oxymethyl]-1-bicyclo[2.2.2]octanyl]methyl 4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carboxylate	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0004	uM
[4-[[4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carbonyl]oxymethyl]phenyl]methyl 4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carboxylate	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0004	uM
tert-butyl 4-[(2S,3R)-2-carbamoyl-3-[3-(diaminomethylideneamino)propyl]-4-oxoazetidine-1-carbonyl]piperazine-1-carboxylate	91664: In vitro inhibition of human tryptase.	ic50	0.0004	uM
[5-[4-[2-[4-(diaminomethylideneamino)phenyl]acetyl]piperazine-1-carbonyl]oxycyclooctyl] 4-[2-[4-(diaminomethylideneamino)phenyl]acetyl]piperazine-1-carboxylate	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0005	uM
[5-[4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carbonyl]oxycyclooctyl] 4-(5-aminopentylcarbamoyl)piperazine-1-carboxylate	213377: Inhibition of Tryptase in human mast cells	ki	0.0005	uM
N-[[4-(diaminomethylideneamino)phenyl]methyl]-4-[9-[4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazin-1-yl]-9-oxononanoyl]piperazine-1-carboxamide	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0005	uM
[4-[[2-[[4-(aminomethyl)phenyl]methylamino]-2-oxoethyl]carbamoyloxymethyl]phenyl]methyl N-[2-[[4-(aminomethyl)phenyl]methylamino]-2-oxoethyl]carbamate	213375: Binding affinity against Tryptase.	ki	0.0006	uM
N-[[4-(diaminomethylideneamino)phenyl]methyl]-4-[10-[4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazin-1-yl]-10-oxodecanoyl]piperazine-1-carboxamide	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0007	uM
(2S,3R)-3-[3-(diaminomethylideneamino)propyl]-4-oxo-1-[4-(2-phenylethoxycarbonyl)piperazine-1-carbonyl]azetidine-2-carboxylic acid	91664: In vitro inhibition of human tryptase.	ic50	0.0007	uM
tert-butyl 4-[(2S,3R)-3-[3-(diaminomethylideneamino)propyl]-2-(methylcarbamoyl)-4-oxoazetidine-1-carbonyl]piperazine-1-carboxylate	91664: In vitro inhibition of human tryptase.	ic50	0.0007	uM
[5-[4-[[(4-carbamimidoylbenzoyl)amino]methyl]piperidine-1-carbonyl]oxycyclooctyl] 4-[[(4-carbamimidoylbenzoyl)amino]methyl]piperidine-1-carboxylate	213377: Inhibition of Tryptase in human mast cells	ki	0.0008	uM
[5-[4-[(4-carbamimidoylphenyl)methylcarbamoyl]piperazine-1-carbonyl]oxycyclooctyl] 4-(2-piperidin-4-ylethylcarbamoyl)piperazine-1-carboxylate	213377: Inhibition of Tryptase in human mast cells	ki	0.0009	uM
(2S,3R)-4-oxo-1-[4-[2-(4-phenylmethoxyphenyl)acetyl]piperazine-1-carbonyl]-3-(piperidin-4-ylmethyl)azetidine-2-carboxylic acid	213372: Inhibitory activity against human tryptase	ic50	0.0010	uM
(2S,3R)-4-oxo-1-[4-(6-phenylhexanoyl)piperazine-1-carbonyl]-3-(piperidin-4-ylmethyl)azetidine-2-carboxylic acid	213371: Inhibitory activity of compound against human tryptase was determined	ic50	0.0010	uM
(2S,3R)-1-[4-(6-naphthalen-1-ylhexanoyl)piperazine-1-carbonyl]-4-oxo-3-(piperidin-4-ylmethyl)azetidine-2-carboxylic acid	213372: Inhibitory activity against human tryptase	ic50	0.0010	uM
(2S,3R)-1-[4-(7-naphthalen-1-ylheptanoyl)piperazine-1-carbonyl]-4-oxo-3-(piperidin-4-ylmethyl)azetidine-2-carboxylic acid	213372: Inhibitory activity against human tryptase	ic50	0.0010	uM
(2S,3R)-1-[4-(6-naphthalen-2-ylhexanoyl)piperazine-1-carbonyl]-4-oxo-3-(piperidin-4-ylmethyl)azetidine-2-carboxylic acid	213372: Inhibitory activity against human tryptase	ic50	0.0010	uM
[5-[4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carbonyl]oxycyclooctyl] 4-[(4-aminocyclohexyl)methylcarbamoyl]piperazine-1-carboxylate	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0010	uM
(2S,3R)-3-[3-(diaminomethylideneamino)propyl]-4-oxo-1-(4-phenylphenyl)sulfonylazetidine-2-carboxylic acid	91664: In vitro inhibition of human tryptase.	ic50	0.0010	uM
(2S,3R)-3-[3-(diaminomethylideneamino)propyl]-4-oxo-1-(thiophene-2-carbonyl)azetidine-2-carboxylic acid	91664: In vitro inhibition of human tryptase.	ic50	0.0010	uM
(2S,3R)-3-[3-(diaminomethylideneamino)propyl]-4-oxo-1-(4-phenylbenzoyl)azetidine-2-carboxylic acid	91664: In vitro inhibition of human tryptase.	ic50	0.0010	uM
[5-[4-[(4-carbamimidoylphenyl)methylcarbamoyl]piperazine-1-carbonyl]oxycyclooctyl] 4-(4-piperidin-4-ylbutanoyl)piperazine-1-carboxylate	213377: Inhibition of Tryptase in human mast cells	ki	0.0011	uM
2-[4-[2-[2-[2-[4-(5-carbamimidoyl-1-benzofuran-2-carbonyl)piperazin-1-yl]-2-oxoethoxy]phenoxy]acetyl]piperazine-1-carbonyl]-1-benzofuran-5-carboximidamide	213504: Inhibition of tryptase activity	ki	0.0011	uM
(2S,3R)-3-[[(3R)-1-carbamimidoylpiperidin-3-yl]methyl]-4-oxo-1-[4-(6-phenylhexanoyl)piperazine-1-carbonyl]azetidine-2-carboxylic acid	213371: Inhibitory activity of compound against human tryptase was determined	ic50	0.0017	uM
(2S,3R)-3-(4-aminobutyl)-4-oxo-1-[4-(6-phenylhexanoyl)piperazine-1-carbonyl]azetidine-2-carboxylic acid	213371: Inhibitory activity of compound against human tryptase was determined	ic50	0.0017	uM
(2S,3R)-3-[(1-carbamimidoylpiperidin-3-yl)methyl]-4-oxo-1-[4-(3-phenoxypropoxycarbonyl)piperazine-1-carbonyl]azetidine-2-carboxylic acid	213382: Inhibitory concentration against human tryptase	ic50	0.0017	uM
(2S,3R)-3-[(1-carbamimidoylpiperidin-3-yl)methyl]-4-oxo-1-[4-(4-phenylbutylcarbamoyl)piperazine-1-carbonyl]azetidine-2-carboxylic acid	213382: Inhibitory concentration against human tryptase	ic50	0.0017	uM
(2S,3R)-3-[[(3S)-1-carbamimidoylpiperidin-3-yl]methyl]-4-oxo-1-[4-(6-phenylhexanoyl)piperazine-1-carbonyl]azetidine-2-carboxylic acid	213371: Inhibitory activity of compound against human tryptase was determined	ic50	0.0017	uM
(2S,3R)-3-[(1-carbamimidoylpiperidin-3-yl)methyl]-4-oxo-1-[4-(6-phenylhexanoyl)piperazine-1-carbonyl]azetidine-2-carboxylic acid	213382: Inhibitory concentration against human tryptase	ic50	0.0017	uM
(2S,3R)-3-[3-(diaminomethylideneamino)propyl]-4-oxo-1-[4-(6-phenylhexanoyl)piperazine-1-carbonyl]azetidine-2-carboxylic acid	213382: Inhibitory concentration against human tryptase	ic50	0.0017	uM
(2S,3R)-4-oxo-1-[4-(6-phenylhexanoyl)piperazine-1-carbonyl]-3-(2-piperidin-3-ylethyl)azetidine-2-carboxylic acid	213371: Inhibitory activity of compound against human tryptase was determined	ic50	0.0018	uM
(2S,3R)-3-[(1-carbamimidoylpiperidin-3-yl)methyl]-1-[4-(6-cyclohexylhexanoyl)piperazine-1-carbonyl]-4-oxoazetidine-2-carboxylic acid	213382: Inhibitory concentration against human tryptase	ic50	0.0019	uM
[5-[4-[3-(1-carbamimidoylpiperidin-4-yl)propanoyl]piperazine-1-carbonyl]oxycyclooctyl] 4-[3-(1-carbamimidoylpiperidin-4-yl)propanoyl]piperazine-1-carboxylate	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0020	uM
[5-[4-[2-[4-(2-aminoethyl)phenyl]acetyl]piperazine-1-carbonyl]oxycyclooctyl] 4-[2-[4-(2-aminoethyl)phenyl]acetyl]piperazine-1-carboxylate	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0020	uM
[4-[[4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carbonyl]oxymethyl]cyclohexyl]methyl 4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carboxylate	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0030	uM
[5-[4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carbonyl]oxycyclooctyl] 4-(2-piperidin-4-ylethylcarbamoyl)piperazine-1-carboxylate	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0030	uM
tert-butyl 4-[(3R,4S)-3-[3-(diaminomethylideneamino)propyl]-2-oxo-4-(piperidine-1-carbonyl)azetidine-1-carbonyl]piperazine-1-carboxylate	91664: In vitro inhibition of human tryptase.	ic50	0.0030	uM
[5-[4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carbonyl]oxycyclooctyl] 4-(4-aminobutylcarbamoyl)piperazine-1-carboxylate	213511: Evaluated for its inhibitory potency against tryptase	ki	0.0040	uM

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, increases abundance	2
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Allergens	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Coal	increases abundance, increases expression	1
Smoke	increases abundance, increases expression	1
Valproic Acid	increases methylation	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

35 unique, capped per target: 35 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3578609	Binding	Inhibition of tryptase (unknown origin) at 100 uM	Novel Small Molecule Inhibitors of Activated Thrombin Activatable Fibrinolysis Inhibitor (TAFIa) from Natural Product Anabaenopeptin. — J Med Chem

Clinical trials (associated diseases)

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