TPSG1

Summary

TPSG1 (tryptase gamma 1, HGNC:14134) is a protein-coding gene on chromosome 16p13.3, encoding Tryptase gamma (Q9NRR2).

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. There is uncertainty regarding the number of genes in this cluster. Currently four functional genes - alpha I, beta I, beta II and gamma I - have been identified. And beta I has an allelic variant named alpha II, beta II has an allelic variant beta III, also gamma I has an allelic variant gamma II. Beta tryptases appear to be the main isoenzymes expressed in mast cells; whereas in basophils, alpha-tryptases predominant. This gene differs from other members of the tryptase gene family in that it has C-terminal hydrophobic domain, which may serve as a membrane anchor. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders.

Source: NCBI Gene 25823 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 98 total
• Druggable target: yes
• MANE Select transcript: NM_012467

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14134
Approved symbol	TPSG1
Name	tryptase gamma 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	TMT, PRSS31
Ensembl gene	ENSG00000116176
Ensembl biotype	protein_coding
OMIM	609341
Entrez	25823

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000234798, ENST00000564684, ENST00000711428, ENST00000711429

RefSeq mRNA: 1 — MANE Select: NM_012467 NM_012467

CCDS: CCDS10430

Canonical transcript exons

ENST00000234798 — 6 exons

Exon	Start	End
ENSE00000772269	1222652	1222917
ENSE00000772270	1222196	1222341
ENSE00000822956	1221651	1222096
ENSE00000822958	1224602	1224628
ENSE00000822959	1225207	1225268
ENSE00003648393	1223423	1223594

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 89.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1179 / max 35.7009, expressed in 25 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155812	0.0626	13
155814	0.0473	13
155813	0.0080	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	89.18	gold quality
transverse colon	UBERON:0001157	84.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.86	gold quality
lower esophagus	UBERON:0013473	81.78	gold quality
jejunal mucosa	UBERON:0000399	80.99	gold quality
mucosa of sigmoid colon	UBERON:0004993	80.67	gold quality
colon	UBERON:0001155	80.57	gold quality
large intestine	UBERON:0000059	80.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	80.16	gold quality
periodontal ligament	UBERON:0008266	79.79	gold quality
colonic mucosa	UBERON:0000317	79.58	gold quality
duodenum	UBERON:0002114	79.55	gold quality
intestine	UBERON:0000160	79.26	gold quality
mucosa of urinary bladder	UBERON:0001259	79.22	gold quality
pituitary gland	UBERON:0000007	78.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	77.94	gold quality
small intestine	UBERON:0002108	77.92	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	77.53	gold quality
adenohypophysis	UBERON:0002196	77.07	gold quality
ileal mucosa	UBERON:0000331	76.75	silver quality
sperm	CL:0000019	76.28	gold quality
triceps brachii	UBERON:0001509	76.13	gold quality
gluteal muscle	UBERON:0002000	76.04	gold quality
jejunum	UBERON:0002115	75.53	gold quality
left ovary	UBERON:0002119	75.51	gold quality
male germ cell	CL:0000015	75.38	gold quality
rectum	UBERON:0001052	75.26	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.20	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	24.98
E-MTAB-8410	yes	14.73
E-ANND-3	yes	4.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MITF

miRNA regulators (miRDB)

9 targeting TPSG1, 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-3658	99.96	73.87	4379
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-4684-3P	98.24	69.91	1075
HSA-MIR-506-5P	98.02	67.41	1065

Literature-anchored findings (GeneRIF, showing 2)

• TMT is an exocytosed MC neutral protease that induces AHR in lungs primarily by activating an IL-13/IL-4Ralpha/STAT6-dependent pathway. (PMID:12194977)
• tryptase promotes breast cancer migration and invasion. (PMID:20126998)

Cross-species orthologs

57 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
mus_musculus	Tpsg1	ENSMUSG00000033200
rattus_norvegicus	Tpsg1	ENSRNOG00000018701
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): TPSD1 (ENSG00000095917), TPSAB1 (ENSG00000172236), TPSB2 (ENSG00000197253)

Protein

Protein identifiers

Tryptase gamma — Q9NRR2 (reviewed: Q9NRR2)

Alternative names: Serine protease 31, Transmembrane tryptase

All UniProt accessions (2): A0AAA9YHS0, Q9NRR2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Expressed in many tissues.

Polymorphism. There are two alleles; gamma-I and gamma-II which differ by 5 residues.

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

RefSeq proteins (1): NP_036599* (*=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
IPR043504

Pfam: PF00089

UniProt features (22 total): sequence variant 7, disulfide bond 5, chain 3, active site 3, signal peptide 1, transmembrane region 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRR2-F1	83.19	0.68

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): 78 (charge relay system); 125 (charge relay system); 222 (charge relay system)

Disulfide bonds (5): 26–145, 63–79, 159–228, 192–210, 218–246

Glycosylation sites (1): 85

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 49 (showing top): GOBP_PROTEOLYSIS, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, GOMF_PEPTIDASE_ACTIVITY, MARTENS_TRETINOIN_RESPONSE_UP, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A12, MAFG_TARGET_GENES, NFE2L1_TARGET_GENES, MIR3658, MIR4684_3P, MIR506_5P, MIR11399, GSE15324_ELF4_KO_VS_WT_ACTIVATED_CD8_TCELL_DN, GSE17721_CTRL_VS_GARDIQUIMOD_1H_BMDC_UP, GAO_LARGE_INTESTINE_ADULT_CF_GOBLET_CELL_SUBTYPE_1, GSE17721_PAM3CSK4_VS_GADIQUIMOD_0.5H_BMDC_DN

GO Biological Process (2): proteolysis (GO:0006508), zymogen activation (GO:0031638)

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 (4): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), extracellular region (GO:0005576), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein metabolic process	1
protein processing	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
membrane	1
cell periphery	1

Protein interactions and networks

STRING

625 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPSG1	CPA3	P15088	491
TPSG1	CPA4	Q9UI42	460
TPSG1	VWCE	Q96DN2	446
TPSG1	TBC1D24	Q9ULP9	410
TPSG1	API5	Q9BZZ5	399
TPSG1	NMU	P48645	379
TPSG1	CCNF	P41002	373
TPSG1	C3orf22	Q8N5N4	370
TPSG1	H3BQ06	H3BQ06	353
TPSG1	VMA12	Q8N511	350
TPSG1	SYT7	O43581	349
TPSG1	RNASE12	Q5GAN4	348
TPSG1	LRRC27	Q9C0I9	348
TPSG1	ZNF503	Q96F45	335
TPSG1	CLEC18C	Q8NCF0	326

IntAct

7 interactions, top by confidence:

A	B	Type	Score
HPCAL1	TPSG1	psi-mi:“MI:0915”(physical association)	0.560
NCALD	TPSG1	psi-mi:“MI:0915”(physical association)	0.560
TPSG1	HPCAL1	psi-mi:“MI:0915”(physical association)	0.000
TPSG1	NCALD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): TPSG1 (Two-hybrid), TPSG1 (Two-hybrid), TPSG1 (Negative Genetic), TPSG1 (Negative Genetic), TPSG1 (Negative Genetic), TPSG1 (Negative Genetic), TPSG1 (Negative Genetic)

ESM2 similar proteins: A1L453, A2VE36, A6NIE9, A8MTI9, O35453, O43240, P05981, P15944, P20231, P21845, P50343, P69526, P83748, Q14B25, Q14BX2, Q15661, Q16651, Q2UVH8, Q3UKY7, Q3V0Q7, Q402U7, Q571E5, Q5K2P8, Q5K2P9, Q6BEA2, Q6IE62, Q6UWB4, Q7RTY5, Q7RTY9, Q7Z410, Q7Z5A4, Q8BJR6, Q8K4I7, Q8VIF2, Q920S2, Q99MS4, Q9BQR3, Q9ER04, Q9ER10, Q9ES87

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	12
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1098 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1222190:GCTCA:G	donor_loss	1.0000
16:1222191:CTCA:C	donor_loss	1.0000
16:1222192:TCACC:T	donor_loss	1.0000
16:1222193:CACC:C	donor_loss	1.0000
16:1222337:AGGCT:A	acceptor_gain	1.0000
16:1222338:GGCT:G	acceptor_gain	1.0000
16:1222340:CT:C	acceptor_gain	1.0000
16:1222341:TC:T	acceptor_loss	1.0000
16:1222342:C:CC	acceptor_gain	1.0000
16:1222342:CT:C	acceptor_loss	1.0000
16:1222343:T:G	acceptor_loss	1.0000
16:1222654:C:A	donor_gain	1.0000
16:1222347:G:GC	acceptor_gain	0.9900
16:1222647:CTCAC:C	donor_loss	0.9900
16:1222648:TCACC:T	donor_loss	0.9900
16:1222649:CA:C	donor_loss	0.9900
16:1222650:ACCTC:A	donor_gain	0.9900
16:1222651:CCTCC:C	donor_gain	0.9900
16:1222720:T:TA	donor_gain	0.9900
16:1222917:CCTGG:C	acceptor_loss	0.9900
16:1222918:C:CC	acceptor_gain	0.9900
16:1222919:T:A	acceptor_loss	0.9900
16:1222097:C:CC	acceptor_gain	0.9800
16:1222194:A:AC	donor_gain	0.9800
16:1222195:C:CC	donor_gain	0.9800
16:1222195:CCTGG:C	donor_gain	0.9800
16:1222650:ACCT:A	donor_gain	0.9800
16:1222651:CCTC:C	donor_gain	0.9800
16:1222653:T:TA	donor_gain	0.9800
16:1222682:CCCA:C	donor_gain	0.9800

AlphaMissense

2017 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1222671:C:A	W164C	0.970
16:1222671:C:G	W164C	0.970
16:1223515:C:A	W51C	0.961
16:1223515:C:G	W51C	0.961
16:1221962:C:A	W264C	0.939
16:1221962:C:G	W264C	0.939
16:1222031:G:C	S241R	0.936
16:1222031:G:T	S241R	0.936
16:1222033:T:G	S241R	0.936
16:1223506:G:C	S54R	0.936
16:1223506:G:T	S54R	0.936
16:1223508:T:G	S54R	0.936
16:1223428:G:C	F80L	0.935
16:1223428:G:T	F80L	0.935
16:1223430:A:G	F80L	0.935
16:1221960:A:G	I265T	0.924
16:1222732:A:T	V144D	0.920
16:1222784:C:G	A127P	0.920
16:1223452:C:A	W72C	0.918
16:1223452:C:G	W72C	0.918
16:1223517:A:G	W51R	0.918
16:1223517:A:T	W51R	0.918
16:1222783:G:T	A127D	0.914
16:1223521:C:A	W49C	0.909
16:1223521:C:G	W49C	0.909
16:1222834:A:G	I110T	0.908
16:1222673:A:G	W164R	0.907
16:1222673:A:T	W164R	0.907
16:1222052:C:A	W234C	0.900
16:1222052:C:G	W234C	0.900

dbSNP variants (sampled 300 via entrez): RS1000230992 (16:1224456 CGA>C), RS1000269272 (16:1221814 C>G), RS1000491486 (16:1223701 G>A), RS1000784460 (16:1221944 T>C), RS1001003807 (16:1221288 C>A,T), RS1001082175 (16:1226235 G>A), RS1001107656 (16:1221501 C>G,T), RS1001164617 (16:1224898 G>A,T), RS1001238054 (16:1225029 C>A,T), RS1001331296 (16:1221417 T>A), RS1001347526 (16:1222523 G>A,C,T), RS1001383667 (16:1221582 C>A), RS1001440737 (16:1224069 C>A), RS1001893526 (16:1224274 C>T), RS1002031501 (16:1226960 C>T)

Disease associations

OMIM: gene MIM:609341 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2095193 (PROTEIN FAMILY), CHEMBL4955 (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
WX-UK1	Inhibition	5.2	pKi

ChEMBL bioactivities

235 potent at pChembl≥5 of 256 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	Kd	0.07	nM	CHEMBL46809
10.15	Ki	0.07	nM	CHEMBL46809
10.00	Ki	0.1	nM	CHEMBL431969
10.00	Ki	0.1	nM	CHEMBL311655
10.00	Kd	0.1	nM	CHEMBL306620
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

PubChem BioAssay actives

245 with measured affinity, of 346 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
[(3R,3aR,6R,6aR)-6-[4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carbonyl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-yl] 4-[[4-(diaminomethylideneamino)phenyl]methylcarbamoyl]piperazine-1-carboxylate	213509: Dissociation constant of compound was evaluated from its IC50 against tryptase at different concentrations	kd	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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
ferrous chloride	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Atrazine	increases expression	1
Azacitidine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	increases expression	1
Bucladesine	decreases expression, affects cotreatment	1
Estradiol	affects cotreatment, decreases expression	1
Mercuric Chloride	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Medroxyprogesterone Acetate	affects cotreatment, decreases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

45 unique, capped per target: 45 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.