TPSAB1

Summary

TPSAB1 (tryptase alpha/beta 1, HGNC:12019) is a protein-coding gene on chromosome 16p13.3, encoding Tryptase alpha/beta-1 (Q15661). 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. These 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. The alleles of this gene exhibit an unusual amount of sequence variation, such that the alleles were once thought to represent two separate genes, alpha and beta 1. Beta tryptases appear to be the main isoenzymes expressed in mast cells; whereas in basophils, alpha tryptases predominate. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders.

Source: NCBI Gene 7177 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 101 total
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity sufficient evidence
• MANE Select transcript: NM_003294

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12019
Approved symbol	TPSAB1
Name	tryptase alpha/beta 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172236
Ensembl biotype	protein_coding
OMIM	191080
Entrez	7177

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000338844, ENST00000461509, ENST00000561736, ENST00000562432, ENST00000677899, ENST00000711395, ENST00000711396, ENST00000907588, ENST00000907589, ENST00000907590, ENST00000907591, ENST00000960445, ENST00000960446

RefSeq mRNA: 1 — MANE Select: NM_003294 NM_003294

CCDS: CCDS10431

Canonical transcript exons

ENST00000338844 — 6 exons

Exon	Start	End
ENSE00001748932	1240705	1240728
ENSE00004015450	1241827	1241990
ENSE00004015451	1242076	1242554
ENSE00004015453	1241153	1241324
ENSE00004015455	1241434	1241699
ENSE00004015457	1240939	1240999

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 98.34.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 7.0492 / max 4628.3097, expressed in 73 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152043	6.4706	70
152052	0.1446	11
152045	0.1329	9
152046	0.0765	8
152048	0.0749	10
152044	0.0539	9
152051	0.0335	7
152042	0.0315	7
152049	0.0130	6
152050	0.0118	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	98.34	gold quality
fundus of stomach	UBERON:0001160	96.46	gold quality
duodenum	UBERON:0002114	96.03	gold quality
right lung	UBERON:0002167	95.95	gold quality
upper lobe of left lung	UBERON:0008952	95.86	gold quality
mucosa of transverse colon	UBERON:0004991	95.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.48	gold quality
mucosa of stomach	UBERON:0001199	95.46	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.46	gold quality
right coronary artery	UBERON:0001625	95.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.34	gold quality
skin of leg	UBERON:0001511	95.31	gold quality
lower esophagus	UBERON:0013473	95.31	gold quality
body of stomach	UBERON:0001161	95.05	gold quality
small intestine	UBERON:0002108	94.48	gold quality
urinary bladder	UBERON:0001255	94.25	gold quality
zone of skin	UBERON:0000014	93.96	gold quality
esophagus	UBERON:0001043	93.32	gold quality
transverse colon	UBERON:0001157	93.29	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.20	gold quality
skin of abdomen	UBERON:0001416	92.90	gold quality
minor salivary gland	UBERON:0001830	92.51	gold quality
adipose tissue	UBERON:0001013	91.72	gold quality
esophagus mucosa	UBERON:0002469	91.68	gold quality
prostate gland	UBERON:0002367	91.33	gold quality
stomach	UBERON:0000945	90.62	gold quality
omental fat pad	UBERON:0010414	90.11	gold quality
lower esophagus mucosa	UBERON:0035834	90.03	gold quality
intestine	UBERON:0000160	89.87	gold quality
saliva-secreting gland	UBERON:0001044	89.79	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 34.

Experiment	Marker?	Max mean expression
E-GEOD-139324	yes	33665.10
E-MTAB-6653	yes	32419.92
E-CURD-114	yes	32381.54
E-MTAB-8410	yes	30917.15
E-MTAB-6308	yes	30501.45
E-CURD-88	yes	29112.82
E-MTAB-10553	yes	24549.23
E-MTAB-8495	yes	23686.65
E-CURD-126	yes	21749.37
E-HCAD-1	yes	20867.83
E-MTAB-8142	yes	17102.61
E-MTAB-9067	yes	16101.31
E-CURD-46	yes	15862.16
E-GEOD-130148	yes	15775.80
E-MTAB-6701	yes	15084.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOS, JUN, MITF, PATZ1, SMAD3, SMAD4

miRNA regulators (miRDB)

25 targeting TPSAB1, 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-4283	100.00	66.42	2097
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-510-5P	97.66	65.82	916
HSA-MIR-6805-5P	95.79	64.86	670

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 3 (sufficient evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• mitogenic effects in human airway smooth muscle cells (PMID:11792624)
• stability and catalytic properties mediated by residues at the S1 pocket (PMID:11876641)
• structure of Bowman-Birk inhibitor derived peptides (PMID:11906611)
• Proliferative action is mediated by PAR2, COX2, prostaglandins, and PPARgamma : possible relevance to human fibrotic disorders. (PMID:12397176)
• Beta-tryptase activates peripheral blood mononuclear cells isolated from healthy donors as well as multiple sclerosis (MS) patients, inducing release of TNF-alpha, IL-6, and IL-1 beta, and is most probably an important mediator of inflammation in MS. (PMID:12742661)
• Results indicate a key role for heparin in the activation of human betaI- and beta2-tryptase. (PMID:15567416)
• Tryptase and chymase and protein levels were determined in mast cells in fibrosarcoma. (PMID:15638376)
• Mast cell tryptase cleaves protease-activated receptor 2 (PAR2) on colonocytes to increase paracellular permeability of the intestine during stress and inflammation. (PMID:16027150)
• crystal structures of both the single and the double mutant forms of recombinant human alphaI-tryptase in complex with the peptide inhibitor leupeptin, as well as the structure of the non-inhibited single mutant (PMID:16414069)
• mast cell beta-tryptase selectively cleaves asthmatic airway smooth muscle (ASM)-derived eotaxin and RANTES and abrogates their chemotactic activities, thus providing an explanation for the eosinophil paucity in asthmatic ASM bundles (PMID:16517749)
• Bikunin was found to localize on the cell membrane, while tryptase was in the secretary granules of the mast cells from psoriatic lesions. (PMID:17146627)
• Mast cell tryptase secretion into rheumatoid arthritis synovial fluid is higher than Osteoarthritis synovial fluid and stimulates the proliferation of Synovial fibrobalst-like cells. (PMID:17205215)
• The disease severity and plasma tryptase levels were not affected by the number of alpha or beta tryptase alleles in mastocytosis patients. (PMID:17449330)
• These results suggest that the characteristic neovascularization observed in pterygium may be sustained, at least in part, by mast cells angiogenic mediators, in particular tryptase. (PMID:17635650)
• siHTbeta is for the most part an inactive species and any active monomer is a consequence of heparin binding to siHTbeta under dilute conditions where unfavorable thermodynamics and/or kinetics restrict formation of active tetramer. (PMID:17655281)
• Up-regulates interleukin-8 expression in airway smooth muscle cells through a protease-activated receptor(PAR)-2-independent proteolytic mechanism. (PMID:18079491)
• Tryptase activates TGFbeta via a PAR2-independent proteolytic mechanism in human ASM cells and may help understanding the role of tryptase in asthma. (PMID:18359288)
• Tryptase stimulation of human small airway epithelial cells increased membrane-associated, calcium-independent phospholipase A(2)gamma (iPLA(2)gamma) activity, resulting in increased arachidonic acid and PGE(2) release. (PMID:18790994)
• alternative mRNA splicing in multiple human tryptase genes has a role in regulating tetramer formation (PMID:18854315)
• Positive correlation between serum tryptase concentration and hemoglobin, hematocrit, red blood cell count, and hepatic cell damage in kidney transplantation. (PMID:19100407)
• MC are immunoreactive to cathepsin-G in human cutaneous mastocytosis, as well as the co-localization of tryptase and cathepsin-G in MC secretory granules. (PMID:19250736)
• SPAG11B/D is both a substrate and a potent inhibitor of TPSAB1 activity. (PMID:19535787)
• Proteolytic cleavage of cathelicidin LL-37 by mast cells (MC) is mediated by beta-tryptase, the the major LL-37 processing enzyme in MC. (PMID:19625657)
• The levels of tryptase and chymase expression are greatly increased in human lung tissue of anaphylactic shock. (PMID:19697770)
• Strong linkage of TPSAB1 and TPSB2 and pairing of deficiency alleles with functional alleles in observed haplotypes protect human subjects from “knockout” genomes and indeed from inheritance of fewer than 2 active alleles. (PMID:19748655)
• Tryptase seems to play an important role in the control of human colonic mucosal permeability, and enhanced tryptase activity was responsible for the increased permeability of rectal mucosa in irritable bowel patients (PMID:20087660)
• MCT gene may play a role in the pathogenesis of scar. (PMID:20540319)
• these data show that patients suffering from active active chronic urticaria (CU) have significantly higher total tryptase levels than asymptomatic CU, atopics without CU and healthy subjects. (PMID:20718781)
• enhanced tryptase staining in media and adventitia of human and mouse abdominal aortic aneurysm lesions (PMID:21493897)
• During breast cancer progression the mast cells may contribute to stromal remodelling and differentiation of myofibroblasts, through tryptase released in stromal microenvironment. (PMID:21707711)
• Mast cell tryptase stimulates production of decorin by human testicular peritubular cells (PMID:21791437)
• Two different populations of mast cells were found in melanocytic skin; one expressing both chymase and tryptase and the other with tryptase only. (PMID:22102069)
• Both IgE and chymase associate with diabetes status. (PMID:22194960)
• As mast cells are an important source of VEGF, tryptase, and chymase, these findings suggest that mast cell activation and mast cell-derived mediators participate in the development of Dengue hemorrhagic fever. (PMID:22363824)
• results suggest that tryptase can induce microglia activation and pro-inflammatory mediator release via PAR-2-MAPK-NF-kappa B signaling pathway, which will contribute to the development of microglia-mediated inflammation in brain (PMID:22613992)
• Tryptase is a biomarker related to the severity of anaphylaxis. (PMID:23018683)
• Our results indicate that sBT levels are associated with a higher risk of severe SR in children with insect venom hypersensitivity. (PMID:23330964)
• The identification of an abundant population of tryptase(+)/Nanog(+) cells in infantile haemangioma is novel. (PMID:23559352)
• The high density of tryptase(+) Mmast cells at invasive margins of tumours was associated with advanced stages of colorectal cancer and was strongly correlated with PAR-2 expression. (PMID:23991686)
• As much as 82% of the variation in serum tryptase is due to genetics factors, and genetic effects overlap serum tryptase and body mass index. (PMID:24054365)

Cross-species orthologs

59 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	Tpsab1	ENSMUSG00000024173
mus_musculus	Tpsb2	ENSMUSG00000033825
rattus_norvegicus	Tpsb2	ENSRNOG00000018611
rattus_norvegicus	Tpsab1	ENSRNOG00000024181
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), TPSG1 (ENSG00000116176), TPSB2 (ENSG00000197253)

Protein

Protein identifiers

Tryptase alpha/beta-1 — Q15661 (reviewed: Q15661)

Alternative names: Tryptase I, Tryptase alpha-1

All UniProt accessions (3): A0A0C4DGM1, Q15661, J3QTS8

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. May play a role in innate immunity. Isoform 2 cleaves large substrates, such as fibronectin, more efficiently than isoform 1, but seems less efficient toward small substrates.

Subunit / interactions. Homotetramer. The active tetramer is converted to inactive monomers at neutral and acidic pH in the absence of heparin. Low concentrations of inactive monomers become active monomers at pH 6.0 in the presence of heparin. When the concentration of active monomers is higher, they convert to active monomers and then to active tetramers. These monomers are active and functionally distinct from the tetrameric enzyme. In contrast to the hidden active sites in the tetrameric form, the active site of the monomeric form is accessible for macromolecular proteins and inhibitors, e.g. fibrinogen which is a substrate for the monomeric but not for the tetrameric form. The monomeric form forms a complex with SERPINB6.

Subcellular location. Secreted.

Tissue specificity. Isoform 1 and isoform 2 are expressed in lung, stomach, spleen, heart and skin; in these tissues, isoform 1 is predominant. Isoform 2 is expressed in aorta, spleen, and breast tumor, with highest levels in the endothelial cells of some blood vessels surrounding the aorta, as well as those surrounding the tumor and low levels, if any, in mast cells (at protein level).

Disease relevance. Hereditary alpha tryptasemia is caused by an increase in the copy number (usually between two and three copies) of the alpha allele. Affected individuals have elevated basal serum tryptase levels that are associated with cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities. It is not clear if the associated multisystem complaints might be due to the coinheritance of a second functional genetic variant.

Polymorphism. There are two alleles alpha and beta-I. The sequence shown is that of allele beta-I.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q15661-1	1	yes
Q15661-2	2

RefSeq proteins (1): NP_003285* (*=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

Enzyme classification (BRENDA):

• EC 3.4.21.59 — Tryptase (BRENDA: 11 organisms, 228 substrates, 287 inhibitors, 92 Km, 110 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
N-P-TOSYL-GLY-PRO-LYS-P-NITROANILIDE	0.19–4.2	9
D-ILE-PRO-ARG-P-NITROANILIDE	0.4–8.2	8
S-2288	0.32–1.6	5
D-PRO-PHE-ARG-P-NITROANILIDE	1.64–13.5	4
D-VAL-LEU-ARG-P-NITROANILIDE	1.12–3.49	4
MEOCO-NLE-GLY-ARG-P-NITROANILIDE	0.58–1.16	4
Z-D-ARG-GLY-ARG-P-NITROANILIDE	0.04–0.36	4
BZ-ARG-P-NITROANILIDE	0.3–2.36	3
D-PHE-PIP-ARG-P-NITROANILIDE	0.7–0.79	3
GLU-PRO-ARG-P-NITROANILIDE	0.37–0.64	3
TOSYL-GLY-PRO-LYS-P-NITROANILIDE	0.35–0.49	3
AC-PANK-AAC	0.1105–0.1333	2
AC-PRNK-AAC	0.0089–0.0145	2
AC-PRNR-AAC	0.0165–0.0186	2
AC-PRTK-AAC	0.0147–0.0234	2

UniProt features (69 total): sequence variant 28, strand 17, helix 5, disulfide bond 4, turn 4, active site 3, glycosylation site 2, signal peptide 1, propeptide 1, splice variant 1, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
2F9N	X-RAY DIFFRACTION	1.6
4MPU	X-RAY DIFFRACTION	1.65
5F03	X-RAY DIFFRACTION	1.94
4MPW	X-RAY DIFFRACTION	1.95
4MPX	X-RAY DIFFRACTION	2
4A6L	X-RAY DIFFRACTION	2.05
2ZEC	X-RAY DIFFRACTION	2.06
2F9O	X-RAY DIFFRACTION	2.1
6O1F	X-RAY DIFFRACTION	2.15
1LTO	X-RAY DIFFRACTION	2.2
4MQA	X-RAY DIFFRACTION	2.25
2F9P	X-RAY DIFFRACTION	2.3
4MPV	X-RAY DIFFRACTION	2.31
8VGK	ELECTRON MICROSCOPY	2.4
2ZEB	X-RAY DIFFRACTION	2.5
8VGJ	ELECTRON MICROSCOPY	2.5
6P0P	X-RAY DIFFRACTION	2.55
8VGI	ELECTRON MICROSCOPY	2.7
5WI6	X-RAY DIFFRACTION	2.72
8VGH	ELECTRON MICROSCOPY	2.9
6VVU	X-RAY DIFFRACTION	3
9MNB	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15661-F1	91.80	0.86

Antibody-complex structures (SAbDab): 6 — 6O1F, 6VVU, 8VGH, 8VGI, 8VGJ, 8VGK

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): 74 (charge relay system); 121 (charge relay system); 224 (charge relay system)

Disulfide bonds (4): 155–230, 188–211, 220–248, 59–75

Glycosylation sites (2): 132, 233

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1592389	Activation of Matrix Metalloproteinases

MSigDB gene sets: 88 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, MODULE_172, VERHAAK_AML_WITH_NPM1_MUTATED_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, JAEGER_METASTASIS_DN, MODULE_151, MODULE_418, MODULE_75, MODULE_109, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, GOBP_EXTRACELLULAR_MATRIX_DISASSEMBLY, MODULE_6, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_UP, MODULE_209, MODULE_60

GO Biological Process (3): proteolysis (GO:0006508), defense response (GO:0006952), extracellular matrix disassembly (GO:0022617)

GO Molecular Function (6): serine-type endopeptidase activity (GO:0004252), serine-type peptidase activity (GO:0008236), identical protein binding (GO:0042802), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Degradation of the extracellular matrix	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
response to stress	1
cellular component disassembly	1
extracellular matrix organization	1
endopeptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
protein binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

11 interactions, top by confidence:

A	B	Type	Score
TPSAB1	TPSAB1	psi-mi:“MI:0407”(direct interaction)	0.560
TPSAB1	TPSAB1	psi-mi:“MI:0408”(disulfide bond)	0.560
NCK1	TPSAB1	psi-mi:“MI:0915”(physical association)	0.400
TPSAB1	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
TPSAB1	rep	psi-mi:“MI:0915”(physical association)	0.400
TPSAB1	rep	psi-mi:“MI:0915”(physical association)	0.370
SLC28A3	IGKC	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): TPSAB1 (Affinity Capture-MS), TPSAB1 (Negative Genetic), TPSAB1 (Negative Genetic), TPSAB1 (Negative Genetic), TPSAB1 (Negative Genetic), TPSAB1 (Negative Genetic), TPSAB1 (Negative Genetic), TPSAB1 (Negative Genetic), TPSAB1 (Negative Genetic), TPSAB1 (Negative Genetic), TPSAB1 (Negative Genetic), TPSAB1 (Positive Genetic), TPSAB1 (Affinity Capture-MS), TPSAB1 (Two-hybrid), TPSAB1 (Co-crystal Structure)

ESM2 similar proteins: A1L453, A2VE36, A6NIE9, A8MTI9, E5RG02, O35453, O70169, P08709, P20231, P21845, P50343, P83748, Q14B25, Q14BX2, Q15661, Q16651, Q2F9P2, Q2F9P4, Q2UVH8, Q3UKY7, Q3V0Q7, Q402U7, Q571E5, Q5FBW1, Q5FBW2, Q5M8S2, Q6AXZ6, Q6BEA2, Q6IE62, Q6IE63, Q6UWB4, Q76HL1, Q7RTY5, Q7Z410, Q7Z5A4, Q8BJR6, Q8K4I7, Q8VIF2, Q920S2, Q99MS4

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

3 interactions.

A	Effect	B	Mechanism
MITF	“up-regulates quantity by expression”	TPSAB1	“transcriptional regulation”
Degranulation	“up-regulates quantity by expression”	TPSAB1
TPSAB1	“up-regulates activity”	F2RL1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	9
Benign	36

Top pathogenic / likely-pathogenic (0)

SpliceAI

880 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1241656:G:T	donor_gain	1.0000
16:1241825:A:AG	acceptor_gain	1.0000
16:1241826:G:GG	acceptor_gain	1.0000
16:1241826:GAGC:G	acceptor_gain	1.0000
16:1241975:G:GT	donor_gain	1.0000
16:1241987:CCAG:C	donor_loss	1.0000
16:1241988:CAG:C	donor_loss	1.0000
16:1241989:AGG:A	donor_loss	1.0000
16:1241990:GGTGG:G	donor_loss	1.0000
16:1241992:T:G	donor_loss	1.0000
16:1241000:G:GG	donor_gain	0.9900
16:1241000:G:T	donor_loss	0.9900
16:1241001:T:TC	donor_loss	0.9900
16:1241433:GGGAC:G	acceptor_gain	0.9900
16:1241582:G:GT	donor_gain	0.9900
16:1241656:G:GT	donor_gain	0.9900
16:1241665:C:G	donor_gain	0.9900
16:1241696:GATG:G	donor_gain	0.9900
16:1241699:GGTG:G	donor_loss	0.9900
16:1241700:GT:G	donor_loss	0.9900
16:1241819:A:AG	acceptor_gain	0.9900
16:1241824:CAG:C	acceptor_gain	0.9900
16:1241825:AG:A	acceptor_loss	0.9900
16:1241825:AGA:A	acceptor_gain	0.9900
16:1241826:GA:G	acceptor_gain	0.9900
16:1241826:GAG:G	acceptor_gain	0.9900
16:1241979:G:T	donor_gain	0.9900
16:1242070:TCCCA:T	acceptor_loss	0.9900
16:1242071:CCCA:C	acceptor_loss	0.9900
16:1242072:CCAG:C	acceptor_loss	0.9900

AlphaMissense

1773 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1241680:G:C	W160C	0.997
16:1241680:G:T	W160C	0.997
16:1242210:G:C	W266C	0.997
16:1242210:G:T	W266C	0.997
16:1241958:T:A	C211S	0.996
16:1241959:G:C	C211S	0.996
16:1241567:G:C	A123P	0.994
16:1241889:T:A	C188S	0.994
16:1241890:G:C	C188S	0.994
16:1241890:G:A	C188Y	0.993
16:1241267:G:A	C59Y	0.992
16:1241315:G:A	C75Y	0.992
16:1241537:T:C	F113L	0.992
16:1241539:C:A	F113L	0.992
16:1241539:C:G	F113L	0.992
16:1241664:G:A	C155Y	0.992
16:1241665:C:G	C155W	0.992
16:1242139:A:C	S243R	0.992
16:1242141:C:A	S243R	0.992
16:1242141:C:G	S243R	0.992
16:1241562:A:T	D121V	0.991
16:1241571:T:C	L124P	0.991
16:1241678:T:A	W160R	0.991
16:1241678:T:C	W160R	0.991
16:1241959:G:A	C211Y	0.991
16:1241985:T:A	C220S	0.991
16:1241986:G:C	C220S	0.991
16:1242080:A:T	D223V	0.991
16:1242086:G:T	G225V	0.991
16:1242154:T:A	C248S	0.991

dbSNP variants (sampled 300 via entrez): RS1000482641 (16:1240887 C>A), RS1002539243 (16:1239141 G>A,C), RS1004875887 (16:1240279 C>G,T), RS1005335140 (16:1240604 G>C), RS1005931707 (16:1242321 C>A,T), RS1008364658 (16:1238868 G>A,T), RS1008709082 (16:1239017 G>A), RS1009068055 (16:1239989 C>A,T), RS1009120345 (16:1240240 G>A,T), RS1010064816 (16:1241196 G>A,C,T), RS1011834206 (16:1239039 T>A), RS1012201822 (16:1240848 C>A,T), RS1012535727 (16:1239670 G>C), RS1013151549 (16:1239178 C>G,T), RS1013197281 (16:1242934 T>C)

Disease associations

OMIM: gene MIM:191080 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_1567	Blood protein levels	2.000000e-76
GCST90000025_248	Appendicular lean mass	1.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2095193 (PROTEIN FAMILY), CHEMBL2617 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs765144578	TPSAB1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
nafamostat	Inhibition	10.0	pIC50
gabexate	Inhibition	8.47	pIC50
RWJ-56423	Inhibition	8.0	pKi

ChEMBL bioactivities

445 potent at pChembl≥5 of 480 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
8.89	Ki	1.3	nM	CHEMBL365062
8.82	Ki	1.5	nM	CHEMBL362874
8.82	Ki	1.5	nM	CHEMBL211357
8.77	Ki	1.7	nM	CHEMBL212774
8.77	Ki	1.7	nM	CHEMBL380293
8.77	IC50	1.7	nM	CHEMBL303437
8.74	Ki	1.8	nM	CHEMBL377890
8.74	Ki	1.8	nM	CHEMBL213928
8.74	IC50	1.8	nM	CHEMBL306448
8.72	Ki	1.9	nM	CHEMBL209395
8.72	Ki	1.9	nM	CHEMBL377656
8.72	IC50	1.9	nM	CHEMBL109504
8.70	Ki	2	nM	CHEMBL214136
8.70	IC50	2	nM	CHEMBL127185
8.70	Ki	2	nM	CHEMBL75749

PubChem BioAssay actives

454 with measured affinity, of 627 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
3-[4-[5-(aminomethyl)-2-fluorophenyl]piperidine-1-carbonyl]-5-(3-thiophen-2-yl-1,2,4-oxadiazol-5-yl)benzamide	238479: Inhibitory activity against human mast cell tryptase beta	ki	0.0013	uM
3-[4-[3-(aminomethyl)phenyl]piperidine-1-carbonyl]-5-(3-thiophen-2-yl-1,2,4-oxadiazol-5-yl)benzamide	238479: Inhibitory activity against human mast cell tryptase beta	ki	0.0015	uM
N-[(2S)-6-amino-1-[5-[[4-[2-(3-chlorophenyl)ethylcarbamoyl]phenyl]methyl]-1,2,4-oxadiazol-3-yl]-1-oxohexan-2-yl]-3,5-difluorobenzamide	269675: Inhibition of human beta tryptase	ki	0.0015	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
N-[(2S)-6-amino-1-[5-[[4-[2-(3-chlorophenyl)ethylcarbamoyl]phenyl]methyl]-1,2,4-oxadiazol-3-yl]-1-oxohexan-2-yl]-3-fluorobenzamide	269675: Inhibition of human beta tryptase	ki	0.0017	uM
N-[(2S)-6-amino-1-[5-[[4-[2-(3-chlorophenyl)ethylcarbamoyl]phenyl]methyl]-1,2,4-oxadiazol-3-yl]-1-oxohexan-2-yl]-3,4-difluorobenzamide	269675: Inhibition of human beta tryptase	ki	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
benzyl N-[(2S)-6-amino-1-[5-[[4-[2-(3-chlorophenyl)ethylcarbamoyl]phenyl]methyl]-1,2,4-oxadiazol-3-yl]-1-oxohexan-2-yl]carbamate	269675: Inhibition of human beta tryptase	ki	0.0018	uM
4-[[3-[(2S)-6-amino-2-[(4-fluorobenzoyl)amino]hexanoyl]-1,2,4-oxadiazol-5-yl]methyl]-N-[2-(3-chlorophenyl)ethyl]benzamide	269675: Inhibition of human beta tryptase	ki	0.0018	uM

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Copper	affects binding, decreases expression	1
Diazinon	increases methylation	1
Disulfiram	affects binding, decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Latex	decreases expression	1
Methapyrilene	increases methylation	1
Methotrexate	increases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Tretinoin	increases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

62 unique, capped per target: 62 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.