PRSS3

Summary

PRSS3 (serine protease 3, HGNC:9486) is a protein-coding gene on chromosome 9p13.3, encoding Trypsin-3 (P35030). Digestive protease that cleaves proteins preferentially after an Arg residue and has proteolytic activity toward Kunitz-type trypsin inhibitors.

This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is expressed in the brain and pancreas and is resistant to common trypsin inhibitors. It is active on peptide linkages involving the carboxyl group of lysine or arginine. This gene is localized to the locus of T cell receptor beta variable orphans on chromosome 9. Four transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 5646 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 35 total
• Phenotypes (HPO): 1
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002771

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9486
Approved symbol	PRSS3
Name	serine protease 3
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	TRY3, TRY4
Ensembl gene	ENSG00000010438
Ensembl biotype	protein_coding
OMIM	613578
Entrez	5646

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000342836, ENST00000361005, ENST00000379405, ENST00000429677, ENST00000468152, ENST00000477653, ENST00000495682

RefSeq mRNA: 4 — MANE Select: NM_002771 NM_001197097, NM_001197098, NM_002771, NM_007343

CCDS: CCDS47958, CCDS56570, CCDS6545

Canonical transcript exons

ENST00000379405 — 5 exons

Exon	Start	End
ENSE00001625216	33798486	33798622
ENSE00001841624	33795561	33795613
ENSE00001859079	33799028	33799231
ENSE00003414827	33797829	33798082
ENSE00003613028	33796643	33796802

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 99.86.

FANTOM5 (CAGE): breadth broad, TPM avg 7.3317 / max 1399.6709, expressed in 656 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96468	6.1582	640
96469	0.8344	4
96467	0.3323	181
96472	0.0044	1
96473	0.0023	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.86	gold quality
pancreas	UBERON:0001264	98.82	gold quality
lower esophagus mucosa	UBERON:0035834	98.76	gold quality
ileal mucosa	UBERON:0000331	98.55	gold quality
mucosa of transverse colon	UBERON:0004991	98.44	gold quality
jejunal mucosa	UBERON:0000399	98.13	gold quality
colonic mucosa	UBERON:0000317	97.92	gold quality
duodenum	UBERON:0002114	97.91	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.76	gold quality
islet of Langerhans	UBERON:0000006	97.57	gold quality
rectum	UBERON:0001052	96.87	gold quality
type B pancreatic cell	CL:0000169	96.82	gold quality
epithelial cell of pancreas	CL:0000083	95.82	gold quality
esophagus mucosa	UBERON:0002469	94.92	gold quality
gingiva	UBERON:0001828	94.59	gold quality
esophagus squamous epithelium	UBERON:0006920	94.59	gold quality
epithelium of esophagus	UBERON:0001976	94.48	gold quality
gingival epithelium	UBERON:0001949	94.36	gold quality
skin of leg	UBERON:0001511	94.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.10	gold quality
cerebellar cortex	UBERON:0002129	93.97	gold quality
cerebellar hemisphere	UBERON:0002245	93.95	gold quality
pancreatic ductal cell	CL:0002079	93.73	gold quality
oral cavity	UBERON:0000167	93.26	gold quality
squamous epithelium	UBERON:0006914	93.23	gold quality
cerebellum	UBERON:0002037	93.18	gold quality
buccal mucosa cell	CL:0002336	92.74	gold quality
right frontal lobe	UBERON:0002810	92.49	gold quality
skin of abdomen	UBERON:0001416	92.42	gold quality
tongue squamous epithelium	UBERON:0006919	92.34	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-11	yes	103.96
E-MTAB-8410	yes	54.40
E-GEOD-81547	yes	29.22
E-GEOD-125970	yes	22.43
E-MTAB-5061	yes	19.50
E-ENAD-27	yes	6.66
E-GEOD-83139	no	2.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 39)

• X-ray structure in complex with the inhibitor benzamidine at 1.7 A resolution; crystal structure reveals basis for inhibitor resistance (PMID:11827488)
• biological function of human mesotrypsin is digestive degradation of trypsin inhibitors (PMID:14507909)
• The results classify E32del mesotrypsinogen as a frequent polymorphic variant, which is not associated with chronic alcoholic pancreatitis (PMID:15855826)
• PRSS3 promoter methylation is associated with advanced bladder cancer (PMID:15987713)
• we determined the promoter hypermethylation status of PRSS3 in a case series study of primary NSCLC, and found methylation of this gene to be common, occurring in 53% (86 of 166) of tumors examined. (PMID:16013053)
• Results suggest that human trypsin 4 may be one of the candidate proteases involved in the pathomechanism of multiple sclerosis via cleavage of myelin basic protein. (PMID:16412431)
• analysis of structural rearrangement during the acylation step in human trypsin 4 on 4-methylumbelliferyl 4-guanidinobenzoate substrate analogue (PMID:16492676)
• mesotrypsin cannot activate pancreatic zymogens, but might activate certain proteinase-activated receptors because of its thrombin-like subsite specificity; alpha1AT Pittsburgh is an effective mesotrypsin inhibitor (PMID:16759229)
• human trypsinogen 4 is widely but unevenly distributed in the human brain. It is localized in neurons and glial cells, predominantly in astrocytes & the extracellular matrix. (PMID:17406981)
• trypsin IV and p23 are inhibitor-resistant trypsins that can cleave and activate PARs, causing PAR(1)- and PAR(2)-dependent inflammation and PAR(2)-dependent hyperalgesia. (PMID:17623652)
• This study reveals enhanced mRNA expression of trypsinogen IV and SERT and a higher 5-HT content in the small intestine of IBS patients compared to healthy subjects. (PMID:18363639)
• Absence of mesotrypsinogen gene (PRSS3) copy number variations in patients with chronic pancreatitis. (PMID:18665091)
• Here, we report that nexin-1 inhibits trypsin-4, and forms stable complexes only with this trypsin-isoenzyme. This result suggests that nexin-1 could modulate trypsin activity in brain where both nexin-1 and trypsin-4 are expressed. (PMID:19249338)
• Processing by mesotrypsin may ablate the protease inhibitory function of APP/protease nexin 2 in vivo and may also modulate other activities of APP/protease nexin 2 that involve the Kunitz domain. (PMID:19920152)
• Because mesotrypsin is resistant to naturally occurring trypsin inhibitors, confined expression of the isoforms of mesotrypsinogens and enteropeptidase may indicate that mesotrypsin is involved in keratinocyte terminal differentiation (PMID:19924134)
• Report PRSS3/mesotrypsin upregulation in breast cancer cells and identify CD109 as the functional proteolytic target of mesotrypsin. (PMID:20035377)
• Investigation did not reveal an association between PRSS3 variants and chronic pancreatitis. (PMID:20484962)
• PRSS3 plays an important role in the progression, metastasis and prognosis of human pancreatic cancer. (PMID:20947888)
• IFN regulatory factor 2 (Irf2) has a regulatory role in trypsinogen5 gene transcription, which is resistant to a major endogenous trypsin inhibitor, Spink3 (PMID:22042864)
• Mesotrypsin generated saposins A-D from prosaposin, and mature caspase-14 contributed to this process by activating mesotrypsinogen to mesotrypsin. Knockdown of these proteases markedly down-regulated saposin A synthesis in skin equivalent models. (PMID:24872419)
• Data suggest that mesotrypsin cleavage of Kunitz domains may contribute to cancer progression. (PMID:25301953)
• High PRSS3 expression in EOC tissues was significantly associated with advanced FIGO stage and lymph node metastasis. (PMID:25735255)
• These findings suggest that inhibitor cleavage represents a functional adaptation of mesotrypsin that may have evolved in response to positive selection pressure. (PMID:26175157)
• Data show that silencing tumor-endothelial cells (EC) for trypsinogen 4 accumulated tissue factor pathway inhibitor-2 (TFPI-2) in the matrix. (PMID:26318044)
• PRSS3 acts as an oncogene in invasive ductal carcinoma of the breast development and progression (PMID:28423522)
• Study developed a new high resolution crystal structure of mesotrypsin complexed with diminazene through a structure-based molecular docking screen that could help facilitate derivatization efforts, addressing current pan-inhibition of human trypsins through rigidification of diminazene to select for a conformation that maximizes interactions with the non-conserved Arg-193 residue. (PMID:28463992)
• PRSS3 is downregulated by intragenic hypermethylation in HCC. * Epigenetic silencing of PRSS3 facilitates growth, migration, and invasion of HCC. * PRSS3 intragenic methylation has implication in diagnosis of HCC. (PMID:28844099)
• EK and EK-X2 trigger Influenza A Virus HA processing by activating the PRSS3 trypsinogen. (PMID:29629340)
• PRSS3/Mesotrypsin and kallikrein-related peptidase 5 are associated with poor prognosis and contribute to tumor cell invasion and growth in lung adenocarcinoma. (PMID:30755669)
• PRSS3 appears to act as an oncogene of gastric cancer. High PRSS3 expression portends postoperative metastasis. (PMID:30908656)
• Circular RNA ADAM9 facilitates the malignant behaviours of pancreatic cancer by sponging miR-217 and upregulating PRSS3 expression (PMID:31810373)
• PRSS contributes to cetuximab resistance in colorectal cancer. (PMID:31911942)
• Inactivation of mesotrypsin by chymotrypsin C prevents trypsin inhibitor degradation. (PMID:32014997)
• Defective binding of SPINK1 variants is an uncommon mechanism for impaired trypsin inhibition in chronic pancreatitis. (PMID:33515547)
• High Expression of PRSS3 Indicates Unfavorable Clinical Outcomes in Colon Adenocarcinoma. (PMID:33758142)
• In-depth proteomics analysis of sentinel lymph nodes from individuals with endometrial cancer. (PMID:34195683)
• Host neuronal PRSS3 interacts with enterovirus A71 3A protein and its role in viral replication. (PMID:35896602)
• Serine Protease 3 Promotes Progression of Diffuse Large B-Cell Lymphoma and Serves as a Novel Prognostic Predictor. (PMID:36618965)
• Shear Stress Drives the Cleavage Activation of Protease-Activated Receptor 2 by PRSS3/Mesotrypsin to Promote Invasion and Metastasis of Circulating Lung Cancer Cells. (PMID:37395651)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	prss1	ENSDARG00000042993
mus_musculus	Try5	ENSMUSG00000036938
mus_musculus	Try4	ENSMUSG00000054106
mus_musculus	Prss2	ENSMUSG00000057163
mus_musculus	Prss1l	ENSMUSG00000058119
mus_musculus	Prss1	ENSMUSG00000062751
mus_musculus	Prss3l	ENSMUSG00000071517
mus_musculus	Prss3	ENSMUSG00000071519
mus_musculus	Try10	ENSMUSG00000071521
rattus_norvegicus	Prss2l1	ENSRNOG00000050493
rattus_norvegicus	Prss1	ENSRNOG00000063605
rattus_norvegicus	Prss2	ENSRNOG00000064731
rattus_norvegicus	Try10	ENSRNOG00000070336
rattus_norvegicus		ENSRNOG00000075892
rattus_norvegicus	Prss3	ENSRNOG00000078399
rattus_norvegicus		ENSRNOG00000089144

Paralogs (3): PLAU (ENSG00000122861), PRSS1 (ENSG00000204983), PRSS2 (ENSG00000275896)

Protein

Protein identifiers

Trypsin-3 — P35030 (reviewed: P35030)

Alternative names: Brain trypsinogen, Mesotrypsin, Mesotrypsinogen, Serine protease 3, Serine protease 4, Trypsin III, Trypsin IV

All UniProt accessions (3): P35030, A0A7P0MNE9, A0A7P0MP65

UniProt curated annotations — full annotation on UniProt →

Function. Digestive protease that cleaves proteins preferentially after an Arg residue and has proteolytic activity toward Kunitz-type trypsin inhibitors.

Subcellular location. Secreted.

Tissue specificity. Detected in pancreas and pancreatic fluid (at protein level). Expressed in pancreas and brain. Detected in ileum.

Activity regulation. Not inhibited by Kunitz-type trypsin inhibitors.

Cofactor. Binds 1 Ca(2+) ion per subunit.

Similarity. Belongs to the peptidase S1 family.

Isoforms (5)

UniProt ID	Names	Canonical?
P35030-1	1, A	yes
P35030-2	2, B
P35030-3	3, C
P35030-4	4, D
P35030-5	5, E

RefSeq proteins (4): NP_001184026, NP_001184027, NP_002762, NP_031369 (=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
IPR050127	Serine_Proteases_S1	Family

Pfam: PF00089

UniProt features (55 total): strand 17, binding site 5, disulfide bond 5, splice variant 4, sequence variant 4, helix 4, sequence conflict 3, turn 3, active site 3, signal peptide 1, propeptide 1, site 1, modified residue 1, chain 1, mutagenesis site 1, domain 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
5TP0	X-RAY DIFFRACTION	1.25
3P95	X-RAY DIFFRACTION	1.3
2R9P	X-RAY DIFFRACTION	1.4
4DG4	X-RAY DIFFRACTION	1.4
5JBT	X-RAY DIFFRACTION	1.4
3P92	X-RAY DIFFRACTION	1.6
9BOT	X-RAY DIFFRACTION	1.6
4U32	X-RAY DIFFRACTION	1.65
1H4W	X-RAY DIFFRACTION	1.7
9BOS	X-RAY DIFFRACTION	1.7
5C67	X-RAY DIFFRACTION	1.83
6BX8	X-RAY DIFFRACTION	1.98
6GFI	X-RAY DIFFRACTION	2.3
3L3T	X-RAY DIFFRACTION	2.38
3L33	X-RAY DIFFRACTION	2.48
4U30	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35030-F1	82.39	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 (4): 251 (required for specificity); 120 (charge relay system); 164 (charge relay system); 257 (charge relay system)

Ligand- & substrate-binding residues (5): 139; 142; 132; 134; 137

Post-translational modifications (1): 211

Disulfide bonds (5): 87–217, 105–121, 196–263, 228–242, 253–277

Mutagenesis-validated functional residues (1):

Position	Phenotype
257	loss of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1462054	Alpha-defensins
R-HSA-6798695	Neutrophil degranulation
R-HSA-6803157	Antimicrobial peptides
R-HSA-9725554	Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin
R-HSA-9758881	Uptake of dietary cobalamins into enterocytes

MSigDB gene sets: 125 (showing top): GOBP_DIGESTION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, JAEGER_METASTASIS_DN, GOCC_SECRETORY_GRANULE, DAZARD_UV_RESPONSE_CLUSTER_G4, MODULE_503, RODRIGUES_NTN1_TARGETS_DN, GOBP_PROTEIN_MATURATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, MODULE_195, chr9p13, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GENTILE_UV_HIGH_DOSE_DN, GOBP_HUMORAL_IMMUNE_RESPONSE

GO Biological Process (5): proteolysis (GO:0006508), digestion (GO:0007586), antimicrobial humoral response (GO:0019730), zymogen activation (GO:0031638), endothelial cell migration (GO:0043542)

GO Molecular Function (7): serine-type endopeptidase activity (GO:0004252), calcium ion binding (GO:0005509), serine-type peptidase activity (GO:0008236), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), tertiary granule lumen (GO:1904724)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Innate Immune System	2
Defensins	1
Developmental Cell Lineages of the Integumentary System	1
Cobalamin (Cbl, vitamin B12) transport and metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
multicellular organismal process	1
humoral immune response	1
defense response to symbiont	1
protein processing	1
cell migration	1
endopeptidase activity	1
serine-type peptidase activity	1
metal ion binding	1
peptidase activity	1
serine hydrolase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
intracellular organelle lumen	1
tertiary granule	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

35 interactions, top by confidence:

A	B	Type	Score
SHC1	AP2A2	psi-mi:“MI:0914”(association)	0.640
SAT1	PRSS3	psi-mi:“MI:0915”(physical association)	0.400
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
IGHA1	PLG	psi-mi:“MI:0914”(association)	0.350
ALB	SH3BP5	psi-mi:“MI:0914”(association)	0.350
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
WTAP	DDX39A	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
TANK	CNOT1	psi-mi:“MI:0914”(association)	0.350
CTCF	ZRANB2	psi-mi:“MI:0914”(association)	0.350
NELFB	PRSS3	psi-mi:“MI:0914”(association)	0.350
NELFCD	H1-2	psi-mi:“MI:0914”(association)	0.350
NELFE	H1-2	psi-mi:“MI:0914”(association)	0.350
PRDM16	GAPDHS	psi-mi:“MI:0914”(association)	0.350
RAD18	H2AC4	psi-mi:“MI:0914”(association)	0.350
SATB1	PLPBP	psi-mi:“MI:0914”(association)	0.350
SATB2	PRSS3	psi-mi:“MI:0914”(association)	0.350
SCML2	CSTA	psi-mi:“MI:0914”(association)	0.350
TDRD5	UBB	psi-mi:“MI:0914”(association)	0.350
C3orf62	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SCRIB	CHD2	psi-mi:“MI:0914”(association)	0.350
PRSS2	POTEF	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
SF3B1	RBM10	psi-mi:“MI:0914”(association)	0.350

BioGRID (64): PRSS3 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS), PRSS3 (Proximity Label-MS), PRSS3 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS), PRSS3 (Affinity Capture-MS)

ESM2 similar proteins: A6NIE9, O35164, O35205, P00752, P00755, P00758, P00770, P06870, P09582, P09650, P11032, P11034, P15946, P20231, P21845, P27435, P35030, P35034, P36368, P36369, P36373, P36374, P36376, P43430, P49862, P49864, P50340, P50342, P50343, Q00356, Q02844, Q06606, Q15661, Q28773, Q3T0A3, Q3V0Q7, Q5FBW1, Q5FBW2, Q76B45, Q7RTY5

Diamond homologs: A0A1S4GMJ4, A6NIE9, A8JUP7, G3V801, O08762, O42207, O60235, P00741, P00745, P00762, P00765, P03951, P05049, P07477, P07478, P0CW18, P15120, P16292, P16295, P19799, P29786, P29787, P35030, P35039, P69525, P79953, Q14B25, Q14BX2, Q14C59, Q1JRP2, Q27081, Q28278, Q28315, Q28412, Q29463, Q2KJ63, Q2VG86, Q5G265, Q5U405, Q6BEA2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRSS3	“up-regulates activity”	F2RL1	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	2
Benign	14

Top pathogenic / likely-pathogenic (0)

SpliceAI

655 predictions. Top by Δscore:

Variant	Effect	Δscore
9:33796641:A:AG	acceptor_gain	1.0000
9:33796642:G:GG	acceptor_gain	1.0000
9:33796775:T:TA	donor_gain	1.0000
9:33796776:G:GA	donor_gain	1.0000
9:33796798:AAGAC:A	donor_gain	1.0000
9:33796799:AGAC:A	donor_gain	1.0000
9:33796800:GAC:G	donor_gain	1.0000
9:33796800:GACG:G	donor_gain	1.0000
9:33796801:AC:A	donor_gain	1.0000
9:33796801:ACG:A	donor_loss	1.0000
9:33796803:G:GG	donor_gain	1.0000
9:33796803:GTA:G	donor_loss	1.0000
9:33796804:T:A	donor_loss	1.0000
9:33797828:GCC:G	acceptor_gain	1.0000
9:33797828:GCCGC:G	acceptor_gain	1.0000
9:33798080:GTG:G	donor_gain	1.0000
9:33798081:TGGTG:T	donor_loss	1.0000
9:33798082:GGT:G	donor_loss	1.0000
9:33798083:G:GA	donor_loss	1.0000
9:33798084:T:A	donor_loss	1.0000
9:33798463:T:TA	acceptor_gain	1.0000
9:33798474:T:TA	acceptor_gain	1.0000
9:33798536:GC:G	donor_gain	1.0000
9:33798562:A:T	donor_gain	1.0000
9:33799027:GC:G	acceptor_gain	1.0000
9:33796636:A:AG	acceptor_gain	0.9900
9:33796637:C:G	acceptor_gain	0.9900
9:33796638:TCCAG:T	acceptor_loss	0.9900
9:33796639:CCAGT:C	acceptor_loss	0.9900
9:33796641:A:AC	acceptor_loss	0.9900

AlphaMissense

1616 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:33798060:G:C	W201C	0.995
9:33798060:G:T	W201C	0.995
9:33799150:G:C	W295C	0.991
9:33799150:G:T	W295C	0.991
9:33796771:T:A	W114R	0.990
9:33796771:T:C	W114R	0.990
9:33797948:A:T	D164V	0.989
9:33796773:G:C	W114C	0.988
9:33796773:G:T	W114C	0.988
9:33798058:T:A	W201R	0.987
9:33798058:T:C	W201R	0.987
9:33797949:C:A	D164E	0.984
9:33797949:C:G	D164E	0.984
9:33799148:T:A	W295R	0.984
9:33799148:T:C	W295R	0.984
9:33797948:A:C	D164A	0.983
9:33798542:T:A	C228S	0.981
9:33798543:G:C	C228S	0.981
9:33798585:G:A	C242Y	0.979
9:33798584:T:A	C242S	0.977
9:33798585:G:C	C242S	0.977
9:33797947:G:C	D164H	0.976
9:33797957:T:C	L167P	0.976
9:33798509:T:A	C217S	0.976
9:33798510:G:C	C217S	0.976
9:33799084:G:C	W273C	0.975
9:33799084:G:T	W273C	0.975
9:33798586:T:G	C242W	0.974
9:33796720:T:C	S97P	0.973
9:33798584:T:C	C242R	0.973

dbSNP variants (sampled 300 via entrez): RS1000098145 (9:33784988 T>A,C), RS1000339985 (9:33792448 T>C), RS1000350529 (9:33769744 GC>G), RS1000531925 (9:33763144 G>A,T), RS1000566988 (9:33756465 G>A), RS1000579029 (9:33776580 T>C), RS1000596411 (9:33756041 C>T), RS1000757547 (9:33797243 C>T), RS1000790158 (9:33797567 G>A), RS1000807881 (9:33749650 G>A), RS1000966134 (9:33763465 C>T), RS1001176601 (9:33749839 C>T), RS1001200234 (9:33766171 A>G), RS1001237450 (9:33759521 C>G), RS1001374930 (9:33791197 C>T)

Disease associations

OMIM: gene MIM:613578 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): thyroiditis (MONDO:0004126)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0100646	Thyroiditis

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005830_27	Hand grip strength	2.000000e-08
GCST006613_82	Triglycerides	6.000000e-11
GCST006865_18	Bipolar disorder	4.000000e-06
GCST010002_319	Refractive error	4.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006941	grip strength measurement
EFO:0004530	triglyceride measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D013966	Thyroiditis	C19.874.871

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2095204 (PROTEIN FAMILY), CHEMBL2096988 (SELECTIVITY GROUP), CHEMBL4551 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 172,350 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1166	ARGATROBAN	4	231
CHEMBL266349	MELAGATRAN	4	5,421
CHEMBL338802	SULFAGUANIDINE	4	4,956
CHEMBL5189739	BEROTRALSTAT	4	7
CHEMBL226335	RUTIN	3	57,988
CHEMBL4112929	MILVEXIAN	3	134
CHEMBL48361	DABIGATRAN	3	13,443
CHEMBL50	QUERCETIN	3	74,559
CHEMBL590799	CAMOSTAT	3	6,733
CHEMBL9509	SILIBININ	3	130
CHEMBL114586	SEPIMOSTAT	2	156
CHEMBL8260	BAICALEIN	2	8,592

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
BPTI-K15R/R17G	Inhibition	8.23	pKi

ChEMBL bioactivities

820 potent at pChembl≥5 of 940 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	Ki	0.03	nM	CHEMBL3623792
10.00	Ki	0.1	nM	CHEMBL239127
10.00	Ki	0.1	nM	CHEMBL453539
9.85	IC50	0.14	nM	CHEMBL3980104
9.85	IC50	0.14	nM	CHEMBL3917451
9.80	Ki	0.16	nM	CHEMBL3623793
9.80	Ki	0.16	nM	CHEMBL4483694
9.77	IC50	0.17	nM	CHEMBL3947949
9.77	IC50	0.17	nM	CHEMBL3985298
9.77	IC50	0.17	nM	CHEMBL3972244
9.77	IC50	0.17	nM	CHEMBL3909962
9.74	IC50	0.18	nM	CHEMBL3961130
9.72	IC50	0.19	nM	CHEMBL3951207
9.72	IC50	0.19	nM	CHEMBL3897484
9.72	IC50	0.19	nM	CHEMBL3939171
9.72	IC50	0.19	nM	CHEMBL3969953
9.70	IC50	0.2	nM	CHEMBL3977211
9.68	IC50	0.21	nM	CHEMBL3940399
9.68	IC50	0.21	nM	CHEMBL3917451
9.66	IC50	0.22	nM	CHEMBL3971081
9.64	IC50	0.23	nM	CHEMBL4109828
9.62	IC50	0.24	nM	CHEMBL3953763
9.60	IC50	0.25	nM	CHEMBL3933667
9.59	IC50	0.26	nM	CHEMBL3947460
9.57	IC50	0.27	nM	CHEMBL3962586
9.55	IC50	0.28	nM	CHEMBL4113549
9.55	IC50	0.28	nM	CHEMBL3893507
9.55	IC50	0.28	nM	CHEMBL3893474
9.52	Ki	0.3	nM	CHEMBL2419745
9.52	IC50	0.3	nM	CHEMBL3957994
9.52	IC50	0.3	nM	CHEMBL4106875
9.52	Ki	0.3	nM	CHEMBL420540
9.51	IC50	0.31	nM	CHEMBL3922459
9.51	IC50	0.31	nM	CHEMBL3941889
9.47	IC50	0.34	nM	CHEMBL3977663
9.47	IC50	0.34	nM	CHEMBL3963997
9.46	IC50	0.35	nM	CHEMBL3940716
9.42	IC50	0.38	nM	CHEMBL3962513
9.42	IC50	0.38	nM	CHEMBL3912722
9.41	IC50	0.39	nM	CHEMBL3925221
9.41	IC50	0.39	nM	CHEMBL3941734
9.41	IC50	0.39	nM	CHEMBL3955210
9.40	IC50	0.4	nM	CHEMBL3964583
9.39	IC50	0.41	nM	CHEMBL3985101
9.36	IC50	0.44	nM	CHEMBL3916887
9.35	IC50	0.45	nM	CHEMBL3926197
9.35	IC50	0.45	nM	CHEMBL3940894
9.35	IC50	0.45	nM	CHEMBL3967403
9.35	IC50	0.45	nM	CHEMBL3929693
9.34	IC50	0.46	nM	CHEMBL3979741

PubChem BioAssay actives

757 with measured affinity, of 2186 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
(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,41S,44S,50S)-50-benzyl-4,19-bis[(2S)-butan-2-yl]-25,34-bis[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,43,49,52-tetradecaoxo-54,55-dithia-2,5,11,17,20,23,26,29,32,35,38,42,48,51-tetradecazapentacyclo[29.21.4.07,11.013,17.044,48]hexapentacontane-41-carboxylic acid	1251573: Inhibition of beta-trypsin (unknown origin) using Bz-FVRpNA substrate by spectrophotometry method	ki	<0.0001	uM
2-[(1R,3aS,7S,10S,13S,16S,19S,22S,25R,28S,31S,34S,37S,40S,43R,49S,55S,58R,61S,64R,67S,73S,79S,82R,88S,94S,97S)-10,19,22-tris(4-aminobutyl)-73-(2-amino-2-oxoethyl)-13,61-bis[(2S)-butan-2-yl]-28,31,67-tris(3-carbamimidamidopropyl)-40,97-bis(carboxymethyl)-37,88,94-tris(hydroxymethyl)-79-[(4-hydroxyphenyl)methyl]-55-methyl-16-(2-methylpropyl)-1a,2,4a,8,11,14,17,20,23,26,29,32,35,38,41,44,50,53,56,59,62,65,68,71,74,77,80,83,86,89,92,95,98-tritriacontaoxo-3a-propan-2-yl-7a,8a,11a,12a,15a,16a-hexathia-2a,3,5a,9,12,15,18,21,24,27,30,33,36,39,42,45,51,54,57,60,63,66,69,72,75,78,81,84,87,90,93,96,99-tritriacontazahexacyclo[56.47.4.425,64.443,82.03,7.045,49]heptadecahectan-34-yl]acetic acid	1533293: Inhibition of trypsin (unknown origin)	ki	<0.0001	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-25-(4-aminobutyl)-49-benzyl-4,19-bis[(2S)-butan-2-yl]-34-[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetic acid	1251580: Inhibition of trypsin (unknown origin)	ki	0.0001	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43R,49S)-25-(4-aminobutyl)-49-benzyl-4,19-bis[(2S)-butan-2-yl]-34-[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetic acid	218709: Compound was tested for inhibition of Sunflower beta-trypsin	ki	0.0001	uM
(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,41S,44S,50S)-50-benzyl-4-[(2S)-butan-2-yl]-25,34-bis[3-(diaminomethylideneamino)propyl]-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,43,49,52-tetradecaoxo-54,55-dithia-2,5,11,17,20,23,26,29,32,35,38,42,48,51-tetradecazapentacyclo[29.21.4.07,11.013,17.044,48]hexapentacontane-41-carboxylic acid	1251573: Inhibition of beta-trypsin (unknown origin) using Bz-FVRpNA substrate by spectrophotometry method	ki	0.0002	uM
(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[2-[[(1S,6S,12S,15S,18S,21S,24S,27S,30R,33S,36S,39S,42S,45S,48R,53S,56S,62S,68S,71R,74S,79S,85S)-6-[[(2S)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-methylbutanoyl]amino]-15,24,27-tris(4-aminobutyl)-62-(2-amino-2-oxoethyl)-18,74-bis[(2S)-butan-2-yl]-33,36,68-tris(3-carbamimidamidopropyl)-39,45-bis(carboxymethyl)-42-(hydroxymethyl)-56-[(4-hydroxyphenyl)methyl]-79-methyl-21-(2-methylpropyl)-7,13,16,19,22,25,28,31,34,37,40,43,46,55,58,61,64,67,70,73,76,78,81,84,90-pentacosaoxo-3,4,50,51,92,93-hexathia-8,14,17,20,23,26,29,32,35,38,41,44,47,54,57,60,63,66,69,72,75,77,80,83,89-pentacosazapentacyclo[46.28.14.430,71.08,12.085,89]tetranonacontane-53-carbonyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]butanedioic acid	1628817: Inhibition of trypsin (unknown origin) using Bz-FVRpNA as substrate incubated for 30 mins measured for 7 mins by morrison plot analysis	ki	0.0002	uM
2-[[(2S)-1-[(2S)-2-[(5-carbamimidoylthiophen-2-yl)methylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]amino]acetic acid	766527: Inhibition of human trypsin	ki	0.0003	uM
2-[[(2R)-1-[(2S)-2-[(5-carbamimidoylthiophen-2-yl)methylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]amino]acetic acid	215245: In vitro inhibition constant (Ki) against human trypsin was determined	ki	0.0003	uM
2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]acetic acid	254278: Inhibitory constant against trypsin	ki	0.0007	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-49-(2-amino-2-oxoethyl)-4,19-bis[(2S)-butan-2-yl]-25-[3-(diaminomethylideneamino)propyl]-28,34-bis[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetamide	1251580: Inhibition of trypsin (unknown origin)	ki	0.0007	uM
[2-[(3,5-dimethyl-1-phenylpyrazol-4-yl)amino]-2-oxoethyl] 2-(6-carbamimidoyl-2-methyl-1H-indol-3-yl)acetate	1387138: Inhibition of trypsin (unknown origin) pre-incubated for 30 mins before N-Boc-FSR-AMC substrate addition and measured after 30 mins	ic50	0.0010	uM
methyl (2S)-2-[[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]carbamoyl]pyrrolidine-1-sulfonate;2,2,2-trifluoroacetic acid	42095: Beta-Trypsin inhibitory activity of compound was determined	ic50	0.0010	uM
(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-N-[(2S)-1-[[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]pentanediamide	682988: Tight binding inhibition of human trypsin expressed in Drosophila melanogaster S2 cells using Boc-QAR-AMC as substrate incubated for 15 mins prior to substrate addition measured for 30 mins by fluorimetric analysis	ki	0.0010	uM
ethyl 2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]acetate	254278: Inhibitory constant against trypsin	ki	0.0013	uM
[4-(diaminomethylideneamino)phenyl] 4-(diaminomethylideneamino)benzoate	1555462: Inhibition of trypsin (unknown origin) using Boc-Val-Pro-Arg-AMC as substrate preincubated with enzyme for 15 mins followed by addition of substrate by fluorescence plate reader analysis	ic50	0.0014	uM
N-[2-(1-benzylpiperidin-2-yl)ethyl]-2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-amine	254278: Inhibitory constant against trypsin	ki	0.0015	uM
2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-N-(2,2-difluoro-2-piperidin-2-ylethyl)-[1,3]oxazolo[4,5-c]pyridin-4-amine	254278: Inhibitory constant against trypsin	ki	0.0015	uM
2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]ethanol	254278: Inhibitory constant against trypsin	ki	0.0016	uM
2-[[(2R)-1-[(2S)-2-[(5-carbamimidoylthiophen-2-yl)methylcarbamoyl]-2,5-dihydropyrrol-1-yl]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid	264686: Inhibition of trypsin	ic50	0.0016	uM
[4-(aminomethyl)phenyl] 4-(diaminomethylideneamino)benzoate	1555462: Inhibition of trypsin (unknown origin) using Boc-Val-Pro-Arg-AMC as substrate preincubated with enzyme for 15 mins followed by addition of substrate by fluorescence plate reader analysis	ic50	0.0016	uM
2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-N-(2-piperidin-2-ylethyl)-[1,3]oxazolo[4,5-c]pyridin-4-amine	254278: Inhibitory constant against trypsin	ki	0.0016	uM
2-[[(2R)-1-[(2S)-2-[(4-carbamimidoylfuran-2-yl)methylcarbamoyl]-2,5-dihydropyrrol-1-yl]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid	264686: Inhibition of trypsin	ic50	0.0019	uM
2-acetamido-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]acetamide;2,2,2-trifluoroacetic acid	42095: Beta-Trypsin inhibitory activity of compound was determined	ic50	0.0020	uM
(2S)-N-[(2S)-1-(1,3-benzoxazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(2R)-2-(3,3-dimethylbutanoylamino)-3-phenylpropanoyl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid	321200: Inhibition of human trypsin	ic50	0.0023	uM
4-[2-[(2S,11S)-11-(2,3-dihydro-1-benzofuran-5-ylsulfonylamino)-12-oxo-1-azatricyclo[6.4.1.04,13]trideca-4,6,8(13)-trien-2-yl]-2-oxoethyl]piperidine-1-carboximidamide	215553: Inhibitory constant against trypsin determined in Vitro	ki	0.0025	uM
[4-(diaminomethylideneamino)phenyl] 4-aminobenzoate	1555462: Inhibition of trypsin (unknown origin) using Boc-Val-Pro-Arg-AMC as substrate preincubated with enzyme for 15 mins followed by addition of substrate by fluorescence plate reader analysis	ic50	0.0028	uM
2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-N-[2-[1-(2,2-difluoroethyl)piperidin-2-yl]ethyl]-[1,3]oxazolo[4,5-c]pyridin-4-amine	254278: Inhibitory constant against trypsin	ki	0.0029	uM
4-[3-[(3S)-3-(2,3-dihydro-1-benzofuran-5-ylsulfonylamino)-2-oxoazepan-1-yl]-2-oxopropyl]benzenecarboximidamide	215553: Inhibitory constant against trypsin determined in Vitro	ki	0.0032	uM
1-(3-carbamimidoylphenyl)-N-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	215244: In vitro activity against human trypsin.	ki	0.0034	uM
3-(3-carbamimidoylphenyl)-N-[4-(2-sulfamoylphenyl)phenyl]triazole-4-carboxamide;2,2,2-trifluoroacetic acid	215413: Binding affinity towards human trypsin	ki	0.0034	uM
[4-[2-[2-(dimethylamino)-2-oxoethoxy]-2-oxoethyl]phenyl] 4-(diaminomethylideneamino)benzoate	1555462: Inhibition of trypsin (unknown origin) using Boc-Val-Pro-Arg-AMC as substrate preincubated with enzyme for 15 mins followed by addition of substrate by fluorescence plate reader analysis	ic50	0.0035	uM
3-[[(2R)-1-[[(2S)-3-[3-(aminomethyl)phenyl]-1-[(4-carbamimidoylphenyl)methylamino]-1-oxopropan-2-yl]amino]-1-oxo-5-phenylpentan-2-yl]sulfamoylmethyl]benzoic acid	1626146: Inhibition of trypsin (unknown origin)	ki	0.0036	uM
benzyl N-[(2S)-6-amino-1-[5-[[4-[4-[(2-fluorophenyl)methyl]piperazine-1-carbonyl]phenyl]methyl]-1,2,4-oxadiazol-3-yl]-1-oxohexan-2-yl]carbamate	269676: Inhibition of human trypsin	ki	0.0037	uM
1-(3-carbamimidoylphenyl)-N-[4-(2-sulfamoylphenyl)phenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	215244: In vitro activity against human trypsin.	ki	0.0039	uM
(2R)-1-acetyl-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid	42095: Beta-Trypsin inhibitory activity of compound was determined	ic50	0.0040	uM
1-(3-carbamimidoylphenyl)-N-[2-fluoro-4-(2-sulfamoylphenyl)phenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	215244: In vitro activity against human trypsin.	ki	0.0040	uM
1-(3-carbamimidoylphenyl)-N-[4-(2-methylsulfonylphenyl)phenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	215244: In vitro activity against human trypsin.	ki	0.0043	uM
2-[[(1R)-2-[(2S)-2-[(4-carbamimidoylphenyl)methylcarbamoyl]azetidin-1-yl]-1-cyclohexyl-2-oxoethyl]amino]acetic acid	766527: Inhibition of human trypsin	ki	0.0043	uM
2-(3-carbamimidoylphenyl)-N-[2-fluoro-4-(2-sulfamoylphenyl)phenyl]-5-methylpyrazole-3-carboxamide	215244: In vitro activity against human trypsin.	ki	0.0046	uM
2-[[(2R)-1-[(2S)-2-[(6-carbamimidoyl-3-pyridinyl)methylcarbamoyl]-2,5-dihydropyrrol-1-yl]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid	264686: Inhibition of trypsin	ic50	0.0048	uM
(2S)-1-acetyl-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]azetidine-2-carboxamide;2,2,2-trifluoroacetic acid	42095: Beta-Trypsin inhibitory activity of compound was determined	ic50	0.0050	uM
5-[3-[(3S)-3-(2,3-dihydro-1-benzofuran-5-ylsulfonylamino)-2-oxoazepan-1-yl]-2-oxopropyl]thiophene-2-carboximidamide	215553: Inhibitory constant against trypsin determined in Vitro	ki	0.0059	uM
(2S,4R)-1-acetyl-N-[1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-4-hydroxypyrrolidine-2-carboxamide	320964: Inhibition of human trypsin by chromogenic assay	ki	0.0060	uM
(2R)-2-(benzylsulfonylamino)-N-[2-[(4-carbamimidoylphenyl)methylamino]-2-oxoethyl]-4-(1-oxidopyridin-1-ium-2-yl)butanamide	290692: Inhibition of trypsin	ki	0.0063	uM
1-(3-carbamimidoylphenyl)-N-[4-(2-sulfamoylphenyl)phenyl]tetrazole-5-carboxamide;2,2,2-trifluoroacetic acid	215413: Binding affinity towards human trypsin	ki	0.0064	uM
2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-N-[2-[1-(2,2,2-trifluoroethyl)piperidin-2-yl]ethyl]-[1,3]oxazolo[4,5-c]pyridin-4-amine	254278: Inhibitory constant against trypsin	ki	0.0069	uM
(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[2-[[(1R,4S,7S,10S,13S,16S,19R,22S,25S,28S,31S,34S,37S,40S,45S,48S,51R,54S,60S,66S,69S,79S,85S)-40-[[(2S)-5-amino-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-5-oxopentanoyl]amino]-22,25-bis(4-aminobutyl)-60-(2-amino-2-oxoethyl)-37-benzyl-31,48-bis[(2S)-butan-2-yl]-13,16,34,54-tetrakis(3-carbamimidamidopropyl)-4,10-bis(carboxymethyl)-7-(hydroxymethyl)-66-[(4-hydroxyphenyl)methyl]-85-methyl-28-(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,46,49,52,55,58,61,64,67,74,80,83,86-pentacosaoxo-42,43,71,72,89,90-hexathia-2,5,8,11,14,17,20,23,26,29,32,35,38,47,50,53,56,59,62,65,68,75,81,84,87-pentacosazatetracyclo[43.28.14.419,51.075,79]hennonacontane-69-carbonyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]butanedioic acid	1628817: Inhibition of trypsin (unknown origin) using Bz-FVRpNA as substrate incubated for 30 mins measured for 7 mins by morrison plot analysis	ki	0.0069	uM
2-[(aR,1R,3aS,4S,10S,16R,19S,22S,25S,28S,31S,34R,37S,40S,43S,46S,49S,52S,55R,58S,67S,70S,76S,82R,85S,91S,97S)-97-(4-aminobutyl)-91-(2-amino-2-oxoethyl)-28,31,37,40,52-pentakis(3-amino-3-oxopropyl)-58-benzyl-3a,46-bis[(2S)-butan-2-yl]-49-(3-carbamimidamidopropyl)-19,67-bis(carboxymethyl)-22,70,76-tris(hydroxymethyl)-85-[(4-hydroxyphenyl)methyl]-4-methyl-43-(2-methylpropyl)-2a,3,5a,6,9,15,18,21,24,27,30,33,36,39,42,45,48,51,54,57,60,63,66,69,72,75,78,81,84,87,90,93,96,99-tetratriacontaoxo-7a,8a,11a,12a,15a,16a-hexathia-1a,2,4a,5,8,14,17,20,23,26,29,32,35,38,41,44,47,50,53,56,59,62,65,68,71,74,77,80,83,86,89,92,95,98-tetratriacontazapentacyclo[53.50.4.416,82.434,100.010,14]heptadecahectan-25-yl]acetic acid	1533299: Inhibition of trypsin (unknown origin) using Bz-FVR-pNA as substrate preincubated for 30 mins followed by substrate addition and measured for 7 mins by spectrophotometric method	ki	0.0069	uM
2-[2-[(6R,6aR,11bR)-2-carbamimidoyl-6,6a,7,11b-tetrahydro-5H-indeno[2,1-c]quinolin-6-yl]-5-hydroxy-4-methoxyphenyl]benzoic acid	760605: Inhibition of purified human trypsin	ki	0.0075	uM
4-[3-[(3S)-3-(2,3-dihydro-1-benzofuran-5-ylsulfonylamino)-2-oxoazepan-1-yl]-2-oxopropyl]-3-fluorobenzenecarboximidamide	215553: Inhibitory constant against trypsin determined in Vitro	ki	0.0076	uM

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	increases methylation, decreases expression, increases abundance	2
Cadmium Chloride	increases expression	2
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenate	decreases expression, increases abundance	1
terbufos	increases methylation	1
beta-lapachone	increases expression	1
butyraldehyde	increases expression	1
aflatoxin B2	decreases methylation	1
hydroquinone	increases expression	1
beta-methylcholine	affects expression	1
S 1 (combination)	increases response to substance	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cyclophosphamide	affects response to substance	1
Diethylnitrosamine	decreases expression	1
Fonofos	increases methylation	1
Formaldehyde	increases expression	1
Lead	increases expression	1
Nickel	increases expression	1
Parathion	increases methylation	1
Silicon Dioxide	decreases expression	1
Sodium Dodecyl Sulfate	decreases expression	1
Thiram	increases expression	1

ChEMBL screening assays

393 unique, capped per target: 342 binding, 51 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1006751	Binding	Inhibition of trypsin-induced elevation in PAI1 production in HUVEC by ELISA	Effects of flavonoids isolated from scutellariae radix on fibrinolytic system induced by trypsin in human umbilical vein endothelial cells. — J Nat Prod
CHEMBL4320630	ADMET	Stability of the compound assessed as trypsin (unknown origin)-mediated compound hydrolysis after 8 hrs by SDS-PAGE analysis	Antimicrobial Peptides with High Proteolytic Resistance for Combating Gram-Negative Bacteria. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07571681	PHASE2/PHASE3	NOT_YET_RECRUITING	Colchicine for Autoimmune and Subacute Thyroiditis
NCT01227499	Not specified	COMPLETED	Differential Diagnosis of STA-PSV in Thyrotoxicosis
NCT01320813	Not specified	TERMINATED	Trial Comparing Complication Rates Associated With Robot-assisted Thyroidectomy to External Thyroidectomy
NCT02778412	Not specified	TERMINATED	ctDNA in Patients With Thyroid Nodules
NCT03009357	Not specified	COMPLETED	Clinical Application of Pulse Rate-monitoring Activity Trackers in Thyrotoxicosis
NCT04410601	Not specified	UNKNOWN	Post-thyroidectomy Dysphagia: An International Multicentric CONSORT - Compatible RCT
NCT04754607	Not specified	COMPLETED	Effects of Low-Level Laser Therapy on Oxidative Stress Levels
NCT05252884	Not specified	COMPLETED	Calcium+Calcitriol Versus PTH for the Prevention of Hypocalcemia in Thyroidectomy. Randomized Clinical Trial
NCT06735040	Not specified	COMPLETED	Effect of Photobiomodulation Therapy in Patients With Hashimoto’s Thyroiditis