MST1

Summary

MST1 (macrophage stimulating 1, HGNC:7380) is a protein-coding gene on chromosome 3p21.31, encoding Hepatocyte growth factor-like protein (P26927).

The protein encoded by this gene contains four kringle domains and a serine protease domain, similar to that found in hepatic growth factor. Despite the presence of the serine protease domain, the encoded protein may not have any proteolytic activity. The receptor for this protein is RON tyrosine kinase, which upon activation stimulates ciliary motility of ciliated epithelial lung cells. This protein is secreted and cleaved to form an alpha chain and a beta chain bridged by disulfide bonds.

Source: NCBI Gene 4485 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined immunodeficiency due to STK4 deficiency (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 28
• Clinical variants (ClinVar): 168 total
• Druggable target: yes
• MANE Select transcript: NM_020998

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7380
Approved symbol	MST1
Name	macrophage stimulating 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	MSP, NF15S2
Ensembl gene	ENSG00000173531
Ensembl biotype	protein_coding
OMIM	142408
Entrez	4485

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 17 retained_intron, 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000448220, ENST00000449682, ENST00000468847, ENST00000479115, ENST00000480268, ENST00000481055, ENST00000481930, ENST00000484144, ENST00000484269, ENST00000484673, ENST00000488350, ENST00000489007, ENST00000490966, ENST00000491943, ENST00000492329, ENST00000492370, ENST00000493836, ENST00000494809, ENST00000494828, ENST00000497359, ENST00000498021

RefSeq mRNA: 6 — MANE Select: NM_020998 NM_001393581, NM_001393582, NM_001393583, NM_001393584, NM_001393585, NM_020998

CCDS: CCDS33757

Canonical transcript exons

ENST00000449682 — 18 exons

Exon	Start	End
ENSE00001669866	49683947	49684189
ENSE00001788980	49688598	49689474
ENSE00003266780	49686062	49686192
ENSE00003461322	49685012	49685089
ENSE00003470779	49686684	49686802
ENSE00003486097	49686313	49686481
ENSE00003501407	49686947	49687067
ENSE00003519488	49685471	49685506
ENSE00003520257	49684550	49684656
ENSE00003527929	49687556	49687668
ENSE00003537356	49685262	49685382
ENSE00003541162	49687750	49687897
ENSE00003578086	49684738	49684884
ENSE00003585154	49685860	49685962
ENSE00003631207	49687364	49687478
ENSE00003636813	49687149	49687285
ENSE00003645012	49685596	49685732
ENSE00003664219	49684314	49684453

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.69.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4139 / max 6.0074, expressed in 230 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42269	0.4139	230

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.69	gold quality
liver	UBERON:0002107	99.30	gold quality
duodenum	UBERON:0002114	97.66	gold quality
metanephros cortex	UBERON:0010533	97.14	gold quality
left testis	UBERON:0004533	97.08	gold quality
left lobe of thyroid gland	UBERON:0001120	96.99	gold quality
right lobe of thyroid gland	UBERON:0001119	96.88	gold quality
right testis	UBERON:0004534	96.88	gold quality
thyroid gland	UBERON:0002046	96.50	gold quality
cortex of kidney	UBERON:0001225	96.25	gold quality
testis	UBERON:0000473	96.10	gold quality
adult mammalian kidney	UBERON:0000082	95.99	gold quality
right uterine tube	UBERON:0001302	95.76	gold quality
pituitary gland	UBERON:0000007	95.04	gold quality
kidney	UBERON:0002113	94.55	gold quality
left adrenal gland cortex	UBERON:0035825	94.43	gold quality
right adrenal gland	UBERON:0001233	94.35	gold quality
right adrenal gland cortex	UBERON:0035827	94.32	gold quality
adenohypophysis	UBERON:0002196	94.19	gold quality
left adrenal gland	UBERON:0001234	93.78	gold quality
adrenal gland	UBERON:0002369	92.20	gold quality
lower esophagus mucosa	UBERON:0035834	92.00	gold quality
body of pancreas	UBERON:0001150	91.58	gold quality
omental fat pad	UBERON:0010414	91.23	gold quality
small intestine	UBERON:0002108	90.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.68	gold quality
skin of abdomen	UBERON:0001416	90.52	gold quality
zone of skin	UBERON:0000014	89.94	gold quality
skin of leg	UBERON:0001511	89.53	gold quality
adrenal tissue	UBERON:0018303	89.40	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.85
E-MTAB-6142	no	18.03

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 37)

• These results suggest that activation of RON by macrophage-stimulating protein inhibits LPS-induced macrophage Cox-2 expression. (PMID:12177064)
• Data show that macrophage stimulating protein (MSP) and its receptor (Ron) induce phosphorylation of both Ron and alpha6beta4 integrin, and result in activation of alpha3beta1 integrin. (PMID:12919677)
• macrophage-stimulating protein-responsive cell growth in culture is suppressed by the ron-sema domain (PMID:14597639)
• Macrophage stimulating protein and its receptor RON are involved in the pathophysiology of endometriosis. (PMID:15764806)
• repression of MSP gene expression by mutant p53 may contribute to oncogenesis in a cell type-specific manner (PMID:16170349)
• overexpression of MSP, MT-SP1, and MST1R was a strong independent indicator of both metastasis and death in human breast cancer (PMID:17456594)
• Cell migration and production of inflammatory cytokines by the brain are enhanced by MSP stimulation in primary microglia. (PMID:18480548)
• The five gene transcripts (aldolase B, elafin, MST-1, simNIPhom and SLC6A14) were changed in patients with ulcerative colitis, and were related to the disease activity. (PMID:18700007)
• Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis. (PMID:19079170)
• Results suggest that hepatocyte growth factor activator is a major serum activator of pro-macrophage-stimulating protein. (PMID:19456860)
• The effect of BSN-MST1 locus on Crohn’s disease predisposition was replicated, but no influence on ulcerative colitis or multiple sclerosis predisposition could be detected (PMID:19657358)
• results suggest that MSP induces uPAR expression via MAPK, AP-1 and NF-kappaB signaling pathways (PMID:21081472)
• the oncogenic effect of BRAF(V600E) is associated with the inhibition of MST1 tumor suppressor pathways, and that the activity of RASSF1A-MST1-FoxO3 pathways determines the phenotypes of BRAF(V600E) tumors. (PMID:21249150)
• MSP-induced RSK2 activation is a critical determinant linking RON signaling to cellular EMT program. (PMID:21619683)
• considerable number of Merkel cell carcinoma cases expressed both RON and MSP, while Merkel cells do not express these molecules (PMID:21723047)
• These findings suggest that the MSP/RON signaling pathway may be regulated by hepsin in tissue homeostasis and in disease pathologies, such as in cancer and immune disorders. (PMID:21875933)
• Studies indicate that the cylindromatosis/turban tumor syndrome gene (CYLD) ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4). (PMID:21931648)
• the missense SNP impairs MSP function by reducing its affinity to RON and perhaps through a secondary effect on in vivo concentration arising from reduced thermodynamic stability, resulting in down-regulation of the MSP/RON signaling pathway. (PMID:22087277)
• HAT cleaves proMSP at the physiological activation site (PMID:22245154)
• The present results refine the known genetic architecture in primary sclerosing cholangitis by confirming MST1 locus association. (PMID:22554193)
• MSP may be one of the major determinants that affects the properties of tumor stroma and that produces a permissive microenvironment to promote cancer metastasis (PMID:23011677)
• Results suggest that the [AA] genotype of the common MST1 variant rs3197999 enhances genetic risk of sporadic extrahepatic cholangiocarcinoma irrespective of primary sclerosing cholangitis status. (PMID:23422030)
• Mst1 has an important role in inhibiting the growth of NSCLC in vitro and in vivo; its antiproliferative effect is associated with induction of apoptosis. (PMID:23928732)
• functional consequences of the macrophage stimulating protein 689C inflammatory bowel disease risk allele (PMID:24409221)
• These results support the hypothesis that the alpha-chain of MSPalphabeta mediates RON dimerization. (PMID:25193665)
• MSP appears to promote the migration of fibroblasts, enhances collagen synthesis and remodeling, and effectively improves wound healing. (PMID:25315688)
• Identify MST1/MSP as a mitogen for tracheal basal cells. (PMID:25551685)
• Elevated serum levels of MST1 were found in subjects with excessive alcohol use. (PMID:25704570)
• These data suggest that MSP is an effective inhibitor of inflammation and lipid accumulation in the stressed liver, thereby indicating that MSP has a key regulatory role in non-alcoholic steatohepatitis. (PMID:27609031)
• Our analysis suggests that MST1 might interact with key susceptibility genes involved in autophagy and bacterial recognition. These findings provide insight into the genetic architecture of Crohn’s disease in Chinese and may partially explain the disparity of genetic signals in Crohn’s disease susceptibility across different ethnic populations by highlighting the contribution of gene-gene interactions. (PMID:29441677)
• Legionella pneumophila effector protein LegK7(lpg1924) hijacks the conserved Hippo signaling pathway by molecularly mimicking host Hippo kinase (MST1 in mammals), which is the key regulator of pathway activation. (PMID:30212651)
• Comparative characterization of the HGF/Met and MSP/Ron systems in primary pancreatic adenocarcinoma. (PMID:31254927)
• Macrophage stimulating 1-induced inflammation response promotes aortic aneurysm formation through triggering endothelial cells death and activating the NF-kappaB signaling pathway. (PMID:32156191)
• Mst1 promotes mitochondrial dysfunction and apoptosis in oxidative stress-induced rheumatoid arthritis synoviocytes. (PMID:32692720)
• Macrophage-stimulating protein is decreased in severe preeclampsia and regulates the biological behavior of HTR-8/SVneo trophoblast cells. (PMID:33070035)
• circCRAMP1L is a novel biomarker of preeclampsia risk and may play a role in preeclampsia pathogenesis via regulation of the MSP/RON axis in trophoblasts. (PMID:33109096)
• Mst1-mediated phosphorylation of Nur77 improves the endometrial receptivity in human and mice. (PMID:36623453)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	mst1	ENSDARG00000103308
mus_musculus	Mst1	ENSMUSG00000032591
rattus_norvegicus	Mst1	ENSRNOG00000019680
drosophila_melanogaster	CG14780	FBGN0025383
drosophila_melanogaster	CG14227	FBGN0031058
drosophila_melanogaster	CG11664	FBGN0040341
drosophila_melanogaster	CG30287	FBGN0050287
drosophila_melanogaster	CG30288	FBGN0050288
drosophila_melanogaster	CG30289	FBGN0050289
drosophila_melanogaster	CG30414	FBGN0050414
drosophila_melanogaster	CG31205	FBGN0051205
drosophila_melanogaster	CG33225	FBGN0053225
drosophila_melanogaster	CG33226	FBGN0069056
drosophila_melanogaster	CG30283	FBGN0260477

Paralogs (5): HGF (ENSG00000019991), PIK3IP1 (ENSG00000100100), GZMK (ENSG00000113088), GZMA (ENSG00000145649), HABP2 (ENSG00000148702)

Protein

Protein identifiers

Hepatocyte growth factor-like protein — P26927 (reviewed: P26927)

Alternative names: Macrophage stimulatory protein, Macrophage-stimulating protein

All UniProt accessions (2): G3XAK1, H7C0F8

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Dimer of an alpha chain and a beta chain linked by a disulfide bond. Interacts (via beta chain) with MST1R (via SEMA domain).

Subcellular location. Secreted.

Post-translational modifications. Cleaved after Arg-483, probably by HPN/Hepsin, to yield the active form consisting of two disulfide-linked chains.

Disease relevance. MST1 variant Cys-689 may be associated with inflammatory bowel disease (IBD), a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is unsure whether Cys-689 itself or a variation in linkage disequilibrium with Cys-689 is responsible for the association with IBD.

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

RefSeq proteins (6): NP_001380510, NP_001380511, NP_001380512, NP_001380513, NP_001380514, NP_066278* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000001	Kringle	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR003609	Pan_app	Domain
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR013806	Kringle-like	Homologous_superfamily
IPR018056	Kringle_CS	Conserved_site
IPR024174	HGF/MST1	Family
IPR038178	Kringle_sf	Homologous_superfamily
IPR043504
IPR043575	MSP_HGFL	Family
IPR050759	Serine_protease_kringle	Family

Pfam: PF00024, PF00051, PF00089

UniProt features (65 total): disulfide bond 20, strand 16, sequence conflict 6, domain 6, sequence variant 4, helix 4, chain 3, glycosylation site 3, turn 2, signal peptide 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2ASU	X-RAY DIFFRACTION	1.85
4QT8	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26927-F1	85.30	0.51

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (20): 56–78, 60–66, 110–186, 131–169, 157–181, 191–268, 194–324, 212–251, 240–263, 283–361, 304–343, 332–355, 370–448, 391–431, 419–443, 468–588, 507–523, 602–667, 632–646, 657–685

Glycosylation sites (3): 72, 296, 615

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8852405	Signaling by MST1

MSigDB gene sets: 321 (showing top): MODULE_172, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, MODULE_308, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, WATANABE_COLON_CANCER_MSI_VS_MSS_UP, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_MONOSACCHARIDE_BIOSYNTHETIC_PROCESS, MODULE_109, MARTIN_VIRAL_GPCR_SIGNALING_UP, HSIAO_LIVER_SPECIFIC_GENES, GOBP_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (11): proteolysis (GO:0006508), negative regulation of gluconeogenesis (GO:0045721), regulation of receptor signaling pathway via JAK-STAT (GO:0046425), regulation of cAMP-dependent protein kinase activity (GO:2000479), chromatin remodeling (GO:0006338), spermatogenesis (GO:0007283), flagellated sperm motility (GO:0030317), positive regulation of apoptotic process (GO:0043065), regulation of macromolecule metabolic process (GO:0060255), cellular response to type II interferon (GO:0071346), cellular response to hypoxia (GO:0071456)

GO Molecular Function (6): receptor tyrosine kinase binding (GO:0030971), serine-type endopeptidase activity (GO:0004252), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), enzyme binding (GO:0019899), histone kinase activity (GO:0035173)

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
Signaling by Receptor Tyrosine Kinases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
gluconeogenesis	1
regulation of gluconeogenesis	1
negative regulation of biosynthetic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of small molecule metabolic process	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via STAT	1
cAMP-dependent protein kinase activity	1
regulation of protein serine/threonine kinase activity	1
chromatin organization	1
developmental process involved in reproduction	1
male gamete generation	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
regulation of metabolic process	1
macromolecule metabolic process	1
response to type II interferon	1
cellular response to cytokine stimulus	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
signaling receptor binding	1
protein tyrosine kinase binding	1
endopeptidase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
protein binding	1
protein kinase activity	1
histone modifying activity	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

1136 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MST1	MST1R	Q04912	999
MST1	APEH	P13798	836
MST1	SAV1	Q9H4B6	818
MST1	MET	P08581	715
MST1	LATS1	O95835	677
MST1	NTRK1	P04629	653
MST1	SRSF1	Q07955	595
MST1	EGFR	P00533	515
MST1	VWF	P04275	501
MST1	SEMA4D	Q92854	462
MST1	TAFAZZIN	Q16635	432
MST1	SCGB1C1	Q8TD33	416
MST1	SCGB1C2	P0DMR2	416
MST1	ITGAL	P20701	414
MST1	NAT9	Q9BTE0	411

IntAct

19 interactions, top by confidence:

A	B	Type	Score
MST1R	MST1	psi-mi:“MI:0407”(direct interaction)	0.720
MST1R	MST1	psi-mi:“MI:0915”(physical association)	0.720
MST1	MST1R	psi-mi:“MI:0407”(direct interaction)	0.720
MST1	SFT2D1	psi-mi:“MI:0915”(physical association)	0.560
STK11	LATS1	psi-mi:“MI:0914”(association)	0.500
STK11	MST1	psi-mi:“MI:0915”(physical association)	0.500
MST1		psi-mi:“MI:0915”(physical association)	0.490
ST14	MST1	psi-mi:“MI:0570”(protein cleavage)	0.440
TMPRSS11D	MST1	psi-mi:“MI:0194”(cleavage reaction)	0.440
MST1	HSPA5	psi-mi:“MI:0915”(physical association)	0.400
MST1	MOB1B	psi-mi:“MI:0915”(physical association)	0.400
SCRIB	LATS1	psi-mi:“MI:0914”(association)	0.350
MARK1	LATS1	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): FOXO1 (Biochemical Activity), MST1 (Two-hybrid), TNNI3 (Affinity Capture-Western), MST1 (Affinity Capture-Western), TNNI3 (Biochemical Activity), TNNC1 (Biochemical Activity), TNNT2 (Biochemical Activity), TNNI3 (Two-hybrid), MST1 (Affinity Capture-MS), MST1 (Affinity Capture-Western), PPM1F (Affinity Capture-Western), BECN1 (Affinity Capture-Western), BECN1 (Biochemical Activity), MST1 (Negative Genetic), HSPA5 (Affinity Capture-MS)

ESM2 similar proteins: D3ZTE0, O35453, O97507, P00743, P00745, P00748, P00750, P04070, P05981, P08709, P11214, P22457, P22891, P26927, P26928, P31394, P33587, P59509, P70375, P98139, P98140, Q04756, Q04962, Q05511, Q0IIH7, Q24K22, Q28198, Q28278, Q28661, Q2F9P2, Q2F9P4, Q2TV78, Q3UZ09, Q5R5E8, Q5R8J0, Q6IE64, Q6QNF4, Q769J6, Q7M761, Q7RTY7

Diamond homologs: A0A7J6K144, O18783, P00734, P06868, P08519, P12545, P14210, P14417, P17945, P20918, P26927, P26928, P80010, Q01177, Q01973, Q08048, Q16609, Q24K22, Q29485, Q2TV78, Q5R537, Q5R8X6, Q76BS1, Q7M323, Q867B7, Q9BH09, Q9V6K3, Q9Z139, D3ZTE0, O35453, P00735, P00747, P00750, P00774, P04813, P05208, P05981, P06867, P06869, P08001

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
MST1	up-regulates	STK4	phosphorylation
MST1	unknown	H2BC3	phosphorylation
MST1	“up-regulates activity”	PRKCA	phosphorylation
MST1	up-regulates	MST1R	binding
KLKB1	“up-regulates activity”	MST1	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	127
Likely benign	14
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4726 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000480874 (3:49690120 G>A), RS1000575003 (3:49690407 A>G), RS1001926363 (3:49689596 C>A,G), RS1002024522 (3:49689770 G>A), RS1003024375 (3:49688246 C>T), RS1004469832 (3:49690886 T>C), RS1004677679 (3:49683818 T>G), RS1005385499 (3:49689459 C>G,T), RS1006828959 (3:49689007 T>C), RS1007830061 (3:49687076 A>G), RS1007967360 (3:49687420 C>G,T), RS1009318982 (3:49689783 G>C), RS1009700274 (3:49690031 C>G), RS1010297678 (3:49688947 A>G), RS1010745022 (3:49688335 C>T)

Disease associations

OMIM: gene MIM:142408 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
combined immunodeficiency due to STK4 deficiency	Moderate	Autosomal recessive
epidermodysplasia verruciformis	Moderate	Unknown

Mondo (2): combined immunodeficiency due to STK4 deficiency (MONDO:0013934), epidermodysplasia verruciformis (MONDO:0009176)

Orphanet (0):

HPO phenotypes

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

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000039_9	Crohn’s disease	5.000000e-08
GCST000042_6	Crohn’s disease	4.000000e-08
GCST000207_13	Crohn’s disease	1.000000e-12
GCST000527_12	Ulcerative colitis	7.000000e-09
GCST000624_17	Ulcerative colitis	4.000000e-09
GCST000879_45	Crohn’s disease	6.000000e-17
GCST000915_1	Primary sclerosing cholangitis	1.000000e-16
GCST000964_6	Ulcerative colitis	2.000000e-17
GCST001725_77	Inflammatory bowel disease	1.000000e-47
GCST002548_9	Ulcerative colitis	8.000000e-07
GCST004030_3	Primary sclerosing cholangitis	5.000000e-26
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST005537_14	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	7.000000e-55
GCST005951_49	Body mass index	1.000000e-08
GCST006670_6	Primary sclerosing cholangitis	2.000000e-26
GCST006920_7	Regular attendance at a gym or sports club	6.000000e-10
GCST006922_9	Regular attendance at a religious group	3.000000e-08
GCST006943_33	Feeling miserable	2.000000e-08
GCST007044_11	Extremely high intelligence	4.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST010002_422	Refractive error	4.000000e-14
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009592	social interaction measurement
EFO:0009598	feeling miserable measurement
EFO:0004337	intelligence
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004819	Epidermodysplasia Verruciformis	C01.925.256.650.810.345; C01.925.825.810.260; C01.925.928.914.345; C17.800.838.790.810.260

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6042 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

6 measured of 6 human assays (6 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-cyclopropyl-4-[[7-(2,6-difluorophenyl)-5,8-dimethyl-6-oxo-7H-pteridin-2-yl]amino]-N-methylbenzenesulfonamide	IC50	31600 nM	US-12318398: MST1 kinase inhibitor and use thereof
4-[[7-(2,6-difluorophenyl)-5,8-dimethyl-6-oxo-7H-pteridin-2-yl]amino]-N-ethylbenzenesulfonamide	IC50	51600 nM	US-12318398: MST1 kinase inhibitor and use thereof
4-[[(7R)-5,8-dimethyl-6-oxo-7-phenyl-7H-pteridin-2-yl]amino]benzenesulfonamide	IC50	98700 nM	US-12318398: MST1 kinase inhibitor and use thereof
N-cyclopropyl-4-[[7-(2,6-difluorophenyl)-5,8-dimethyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	IC50	113000 nM	US-12318398: MST1 kinase inhibitor and use thereof
N-cyclopropyl-4-[(5,8-dimethyl-6-oxo-7-phenyl-7H-pteridin-2-yl)amino]benzenesulfonamide	IC50	143000 nM	US-12318398: MST1 kinase inhibitor and use thereof
4-[[(7S)-5,8-dimethyl-6-oxo-7-phenyl-7H-pteridin-2-yl]amino]benzenesulfonamide	IC50	197000 nM	US-12318398: MST1 kinase inhibitor and use thereof

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.47	IC50	34	nM	CHEMBL3393348
6.75	IC50	177	nM	CHEMBL2006765
5.63	IC50	2320	nM	CHEMBL4069365
5.04	IC50	9080	nM	CHEMBL4078893

PubChem BioAssay actives

3 with measured affinity, of 75 total; 3 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
N-propyl-4-[[4-(2,2,2-trifluoroethylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]benzamide	1440140: Inhibition of MST1 (unknown origin) after 60 mins by TR-FRET assay	ic50	0.1770	uM
5,5-dimethyl-8-[[4-(2,2,2-trifluoroethylamino)furo[3,2-d]pyrimidin-2-yl]amino]-1H-4,1-benzoxazepin-2-one	1440140: Inhibition of MST1 (unknown origin) after 60 mins by TR-FRET assay	ic50	2.3200	uM
2-N-(3-chloro-4-morpholin-4-ylphenyl)-4-N-(2,2,2-trifluoroethyl)furo[3,2-d]pyrimidine-2,4-diamine	1440140: Inhibition of MST1 (unknown origin) after 60 mins by TR-FRET assay	ic50	9.0800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects expression, increases expression	4
Aflatoxin B1	affects expression, decreases expression	3
bisphenol A	affects expression, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression	2
Estradiol	decreases expression, increases expression	2
Nickel	decreases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
afuresertib	increases expression	1
XMU-MP-1	decreases reaction, increases expression, decreases expression	1
methyleugenol	decreases expression	1
butyraldehyde	decreases expression	1
periodate-oxidized adenosine	affects expression	1
evodiamine	increases expression, decreases reaction	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
abrine	increases expression	1
prothioconazole	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Ascorbic Acid	affects cotreatment, decreases expression	1
Atrazine	decreases expression	1
Cadmium	affects binding	1
Chlorpromazine	increases phosphorylation	1
Disulfiram	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Nicotine	decreases expression	1
Oxygen	increases expression	1
Quercetin	affects cotreatment, decreases expression	1

ChEMBL screening assays

91 unique, capped per target: 91 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4007728	Binding	Inhibition of MST1 (unknown origin) after 60 mins by TR-FRET assay	Synthesis and optimization of furano[3,2-d]pyrimidines as selective spleen tyrosine kinase (Syk) inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2CT	HAP1 MST1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00973856	Not specified	COMPLETED	Evaluation of the Effectiveness of an Alcohol Based Hand Gel for the Reduction of Warts on the Hands