STK26

Summary

STK26 (serine/threonine kinase 26, HGNC:18174) is a protein-coding gene on chromosome Xq26.2, encoding Serine/threonine-protein kinase 26 (Q9P289). Serine/threonine-protein kinase that acts as a mediator of cell growth.

The product of this gene is a member of the GCK group III family of kinases, which are a subset of the Ste20-like kinases. The encoded protein contains an amino-terminal kinase domain, and a carboxy-terminal regulatory domain that mediates homodimerization. The protein kinase localizes to the Golgi apparatus and is specifically activated by binding to the Golgi matrix protein GM130. It is also cleaved by caspase-3 in vitro, and may function in the apoptotic pathway. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.

Source: NCBI Gene 51765 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 82 total
• Druggable target: yes — 29 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016542

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18174
Approved symbol	STK26
Name	serine/threonine kinase 26
Location	Xq26.2
Locus type	gene with protein product
Status	Approved
Aliases	MST4, MASK
Ensembl gene	ENSG00000134602
Ensembl biotype	protein_coding
OMIM	300547
Entrez	51765

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000354719, ENST00000394334, ENST00000394335, ENST00000481105, ENST00000496850, ENST00000891019, ENST00000891020, ENST00000891021, ENST00000891022, ENST00000891023, ENST00000927234, ENST00000927235, ENST00000927236, ENST00000927237, ENST00000927238

RefSeq mRNA: 3 — MANE Select: NM_016542 NM_001042452, NM_001042453, NM_016542

CCDS: CCDS14631, CCDS43995, CCDS48168

Canonical transcript exons

ENST00000394334 — 12 exons

Exon	Start	End
ENSE00000407185	132072268	132072361
ENSE00000676807	132071069	132071217
ENSE00000676808	132069478	132069663
ENSE00000676809	132068412	132068569
ENSE00000676811	132063433	132063489
ENSE00001221401	132068215	132068323
ENSE00001294983	132054631	132054861
ENSE00001608872	132023508	132023659
ENSE00001763940	132074135	132075943
ENSE00001768849	132072813	132072875
ENSE00001803018	132072957	132073093
ENSE00001892658	132023302	132023407

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.7821 / max 460.3188, expressed in 1666 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197573	23.5745	1548
197572	7.9769	1359
197574	3.7838	1058
197575	0.8290	497
197571	0.6178	362

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	99.26	gold quality
tibia	UBERON:0000979	99.09	gold quality
cauda epididymis	UBERON:0004360	98.42	gold quality
palpebral conjunctiva	UBERON:0001812	97.88	gold quality
seminal vesicle	UBERON:0000998	97.24	gold quality
cartilage tissue	UBERON:0002418	95.70	gold quality
esophagus squamous epithelium	UBERON:0006920	94.89	gold quality
epithelium of nasopharynx	UBERON:0001951	94.48	gold quality
bone marrow	UBERON:0002371	93.93	gold quality
trabecular bone tissue	UBERON:0002483	93.85	gold quality
amniotic fluid	UBERON:0000173	93.40	gold quality
parietal pleura	UBERON:0002400	93.33	gold quality
epithelium of esophagus	UBERON:0001976	93.05	gold quality
corpus epididymis	UBERON:0004359	92.81	gold quality
gingival epithelium	UBERON:0001949	92.26	gold quality
placenta	UBERON:0001987	92.16	gold quality
body of uterus	UBERON:0009853	91.80	gold quality
tongue squamous epithelium	UBERON:0006919	91.45	gold quality
myometrium	UBERON:0001296	91.21	gold quality
pleura	UBERON:0000977	90.84	gold quality
gingiva	UBERON:0001828	90.70	gold quality
squamous epithelium	UBERON:0006914	90.65	gold quality
leukocyte	CL:0000738	90.56	gold quality
mononuclear cell	CL:0000842	90.42	gold quality
monocyte	CL:0000576	90.29	gold quality
calcaneal tendon	UBERON:0003701	90.04	gold quality
oral cavity	UBERON:0000167	89.62	gold quality
bone marrow cell	CL:0002092	89.56	gold quality
choroid plexus epithelium	UBERON:0003911	89.33	gold quality
thymus	UBERON:0002370	89.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.75
E-MTAB-6386	no	934.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

123 targeting STK26, 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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-124-3P	99.89	73.74	3043

Literature-anchored findings (GeneRIF, showing 27)

• cloning of a germinal center iii kinase that induces apoptosis (PMID:11741893)
• MST4 expression in prostate carcinoma tumor samples & cell lines correlated with tumorigenicity & AR status. Overexpression induced anchorage-independent growth & tumorigenesis.It may have a role in the signal transduction in prostate cancer progression. (PMID:12810671)
• Results show that PDCD10 modulation of ERK signaling is mediated by MST4, and that PDCD10 may be a regulatory adaptor necessary for MST4 function, suggesting a link between cerebral cavernous malformation and the ERK-MAPK cascade via PDCD10/MST4. (PMID:17360971)
• These data define a brush border induction pathway downstream of the Lkb1/Strad/Mo25 polarization complex, yet separate from other polarity events. (PMID:19386264)
• crystal of the CCM3-MST4 C-terminal domain complex belonged to space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = 69.10, b = 69.10, c = 117.57 A (PMID:22750858)
• CCM3 forms a stable complex with MST4 in vivo to promote cell proliferation and migration synergistically in a manner dependent on MST4 kinase activity. (PMID:23541896)
• In this review, the germinal center kinase III subfamily of mammalian Ste20 (sterile 20)-like group of serine/threonine protein kinases comprises Ste20-like/oxidant-stress-response kinase 1, MST3 mammalian Ste20-like kinase 3 and MST4. (PMID:23889253)
• Mutation of this residue was sufficient to switch the phosphorylation site preference for multiple kinases, including the serine-specific kinase PAK4 and the threonine-specific kinase MST4. (PMID:24374310)
• This study describes the key role of MST4 in facilitating the epithelial-mesenchymal transition process in hepatocellular carcinoma (PMID:24859810)
• Our results suggest that MST4, STK25 and PDCD10 are upregulated in prostate cancer and may play roles in prostate tumorigenesis. MST4 may be a helpful marker for identifying prostate cancer. (PMID:25550858)
• Findings reveal a mechanism by which TRAF6 is regulated and highlight a role for MST4 in limiting inflammatory responses. (PMID:25642822)
• these data identify the MST4 kinase as a novel candidate to mediate human pituitary tumorigenesis in a hypoxic environment and position it as a potential therapeutic target. (PMID:25650755)
• Low MST-4 expression is associated with Graves’ disease. (PMID:28219358)
• Our work describes an MST4-ATG4B signaling axis that influences glioblastoma autophagy and malignancy (PMID:29232556)
• Because of divergent evolution of key interface residues, MST4 and MOB4 could disrupt assembly of the MST1-MOB1 complex through alternative pairing and thereby increased YAP activity. Collectively, these findings identify the MST4-MOB4 complex as a noncanonical regulator of the Hippo-YAP pathway with an oncogenic role in PC (PMID:30072378)
• A network-based variable selection approach for identification of modules and biomarker genes associated with end-stage kidney disease. (PMID:31464346)
• MicroRNA-486-5p inhibits ovarian granulosa cell proliferation and participates in the development of PCOS via targeting MST4. (PMID:31539108)
• The expression of three genes (STK26, KCNT2, CASP12) was correlated with the prognosis of skin cutaneous melanoma (SCM). STK26 and KCNT2 were significantly different between normal skin and SCM. These three hub genes have potential value as predictors for accurate diagnosis and prognosis of SCM in the future. (PMID:31557882)
• MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway. (PMID:32271880)
• Tripartite motif containing 59 (TRIM59) promotes esophageal cancer progression via promoting MST4 expression and ERK pathway. (PMID:32340525)
• Downregulation of MST4 Underlies a Novel Inhibitory Role of MicroRNA Let-7a in the Progression of Retinoblastoma. (PMID:32539131)
• An MST4-pbeta-Catenin(Thr40) Signaling Axis Controls Intestinal Stem Cell and Tumorigenesis. (PMID:34240584)
• MST4: A Potential Oncogene and Therapeutic Target in Breast Cancer. (PMID:36552828)
• The mammalian Sterile 20-like kinase 4 (MST4) signaling in tumor progression: Implications for therapy. (PMID:37094736)
• STE20-type kinases MST3 and MST4 promote the progression of hepatocellular carcinoma: Evidence from human cell culture and expression profiling of liver biopsies. (PMID:37490000)
• MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages. (PMID:37833401)
• Mst4, a novel cardiac STRIPAK complex-associated kinase, regulates cardiomyocyte growth and survival and is upregulated in human cardiomyopathy. (PMID:38579991)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	stk26	ENSDARG00000060390
mus_musculus	Stk26	ENSMUSG00000031112
rattus_norvegicus	Stk26	ENSRNOG00000007879

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), PAK3 (ENSG00000077264), STRADB (ENSG00000082146), MAP3K1 (ENSG00000095015), STK4 (ENSG00000101109), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), STK25 (ENSG00000115694), NRK (ENSG00000123572), PAK4 (ENSG00000130669), TAOK3 (ENSG00000135090), PAK6 (ENSG00000137843), MINK1 (ENSG00000141503), PAK1 (ENSG00000149269), TAOK2 (ENSG00000149930), TNIK (ENSG00000154310), TAOK1 (ENSG00000160551), MAP4K2 (ENSG00000168067), OXSR1 (ENSG00000172939), MAP3K19 (ENSG00000176601), PAK2 (ENSG00000180370), SBK2 (ENSG00000187550), STK39 (ENSG00000198648), STRADA (ENSG00000266173)

Protein

Protein identifiers

Serine/threonine-protein kinase 26 — Q9P289 (reviewed: Q9P289)

Alternative names: MST3 and SOK1-related kinase, Mammalian STE20-like protein kinase 4, Serine/threonine-protein kinase MASK

All UniProt accessions (3): Q9P289, B4E0Y9, Q8NBY1

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that acts as a mediator of cell growth. Modulates apoptosis. In association with STK24 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation. Phosphorylates ATG4B at ‘Ser-383’, thereby increasing autophagic flux. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation.

Subunit / interactions. Homodimer. Interacts with PDCD10. Interacts with GOLGA2. Interacts with CTTNBP2NL. Interacts with RIPOR1 (via C-terminus); this interaction occurs in a PDCD10-dependent and Rho-independent manner. Interacts with PDCD10; this interaction is required for the association of STK26 with RIPOR1. Part of the core of STRIPAK complexes composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26.

Subcellular location. Cytoplasm. Golgi apparatus.

Activity regulation. Interaction with Golgi matrix protein GOLGA2 leads to autophosphorylation on Thr-178, possibly as a consequence of stabilization of dimer formation. May also be activated by C-terminal cleavage.

Similarity. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9P289-1	1	yes
Q9P289-2	2
Q9P289-3	3, MST4a

RefSeq proteins (3): NP_001035917, NP_001035918, NP_057626* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR035056	STK_MST4	Domain
IPR046409	PDC10_dimerisation_sf	Homologous_superfamily
IPR048288	PDCD10_N	Domain
IPR050629	STE20/SPS1-PAK	Family

Pfam: PF00069, PF20929

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (61 total): helix 19, strand 12, modified residue 10, turn 7, sequence variant 3, splice variant 2, binding site 2, initiator methionine 1, chain 1, domain 1, mutagenesis site 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
5YF4	X-RAY DIFFRACTION	1.9
4GEH	X-RAY DIFFRACTION	1.95
7B36	X-RAY DIFFRACTION	2.11
5XY9	X-RAY DIFFRACTION	2.3
3GGF	X-RAY DIFFRACTION	2.35
3W8I	X-RAY DIFFRACTION	2.4
4FZA	X-RAY DIFFRACTION	3.15
4FZD	X-RAY DIFFRACTION	3.25
4FZF	X-RAY DIFFRACTION	3.64

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P289-F1	80.03	0.52

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 (1): 144 (proton acceptor)

Ligand- & substrate-binding residues (2): 30–38; 53

Post-translational modifications (10): 300, 304, 306, 309, 325, 327, 328, 2, 4, 178

Mutagenesis-validated functional residues (1):

Position	Phenotype
53	abolished serine/threonine-protein kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-111465	Apoptotic cleavage of cellular proteins
R-HSA-109581	Apoptosis
R-HSA-5357801	Programmed Cell Death
R-HSA-75153	Apoptotic execution phase

MSigDB gene sets: 251 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, CHUNG_BLISTER_CYTOTOXICITY_DN, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GTGCCTT_MIR506, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, JIANG_TIP30_TARGETS_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOCC_GOLGI_ASSOCIATED_VESICLE, VANHARANTA_UTERINE_FIBROID_DN, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_CELLULAR_RESPONSE_TO_STARVATION, GOBP_REGULATION_OF_MICROVILLUS_ORGANIZATION, SENESE_HDAC1_TARGETS_UP

GO Biological Process (9): protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), cellular response to starvation (GO:0009267), negative regulation of cell migration (GO:0030336), cellular response to oxidative stress (GO:0034599), intracellular signal transduction (GO:0035556), regulation of apoptotic process (GO:0042981), protein autophosphorylation (GO:0046777), positive regulation of microvillus assembly (GO:1903698)

GO Molecular Function (12): magnesium ion binding (GO:0000287), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (11): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), Golgi-associated vesicle (GO:0005798), cytosol (GO:0005829), vesicle membrane (GO:0012506), membrane (GO:0016020), apical plasma membrane (GO:0016324), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cell periphery (GO:0071944), FAR/SIN/STRIPAK complex (GO:0090443)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Apoptotic execution phase	1
Programmed Cell Death	1
Apoptosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	3
intracellular anatomical structure	2
protein kinase activity	2
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
response to oxidative stress	1
cellular response to chemical stress	1
signal transduction	1
apoptotic process	1
regulation of programmed cell death	1
protein phosphorylation	1
microvillus assembly	1
regulation of microvillus assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
metal ion binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1
endomembrane system	1

Protein interactions and networks

STRING

1352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK26	PDCD10	Q9BUL8	996
STK26	MOB4	Q9Y3A3	991
STK26	STRIP1	Q5VSL9	924
STK26	STK25	O00506	883
STK26	STRN	O43815	874
STK26	STRIP2	Q9ULQ0	799
STK26	STRN3	Q13033	738
STK26	STK24	Q9Y6E0	707
STK26	SLMAP	Q14BN4	698
STK26	SIKE1	Q9BRV8	692
STK26	STRN4	Q9NRL3	677
STK26	CAB39	Q9Y376	636
STK26	GOLGA2	Q08379	599
STK26	CCM2	Q9BSQ5	593
STK26	KRIT1	O00522	530

IntAct

126 interactions, top by confidence:

A	B	Type	Score
PDCD10	STK25	psi-mi:“MI:0914”(association)	0.980
CCM2	KRIT1	psi-mi:“MI:0914”(association)	0.960
STK26	PDCD10	psi-mi:“MI:0915”(physical association)	0.920
PDCD10	STK26	psi-mi:“MI:0915”(physical association)	0.920
STRN3	PPP2R1A	psi-mi:“MI:0914”(association)	0.920
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
STK24	STK25	psi-mi:“MI:0914”(association)	0.890
STRN3	STK25	psi-mi:“MI:0914”(association)	0.880
CTTNBP2NL	STK25	psi-mi:“MI:0914”(association)	0.880
STRN3	STRN	psi-mi:“MI:0914”(association)	0.880
STK24	STRN	psi-mi:“MI:0914”(association)	0.870
STK26	STRN	psi-mi:“MI:0915”(physical association)	0.860
STK26	STRN	psi-mi:“MI:0914”(association)	0.860
STRIP1	STK25	psi-mi:“MI:0914”(association)	0.840
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
GOLGA2	STK26	psi-mi:“MI:0915”(physical association)	0.810
STK26	GOLGA2	psi-mi:“MI:0915”(physical association)	0.810
STK26	GOLGA2	psi-mi:“MI:0403”(colocalization)	0.810
NDUFAF1	NDUFS3	psi-mi:“MI:0914”(association)	0.790
STK26	CTTNBP2NL	psi-mi:“MI:0915”(physical association)	0.790
STK26	STK25	psi-mi:“MI:0914”(association)	0.790
MOB4	STK25	psi-mi:“MI:0914”(association)	0.730

BioGRID (330): STK26 (Two-hybrid), STK26 (Two-hybrid), STK26 (Affinity Capture-MS), STK26 (Affinity Capture-MS), STK26 (Affinity Capture-MS), STK26 (Affinity Capture-MS), STK26 (Affinity Capture-MS), STK26 (Affinity Capture-MS), STK26 (Affinity Capture-MS), STK26 (Affinity Capture-MS), STK26 (Co-fractionation), STK26 (Co-fractionation), STK26 (Co-fractionation), TTC4 (Co-fractionation), STK26 (Two-hybrid)

ESM2 similar proteins: A0A1S4CGX4, A9RWC9, A9S5R3, A9SR33, O01775, O14047, O14733, O44408, O80396, P10506, P18652, P18654, P29678, P31938, P36506, P36507, P51812, Q01986, Q02750, Q03428, Q05116, Q08942, Q10664, Q13163, Q18846, Q1HG70, Q20347, Q21307, Q24324, Q4KSH7, Q4V3C8, Q5QN75, Q62862, Q63932, Q63980, Q7TPS0, Q8MXI4, Q91447, Q94A06, Q99JT2

Diamond homologs: A0A078CGE6, A0A194W8T8, A2AQW0, A2QHV0, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A7A1P0, A8XJW8, A9RVK2, A9SY39, B0LT89, B0XXN8, B5VNQ3, C4YRB7, E9Q3S4, F4HRJ4, G4N7X0, G4NDR3, H2L099, O00506, O14047, O14305, O22040, O22042, O24527, O54748, O61122, O61125, O81472, O95382, P0CY23, P0CY24, P23561, P27636, P28829

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
STK26	up-regulates	EZR	phosphorylation
STK26	“up-regulates activity”	ASAP3	phosphorylation
STK26	“up-regulates activity”	ATG4B	phosphorylation
STK26	“down-regulates activity”	YAP1	phosphorylation
STK26	“up-regulates quantity by stabilization”	CTNNB1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 123 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of hippo signaling	7	44.3×	1e-07
intracellular signal transduction	13	4.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2054 predictions. Top by Δscore:

Variant	Effect	Δscore
X:132023354:G:GT	donor_gain	1.0000
X:132054612:C:A	acceptor_gain	1.0000
X:132054620:A:AG	acceptor_gain	1.0000
X:132054621:C:G	acceptor_gain	1.0000
X:132054627:TCA:T	acceptor_loss	1.0000
X:132054628:CAG:C	acceptor_loss	1.0000
X:132054629:A:AC	acceptor_loss	1.0000
X:132054629:A:AG	acceptor_gain	1.0000
X:132054630:G:GT	acceptor_gain	1.0000
X:132054630:GA:G	acceptor_gain	1.0000
X:132054630:GAA:G	acceptor_gain	1.0000
X:132054630:GAAT:G	acceptor_gain	1.0000
X:132054630:GAATA:G	acceptor_gain	1.0000
X:132068409:TA:T	acceptor_loss	1.0000
X:132068410:A:AG	acceptor_gain	1.0000
X:132068410:AGCT:A	acceptor_gain	1.0000
X:132068410:AGCTG:A	acceptor_loss	1.0000
X:132068411:G:GC	acceptor_gain	1.0000
X:132068411:GC:G	acceptor_gain	1.0000
X:132068411:GCT:G	acceptor_gain	1.0000
X:132068411:GCTG:G	acceptor_gain	1.0000
X:132068411:GCTGC:G	acceptor_gain	1.0000
X:132068537:G:GT	donor_gain	1.0000
X:132068550:A:AG	donor_gain	1.0000
X:132068551:G:GG	donor_gain	1.0000
X:132068566:AAAA:A	donor_gain	1.0000
X:132068567:AAA:A	donor_gain	1.0000
X:132068568:AA:A	donor_gain	1.0000
X:132068568:AAGTA:A	donor_loss	1.0000
X:132068569:AG:A	donor_loss	1.0000

AlphaMissense

2748 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:132054659:T:C	F24S	1.000
X:132054679:G:A	G31R	1.000
X:132054679:G:C	G31R	1.000
X:132054679:G:T	G31W	1.000
X:132054680:G:A	G31E	1.000
X:132054680:G:T	G31V	1.000
X:132054685:G:A	G33S	1.000
X:132054685:G:C	G33R	1.000
X:132054685:G:T	G33C	1.000
X:132054686:G:A	G33D	1.000
X:132054686:G:C	G33A	1.000
X:132054686:G:T	G33V	1.000
X:132054691:T:A	F35I	1.000
X:132054691:T:C	F35L	1.000
X:132054691:T:G	F35V	1.000
X:132054692:T:C	F35S	1.000
X:132054692:T:G	F35C	1.000
X:132054693:T:A	F35L	1.000
X:132054693:T:G	F35L	1.000
X:132054694:G:A	G36R	1.000
X:132054694:G:C	G36R	1.000
X:132054694:G:T	G36W	1.000
X:132054695:G:A	G36E	1.000
X:132054695:G:T	G36V	1.000
X:132054700:G:C	V38L	1.000
X:132054700:G:T	V38F	1.000
X:132054701:T:A	V38D	1.000
X:132054701:T:C	V38A	1.000
X:132054708:A:C	K40N	1.000
X:132054708:A:T	K40N	1.000

dbSNP variants (sampled 300 via entrez): RS1000039481 (X:132053722 G>A), RS1000244130 (X:132023838 T>C), RS1000248310 (X:132028571 A>G), RS1000255842 (X:132039522 A>G), RS1000316074 (X:132023307 T>G), RS1000493844 (X:132061002 C>A), RS1000566900 (X:132060632 T>C), RS1000736461 (X:132065337 T>C), RS1000840519 (X:132029524 C>G), RS1000937506 (X:132039659 G>A), RS1001107060 (X:132050594 C>A,T), RS1001204373 (X:132051846 T>C), RS1001307689 (X:132076375 T>C), RS1001319683 (X:132027422 T>G), RS1001380719 (X:132076021 T>C)

Disease associations

OMIM: gene MIM:300547 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004899_2	Gestational age at birth (maternal effect)	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005112	gestational age
EFO:0005939	parental genotype effect measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5941 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

29 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 171,680 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL180022	NERATINIB	4	9,404
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1721885	SU-014813	2	363
CHEMBL3039513	DECERNOTINIB	2	1,418
CHEMBL402548	DANUSERTIB	2	1,928
CHEMBL572878	TOZASERTIB	2
CHEMBL1084546	PF-00562271	1
CHEMBL1230607	PHA-793887	1
CHEMBL1908397	KW-2449	1
CHEMBL2140408	AMG-900	1
CHEMBL3128043	PF-03758309	1
CHEMBL3545083	RGB-286638	1
CHEMBL482967	CYC-116	1
CHEMBL494089	GSK-690693	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — YSK subfamily

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
Staurosporine	KD	1.7 nM
BMS-354825	KD	27 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

123 potent at pChembl≥5 of 140 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.54	IC50	2.87	nM	STAUROSPORINE
8.53	IC50	2.93	nM	STAUROSPORINE
8.22	IC50	6	nM	HESPERADIN
8.20	IC50	6.3	nM	CHEMBL4568087
8.15	IC50	7	nM	NERATINIB
8.13	Kd	7.4	nM	NERATINIB
7.92	Kd	12	nM	PF-00562271
7.89	Kd	13	nM	CRENOLANIB
7.89	Kd	13	nM	CYC-116
7.80	Kd	16	nM	CHEMBL4554938
7.77	Kd	17	nM	PF-03758309
7.70	IC50	20	nM	CHEMBL3770443
7.66	IC50	21.9	nM	STAUROSPORINE
7.56	IC50	27.3	nM	CHEMBL4554938
7.54	Kd	29	nM	Cerdulatinib Hydrochloride
7.43	Kd	37	nM	BOSUTINIB
7.36	EC50	44	nM	CHEMBL5569777
7.36	EC50	44	nM	CHEMBL5571948
7.32	EC50	48	nM	CHEMBL5571159
7.31	Kd	49	nM	NINTEDANIB
7.22	EC50	60	nM	CHEMBL5594538
7.01	Kd	98	nM	DINACICLIB
6.94	EC50	115	nM	CHEMBL5565155
6.94	Kd	115	nM	CHEMBL5562742
6.85	EC50	140	nM	STAUROSPORINE
6.85	Kd	140	nM	STAUROSPORINE
6.77	IC50	170	nM	CHEMBL4552628
6.76	Kd	175	nM	PHA-793887
6.75	IC50	178	nM	CHEMBL3393348
6.68	Kd	210	nM	JNJ-7706621
6.64	EC50	230	nM	CHEMBL1235645
6.64	Kd	230	nM	LESTAURTINIB
6.63	Kd	236.7	nM	CHEMBL3752910
6.57	ED50	269.5	nM	CHEMBL3752910
6.54	IC50	290	nM	CHEMBL4550702
6.48	Kd	330	nM	SU-014813
6.47	Kd	340	nM	SUNITINIB
6.44	EC50	360	nM	CHEMBL5562742
6.38	IC50	412	nM	CHEMBL1258913
6.34	EC50	457	nM	CHEMBL5567421
6.30	EC50	500	nM	CHEMBL5575508
6.29	Kd	510	nM	TAE-684
6.27	Kd	540	nM	DOVITINIB
6.23	EC50	583	nM	CHEMBL5573797
6.17	EC50	681	nM	CHEMBL5572995
6.16	Kd	687	nM	CHEMBL4465866
6.10	EC50	800	nM	CHEMBL5555859
6.10	EC50	793	nM	CHEMBL5590631
6.06	IC50	880	nM	ERKi
6.03	Kd	926	nM	NERATINIB

PubChem BioAssay actives

115 with measured affinity, of 1203 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
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1531791: Inhibition of human MST4 using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.0029	uM
N-[2-hydroxy-3-[C-phenyl-N-[4-(piperidin-1-ylmethyl)phenyl]carbonimidoyl]-1H-indol-5-yl]ethanesulfonamide	2090803: Inhibition of MST4 (unknown origin)	ic50	0.0060	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637110: Inhibition of full-length recombinant human GST-tagged MST4 expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0063	uM
Neratinib	2090803: Inhibition of MST4 (unknown origin)	ic50	0.0070	uM
N-methyl-N-[3-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]-2-pyridinyl]methanesulfonamide	1425181: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0120	uM
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine	1425181: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0130	uM
4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine	1425181: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0130	uM
4-[(2,9-dimethyl-8-oxo-6-thia-2,9,12,14-tetrazatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-13-yl)amino]benzenesulfonamide	2189143: Binding affinity to MST4 (unknown origin) assessed as dissociation constant	kd	0.0160	uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	1425181: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0170	uM
8-[(5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one	1280637: Inhibition of human recombinant MST4	ic50	0.0200	uM
4-(cyclopropylamino)-2-[4-(4-ethylsulfonylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide;hydrochloride	1425181: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0290	uM
Bosutinib	625103: Binding constant for MST4 kinase domain	kd	0.0370	uM
8-(4-aminobutyl)-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(4-hydroxyanilino)pyrido[2,3-d]pyrimidin-7-one	2090807: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.0440	uM
8-(4-aminobutyl)-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-[4-fluoro-3-(hydroxymethyl)anilino]pyrido[2,3-d]pyrimidin-7-one	2090807: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.0440	uM
8-(4-aminobutyl)-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-[4-(3-hydroxypropyl)anilino]pyrido[2,3-d]pyrimidin-7-one	2090807: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.0480	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625103: Binding constant for MST4 kinase domain	kd	0.0490	uM
8-(4-aminobutyl)-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(3-hydroxy-4-methylanilino)pyrido[2,3-d]pyrimidin-7-one	2090807: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.0600	uM
2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol	1425181: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0980	uM
8-(4-aminobutyl)-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(3-morpholin-4-ylpropylamino)pyrido[2,3-d]pyrimidin-7-one	2090807: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.1150	uM
2,4,5,8,14,16,23-heptazatetracyclo[13.7.1.13,6.017,22]tetracosa-1(23),3,6(24),15,17,19,21-heptaen-7-one	2093076: Binding affinity to N-terminal 6His-tagged TEV fused MST4 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by ITC analysis	kd	0.1150	uM
N-[(1R,6R)-6-amino-2,2-difluorocyclohexyl]-4-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-5-methylthiophene-2-carboxamide	1637110: Inhibition of full-length recombinant human GST-tagged MST4 expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.1700	uM
N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-3-methylbutanamide	1425181: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1750	uM
3-(4-morpholin-4-yl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)benzonitrile	1189427: Inhibition of human recombinant MST4 using Ser/Thr peptide 7 substrate after 60 mins by Z-Lyte assay	ic50	0.1780	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435663: Binding constant for full-length MST4	kd	0.2100	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507635: Binding affinity to MST4	kd	0.2300	uM
2-[4-[[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]amino]phenyl]acetonitrile	2093082: Binding affinity to C-terminal full length human MST4 expressed in permeabilized HEK293T cells incubated for 2 hrs by NanoBRET assay	ec50	0.2300	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149510: Binding affinity to human STK26 incubated for 45 mins by Kinobead based pull down assay	kd	0.2367	uM
4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637110: Inhibition of full-length recombinant human GST-tagged MST4 expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.2900	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435663: Binding constant for full-length MST4	kd	0.3300	uM
Sunitinib	435663: Binding constant for full-length MST4	kd	0.3400	uM
3-[(4-morpholin-4-ylbenzoyl)amino]-N-[(1S)-1-phenyl-2-pyrrolidin-1-ylethyl]-1H-thieno[3,2-c]pyrazole-5-carboxamide	517192: Inhibition of MST4	ic50	0.4120	uM
8-(4-aminobutyl)-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one	2090807: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.4570	uM
8-[(4-aminocyclohexyl)methyl]-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one	2090807: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.5000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625103: Binding constant for MST4 kinase domain	kd	0.5100	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435663: Binding constant for full-length MST4	kd	0.5400	uM
8-(4-aminobutyl)-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(1,3-dihydroxypropan-2-ylamino)pyrido[2,3-d]pyrimidin-7-one	2090807: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.5830	uM
8-(4-aminobutyl)-2-[3-(4-aminophenyl)propylamino]-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]pyrido[2,3-d]pyrimidin-7-one	2090807: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.6810	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526185: Binding affinity to recombinant full-length N-terminal His-FLAG-tagged MST4 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.6870	uM
8-(4-aminobutyl)-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(2-hydroxy-5-methoxyanilino)pyrido[2,3-d]pyrimidin-7-one	2090807: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.7930	uM
6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(methylamino)-8-(2-piperidin-4-ylethyl)pyrido[2,3-d]pyrimidin-7-one	2090807: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.8000	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526185: Binding affinity to recombinant full-length N-terminal His-FLAG-tagged MST4 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.9830	uM
Momelotinib	2183910: Inhibition of MST4 (unknown origin)	ic50	1.0000	uM
1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]-3-morpholin-4-ylurea	1425181: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.0520	uM
3-[4-[(2S)-2-methylmorpholin-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile	1189427: Inhibition of human recombinant MST4 using Ser/Thr peptide 7 substrate after 60 mins by Z-Lyte assay	ic50	1.0990	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625103: Binding constant for MST4 kinase domain	kd	1.1000	uM
8-(4-aminobutyl)-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-[3-(2-oxopyrrolidin-1-yl)propylamino]pyrido[2,3-d]pyrimidin-7-one	2090807: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	1.1000	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637110: Inhibition of full-length recombinant human GST-tagged MST4 expressed in baculovirus expression system by Z’-LYTE assay	ic50	1.1000	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1425181: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.1200	uM
(2R)-2-methyl-2-[[2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]-N-(2,2,2-trifluoroethyl)butanamide	1425181: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.1350	uM
Gilteritinib	1425181: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.1430	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	2
cobaltous chloride	decreases expression, affects cotreatment, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Quercetin	decreases expression, decreases phosphorylation	2
Tobacco Smoke Pollution	affects expression, increases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
glycidyl methacrylate	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
afimoxifene	decreases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	increases expression	1
sodium tungstate(VI)	increases expression	1
lead chloride	affects cotreatment, increases expression	1
coumarin	increases phosphorylation	1
cadmium sulfate	increases expression, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression	1
Calcitriol	increases expression	1

ChEMBL screening assays

355 unique, capped per target: 355 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1011044	Binding	Inhibition of MST4	First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SZ07	HAP1 MST4 (-) 1	Cancer cell line	Male
CVCL_SZ08	HAP1 MST4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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