STK3

Summary

STK3 (serine/threonine kinase 3, HGNC:11406) is a protein-coding gene on chromosome 8q22.2, encoding Serine/threonine-protein kinase 3 (Q13188). Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation.

This gene encodes a serine/threonine protein kinase activated by proapoptotic molecules indicating the encoded protein functions as a growth suppressor. Cleavage of the protein product by caspase removes the inhibitory C-terminal portion. The N-terminal portion is transported to the nucleus where it homodimerizes to form the active kinase which promotes the condensation of chromatin during apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6788 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 75 total
• Druggable target: yes — 50 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006281

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11406
Approved symbol	STK3
Name	serine/threonine kinase 3
Location	8q22.2
Locus type	gene with protein product
Status	Approved
Aliases	MST2, KRS1
Ensembl gene	ENSG00000104375
Ensembl biotype	protein_coding
OMIM	605030
Entrez	6788

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 12 protein_coding, 10 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000419617, ENST00000424861, ENST00000517832, ENST00000518165, ENST00000518582, ENST00000518627, ENST00000518704, ENST00000519420, ENST00000520053, ENST00000520440, ENST00000520653, ENST00000521649, ENST00000521768, ENST00000522924, ENST00000523159, ENST00000523567, ENST00000523601, ENST00000523960, ENST00000617590, ENST00000649151, ENST00000862737, ENST00000862738, ENST00000862739, ENST00000862740, ENST00000862741, ENST00000934522, ENST00000971219

RefSeq mRNA: 3 — MANE Select: NM_006281 NM_001256312, NM_001256313, NM_006281

CCDS: CCDS47900, CCDS59108, CCDS75774

Canonical transcript exons

ENST00000419617 — 11 exons

Exon	Start	End
ENSE00000701598	98547969	98548161
ENSE00000888426	98526742	98526917
ENSE00001026793	98749276	98749390
ENSE00001259462	98774739	98774819
ENSE00001478384	98825515	98825688
ENSE00001706630	98767243	98767371
ENSE00002103243	98454633	98456000
ENSE00003461113	98579664	98579789
ENSE00003477490	98706467	98706634
ENSE00003544745	98596032	98596169
ENSE00003561096	98707147	98707311

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 95.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.5268 / max 165.9154, expressed in 1793 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94099	14.1929	1792
94098	0.1957	65
94101	0.0678	33
94102	0.0361	18
94100	0.0203	9
94096	0.0139	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.17	gold quality
cauda epididymis	UBERON:0004360	93.61	gold quality
caput epididymis	UBERON:0004358	93.04	gold quality
germinal epithelium of ovary	UBERON:0001304	92.85	gold quality
placenta	UBERON:0001987	92.69	gold quality
sural nerve	UBERON:0015488	92.08	gold quality
cranial nerve II	UBERON:0000941	92.06	gold quality
corpus epididymis	UBERON:0004359	91.77	gold quality
adrenal tissue	UBERON:0018303	91.73	gold quality
seminal vesicle	UBERON:0000998	91.30	gold quality
cartilage tissue	UBERON:0002418	91.02	gold quality
amniotic fluid	UBERON:0000173	90.91	gold quality
palpebral conjunctiva	UBERON:0001812	90.62	gold quality
right ovary	UBERON:0002118	90.60	gold quality
ovary	UBERON:0000992	90.55	gold quality
body of uterus	UBERON:0009853	90.43	gold quality
endometrium	UBERON:0001295	90.34	gold quality
parotid gland	UBERON:0001831	90.31	silver quality
left ovary	UBERON:0002119	90.01	gold quality
endocervix	UBERON:0000458	89.95	gold quality
female reproductive system	UBERON:0000474	89.49	gold quality
heart right ventricle	UBERON:0002080	89.44	gold quality
choroid plexus epithelium	UBERON:0003911	89.24	gold quality
uterus	UBERON:0000995	89.14	gold quality
ectocervix	UBERON:0012249	89.07	gold quality
left uterine tube	UBERON:0001303	88.91	gold quality
visceral pleura	UBERON:0002401	88.90	gold quality
right testis	UBERON:0004534	88.27	gold quality
left testis	UBERON:0004533	88.25	gold quality
right adrenal gland	UBERON:0001233	88.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

84 targeting STK3, 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-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-494-3P	99.70	71.45	2795

Literature-anchored findings (GeneRIF, showing 40)

• Caspase-catalyzed cleavage and activation of Mst2 correlates with eosinophil but not neutrophil apoptosis. (PMID:11964314)
• novel mechanism for MST2 regulation in apoptotic cells postulated; during apoptosis MST2 is cleaved by caspase-3 and undergoes irreversible autophosphorylation resulting in the accumulation of active MST2 (PMID:12554736)
• proteomic analysis of Raf-1 signaling complexes was used to show that Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (MST2) (PMID:15618521)
• Mst2-like kinases regulate Lats kinase activities in an evolutionarily conserved regulatory pathway. (PMID:15688006)
• our results suggest that alteration of the Sav-RASSF1-Hpo tumor suppressor pathway may occur through hypermethylation of the CpG island promoter of MST1, MST2 and/or RASSF1A in human sarcomas. (PMID:17538946)
• These results describe an MST2-dependent effector pathway for RASSF1A proapoptotic signaling and indicate that silencing of RASSF1A in tumors removes a proapoptotic signal emanating from p73. (PMID:17889669)
• phosphorylation of MOB1 at Thr74 by MST2 is essential to make a complex of MOB1, MST2 and NDR1, and to fully activate NDR1 (PMID:18362890)
• Overexpression of YAP2 in cells promoted apoptosis, whereas the Mst2/Lats1-induced phosphorylation of YAP partially rescued the cells from apoptotic death. (PMID:18640976)
• Results suggest that MST2-, Fry-, and MOB2-mediated activation of NDR1 is crucial for the fidelity of mitotic chromosome alignment in mammalian cells. (PMID:19327996)
• MST2 and RASSF2 form an active complex in vivo, in which RASSF2 is maintained in a phosphorylated state and protects MST2 from degradation and turnover (PMID:19525978)
• Data suggest thta MST kinases 1/2 serve to monitor cytoskeletal integrity and couple the JNK1/SAPK1 pathway to the regulation of the cell cycle regulatory protein p21Waf1. (PMID:19822666)
• Data show T117/T384 as Akt phosphorylation sites in MST2, and mutation of these sites inhibited MST2 binding to Raf-1 but enhanced binding to RASSF1A, accentuating downstream c-jun N-Terminal Kinase and p38 MAPK signaling and promoting apoptosis. (PMID:20086174)
• hnRNP H blocks MST2-mediated apoptosis in cancer cells by regulating A-Raf transcription. (PMID:20145135)
• studies reveal a more complex role for Mst2 than previously thought. The Mst2 –> LATS1/2 pathway, by maintaining PP2A-C levels, may, in some situations, positively affect mitogenic signaling (PMID:20212043)
• Study reports that two Hippo pathway components, Mst2 and the scaffold protein hSav1, directly interact with Nek2A and regulate its ability to localize to centrosomes, and phosphorylate C-Nap1 and rootletin. (PMID:21076410)
• MST and hSAV act as novel co-regulators of ERalpha and may play an important role in breast cancer pathogenesis. (PMID:21104395)
• Through binding to MST1/2, RASSF1A supports maintenance of MST1/2 phosphorylation, promoting an active state of the MST kinases and favoring induction of apoptosis. (PMID:21199877)
• The mammalian ste20-like kinase mediated phosphorylation of four residues within SAV1 may be important in the induction of cell death by the MST pathway. (PMID:21944251)
• crystals of MST2 belonged to space group P2, with unit-cell parameters a = 62.0, b = 119.2, c = 62.0 A, alpha = 90.0, beta = 90.5, gamma = 90.0 degrees , or to space group P6(1)22, with unit-cell parameters a = 54.5, b = 54.5, c = 303.1 A (PMID:22102242)
• The small number of tumors with co-expression of mutant K-Ras and MST2 has elevated apoptosis rates. (PMID:22195963)
• The identification of the c-Abl tyrosine kinase as a novel upstream activator of MST2 suggests that the conserved c-Abl-MST signaling cascade plays an important role in oxidative stress-induced neuronal cell death. (PMID:22590567)
• The ability of K-Ras to activate MST2 and MST2-dependent apoptosis is determined by the differential activation kinetics of mutant K-Ras and wild type K-Ras. (PMID:23459937)
• RASSF5 can act as an inhibitor or a potential positive regulator of Mst2, depending on whether it binds to Mst2 before or after activation-loop phosphorylation. (PMID:23972470)
• results of the present study revealed that, in addition to the phosphorylated YAP/TAZ, the Hippo pathway can suppress the Wnt/beta-catenin pathway directly through MST1/2 (PMID:24180524)
• Results indicate that changes in phosphorylation orchestrate interactions between kinases and phosphatases in Hippo (MST1/2 protein kinases) signaling, providing a putative mechanism for pathway regulation. (PMID:24255178)
• Hippo and Yap regulate cardiomyocyte death and regeneration. (PMID:24881775)
• These results suggest that AIF downregulation is a common event in kidney tumor development. AIF loss may lead to decreased STK3 activity, defective apoptosis and malignant transformation (PMID:24992339)
• results reveal a novel role of Mst2 in stress-dependent cardiac hypertrophy and remodeling in the adult mouse and likely human heart (PMID:25035424)
• The MST1/2-SAV1 complex, a core component of the Hippo pathway, promotes ciliogenesis. (PMID:25367221)
• using an Mst2 mutation that disrupts homotypic dimerization, we showed that the monomeric Mst2-SARAH domain could form a stable complex of 1:1 stoichiometric ratio with WW45 refolded under acidic pH. (PMID:25814670)
• Results show that STK3 is targeted by Casp6 and demonstrate that alterations in STK3 protein expression levels and post-translational modifications are detected in a cellular model of HD and caspase-mediated generation of STK3 fragments observed under conditions of stress in cells expressing mhtt. (PMID:26908611)
• H-ras, via an Erk-dependent mechanism, downregulates Mst1/Mst2 activity by inducing the formation of inactive Mst1/Mst2 heterodimers. (PMID:27238285)
• These findings reveal a novel layer of regulation for MST2 in mitosis and its role in tumorigenesis. (PMID:27566175)
• Data suggest that Hippo (MST1/2 protein kinases) - Yes associated protein 1 (YAP) pathway involved in carcinogenesis of pancreatic cancer and in the inhibition effect of stiehopus japonieus acidic mucopolysaccharide (SJAMP) to the proliferation of pancreatic cancer cell. (PMID:28099921)
• Findings indicate that long-term exposure to IM results in dysregulation of stem cell renewal-regulatory Hippo (MST1/2)/YAP signaling, and that inhibition of miR-181a using a microRNA sponge inhibitor resulted in decreased transcription of SOX2 and SALL4. (PMID:28103766)
• TNFAIP8 regulates Hippo (MST1/2) signaling through its interaction with LATS1. (PMID:28152516)
• Through a comprehensive set of biochemical, biophysical, mutational and structural studies, we quantitatively assess how phosphorylation of MOB1A regulates its interaction with both MST kinases and LATS/NDR family kinases in vitro. (PMID:28373297)
• In this study, we investigated the mechanisms behind the recruitment of MST1 and MST2 kinases to MOB1, which facilitate signal transmission in the Hippo pathway by bringing the MST1 and MST2 kinases in close vicinity to their substrates, the LATS family kinases. (PMID:28373298)
• High MST2 expression is associated with malignant melanoma. (PMID:28677804)
• Here, the authors discover SAV1-mediated inhibition of the PP2A complex STRIPAK(SLMAP) as a key mechanism of MST1/2 activation. (PMID:29063833)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	stk3	ENSDARG00000011312
mus_musculus	Stk3	ENSMUSG00000022329
rattus_norvegicus	Stk3	ENSRNOG00000011278
drosophila_melanogaster	hpo	FBGN0261456
caenorhabditis_elegans		WBGENE00016038
caenorhabditis_elegans		WBGENE00017472

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), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), STK25 (ENSG00000115694), NRK (ENSG00000123572), PAK4 (ENSG00000130669), STK26 (ENSG00000134602), 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 3 — Q13188 (reviewed: Q13188)

Alternative names: Mammalian STE20-like protein kinase 2, STE20-like kinase MST2, Serine/threonine-protein kinase Krs-1

All UniProt accessions (6): Q13188, A0A087WZ06, A0A384MR07, E5RFQ9, E5RIM6, Q8NBU1

UniProt curated annotations — full annotation on UniProt →

Function. Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates NKX2-1. Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on ‘Ser-259’. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on ‘Thr-74’. Acts cooperatively with MOBKL1B to activate STK38.

Subunit / interactions. Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation. Interacts with and stabilizes SAV1. Interacts with RAF1, which prevents dimerization and phosphorylation. Interacts with RASSF1. Interacts (via SARAH domain) with isoform 1 of NEK2. Interacts with ESR1 only in the presence of SAV1. Interacts with PKB/AKT1. Forms a tripartite complex with MOBKL1B and STK38. Interacts with RASSF2 (via SARAH domain). Interacts with DLG5 (via PDZ domain 3). Interacts with LATS1; this interaction is inhibited in the presence of DLG5. Interacts with MARK3 in the presence of DLG5. Interacts with RASSF5; this interaction inhibits STK3 autoactivation through heterodimerization. Interacts (when phosphorylated) with SLMAP (via FHA domain); the interaction associates STK3 with the STRIPAK complex.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Expressed at high levels in adult kidney, skeletal and placenta tissues and at very low levels in adult heart, lung and brain tissues.

Post-translational modifications. Autophosphorylated on two residues Thr-174 and Thr-180, leading to activation. Phosphorylation at Thr-117 and Thr-384 by PKB/AKT1, leads to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation, and increase in its binding to RAF1. Phosphorylated at Ser-15 by PLK1, leading to activation. When autophosphorylated at Thr-180, recruits STRIPAK complex and promotes PP2A-mediated dephosphorylation and inactivation of STK3. Proteolytically cleaved by caspase-3 during apoptosis. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N). Ubiquitinated by TRIM69; leading to its redistribution to the perinuclear cytoskeleton, where it is phosphorylated by PLK1 and subsequently activated.

Activity regulation. Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-180, which are inhibited by the proto-oncogene product RAF1. Activated by RASSF1 which acts by preventing its dephosphorylation. When autophosphorylated at Thr-180, recruits STRIPAK complex and promotes PP2A-mediated dephosphorylation and inactivation of STK3.

Induction. Activity increases during mitosis.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q13188-1	1	yes
Q13188-2	2

RefSeq proteins (3): NP_001243241, NP_001243242, NP_006272* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011524	SARAH_dom	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR024205	Mst1_2_SARAH_domain	Domain
IPR036674	p53_tetramer_sf	Homologous_superfamily
IPR049568	Mst2_SARAH	Domain
IPR050629	STE20/SPS1-PAK	Family

Pfam: PF00069, PF11629

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

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 (78 total): helix 22, modified residue 11, strand 10, mutagenesis site 5, sequence conflict 5, turn 5, binding site 4, chain 3, compositionally biased region 2, sequence variant 2, domain 2, region of interest 2, coiled-coil region 2, active site 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
4L0N	X-RAY DIFFRACTION	1.4
4HKD	X-RAY DIFFRACTION	1.5
6AR2	X-RAY DIFFRACTION	1.55
4OH9	X-RAY DIFFRACTION	1.7
8A66	X-RAY DIFFRACTION	1.9
3WWS	X-RAY DIFFRACTION	2.01
4LG4	X-RAY DIFFRACTION	2.42
5DH3	X-RAY DIFFRACTION	2.47
5BRM	X-RAY DIFFRACTION	2.65
6AO5	X-RAY DIFFRACTION	2.96
4LGD	X-RAY DIFFRACTION	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13188-F1	76.77	0.49

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 (2): 146 (proton acceptor); 322–323 (cleavage; by caspase-3)

Ligand- & substrate-binding residues (4): 33–41; 56; 151; 164

Post-translational modifications (11): 1, 15, 117, 174, 180, 316, 336, 378, 384, 385, 444

Mutagenesis-validated functional residues (5):

Position	Phenotype
56	loss of kinase activity. loss of interaction with components of the stripak complex.
146	loss of kinase activity.
174	fully active.
180	loss of kinase activity. loss of interaction with slmap.
322	resistant to proteolytic cleavage.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2028269	Signaling by Hippo
R-HSA-162582	Signal Transduction

MSigDB gene sets: 299 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, WENDT_COHESIN_TARGETS_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GGGACCA_MIR133A_MIR133B, GOBP_EMBRYONIC_HEMOPOIESIS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, FREAC2_01, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_POSITIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION

GO Biological Process (37): neural tube formation (GO:0001841), endocardium development (GO:0003157), protein phosphorylation (GO:0006468), protein import into nucleus (GO:0006606), apoptotic process (GO:0006915), JNK cascade (GO:0007254), central nervous system development (GO:0007417), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), organ growth (GO:0035265), hippo signaling (GO:0035329), positive regulation of hippo signaling (GO:0035332), intracellular signal transduction (GO:0035556), positive regulation of apoptotic process (GO:0043065), regulation of MAPK cascade (GO:0043408), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), positive regulation of fat cell differentiation (GO:0045600), positive regulation of JNK cascade (GO:0046330), negative regulation of organ growth (GO:0046621), epithelial cell proliferation (GO:0050673), negative regulation of epithelial cell proliferation (GO:0050680), protein stabilization (GO:0050821), protein tetramerization (GO:0051262), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), canonical Wnt signaling pathway (GO:0060070), primitive hemopoiesis (GO:0060215), negative regulation of cell growth involved in contact inhibition (GO:0060243), cell differentiation involved in embryonic placenta development (GO:0060706), regulation of cell differentiation involved in embryonic placenta development (GO:0060800), protein localization to centrosome (GO:0071539), negative regulation of canonical Wnt signaling pathway (GO:0090090), hepatocyte apoptotic process (GO:0097284), positive regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902043), signal transduction (GO:0007165), cell population proliferation (GO:0008283), negative regulation of cell population proliferation (GO:0008285), regulation of gene expression (GO:0010468), centrosome separation (GO:0051299)

GO Molecular Function (13): 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 serine/threonine kinase activator activity (GO:0043539), protein serine kinase activity (GO:0106310), transcription regulator activator activity (GO:0140537), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), protein-containing complex (GO:0032991), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
MAPK cascade	2
intracellular anatomical structure	2
protein kinase activity	2
cellular anatomical structure	2
embryonic epithelial tube formation	1
neural tube development	1
heart development	1
anatomical structure development	1
phosphorylation	1
protein modification process	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nervous system development	1
system development	1
extrinsic apoptotic signaling pathway	1
multicellular organismal process	1
developmental growth	1
intracellular signal transduction	1
hippo signaling	1
regulation of hippo signaling	1
positive regulation of intracellular signal transduction	1
signal transduction	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
regulation of intracellular signal transduction	1
intracellular signaling cassette	1
fat cell differentiation	1
positive regulation of cell differentiation	1
regulation of fat cell differentiation	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
organ growth	1
regulation of organ growth	1

Protein interactions and networks

STRING

604 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK3	SAV1	Q9H4B6	711
STK3	MBP	P02686	521
STK3	H1-0	P07305	490
STK3	ARAF	P07557	452
STK3	YAP1	P46937	431
STK3	NEK2	P51955	427
STK3	WWTR1	Q9GZV5	420
STK3	GFER	P55789	417
STK3	RIPK3	Q9Y572	404
STK3	SYT8	Q8NBV8	376
STK3	KARS1	Q15046	349
STK3	TSSK3	Q96PN8	349
STK3	DIAPH1	O60610	335
STK3	MOB1A	Q9H8S9	319
STK3	MOB1B	Q7L9L4	311

IntAct

304 interactions, top by confidence:

A	B	Type	Score
STK3	SAV1	psi-mi:“MI:0915”(physical association)	0.960
SAV1	STK3	psi-mi:“MI:0217”(phosphorylation reaction)	0.960
SAV1	STK3	psi-mi:“MI:0915”(physical association)	0.960
STK3	RASSF2	psi-mi:“MI:0915”(physical association)	0.950
RASSF2	STK3	psi-mi:“MI:0915”(physical association)	0.950
STK3	RASSF2	psi-mi:“MI:0914”(association)	0.950
STK4	RASSF2	psi-mi:“MI:0914”(association)	0.930
STK3	STK4	psi-mi:“MI:0915”(physical association)	0.910
RASSF4	STK3	psi-mi:“MI:0915”(physical association)	0.900
STK3	RASSF4	psi-mi:“MI:0915”(physical association)	0.900
STK3	RASSF5	psi-mi:“MI:0915”(physical association)	0.890
STK3	RASSF1	psi-mi:“MI:0915”(physical association)	0.850
RASSF1	STK3	psi-mi:“MI:0915”(physical association)	0.850
RASSF3	STK3	psi-mi:“MI:0915”(physical association)	0.790
STK3	SLMAP	psi-mi:“MI:0915”(physical association)	0.770
SLMAP	STK3	psi-mi:“MI:0915”(physical association)	0.770

BioGRID (401): STK3 (Affinity Capture-Western), STK3 (Affinity Capture-MS), STK3 (Two-hybrid), TRAF1 (Two-hybrid), SLMAP (Two-hybrid), RASSF2 (Two-hybrid), TFPT (Two-hybrid), GMCL1 (Two-hybrid), RASSF4 (Two-hybrid), FAM9B (Two-hybrid), STK3 (Two-hybrid), STK3 (Biochemical Activity), STK3 (Affinity Capture-MS), STK3 (Affinity Capture-MS), STK3 (Affinity Capture-MS)

ESM2 similar proteins: A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A8XJW8, O00506, O54748, O61125, O75914, O88643, P29678, P31938, P35465, P36583, Q01986, Q02750, Q07192, Q08E52, Q13043, Q13153, Q13177, Q13188, Q17850, Q29502, Q5E9L6, Q5ZJK4, Q61036, Q62829, Q63980, Q64303, Q6IP06, Q6P3Q4, Q6PA14, Q7YQL3, Q7YQL4, Q7ZUQ3, Q802A6

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

55 interactions.

A	Effect	B	Mechanism
RAF1	down-regulates	STK3	binding
STK3	up-regulates	LATS1	phosphorylation
AKT1	down-regulates	STK3	phosphorylation
AKT	down-regulates	STK3	phosphorylation
AKT2	down-regulates	STK3	phosphorylation
AKT3	down-regulates	STK3	phosphorylation
STK3	up-regulates	STK3	phosphorylation
STK3	up-regulates	NEK2	phosphorylation
SAV1	up-regulates	STK3	binding
RASSF1	up-regulates	STK3	binding
STK3	up-regulates	LATS2	phosphorylation
STK3	up-regulates	MOB1A	phosphorylation
STK3	up-regulates	MOB1B	phosphorylation
STK3	down-regulates	ABL1	phosphorylation
ABL1	up-regulates	STK3	phosphorylation
RASSF6	down-regulates	STK3	binding
PPP2CA	down-regulates	STK3	dephosphorylation
TAOK1	up-regulates	STK3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by Hippo	6	46.6×	1e-06
Macroautophagy	7	11.5×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
hippo signaling	6	44.9×	7e-07
mitophagy	8	26.0×	2e-07
autophagosome maturation	6	21.5×	6e-05
autophagosome assembly	6	13.8×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3319 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:98455880:C:G	A480P	1.000
8:98455888:A:C	I477S	1.000
8:98455888:A:G	I477T	1.000
8:98455888:A:T	I477N	1.000
8:98455921:A:G	L466P	1.000
8:98455975:A:G	L448P	1.000
8:98596039:A:G	L272P	1.000
8:98596048:G:T	A269E	1.000
8:98596056:T:A	R266S	1.000
8:98596056:T:G	R266S	1.000
8:98596057:C:A	R266I	1.000
8:98596057:C:G	R266T	1.000
8:98596058:T:C	R266G	1.000
8:98596078:A:C	L259W	1.000
8:98596080:A:C	C258W	1.000
8:98596081:C:T	C258Y	1.000
8:98596082:A:G	C258R	1.000
8:98596156:A:C	I233S	1.000
8:98596156:A:G	I233T	1.000
8:98596156:A:T	I233N	1.000
8:98596161:A:C	F231L	1.000
8:98596161:A:T	F231L	1.000
8:98596162:A:C	F231C	1.000
8:98596162:A:G	F231S	1.000
8:98596163:A:C	F231V	1.000
8:98596163:A:G	F231L	1.000
8:98596165:A:T	I230N	1.000
8:98596168:G:T	A229D	1.000
8:98596169:C:G	A229P	1.000
8:98706467:C:A	R228S	1.000

dbSNP variants (sampled 300 via entrez): RS1000003045 (8:98835825 C>T), RS1000006679 (8:98831879 C>A), RS1000007005 (8:98873981 C>T), RS1000011098 (8:98546297 C>T), RS1000035686 (8:98361386 G>A,T), RS1000039496 (8:98446647 T>A,C), RS1000046988 (8:98747002 A>G), RS1000049524 (8:98551195 C>T), RS1000054375 (8:98737938 G>A), RS1000054896 (8:98458340 A>G), RS1000059550 (8:98874290 T>C), RS1000062061 (8:98661114 C>T), RS1000064303 (8:98918008 G>A), RS1000064803 (8:98491974 T>G), RS1000074464 (8:98827456 A>G)

Disease associations

OMIM: gene MIM:605030 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002969_5	Suicide behavior	8.000000e-06
GCST005790_10	Rosacea symptom severity	8.000000e-06
GCST006979_470	Heel bone mineral density	8.000000e-10
GCST007666_16	Depressive symptom improvement	5.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007623	suicide behaviour
EFO:0009180	rosacea severity measurement
EFO:0009270	heel bone mineral density
EFO:0007006	depressive symptom measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523663 (PROTEIN FAMILY), CHEMBL4708 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

50 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 231,293 (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
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2005186	BELUMOSUDIL	4	1,817
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL101253	VATALANIB	3	11,319
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL274654	ORANTINIB	3	3,596
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL1231124	AZD-1480	2
CHEMBL1721885	SU-014813	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL1967878	CENISERTIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL1980715	LAUROGUADINE	2
CHEMBL2010872	CEP-11981	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — MST subfamily

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
staurosporine	Inhibition	9.39	pIC50
CEP-11981	Inhibition	7.68	pIC50
SBP-3264	Inhibition	7.44	pIC50
XMU-MP-1	Inhibition	6.79	pIC50

Binding affinities (BindingDB)

14 measured of 15 human assays (15 total across all organisms); most potent 14 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM
2-[(3,5-difluoro-4-hydroxyphenyl)amino]-5,7-dimethyl-8-(3-methylbutyl)-5,6,7,8-tetrahydropteridin-6-one	IC50	340 nM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 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
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 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
3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile	KD	5000 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM

ChEMBL bioactivities

627 potent at pChembl≥5 of 643 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.74	EC50	0.18	nM	STAUROSPORINE
9.74	Kd	0.18	nM	STAUROSPORINE
9.40	Ki	0.3981	nM	CHEMBL1980995
9.39	IC50	0.41	nM	STAUROSPORINE
8.80	Ki	1.585	nM	CHEMBL1997924
8.62	Kd	2.4	nM	LESTAURTINIB
8.55	IC50	2.83	nM	STAUROSPORINE
8.52	Kd	3	nM	CHEMBL4576489
8.50	Ki	3.162	nM	CHEMBL1994669
8.47	IC50	3.41	nM	STAUROSPORINE
8.40	IC50	4	nM	CERDULATINIB
8.40	Ki	3.981	nM	CHEMBL1984548
8.33	IC50	4.72	nM	STAUROSPORINE
8.26	IC50	5.49	nM	STAUROSPORINE
8.22	Kd	6	nM	CHEMBL4465866
8.10	Ki	7.943	nM	CHEMBL1976936
8.00	Ki	10	nM	CHEMBL1971029
7.96	Kd	11	nM	CHEMBL4554938
7.90	Ki	12.59	nM	CHEMBL1977148
7.90	Ki	12.59	nM	CHEMBL2001751
7.90	Ki	12.59	nM	CENISERTIB
7.80	Ki	15.85	nM	ILORASERTIB
7.74	IC50	18.2	nM	CHEMBL4554938
7.70	Ki	19.95	nM	CHEMBL1982476
7.70	Ki	19.95	nM	CHEMBL1967116
7.68	IC50	21	nM	CEP-11981
7.66	IC50	22	nM	CHEMBL3393348
7.60	Ki	25.12	nM	CHEMBL379975
7.60	Ki	25.12	nM	CHEMBL1970317
7.60	Ki	25.12	nM	CHEMBL1973395
7.57	Kd	27	nM	CHEMBL3393355
7.52	Kd	30	nM	LESTAURTINIB
7.50	Ki	31.62	nM	CHEMBL1982466
7.50	Ki	31.62	nM	CHEMBL1986855
7.50	Ki	31.62	nM	CHEMBL1970142
7.50	Ki	31.62	nM	CHEMBL2002649
7.50	Ki	31.62	nM	CHEMBL2002165
7.50	Ki	31.62	nM	CHEMBL1974254
7.50	Ki	31.62	nM	CHEMBL1998432
7.50	Ki	31.62	nM	CHEMBL1241473
7.47	IC50	34	nM	CHEMBL4554938
7.44	IC50	36	nM	CHEMBL5089935
7.42	IC50	38.1	nM	CHEMBL4554938
7.42	IC50	38.2	nM	CHEMBL4554938
7.42	Kd	38	nM	NINTEDANIB
7.41	IC50	38.8	nM	CHEMBL4554938
7.40	Kd	40	nM	MIDOSTAURIN
7.40	Ki	39.81	nM	CHEMBL1968930
7.40	Ki	39.81	nM	RG-1530
7.40	Ki	39.81	nM	CHEMBL1966628

PubChem BioAssay actives

190 with measured affinity, of 2426 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	2090805: Inhibition of MST2 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.0002	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	507633: Binding affinity to MST2	kd	0.0024	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	1526302: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged STK3 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0030	uM
4-(cyclopropylamino)-2-[4-(4-ethylsulfonylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide	1993899: Inhibition of MST2 (unknown origin)	ic50	0.0040	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	1526302: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged STK3 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0060	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	2189141: Binding affinity to MST2 (unknown origin) assessed as dissociation constant	kd	0.0110	uM
19-methyl-3-(2-methylpropyl)-7-(pyrimidin-2-ylamino)-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-14-one	653724: Inhibition of human MST2 using ATP as substrate	ic50	0.0210	uM
3-(4-morpholin-4-yl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)benzonitrile	1189426: Inhibition of human recombinant MST2 using Ser/Thr peptide 7 substrate after 45 mins by Z-Lyte assay	ic50	0.0220	uM
4-[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]morpholine	1820711: Binding affinity to recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli assessed as dissociation constant by isothermal titration calorimetry	kd	0.0270	uM
N-[1-[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl]acetamide	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0360	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625054: Binding constant for MST2 kinase domain	kd	0.0380	uM
Midostaurin	507633: Binding affinity to MST2	kd	0.0400	uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-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-nonaene-16-carboxylate	1425182: 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	0.0430	uM
(2S,3R,4R,6R,18S)-18-hydroxy-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	1425182: 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	0.0450	uM
4-[3-(3-chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]morpholine	1820711: Binding affinity to recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli assessed as dissociation constant by isothermal titration calorimetry	kd	0.0480	uM
1-[5-(4-amino-7-ethylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[3-(trifluoromethoxy)phenyl]ethanone	1415208: Inhibition of recombinant human MST2 (2 to end residues) using myelin basic protein as substrate after 40 mins in presence of [gamma-33P]-ATP by scintillation counting analysis	ic50	0.0500	uM
Sunitinib	435662: Binding constant for MST2 kinase domain	kd	0.0560	uM
3-[[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-methylamino]-2-methylpropan-1-ol	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0580	uM
Neratinib	2090801: Inhibition of MST2 (unknown origin)	ic50	0.0580	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435662: Binding constant for MST2 kinase domain	kd	0.0610	uM
4-(cyclopropylamino)-2-[4-(4-ethylsulfonylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide;hydrochloride	1425182: 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	0.0620	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	435662: Binding constant for MST2 kinase domain	kd	0.0650	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425182: 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	0.0700	uM
N-[5-(4-cyanophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide	389035: Binding affinity to human MST2	kd	0.0750	uM
3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide	1425182: 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	0.0850	uM
2-[4-[[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]amino]phenyl]acetonitrile	2093078: Binding affinity to N-terminal full length human MST2 expressed in intact HEK293T cells incubated for 2 hrs by NanoBRET assay	ec50	0.1100	uM
(3Z)-N,N-dimethyl-2-oxo-3-(4,5,6,7-tetrahydro-1H-indol-2-ylmethylidene)-1H-indole-5-sulfonamide	435210: Inhibition of MST2 in the presence of 50uM ATP	ic50	0.1100	uM
2-[[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-methylamino]ethanol	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.1170	uM
4-[5-(3-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]morpholine	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.1210	uM
1-[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-ol	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.1270	uM
N-[(2S,3R,4R,6R,18S)-18-hydroxy-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]-N-methylbenzamide	507633: Binding affinity to MST2	kd	0.1300	uM
3-(4-morpholin-4-yl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)benzamide	1820720: Binding affinity to recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli assessed as inhibition constant	ki	0.1500	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625054: Binding constant for MST2 kinase domain	kd	0.1600	uM
5-(3-chlorophenyl)-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.1670	uM
3-[[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]propan-1-ol	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.1730	uM
3-[4-[(2S)-2-methylmorpholin-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile	1189426: Inhibition of human recombinant MST2 using Ser/Thr peptide 7 substrate after 45 mins by Z-Lyte assay	ic50	0.1790	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	2090805: Inhibition of MST2 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.1840	uM
1-[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-4-methylpiperidin-4-ol	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.1890	uM
4-[5-(3-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]morpholine	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.1910	uM
3-[4-[2-(cyanomethyl)morpholin-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile	1189426: Inhibition of human recombinant MST2 using Ser/Thr peptide 7 substrate after 45 mins by Z-Lyte assay	ic50	0.1960	uM
4-(5-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)morpholine	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.1970	uM
N-cyclopropyl-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	2189265: Inhibition of recombinant His-tagged full-length MST2 (unknown origin) expressing in Escherichia coli assessed as GST-tagged MOB1a phosphorylation level incubated for 30 mins by immunoblot analysis	ic50	0.2071	uM
5-(3-chlorophenyl)-N-(cyclopropylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.2130	uM
5-(3-chlorophenyl)-N-methyl-N-propyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.2180	uM
2-[[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-ethylamino]ethanol	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.2260	uM
4-[5-(2-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]morpholine	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.2300	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	2090805: Inhibition of MST2 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay	ec50	0.2490	uM
4-(5-thiophen-2-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)morpholine	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.2670	uM
1-[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-4-methylpiperidin-4-amine	1820717: Inhibition of recombinant N-terminal His6-tagged human STK3 (18 to 311 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.2780	uM
4-[5-(3-cyanophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]morpholine-2-carbonitrile	1189426: Inhibition of human recombinant MST2 using Ser/Thr peptide 7 substrate after 45 mins by Z-Lyte assay	ic50	0.2880	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression	3
bisphenol A	decreases methylation, increases expression	2
Arsenic	increases abundance, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression, decreases reaction	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
XMU-MP-1	decreases reaction, increases expression, decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
evodiamine	decreases expression, increases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
ginsenoside Rg3	increases expression	1
CD 437	increases expression	1
chloropicrin	increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
asparanin A	decreases expression	1
bisphenol S	decreases methylation	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Cycloheximide	decreases expression, decreases reaction	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1

ChEMBL screening assays

551 unique, capped per target: 550 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4345771	Binding	Activation of MST1/2 in human SUM159 cells assessed as effect on phosphorylation at T183/T180 residues at 0.25 to 1.5 uM measured after 12 hrs by Western blot analysis	Targeting YAP Degradation by a Novel 1,2,4-Oxadiazole Derivative via Restoration of the Function of the Hippo Pathway. — ACS Med Chem Lett
CHEMBL1964119	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: STK3	PubChem BioAssay data set

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2HP	Abcam HeLa STK3 KO	Cancer cell line	Female
CVCL_D8BS	Ubigene A-549 STK3 KO	Cancer cell line	Male
CVCL_D9TD	Ubigene HEK293 STK3 KO	Transformed cell line	Female
CVCL_TQ83	HAP1 STK3 (-) 1	Cancer cell line	Male
CVCL_TQ84	HAP1 STK3 (-) 2	Cancer cell line	Male
CVCL_TQ85	HAP1 STK3 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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