STK4

Summary

STK4 (serine/threonine kinase 4, HGNC:11408) is a protein-coding gene on chromosome 20q13.12, encoding Serine/threonine-protein kinase 4 (Q13043). Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation.

The protein encoded by this gene is a cytoplasmic kinase that is structurally similar to the yeast Ste20p kinase, which acts upstream of the stress-induced mitogen-activated protein kinase cascade. The encoded protein can phosphorylate myelin basic protein and undergoes autophosphorylation. A caspase-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating histone H2B. The particular phosphorylation catalyzed by this protein has been correlated with apoptosis, and it’s possible that this protein induces the chromatin condensation observed in this process.

Source: NCBI Gene 6789 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined immunodeficiency due to STK4 deficiency (Definitive, ClinGen)
• GWAS associations: 7
• Clinical variants (ClinVar): 310 total — 15 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 84
• Druggable target: yes — 38 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006282

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11408
Approved symbol	STK4
Name	serine/threonine kinase 4
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	MST1, KRS2, YSK3
Ensembl gene	ENSG00000101109
Ensembl biotype	protein_coding
OMIM	604965
Entrez	6789

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 7 nonsense_mediated_decay, 5 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000372801, ENST00000372806, ENST00000474717, ENST00000487587, ENST00000488618, ENST00000499879, ENST00000698218, ENST00000698219, ENST00000698220, ENST00000698221, ENST00000698222, ENST00000698223, ENST00000698224, ENST00000698225, ENST00000698226, ENST00000698227, ENST00000698228, ENST00000925605

RefSeq mRNA: 2 — MANE Select: NM_006282 NM_001352385, NM_006282

CCDS: CCDS13341, CCDS86957

Canonical transcript exons

ENST00000372806 — 11 exons

Exon	Start	End
ENSE00000662330	44997169	44997306
ENSE00000662331	45000392	45000520
ENSE00000662332	45001167	45001353
ENSE00000662333	45024973	45025130
ENSE00001458697	45075018	45080021
ENSE00003498696	44978443	44978571
ENSE00003528774	44972078	44972158
ENSE00003741458	44981829	44981943
ENSE00003751036	44987132	44987296
ENSE00003789167	44995090	44995257
ENSE00003973020	44966512	44966603

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 95.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.2779 / max 1320.2105, expressed in 1767 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184766	27.0464	1767
184767	0.2315	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	95.67	gold quality
buccal mucosa cell	CL:0002336	95.64	gold quality
blood	UBERON:0000178	95.49	gold quality
monocyte	CL:0000576	95.14	gold quality
leukocyte	CL:0000738	94.56	gold quality
mononuclear cell	CL:0000842	94.50	gold quality
superficial temporal artery	UBERON:0001614	94.35	gold quality
trabecular bone tissue	UBERON:0002483	94.12	gold quality
pylorus	UBERON:0001166	93.71	gold quality
tonsil	UBERON:0002372	93.38	gold quality
lymph node	UBERON:0000029	93.13	gold quality
saphenous vein	UBERON:0007318	92.94	gold quality
cardia of stomach	UBERON:0001162	92.90	gold quality
medial globus pallidus	UBERON:0002477	92.53	gold quality
lower lobe of lung	UBERON:0008949	92.31	gold quality
bone marrow	UBERON:0002371	92.28	gold quality
superior surface of tongue	UBERON:0007371	92.17	gold quality
nipple	UBERON:0002030	92.03	gold quality
globus pallidus	UBERON:0001875	91.56	gold quality
trigeminal ganglion	UBERON:0001675	91.37	gold quality
granulocyte	CL:0000094	91.20	gold quality
epithelium of nasopharynx	UBERON:0001951	91.15	gold quality
inferior vagus X ganglion	UBERON:0005363	91.10	gold quality
superior vestibular nucleus	UBERON:0007227	90.62	gold quality
mammary duct	UBERON:0001765	90.32	gold quality
ventral tegmental area	UBERON:0002691	90.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.04	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.77	gold quality
tendon of biceps brachii	UBERON:0008188	89.76	gold quality
adrenal tissue	UBERON:0018303	89.70	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	583.93
E-GEOD-135922	yes	456.70
E-MTAB-10885	yes	390.20
E-MTAB-8142	yes	104.63
E-CURD-46	yes	43.17
E-MTAB-10287	yes	34.62
E-HCAD-1	yes	30.01
E-CURD-122	yes	24.28
E-HCAD-10	yes	20.90
E-MTAB-8498	yes	8.75
E-CURD-119	yes	4.23
E-CURD-97	no	1956.21
E-HCAD-8	no	390.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

259 targeting STK4, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910

Literature-anchored findings (GeneRIF, showing 40)

• Caspase-catalyzed cleavage and activation of Mst1 correlates with eosinophil but not neutrophil apoptosis. (PMID:11964314)
• promotion of MST1-induced apoptosis by DAP4 by enabling colocalization of MST with p53 (PMID:12384512)
• Mammalian Sterile20-like kinase 1 has a role in the regulation of apoptosis [review] (PMID:15157167)
• 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)
• Akt blocks MstI-triggered FOXO3 nuclear translocation by phosphorylating MstI, promoting cell survival. (PMID:17726016)
• Mst1 and its caspase cleavage products are direct inhibitors of Akt (PMID:17932490)
• Studies provide new insights into how MST1 substrate selectivity is modulated with implications for understanding apoptotic signaling through MST1 kinase. (PMID:18510339)
• Mst1 is a novel mediator of cardiac troponin I phosphorylation in the heart and may contribute to the modulation of myofilament function under a variety of physiological and pathophysiological conditions (PMID:18986304)
• findings identify NDR1/2 as novel proapoptotic kinases and key members of the RASSF1A/MST1 signaling cascade (PMID:19062280)
• hWW45 is required to enhance MST1-mediated apoptosis in vivo and thus is a critical player in an MST1-driven cell death signaling pathway. (PMID:19212654)
• MST1-FOXO1 signaling is an important link survival factor deprivation-induced neuronal cell death (PMID:19221179)
• 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)
• MST1 and hMOB1 signaling controls centrosome duplication. (PMID:19836237)
• hSav1 is a newly identified protein that interacts with Mst1 and augments Mst1-mediated apoptosis. (PMID:19950692)
• tolerance to increased levels of intracellular ROS provided by the Mst1-FoxOs signaling pathway is crucial for the maintenance of naive T cell homeostasis in the periphery (PMID:19956688)
• these findings indicate that MST1 is a major determinant of RASSF2 protein stability, and suggest that RASSF2 acts in a complex manner that extends beyond simple protein-protein association to play an important role in MST1 regulation. (PMID:19962960)
• MST1 directly phosphorylated Aurora B and inhibited its kinase activity in vitro; depletion of Aurora B restored the stability of kinetochore-microtubule attachment in cells depleted of MST1 or NDR1. (PMID:20171103)
• The identified Mst1 as a binding partner that interacts with PHLPPs both in vivo and in vitro. PHLPPs dephosphorylate Mst1 on the T387 inhibitory site, which activate Mst1 and its downstream effectors p38 and JNK to induce apoptosis. (PMID:20513427)
• H2AX is a substrate of MST1, which functions to induce apoptotic chromatin condensation and DNA fragmentation (PMID:20921231)
• 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)
• novel regulatory mechanism involving the phosphorylation of Sirt1 by MST1 kinase which leads to p53 activation, with implications for our understanding of signaling mechanisms during DNA damage-induced apoptosis (PMID:21212262)
• Phage microarrays containing colorectal cancer cDNA libraries were prepared to identify phage-expressed peptides recognized by tumor-specific autoantibodies from patient sera. (PMID:21228115)
• MST1 was also found in androgen receptor (AR)-chromatin complexes, and enforced expression of MST1 reduced the binding of AR to a well-characterized, androgen-responsive region within the prostate-specific antigen promo (PMID:21512132)
• results show a novel PRX-I function to cause cell death in response to high levels of oxidative stress by activating MST1, which underlies the p53-dependent cytotoxicity caused by anticancer agents (PMID:21516123)
• Findings show a biological role for MICAL-1 in apoptosis and define a novel negative regulatory mechanism of MST-NDR signaling. (PMID:21730291)
• Data indicate that dimerization domain of MST1 is unstructured as monomer and undergoes dimerization-induced folding. Data indicate that inhibitory domain of MST1 is disordered region both as single domain and as construct with dimerization domain. (PMID:22112013)
• MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival. (PMID:22174160)
• STK4 deficiency is a novel human primary immunodeficiency syndrome. (PMID:22294732)
• Data suggest that phosphoinositide-3-kinase/Akt and mammalian target of rapamycin (mTOR) pathway signaling differentially regulate phospho-Mst1-Thr-120/Thr-183. (PMID:22619175)
• Low expression of MST1 may be related with the pathogenesis and prognosis of acute leukemia. (PMID:22739148)
• Mst1 exhibits a growth promoting activity in HCC cells upon NORE1B downregulation. (PMID:23347832)
• Mst1 inactivates Prdx1 by phosphorylating it at Thr-90 and Thr-183, leading to accumulation of hydrogen peroxide in cells. (PMID:23386615)
• Results indicated that Mst1 might be a promising anticancer target. (PMID:23419720)
• In a yeast two-hybrid screen of a heart cDNA library with Mst1 as bait, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified as an Mst1-interacting protein. (PMID:23527007)
• Inhibition of Mst1 kinase activation in cardiomyocytes protects against cell hypoxia. (PMID:23647599)
• MST1 plays a tumor suppressive role and is a prognostic factor in human breast cancer. (PMID:23737290)
• Phosphorylated by the MST1. (PMID:23893242)
• results suggest that Mst1 coordinately regulates autophagy and apoptosis by phosphorylating Beclin1 and consequently modulating a three-way interaction among Bcl-2 proteins, Beclin1 and Bax (PMID:24141421)
• 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)
• PHLPP1 is a binding protein for Mst1 and it modulates the Hippo pathway by dephosphorylating Mst1 at the inhibitory Thr(387) of Mst1. (PMID:24393845)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Stk4	ENSMUSG00000018209
rattus_norvegicus	Stk4	ENSRNOG00000013529

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), PAK3 (ENSG00000077264), STRADB (ENSG00000082146), MAP3K1 (ENSG00000095015), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), 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 4 — Q13043 (reviewed: Q13043)

Alternative names: Mammalian STE20-like protein kinase 1, STE20-like kinase MST1, Serine/threonine-protein kinase Krs-2

All UniProt accessions (10): Q13043, A0A087WVN8, A0A087WYT4, A0A8V8TLH7, A0A8V8TLK1, A0A8V8TM13, A0A8V8TM18, A0A8V8TN08, A0A8V8TNA0, F5H5B4

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 ‘Ser-14’ of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on ‘Ser-212’ and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on ‘Ser-650’ and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes.

Subunit / interactions. Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation. Interacts with and stabilizes SAV1. Interacts with RASSF1. Interacts with FOXO3. Interacts with RASSF2 (via SARAH domain). Interacts with AR, PKB/AKT1, TNNI3 and SIRT1. Interacts with DLG5 (via PDZ domain 3). Interacts with MARK3 in the presence of DLG5. Interacts with SCRIB in the presence of DLG5.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Ubiquitously expressed.

Post-translational modifications. Autophosphorylated on serine and threonine residues. Phosphorylation at Thr-387 by PKB/AKT1, leads to inhibition of its: kinase activity, nuclear translocation and autophosphorylation at Thr-183. It also diminishes its cleavage by caspases and its ability to phosphorylate FOXO3. Proteolytically cleaved by caspase-3 during apoptosis at Asp-326 and Asp-349 resulting in a 37 kDa or a 39 kDa subunit respectively. The 39 kDa subunit is further cleaved into the 37 kDa form. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N). It is less likely that cleavage at Asp-349 is a prerequisite for activation as this site is not conserved in the murine ortholog.

Disease relevance. Immunodeficiency 110 with lymphoproliferation (IMD110) [MIM:614868] An autosomal recessive, primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T-cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, autoimmune manifestations, and cardiac malformations, including atrial septal defect. Patients are at risk for developing lymphoproliferative disorders or lymphoma. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-183. Activated by RASSF1 which acts by preventing its dephosphorylation.

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?
Q13043-1	1	yes
Q13043-2	2

RefSeq proteins (2): NP_001339314, NP_006273* (*=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
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 (71 total): helix 18, modified residue 11, strand 9, mutagenesis site 7, sequence variant 5, turn 4, chain 3, binding site 2, site 2, splice variant 2, domain 2, compositionally biased region 2, sequence conflict 1, region of interest 1, coiled-coil region 1, active site 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
8PAV	X-RAY DIFFRACTION	1.9
4NR2	X-RAY DIFFRACTION	2
8A5J	X-RAY DIFFRACTION	2.12
8PAW	X-RAY DIFFRACTION	2.14
3COM	X-RAY DIFFRACTION	2.2
4OH8	X-RAY DIFFRACTION	2.28
5TWG	X-RAY DIFFRACTION	2.3
9VX3	X-RAY DIFFRACTION	2.39
5TWH	X-RAY DIFFRACTION	2.5
7CEA	X-RAY DIFFRACTION	2.55
6YAT	X-RAY DIFFRACTION	2.58
9IIC	X-RAY DIFFRACTION	2.78
7CEB	X-RAY DIFFRACTION	2.89
8JG5	ELECTRON MICROSCOPY	3.04
7CEC	ELECTRON MICROSCOPY	3.9
2JO8	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13043-F1	76.45	0.49

Antibody-complex structures (SAbDab): 5 — 7CEA, 7CEB, 7CEC, 8JG5, 9VX3

Functional residue map

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

Catalytic / active sites (3): 326–327 (cleavage; by caspase-3); 349–350 (cleavage; by caspase-3); 149 (proton acceptor)

Ligand- & substrate-binding residues (2): 36–44; 59

Post-translational modifications (11): 1, 3, 183, 265, 320, 340, 367, 387, 410, 414, 433

Mutagenesis-validated functional residues (7):

Position	Phenotype
59	loss of activity.
175	no effect on activity.
177	no effect on activity.
183	loss of activity.
326	resistant to proteolytic cleavage by caspase during apoptosis; when associated with n-349.
349	resistant to proteolytic cleavage by caspase during apoptosis; when associated with n-326.
444	loss of homodimerization, activation, and autophosphorylation.

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: 763 (showing top): MODULE_172, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GCACCTT_MIR18A_MIR18B, VERHAAK_AML_WITH_NPM1_MUTATED_DN, MODULE_97, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYONIC_HEMOPOIESIS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GRUETZMANN_PANCREATIC_CANCER_DN, LU_IL4_SIGNALING, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GAANYNYGACNY_UNKNOWN

GO Biological Process (43): cell morphogenesis (GO:0000902), branching involved in blood vessel morphogenesis (GO:0001569), neural tube formation (GO:0001841), positive regulation of protein phosphorylation (GO:0001934), endocardium development (GO:0003157), protein phosphorylation (GO:0006468), protein import into nucleus (GO:0006606), apoptotic process (GO:0006915), signal transduction (GO:0007165), central nervous system development (GO:0007417), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), peptidyl-serine phosphorylation (GO:0018105), keratinocyte differentiation (GO:0030216), positive regulation of peptidyl-serine phosphorylation (GO:0033138), 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), positive regulation of fat cell differentiation (GO:0045600), negative regulation of organ growth (GO:0046621), protein autophosphorylation (GO:0046777), epithelial cell proliferation (GO:0050673), negative regulation of epithelial cell proliferation (GO:0050680), protein stabilization (GO:0050821), protein tetramerization (GO:0051262), canonical Wnt signaling pathway (GO:0060070), primitive hemopoiesis (GO:0060215), cell differentiation involved in embryonic placenta development (GO:0060706), regulation of cell differentiation involved in embryonic placenta development (GO:0060800), 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), positive regulation of hepatocyte apoptotic process (GO:1903945), positive regulation of substrate-dependent cell migration, cell attachment to substrate (GO:1904237), MAPK cascade (GO:0000165), cell population proliferation (GO:0008283), negative regulation of cell population proliferation (GO:0008285), anatomical structure morphogenesis (GO:0009653)

GO Molecular Function (16): 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/threonine kinase activator activity (GO:0043539), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), MAP kinase kinase activity (GO:0004708), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), protein kinase binding (GO:0019901), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear body (GO:0016604), protein-containing complex (GO:0032991)

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
cellular anatomical structure	3
protein phosphorylation	2
intracellular anatomical structure	2
MAPK cascade	2
protein kinase activity	2
anatomical structure morphogenesis	1
angiogenesis	1
blood vessel morphogenesis	1
branching morphogenesis of an epithelial tube	1
embryonic epithelial tube formation	1
neural tube development	1
regulation of protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	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
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
nervous system development	1
system development	1
extrinsic apoptotic signaling pathway	1
peptidyl-serine modification	1
epidermal cell differentiation	1
skin development	1
positive regulation of protein phosphorylation	1
peptidyl-serine phosphorylation	1
regulation of peptidyl-serine phosphorylation	1
multicellular organismal process	1

Protein interactions and networks

STRING

1070 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK4	SAV1	Q9H4B6	995
STK4	MOB1A	Q9H8S9	904
STK4	RASSF1	Q9NS23	756
STK4	MOB1B	Q7L9L4	707
STK4	WWTR1	Q9GZV5	683
STK4	RASSF5	Q8WWW0	679
STK4	YAP1	P46937	676
STK4	TEAD1	P28347	623
STK4	SCRIB	Q14160	607
STK4	RASSF2	P50749	600
STK4	MOB3A	Q96BX8	583
STK4	LATS1	O95835	569
STK4	MBP	P02686	568
STK4	FOXO3	O43524	563
STK4	LATS2	Q9NRM7	560

IntAct

229 interactions, top by confidence:

A	B	Type	Score
STK3	RASSF2	psi-mi:“MI:0914”(association)	0.950
SAV1	STK4	psi-mi:“MI:0915”(physical association)	0.940
STK4	SAV1	psi-mi:“MI:0915”(physical association)	0.940
SAV1	STK4	psi-mi:“MI:0914”(association)	0.940
STK4	RASSF2	psi-mi:“MI:0914”(association)	0.930
STK4	RASSF2	psi-mi:“MI:0915”(physical association)	0.930
RASSF2	STK4	psi-mi:“MI:0914”(association)	0.930
STK3	STK4	psi-mi:“MI:0915”(physical association)	0.910
RASSF5	STK4	psi-mi:“MI:0915”(physical association)	0.880
STK4	RASSF4	psi-mi:“MI:0915”(physical association)	0.830
RASSF4	STK4	psi-mi:“MI:0915”(physical association)	0.830
RASSF4	STK4	psi-mi:“MI:0914”(association)	0.830
RASSF3	STK4	psi-mi:“MI:0915”(physical association)	0.820
STK4	RASSF3	psi-mi:“MI:0915”(physical association)	0.820
SLMAP	STK4	psi-mi:“MI:0915”(physical association)	0.790
RASSF6	STK4	psi-mi:“MI:0915”(physical association)	0.780
STK4	RASSF6	psi-mi:“MI:0915”(physical association)	0.780
RASSF6	STK4	psi-mi:“MI:0914”(association)	0.780
STK4	RASSF1	psi-mi:“MI:0915”(physical association)	0.730
STK4	MAP1B	psi-mi:“MI:0914”(association)	0.730

BioGRID (2168): STK4 (Affinity Capture-Western), STK4 (Affinity Capture-MS), STK4 (Affinity Capture-MS), STK4 (Affinity Capture-MS), STK4 (Affinity Capture-MS), STK4 (Affinity Capture-MS), STK4 (Affinity Capture-MS), STK4 (Affinity Capture-MS), STK4 (Affinity Capture-MS), STK4 (Affinity Capture-MS), STK4 (Affinity Capture-MS), ANXA1 (Affinity Capture-MS), CDC37 (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1S (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

86 interactions.

A	Effect	B	Mechanism
MST1	up-regulates	STK4	phosphorylation
STK4	up-regulates	LATS1	phosphorylation
AKT	down-regulates	STK4	phosphorylation
MAPK8	up-regulates	STK4	phosphorylation
SAV1	up-regulates	STK4	binding
STK4	unknown	H2BC3	phosphorylation
RASSF1	up-regulates	STK4	binding
STK4	up-regulates	LATS2	phosphorylation
STK4	up-regulates	MOB1A	phosphorylation
STK4	up-regulates	MOB1B	phosphorylation
STK4	up-regulates	FOXO1	phosphorylation
STK4	up-regulates	FOXO3	phosphorylation
STK4	up-regulates	FOXO4	phosphorylation
STK4	down-regulates	ABL1	phosphorylation
STK4	unknown	TNNI3	phosphorylation
RAF1	down-regulates	STK4	binding
TAOK3	up-regulates	STK4	phosphorylation
AKT2	down-regulates	STK4	phosphorylation
AKT3	down-regulates	STK4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 148 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
Activation of BAD and translocation to mitochondria	5	38.1×	7e-05
Signaling by Hippo	5	27.2×	2e-04
Activation of BH3-only proteins	5	24.8×	2e-04
Intrinsic Pathway for Apoptosis	6	17.6×	2e-04
Apoptosis	7	11.8×	2e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	10.8×	3e-04
Macroautophagy	9	10.4×	7e-05
Programmed Cell Death	7	10.2×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	11	27.3×	1e-10
autophagosome maturation	7	19.2×	3e-05
regulation of signal transduction by p53 class mediator	5	15.0×	4e-03
autophagosome assembly	8	14.0×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	5
Uncertain significance	127
Likely benign	128
Benign	12

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
1068530	NM_006282.5(STK4):c.922C>T (p.Gln308Ter)	Pathogenic
1075656	NM_006282.5(STK4):c.442C>T (p.Arg148Ter)	Pathogenic
1455329	NM_006282.5(STK4):c.373G>T (p.Glu125Ter)	Pathogenic
2727529	NM_006282.5(STK4):c.871C>T (p.Arg291Ter)	Pathogenic
2993502	NM_006282.5(STK4):c.994C>T (p.Arg332Ter)	Pathogenic
3587269	NM_006282.5(STK4):c.343C>T (p.Arg115Ter)	Pathogenic
3642667	NM_006282.5(STK4):c.964G>T (p.Glu322Ter)	Pathogenic
3727861	NM_006282.5(STK4):c.92dup (p.Asp31fs)	Pathogenic
37323	NM_006282.5(STK4):c.349C>T (p.Arg117Ter)	Pathogenic
37324	NM_006282.5(STK4):c.1103del (p.Met368fs)	Pathogenic
37325	NM_006282.5(STK4):c.749G>A (p.Trp250Ter)	Pathogenic
4695606	NM_006282.5(STK4):c.297G>A (p.Trp99Ter)	Pathogenic
4717418	NM_006282.5(STK4):c.1135_1138del (p.Gly379fs)	Pathogenic
4849144	NC_000020.10:g.(?43595152)(43708663_?)del	Pathogenic
835262	NM_006282.5(STK4):c.733C>T (p.Arg245Ter)	Pathogenic
1722416	NM_006282.5(STK4):c.831+2T>C	Likely pathogenic
2020904	NM_006282.5(STK4):c.36-1G>A	Likely pathogenic
2050900	NM_006282.5(STK4):c.961-2A>G	Likely pathogenic
2429218	NM_006282.5(STK4):c.395C>A (p.Ser132Ter)	Likely pathogenic
3587270	NM_006282.5(STK4):c.775A>T (p.Lys259Ter)	Likely pathogenic

SpliceAI

5127 predictions. Top by Δscore:

Variant	Effect	Δscore
20:44972070:A:AG	acceptor_gain	1.0000
20:44972073:CACA:C	acceptor_loss	1.0000
20:44972076:A:AG	acceptor_gain	1.0000
20:44972076:AG:A	acceptor_gain	1.0000
20:44972077:G:GG	acceptor_gain	1.0000
20:44972077:G:GT	acceptor_loss	1.0000
20:44972077:GG:G	acceptor_gain	1.0000
20:44972077:GGC:G	acceptor_gain	1.0000
20:44972077:GGCA:G	acceptor_gain	1.0000
20:44972154:GAAGG:G	donor_gain	1.0000
20:44972157:GG:G	donor_gain	1.0000
20:44972158:GG:G	donor_gain	1.0000
20:44973298:A:AG	acceptor_gain	1.0000
20:44973298:AAGTT:A	acceptor_gain	1.0000
20:44973299:A:G	acceptor_gain	1.0000
20:44973300:G:GG	acceptor_gain	1.0000
20:44978433:A:AG	acceptor_gain	1.0000
20:44978434:A:G	acceptor_gain	1.0000
20:44978436:T:G	acceptor_gain	1.0000
20:44978439:A:AG	acceptor_gain	1.0000
20:44978439:ATAG:A	acceptor_gain	1.0000
20:44978440:T:G	acceptor_gain	1.0000
20:44978440:TA:T	acceptor_loss	1.0000
20:44978441:A:AG	acceptor_gain	1.0000
20:44978441:AGGTC:A	acceptor_loss	1.0000
20:44978442:G:GA	acceptor_gain	1.0000
20:44978442:G:GT	acceptor_loss	1.0000
20:44978442:GGTC:G	acceptor_gain	1.0000
20:44978568:ACAG:A	donor_gain	1.0000
20:44978569:CAG:C	donor_loss	1.0000

AlphaMissense

3241 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:44972119:C:A	P26Q	1.000
20:44972130:T:C	F30L	1.000
20:44972131:T:C	F30S	1.000
20:44972132:T:A	F30L	1.000
20:44972132:T:G	F30L	1.000
20:44972149:T:A	L36H	1.000
20:44972149:T:C	L36P	1.000
20:44972151:G:A	G37R	1.000
20:44972151:G:C	G37R	1.000
20:44972152:G:A	G37E	1.000
20:44972152:G:T	G37V	1.000
20:44972157:G:A	G39R	1.000
20:44972157:G:C	G39R	1.000
20:44972157:G:T	G39W	1.000
20:44972158:G:A	G39E	1.000
20:44972158:G:C	G39A	1.000
20:44972158:G:T	G39V	1.000
20:44978444:T:C	S40P	1.000
20:44978447:T:C	Y41H	1.000
20:44978450:G:A	G42S	1.000
20:44978450:G:C	G42R	1.000
20:44978450:G:T	G42C	1.000
20:44978451:G:A	G42D	1.000
20:44978451:G:T	G42V	1.000
20:44978456:G:C	V44L	1.000
20:44978456:G:T	V44L	1.000
20:44978457:T:A	V44E	1.000
20:44978457:T:C	V44A	1.000
20:44978464:A:C	K46N	1.000
20:44978464:A:T	K46N	1.000

dbSNP variants (sampled 300 via entrez): RS1000008293 (20:45003845 T>C), RS1000012317 (20:45065105 T>C), RS1000075904 (20:44972621 A>C,T), RS1000078337 (20:45002389 T>A), RS1000091481 (20:44968797 T>G), RS1000109848 (20:45010814 C>G,T), RS1000148788 (20:45057889 C>G), RS1000200515 (20:44979556 C>T), RS1000239735 (20:45072701 T>G), RS1000254637 (20:45025240 C>A,T), RS1000278333 (20:44997042 G>A,T), RS1000284228 (20:45058872 T>A), RS1000315488 (20:45058266 A>G), RS1000319025 (20:45079273 T>A), RS1000346942 (20:45079646 C>T)

Disease associations

OMIM: gene MIM:604965 | disease phenotypes: MIM:614868

GenCC curated gene-disease

Disease	Classification	Inheritance
combined immunodeficiency due to STK4 deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
combined immunodeficiency due to STK4 deficiency	Definitive	AR

Mondo (2): combined immunodeficiency due to STK4 deficiency (MONDO:0013934), severe combined immunodeficiency (MONDO:0015974)

Orphanet (2): Combined immunodeficiency due to STK4 deficiency (Orphanet:314689), Severe combined immunodeficiency (Orphanet:183660)

HPO phenotypes

84 total (30 of 84 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000554	Uveitis
HP:0000716	Depression
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000952	Jaundice
HP:0000989	Pruritus
HP:0001081	Cholelithiasis
HP:0001298	Encephalopathy
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001396	Cholestasis
HP:0001402	Hepatocellular carcinoma
HP:0001409	Portal hypertension
HP:0001433	Hepatosplenomegaly
HP:0001541	Ascites
HP:0001581	Recurrent skin infections
HP:0001635	Congestive heart failure
HP:0001655	Patent foramen ovale
HP:0001684	Secundum atrial septal defect
HP:0001733	Pancreatitis
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001875	Decreased total neutrophil count
HP:0001879	Abnormal eosinophil morphology
HP:0001888	Decreased total lymphocyte count
HP:0001890	Autoimmune hemolytic anemia
HP:0001945	Fever
HP:0001954	Recurrent fever

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST008103_18	Bipolar disorder	1.000000e-08
GCST008103_27	Bipolar disorder	3.000000e-08
GCST011102_23	Bipolar disorder	6.000000e-09
GCST012465_42	Bipolar disorder	1.000000e-09
GCST90002395_597	Mean platelet volume	8.000000e-17
GCST90002395_598	Mean platelet volume	1.000000e-15
GCST90002402_592	Platelet count	6.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523663 (PROTEIN FAMILY), CHEMBL4598 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

38 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 178,882 (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
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL274654	ORANTINIB	3	3,596
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1231124	AZD-1480	2	1,576
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL1721885	SU-014813	2	363
CHEMBL1738757	REBASTINIB	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL402548	DANUSERTIB	2
CHEMBL4116008	CERDULATINIB	2
CHEMBL572878	TOZASERTIB	2
CHEMBL574737	UCN-01	2
CHEMBL607707	PELITINIB	2
CHEMBL1084546	PF-00562271	1
CHEMBL1908397	KW-2449	1
CHEMBL2041933	AZD-7762	1

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 (6 total), top 6:

Ligand	Action	Affinity	Parameter
cerdulatinib	Inhibition	8.4	pIC50
IHMT-MST1-58	Inhibition	7.64	pIC50
SBP-3264	Inhibition	7.59	pIC50
bosutinib	Inhibition	6.72	pIC50
compound 38 [PMID: 20817473]	Inhibition	6.39	pIC50
XMU-MP-1	Inhibition	6.31	pIC50

Binding affinities (BindingDB)

9 measured of 10 human assays (10 total across all organisms); most potent 9 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 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
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 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

ChEMBL bioactivities

362 potent at pChembl≥5 of 371 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.72	EC50	0.19	nM	STAUROSPORINE
9.72	Kd	0.19	nM	STAUROSPORINE
9.70	Kd	0.2	nM	STAUROSPORINE
9.00	Kd	1	nM	STAUROSPORINE
8.99	IC50	1.02	nM	STAUROSPORINE
8.85	IC50	1.42	nM	STAUROSPORINE
8.80	IC50	1.58	nM	STAUROSPORINE
8.52	Kd	3	nM	LESTAURTINIB
8.40	Kd	4	nM	CHEMBL4576489
8.40	IC50	4	nM	CERDULATINIB
8.15	Kd	7	nM	CHEMBL4465866
8.05	Kd	9	nM	NINTEDANIB
8.01	IC50	9.8	nM	CHEMBL4554938
7.77	Kd	17	nM	CHEMBL4554938
7.77	Kd	17	nM	MIDOSTAURIN
7.72	Kd	19	nM	SUNITINIB
7.64	IC50	23	nM	CHEMBL5183592
7.58	IC50	26	nM	CHEMBL5089935
7.54	Kd	29	nM	K-252A
7.48	Ki	33	nM	CHEMBL5093114
7.47	IC50	34	nM	CHEMBL3393348
7.46	IC50	35	nM	CHEMBL3942417
7.46	IC50	35	nM	CHEMBL3393355
7.42	IC50	38	nM	CHEMBL5092052
7.42	Kd	37.96	nM	CHEMBL5653589
7.40	Kd	40	nM	MIDOSTAURIN
7.38	IC50	42	nM	CHEMBL5207166
7.35	Kd	45	nM	LESTAURTINIB
7.32	IC50	48	nM	CHEMBL5082941
7.32	Kd	48	nM	CHEMBL1908395
7.30	IC50	50	nM	CHEMBL3893023
7.30	Ki	50	nM	CHEMBL3393355
7.30	ED50	49.78	nM	CHEMBL5653589
7.29	IC50	51	nM	CHEMBL5189483
7.28	IC50	53	nM	CHEMBL5176278
7.25	Kd	56	nM	AZD-7762
7.25	IC50	56	nM	CHEMBL5204087
7.24	IC50	57	nM	CHEMBL5188177
7.23	IC50	59	nM	CHEMBL3923604
7.22	IC50	60	nM	CHEMBL5200426
7.18	IC50	66	nM	CHEMBL5093114
7.17	Kd	67	nM	CHEMBL3688339
7.15	IC50	71.1	nM	CHEMBL4554938
7.15	IC50	70.7	nM	CHEMBL4554938
7.12	IC50	75	nM	CHEMBL5200209
7.11	IC50	77	nM	CHEMBL5187804
7.10	IC50	80	nM	CHEMBL5089132
7.10	IC50	79	nM	CHEMBL5076098
7.10	IC50	79	nM	CHEMBL5170557
7.09	IC50	81	nM	CHEMBL5087454

PubChem BioAssay actives

211 with measured affinity, of 1500 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	2090804: Inhibition of MST1 (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	507631: Binding affinity to MST1	kd	0.0030	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	1526304: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged STK4 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0040	uM
4-(cyclopropylamino)-2-[4-(4-ethylsulfonylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide	1993890: Inhibition of MST1 (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	1526304: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged STK4 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0070	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625055: Binding constant for MST1 kinase domain	kd	0.0090	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	2189163: Inhibition of MST1 (unknown origin) in presence of ATP by enzymatic assay	ic50	0.0098	uM
Midostaurin	507631: Binding affinity to MST1	kd	0.0170	uM
Sunitinib	435433: Binding constant for full-length MST1	kd	0.0190	uM
4-[[5,8-dimethyl-7-(2-methylphenyl)-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.0230	uM
N-[1-[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl]acetamide	1820716: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0260	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	1425185: 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
4-[3-(3-chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]morpholine	1820721: Binding affinity to recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli assessed as inhibition constant	ki	0.0330	uM
4-[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]morpholine	1820716: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0350	uM
4-[5-(3-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]morpholine	1820716: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0350	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149512: Binding affinity to human STK4 incubated for 45 mins by Kinobead based pull down assay	kd	0.0380	uM
3-[[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-methylamino]-2-methylpropan-1-ol	1820716: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0380	uM
4-[[7-(2,6-difluorophenyl)-5,8-dimethyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.0420	uM
5-(3-chlorophenyl)-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine	1820716: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0480	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625055: Binding constant for MST1 kinase domain	kd	0.0480	uM
3-(4-morpholin-4-yl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)benzamide	1820716: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0500	uM
4-[[7-(2-ethylphenyl)-5,8-dimethyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.0510	uM
N-cyclopropyl-4-[[5,8-dimethyl-7-(2-methylphenyl)-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.0530	uM
3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide	1425185: 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	0.0560	uM
4-[[5,8-dimethyl-6-oxo-7-[2-(trifluoromethyl)phenyl]-7H-pteridin-2-yl]amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.0560	uM
4-[[7-(2-bromophenyl)-5,8-dimethyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.0570	uM
4-[5-(3-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]morpholine	1820716: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0590	uM
N-(cyclopropylmethyl)-4-[[5,8-dimethyl-7-(2-methylphenyl)-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.0600	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425185: 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	0.0670	uM
4-[[7-(2-fluorophenyl)-5,8-dimethyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.0750	uM
4-[[5,8-dimethyl-7-(2-methylpropyl)-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.0770	uM
N-(cyclopropylmethyl)-4-[[7-(2,6-difluorophenyl)-5,8-dimethyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.0790	uM
2-[[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-methylamino]ethanol	1820716: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0790	uM
1-[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-ol	1820716: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0800	uM
5-(3-chlorophenyl)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1820716: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0810	uM
4-[(5,8-dimethyl-6-oxo-7-thiophen-2-yl-7H-pteridin-2-yl)amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.0880	uM
4-(5-thiophen-2-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)morpholine	1820716: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0910	uM
N-[2-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide	1922873: Inhibition of STK4 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay	ic50	0.0940	uM
3-[[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]propan-1-ol	1820716: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay	ic50	0.0940	uM
4-(cyclopropylamino)-2-[4-(4-ethylsulfonylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide;hydrochloride	1425185: 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	0.1020	uM
4-[(5’,8’-dimethyl-6’-oxospiro[cyclopropane-1,7’-pteridine]-2’-yl)amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.1030	uM
4-[[5,8-dimethyl-7-(2-methylphenyl)-6-oxo-7H-pteridin-2-yl]amino]-N-methylbenzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.1040	uM
N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(2-methyl-3-pyridinyl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide	1922873: Inhibition of STK4 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay	ic50	0.1120	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	1425185: 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	0.1140	uM
4-[[5,8-dimethyl-7-(2-methylphenyl)-6-oxo-7H-pteridin-2-yl]amino]-N-ethylbenzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.1190	uM
N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-4-(2-methyl-3-pyridinyl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide	1922873: Inhibition of STK4 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay	ic50	0.1220	uM
4-[[7-(2-chlorophenyl)-5,8-dimethyl-6-oxo-7H-pteridin-2-yl]amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.1290	uM
4-[(5’,8’-dimethyl-6’-oxospiro[cyclopentane-1,7’-pteridine]-2’-yl)amino]benzenesulfonamide	1887162: Inhibition of recombinant full length N-terminal GST -tagged human MST1 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay	ic50	0.1290	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	435433: Binding constant for full-length MST1	kd	0.1300	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435433: Binding constant for full-length MST1	kd	0.1300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
methylmercuric chloride	increases expression, affects cotreatment	3
sodium arsenite	affects methylation, affects cotreatment, increases abundance, increases expression	3
trichostatin A	affects expression, decreases expression, increases expression	2
Irinotecan	decreases expression, affects cotreatment, affects response to substance	2
Acetaminophen	increases expression	2
Nickel	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
FR900359	decreases phosphorylation	1
XMU-MP-1	decreases reaction, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
leptomycin B	increases activity, increases reaction	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
licochalcone A	decreases expression, increases expression, decreases reaction	1
ginsenoside Rg3	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
torcetrapib	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Bortezomib	increases localization, increases reaction, decreases reaction, increases response to substance, increases activity	1
Sunitinib	increases expression	1
Acrolein	increases oxidation, affects cotreatment	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Benzo(a)pyrene	increases expression	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1

ChEMBL screening assays

362 unique, capped per target: 362 binding

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

Cellosaurus cell lines

10 cell lines: 9 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2HR	Abcam HeLa STK4 KO	Cancer cell line	Female
CVCL_B7ZP	Abcam Raji STK4 KO	Cancer cell line	Male
CVCL_C0AH	Abcam THP-1 STK4 KO	Cancer cell line	Male
CVCL_C7C5	Abcam PC-3 STK4 KO	Cancer cell line	Male
CVCL_D8BT	Ubigene A-549 STK4 KO	Cancer cell line	Male
CVCL_D8WL	Ubigene HCT 116 STK4 KO	Cancer cell line	Male
CVCL_D9TE	Ubigene HEK293 STK4 KO	Transformed cell line	Female
CVCL_E0QB	Ubigene HeLa STK4 KO	Cancer cell line	Female
CVCL_TQ95	HAP1 STK4 (-) 1	Cancer cell line	Male
CVCL_TQ96	HAP1 STK4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	PHASE3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	PHASE2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	PHASE2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	PHASE2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
NCT00008450	PHASE1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT00028236	PHASE1	COMPLETED	Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
NCT00152100	PHASE1	COMPLETED	Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT02860559	PHASE1	UNKNOWN	Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00228852	PHASE1/PHASE2	COMPLETED	IMM 0212: Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency
NCT00579137	PHASE1/PHASE2	TERMINATED	Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
NCT01129544	PHASE1/PHASE2	COMPLETED	Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02127892	PHASE1/PHASE2	TERMINATED	SCID Bu/Flu/ATG Study With T Cell Depletion
NCT02963064	PHASE1/PHASE2	TERMINATED	JSP191 Antibody Targeting Conditioning in SCID Patients
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03538899	PHASE1/PHASE2	RECRUITING	Autologous Gene Therapy for Artemis-Deficient SCID
NCT03597594	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID)
NCT00001255	Not specified	COMPLETED	Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006335	Not specified	COMPLETED	Influences on Female Adolescents’ Decisions Regarding Testing for Carrier Status of XSCID
NCT00055172	Not specified	RECRUITING	Genetic Basis of Immunodeficiency
NCT00695279	Not specified	COMPLETED	Long Term Follow Up Of Patients Who Have Received Gene Therapy Or Gene Marked Products
NCT00845416	Not specified	COMPLETED	Newborn Screening for Severe Combined Immunodeficiency (SCID) in a High-Risk Population
NCT01186913	Not specified	ENROLLING_BY_INVITATION	Natural History Study of SCID Disorders
NCT01346150	Not specified	UNKNOWN	Patients Treated for SCID (1968-Present)
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT01953016	Not specified	COMPLETED	Participation in a Research Registry for Immune Disorders
NCT02231983	Not specified	UNKNOWN	Clinical Characteristics and Genetic Profiles of Severe Combined Immunodeficiency in China
NCT02590328	Not specified	COMPLETED	Neonatal Screening of Severe Combined Immunodeficiencies
NCT04049084	Not specified	ENROLLING_BY_INVITATION	An Observational LTFU Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for ADA-SCID
NCT04172181	Not specified	UNKNOWN	Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for SCID
NCT04246840	Not specified	COMPLETED	Study Through Imaging of Visceral Lymphoid Organs in Patients With SCID Who Have Recieved Bone Marrow Allograft
NCT04331483	Not specified	WITHDRAWN	A Study to Assess a Physical Activity Program in Children, Adolescents and Young Adults Requiring Hematopoietic Stem Cell Allografts