STK25

Summary

STK25 (serine/threonine kinase 25, HGNC:11404) is a protein-coding gene on chromosome 2q37.3, encoding Serine/threonine-protein kinase 25 (O00506). Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress.

This gene encodes a member of the germinal centre kinase III (GCK III) subfamily of the sterile 20 superfamily of kinases. The encoded enzyme plays a role in serine-threonine liver kinase B1 (LKB1) signaling pathway to regulate neuronal polarization and morphology of the Golgi apparatus. The protein is translocated from the Golgi apparatus to the nucleus in response to chemical anoxia and plays a role in regulation of cell death. A pseudogene associated with this gene is located on chromosome 18. Multiple alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 10494 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 66 total
• Druggable target: yes — 18 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001271977

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11404
Approved symbol	STK25
Name	serine/threonine kinase 25
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	SOK1, YSK1
Ensembl gene	ENSG00000115694
Ensembl biotype	protein_coding
OMIM	602255
Entrez	10494

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 30 protein_coding, 9 retained_intron, 7 protein_coding_CDS_not_defined

ENST00000316586, ENST00000401869, ENST00000403346, ENST00000405585, ENST00000405883, ENST00000413760, ENST00000420551, ENST00000423004, ENST00000424537, ENST00000426941, ENST00000429279, ENST00000435225, ENST00000436402, ENST00000436917, ENST00000439101, ENST00000440109, ENST00000442307, ENST00000450497, ENST00000452891, ENST00000461760, ENST00000462953, ENST00000465009, ENST00000470438, ENST00000472181, ENST00000478403, ENST00000479442, ENST00000483603, ENST00000487962, ENST00000492127, ENST00000494699, ENST00000495143, ENST00000495372, ENST00000496159, ENST00000535007, ENST00000543554, ENST00000903350, ENST00000903351, ENST00000903352, ENST00000903353, ENST00000903354, ENST00000903355, ENST00000903356, ENST00000930802, ENST00000930803, ENST00000942587, ENST00000942588

RefSeq mRNA: 9 — MANE Select: NM_001271977 NM_001271977, NM_001271978, NM_001271979, NM_001271980, NM_001282305, NM_001282306, NM_001282307, NM_001282308, NM_006374

CCDS: CCDS2549, CCDS63199, CCDS63200

Canonical transcript exons

ENST00000316586 — 12 exons

Exon	Start	End
ENSE00001862175	241508443	241508584
ENSE00001915587	241492670	241495701
ENSE00003479314	241496398	241496534
ENSE00003491340	241508006	241508135
ENSE00003531215	241498639	241498784
ENSE00003580036	241501478	241501708
ENSE00003590265	241497616	241497687
ENSE00003598159	241500740	241500796
ENSE00003608367	241499257	241499414
ENSE00003672533	241500173	241500281
ENSE00003679578	241498235	241498349
ENSE00003785794	241498989	241499174

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 98.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.0586 / max 223.1221, expressed in 1822 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34922	39.8833	1818
34921	3.6050	1503
34919	2.8475	1414
202646	1.5435	1177
34918	1.4237	850
34917	0.3671	193
34920	0.2730	109
34923	0.1154	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	98.98	gold quality
right lobe of thyroid gland	UBERON:0001119	98.95	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.93	gold quality
gastrocnemius	UBERON:0001388	98.88	gold quality
left lobe of thyroid gland	UBERON:0001120	98.79	gold quality
right frontal lobe	UBERON:0002810	98.73	gold quality
muscle of leg	UBERON:0001383	98.67	gold quality
cerebellar hemisphere	UBERON:0002245	98.67	gold quality
cortical plate	UBERON:0005343	98.57	gold quality
apex of heart	UBERON:0002098	98.56	gold quality
ventricular zone	UBERON:0003053	98.56	gold quality
adenohypophysis	UBERON:0002196	98.55	gold quality
metanephros cortex	UBERON:0010533	98.54	gold quality
ganglionic eminence	UBERON:0004023	98.50	gold quality
right uterine tube	UBERON:0001302	98.46	gold quality
cerebellar cortex	UBERON:0002129	98.44	gold quality
body of pancreas	UBERON:0001150	98.35	gold quality
lower esophagus mucosa	UBERON:0035834	98.34	gold quality
endocervix	UBERON:0000458	98.27	gold quality
right ovary	UBERON:0002118	98.24	gold quality
left ovary	UBERON:0002119	98.20	gold quality
body of uterus	UBERON:0009853	98.20	gold quality
right testis	UBERON:0004534	98.18	gold quality
left testis	UBERON:0004533	98.14	gold quality
stromal cell of endometrium	CL:0002255	98.05	gold quality
ectocervix	UBERON:0012249	98.04	gold quality
body of stomach	UBERON:0001161	97.99	gold quality
left uterine tube	UBERON:0001303	97.96	gold quality
lower esophagus	UBERON:0013473	97.94	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.16
E-MTAB-6142	no	169.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting STK25, 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-6744-5P	99.93	66.82	748
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-631	97.05	66.93	602
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-4529-5P	96.74	65.77	569
HSA-MIR-7976	95.75	65.67	1186
HSA-MIR-874-3P	95.02	65.66	806
HSA-MIR-4800-3P	88.42	63.07	35

Literature-anchored findings (GeneRIF, showing 21)

• 14-3-3zeta is a specific substrate for YSK1 that localizes to the Golgi apparatus, and potentially links YSK1 signaling at the Golgi apparatus with protein transport. (PMID:15037601)
• Ste20 family member (MAP4K3) that is required for maximal S6K (S6 kinase)/4E-BP1 [eIF4E (eukaryotic initiation factor 4E) that is required for maximal S6K (S6 kinase). (PMID:17253963)
• SOK1 entry into the nucleus is important for the cell death response (PMID:18364353)
• In cultured human endothelial cells, CCM3 and STK25 regulated barrier function in a manner similar to CCM2, and STKs negatively regulated Rho by directly activating moesin. (PMID:20592472)
• The results of the study results indicate that attenuation of SOK1 enhanced cell migration and lead to changes in the expression of migration-associated proteins such as FAK and GM130. (PMID:21396913)
• Significantly higher STK25 levels were observed in the skeletal muscle of type 2 diabetic patients, compared with individuals with normal glucose tolerance. (PMID:22391949)
• PDCD10 might be a regulatory adaptor required for STK25 functions, which differ distinctly depending on the redox status of the cells that may be potentially related to tumor progression. (PMID:22652780)
• Down-modulation of STK25, but not STK24, rescued medulloblastoma cells from NGF-induced TrkA-dependent cell death, suggesting that STK25 is part of the death-signaling pathway initiated by TrkA and CCM2. (PMID:22782892)
• This review notes that all 3 human germinal center kinase III genes consist of 12 exons and are ubiquitously expressed. In SOK1 and MST4, exon 1 encodes a 5’ untranslated region, but this is not the case for MST3. (PMID:23889253)
• Our results suggest that MST4, STK25 and PDCD10 are upregulated in prostate cancer and may play roles in prostate tumorigenesis. (PMID:25550858)
• STK25 regulates lipid partitioning in human liver cells by controlling TAG synthesis as well as lipolytic activity and thereby NEFA release from lipid droplets for beta-oxidation and TAG secretion. (PMID:26553096)
• Our results demonstrated that STK25 negatively regulates the proliferation and glycolysis via GOLPH3-dependent mTOR signaling. Accordingly, STK25 could be a potential therapeutic target for the treatment of CRC. (PMID:29996891)
• hYSK1 blocks the p21(WAF1/Cip1) functions by direct interaction and inhibits the p16(INK4a) expression and induces MMP-2 expression by its regulations of SP-1 transcriptional activity under the hypoxia conditions. (PMID:30646538)
• Loss of STK25 promotes YAP/TAZ activation and enhanced cellular proliferation, even under normally growth-suppressive conditions both in vitro and in vivo. (PMID:30948712)
• STK25 suppresses Hippo signaling by regulating SAV1-STRIPAK antagonism. (PMID:32292165)
• Depletion of protein kinase STK25 ameliorates renal lipotoxicity and protects against diabetic kidney disease. (PMID:33170807)
• Antagonizing STK25 Signaling Suppresses the Development of Hepatocellular Carcinoma Through Targeting Metabolic, Inflammatory, and Pro-Oncogenic Pathways. (PMID:34624527)
• Loss of serine/threonine protein kinase 25 in retinal ganglion cells ameliorates high glucose-elicited damage through regulation of the AKT-GSK-3beta/Nrf2 pathway. (PMID:35217361)
• Downregulation of STK25 promotes autophagy via the Janus kinase 2/signal transducer and activator of transcription 3 pathway in colorectal cancer. (PMID:35349179)
• STK25 inhibits PKA signaling by phosphorylating PRKAR1A. (PMID:35977512)
• STK25: a viable therapeutic target for cancer treatments? (PMID:36728989)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stk25a	ENSDARG00000002210
danio_rerio	stk25b	ENSDARG00000039022
mus_musculus	Stk25	ENSMUSG00000026277
rattus_norvegicus	Stk25	ENSRNOG00000018181
drosophila_melanogaster	GckIII	FBGN0266465

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), PAK3 (ENSG00000077264), STRADB (ENSG00000082146), MAP3K1 (ENSG00000095015), STK4 (ENSG00000101109), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), 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 25 — O00506 (reviewed: O00506)

Alternative names: Ste20-like kinase, Sterile 20/oxidant stress-response kinase 1

All UniProt accessions (15): O00506, A0A024R4B2, A0A0S2Z4Y2, C9J232, C9J6L2, C9J8E8, C9JCC0, C9JDH9, C9JFA1, C9JIH8, C9JJV0, C9JN58, C9K0M6, E7EM58, H7C279

UniProt curated annotations — full annotation on UniProt →

Function. Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress. Targets to the Golgi apparatus where it appears to regulate protein transport events, cell adhesion, and polarity complexes important for cell migration. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation.

Subunit / interactions. Homodimer. Interacts with CTTNBP2NL. Part of the core of STRIPAK complexes composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26. Interacts with TAOK3 (via N-terminus); the interaction promotes STK25 abundance at the level of protein expression and/or stability.

Subcellular location. Cytoplasm. Golgi apparatus.

Tissue specificity. Ubiquitously expressed. Highest levels are found in testis, large intestine, brain and stomach followed by heart and lung.

Activity regulation. Interaction with Golgi matrix protein GOLGA2 leads to autophosphorylation on Thr-174, possibly as a consequence of stabilization of dimer formation. The C-terminal non-catalytic region inhibits the kinase activity.

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

Isoforms (3)

UniProt ID	Names	Canonical?
O00506-1	1	yes
O00506-2	2
O00506-3	3

RefSeq proteins (9): NP_001258906, NP_001258907, NP_001258908, NP_001258909, NP_001269234, NP_001269235, NP_001269236, NP_001269237, NP_006365 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR035060	STK_STK25	Domain
IPR046409	PDC10_dimerisation_sf	Homologous_superfamily
IPR048288	PDCD10_N	Domain
IPR050629	STE20/SPS1-PAK	Family

Pfam: PF00069, PF20929

Catalyzed reactions (Rhea), 2 shown:

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

UniProt features (51 total): helix 21, strand 8, turn 7, splice variant 2, mutagenesis site 2, binding site 2, modified residue 2, chain 1, domain 1, sequence variant 1, sequence conflict 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7Z4V	X-RAY DIFFRACTION	1.64
2XIK	X-RAY DIFFRACTION	1.97
3W8H	X-RAY DIFFRACTION	2.43
4NZW	X-RAY DIFFRACTION	3.58

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00506-F1	80.19	0.53

Functional residue map

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

Catalytic / active sites (1): 140 (proton acceptor)

Ligand- & substrate-binding residues (2): 26–34; 49

Post-translational modifications (2): 174, 278

Mutagenesis-validated functional residues (2):

Position	Phenotype
49	loss of kinase activity and autophosphorylation.
158	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 175 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, SASSON_RESPONSE_TO_FORSKOLIN_DN

GO Biological Process (14): protein phosphorylation (GO:0006468), response to oxidative stress (GO:0006979), establishment or maintenance of cell polarity (GO:0007163), signal transduction (GO:0007165), axonogenesis (GO:0007409), positive regulation of stress-activated MAPK cascade (GO:0032874), cellular response to oxidative stress (GO:0034599), intracellular signal transduction (GO:0035556), intrinsic apoptotic signaling pathway in response to hydrogen peroxide (GO:0036481), protein autophosphorylation (GO:0046777), positive regulation of axonogenesis (GO:0050772), Golgi localization (GO:0051645), establishment of Golgi localization (GO:0051683), Golgi reassembly (GO:0090168)

GO Molecular Function (10): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (4): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), extracellular exosome (GO:0070062), FAR/SIN/STRIPAK complex (GO:0090443)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
intracellular anatomical structure	2
protein kinase activity	2
phosphorylation	1
protein modification process	1
response to stress	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
regulation of stress-activated MAPK cascade	1
positive regulation of MAPK cascade	1
stress-activated MAPK cascade	1
positive regulation of stress-activated protein kinase signaling cascade	1
response to oxidative stress	1
cellular response to chemical stress	1
signal transduction	1
intrinsic apoptotic signaling pathway in response to oxidative stress	1
hydrogen peroxide-mediated programmed cell death	1
protein phosphorylation	1
axonogenesis	1
positive regulation of cell projection organization	1
positive regulation of neurogenesis	1
regulation of axonogenesis	1
organelle localization	1
Golgi localization	1
establishment of localization in cell	1
establishment of organelle localization	1
Golgi organization	1
cellular component assembly	1
Golgi inheritance	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
identical protein binding	1

Protein interactions and networks

STRING

1436 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK25	PDCD10	Q9BUL8	997
STK25	MOB4	Q9Y3A3	952
STK25	GOLGA2	Q08379	941
STK25	STRIP1	Q5VSL9	899
STK25	STRN	O43815	889
STK25	STK26	Q9P289	883
STK25	STK24	Q9Y6E0	857
STK25	STRIP2	Q9ULQ0	853
STK25	KRIT1	O00522	847
STK25	GOLPH3	Q9H4A6	838
STK25	CAB39	Q9Y376	837
STK25	CCM2	Q9BSQ5	804
STK25	STRADA	Q7RTN6	764
STK25	GORASP1	Q9BQQ3	734
STK25	STRN4	Q9NRL3	715

IntAct

132 interactions, top by confidence:

A	B	Type	Score
PDCD10	STK25	psi-mi:“MI:0915”(physical association)	0.980
STK25	PDCD10	psi-mi:“MI:0915”(physical association)	0.980
PDCD10	STK25	psi-mi:“MI:0914”(association)	0.980
STK25	PDCD10	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
PDCD10	STK25	psi-mi:“MI:0407”(direct interaction)	0.980
GOLGA2	STK25	psi-mi:“MI:0915”(physical association)	0.960
STK25	GOLGA2	psi-mi:“MI:0915”(physical association)	0.960

BioGRID (228): STK25 (Two-hybrid), STK25 (Two-hybrid), PDCD10 (Two-hybrid), CCNDBP1 (Two-hybrid), CEP70 (Two-hybrid), CCDC36 (Two-hybrid), STK25 (Two-hybrid), STK25 (Affinity Capture-MS), STK25 (Affinity Capture-MS), ACAD11 (Affinity Capture-MS), STK26 (Affinity Capture-MS), STK24 (Affinity Capture-MS), STRN (Affinity Capture-MS), STRN3 (Affinity Capture-MS), PDCD10 (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

7 interactions.

A	Effect	B	Mechanism
STK25	unknown	PDCD10	phosphorylation
PTPN13	“down-regulates activity”	STK25	dephosphorylation
STK25	up-regulates	CCM2	phosphorylation
STK25	“down-regulates activity”	SAV1	phosphorylation
STK25	“up-regulates activity”	YAP1	phosphorylation
STK25	“up-regulates activity”	LAT	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3110 predictions. Top by Δscore:

Variant	Effect	Δscore
2:241492927:A:AG	acceptor_gain	1.0000
2:241492928:G:GG	acceptor_gain	1.0000
2:241493287:TTGCA:T	acceptor_loss	1.0000
2:241493288:TGCA:T	acceptor_loss	1.0000
2:241493289:GCAG:G	acceptor_loss	1.0000
2:241493290:CA:C	acceptor_loss	1.0000
2:241493291:A:AG	acceptor_gain	1.0000
2:241493291:AG:A	acceptor_gain	1.0000
2:241493291:AGGAT:A	acceptor_gain	1.0000
2:241493292:G:A	acceptor_loss	1.0000
2:241493292:G:GT	acceptor_gain	1.0000
2:241493292:GG:G	acceptor_gain	1.0000
2:241493292:GGAT:G	acceptor_gain	1.0000
2:241493292:GGATG:G	acceptor_gain	1.0000
2:241493427:C:T	donor_gain	1.0000
2:241493442:AAGG:A	donor_loss	1.0000
2:241493443:AGGT:A	donor_loss	1.0000
2:241493444:GGT:G	donor_loss	1.0000
2:241493445:G:C	donor_loss	1.0000
2:241493446:T:A	donor_loss	1.0000
2:241496397:CCT:C	donor_gain	1.0000
2:241496535:C:CC	acceptor_gain	1.0000
2:241497610:CCTCA:C	donor_loss	1.0000
2:241497611:CTCA:C	donor_loss	1.0000
2:241497612:TCA:T	donor_loss	1.0000
2:241497613:CACCT:C	donor_loss	1.0000
2:241497684:CAGG:C	acceptor_gain	1.0000
2:241497685:AGGCT:A	acceptor_loss	1.0000
2:241497687:GCTGC:G	acceptor_loss	1.0000
2:241497688:C:CC	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000073223 (2:241503142 C>T), RS1000129235 (2:241504589 G>C), RS1000319625 (2:241508972 G>C), RS1000386076 (2:241511427 G>A,C), RS1000532668 (2:241492206 C>T), RS1000569589 (2:241496759 C>T), RS1000669633 (2:241502054 C>G,T), RS1000677131 (2:241507026 C>A,G,T), RS1000742053 (2:241511132 T>G), RS1000883518 (2:241504829 G>A), RS1000896900 (2:241495403 C>T), RS1001304653 (2:241505920 G>A), RS1001387383 (2:241510230 C>T), RS1001431796 (2:241505901 C>G,T), RS1001729881 (2:241509930 C>G)

Disease associations

OMIM: gene MIM:602255 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001942_6	Prostate cancer	5.000000e-09
GCST004785_21	Vitiligo	4.000000e-09
GCST007932_80	Medication use (thyroid preparations)	6.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009933	Thyroid preparation use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5552 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

18 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 147,367 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL180022	NERATINIB	4	9,404
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL475251	R-406	2	762
CHEMBL495727	AT-9283	2	1,376
CHEMBL558752	RAF-265	2	2,721
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL607707	PELITINIB	2	6,340
CHEMBL1908397	KW-2449	1	622
CHEMBL574738	AST-487	1	451

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — YSK subfamily

Binding affinities (BindingDB)

9 measured of 9 human assays (9 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
(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
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

ChEMBL bioactivities

48 potent at pChembl≥5 of 48 total, top 37 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.72	IC50	1.9	nM	STAUROSPORINE
8.62	IC50	2.41	nM	STAUROSPORINE
8.57	IC50	2.71	nM	STAUROSPORINE
8.40	IC50	3.98	nM	STAUROSPORINE
7.92	IC50	12	nM	CHEMBL3943675
7.92	Kd	12	nM	NERATINIB
7.47	IC50	34	nM	CHEMBL3770443
7.01	Kd	97	nM	LESTAURTINIB
6.96	Kd	110	nM	STAUROSPORINE
6.68	IC50	211	nM	CHEMBL5276146
6.64	IC50	228	nM	CHEMBL5276146
6.54	Kd	290	nM	SUNITINIB
6.44	Kd	360	nM	JNJ-7706621
6.44	Kd	360	nM	SU-014813
6.35	Kd	444	nM	CHEMBL4465866
6.35	Kd	443	nM	CHEMBL4576489
6.34	IC50	460	nM	AT-9283
6.21	IC50	616	nM	CHEMBL5278528
6.06	IC50	865	nM	CHEMBL5286173
6.05	Kd	900	nM	BOSUTINIB
6.00	IC50	1000	nM	TP-030n
5.92	Kd	1200	nM	AST-487
5.92	Kd	1200	nM	DOVITINIB
5.75	Kd	1800	nM	MIDOSTAURIN
5.57	Kd	2700	nM	CHEMBL386051
5.51	Kd	3100	nM	CHEMBL1908395
5.47	Kd	3400	nM	PELITINIB
5.47	Kd	3400	nM	DASATINIB
5.37	Kd	4300	nM	KW-2449
5.32	Kd	4800	nM	TOZASERTIB
5.29	IC50	5160	nM	CHEMBL5279218
5.24	Kd	5700	nM	FORETINIB
5.20	Kd	6300	nM	RUXOLITINIB
5.17	Kd	6800	nM	RAF-265
5.14	Kd	7200	nM	FEDRATINIB
5.11	Kd	7700	nM	TAE-684
5.04	Kd	9200	nM	R-406

PubChem BioAssay actives

46 with measured affinity, of 507 total; 31 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	1612689: Inhibition of human STK25 using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.0019	uM
N-(5-tert-butyl-1H-pyrazol-3-yl)-4-methyl-3-[4-(5-morpholin-4-yl-3-pyridinyl)triazol-1-yl]benzamide	1921623: Inhibition of STK25 (unknown origin)	ic50	0.0120	uM
Neratinib	625059: Binding constant for YSK1 kinase domain	kd	0.0120	uM
8-[(5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one	1280642: Inhibition of human recombinant YSK1	ic50	0.0340	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	508135: Binding affinity to YSK1	kd	0.0970	uM
N-(5-tert-butyl-1H-pyrazol-3-yl)-4-pyrrolidin-1-ylsulfonylbenzamide	1921625: Inhibition of STK25 (unknown origin) by cellular target engagement assay	ic50	0.2110	uM
Sunitinib	435329: Binding constant for YSK1 kinase domain	kd	0.2900	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435329: Binding constant for YSK1 kinase domain	kd	0.3600	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435329: Binding constant for YSK1 kinase domain	kd	0.3600	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	1526242: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged STK25 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.4430	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	1526242: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged STK25 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.4440	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	1921623: Inhibition of STK25 (unknown origin)	ic50	0.4600	uM
4-butoxy-N-(5-tert-butyl-1H-pyrazol-3-yl)benzamide	1921624: Inhibition of STK25 (unknown origin) by FRET assay	ic50	0.6160	uM
N-(5-tert-butyl-1H-pyrazol-3-yl)-4-(cyclopentylsulfamoyl)benzamide	1921624: Inhibition of STK25 (unknown origin) by FRET assay	ic50	0.8650	uM
Bosutinib	625059: Binding constant for YSK1 kinase domain	kd	0.9000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435329: Binding constant for YSK1 kinase domain	kd	1.2000	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435329: Binding constant for YSK1 kinase domain	kd	1.2000	uM
Midostaurin	435329: Binding constant for YSK1 kinase domain	kd	1.8000	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625059: Binding constant for YSK1 kinase domain	kd	2.7000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625059: Binding constant for YSK1 kinase domain	kd	3.1000	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	625059: Binding constant for YSK1 kinase domain	kd	3.4000	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	435329: Binding constant for YSK1 kinase domain	kd	3.4000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625059: Binding constant for YSK1 kinase domain	kd	4.3000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435329: Binding constant for YSK1 kinase domain	kd	4.8000	uM
N-(5-tert-butyl-1H-pyrazol-3-yl)-4-(pyrrolidine-1-carbonyl)benzamide	1921624: Inhibition of STK25 (unknown origin) by FRET assay	ic50	5.1600	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625059: Binding constant for YSK1 kinase domain	kd	5.7000	uM
Ruxolitinib	625059: Binding constant for YSK1 kinase domain	kd	6.3000	uM
1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	625059: Binding constant for YSK1 kinase domain	kd	6.8000	uM
Fedratinib	625059: Binding constant for YSK1 kinase domain	kd	7.2000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625059: Binding constant for YSK1 kinase domain	kd	7.7000	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625059: Binding constant for YSK1 kinase domain	kd	9.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression	3
bisphenol A	decreases expression, increases methylation	2
Vehicle Emissions	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
cerous chloride	affects cotreatment, decreases expression	1
lanthanum chloride	affects cotreatment, decreases expression	1
cadmium sulfide	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
monomethylarsonous acid	decreases expression	1
fenpyroximate	decreases expression	1
pyrachlostrobin	decreases expression	1
jinfukang	increases expression	1
picoxystrobin	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Aerosols	decreases expression	1
Antimycin A	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases expression	1
Cannabidiol	increases expression	1

ChEMBL screening assays

211 unique, capped per target: 211 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1049985	Binding	Inhibition of STK25 at 2 uM	Discovery of potent and selective inhibitors of the mammalian target of rapamycin (mTOR) kinase. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TQ80	HAP1 STK25 (-) 1	Cancer cell line	Male
CVCL_TQ81	HAP1 STK25 (-) 2	Cancer cell line	Male
CVCL_TQ82	HAP1 STK25 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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