STK39

Summary

STK39 (serine/threonine kinase 39, HGNC:17717) is a protein-coding gene on chromosome 2q24.3, encoding STE20/SPS1-related proline-alanine-rich protein kinase (Q9UEW8). Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure.

This gene encodes a serine/threonine kinase that is thought to function in the cellular stress response pathway. The kinase is activated in response to hypotonic stress, leading to phosphorylation of several cation-chloride-coupled cotransporters. The catalytically active kinase specifically activates the p38 MAP kinase pathway, and its interaction with p38 decreases upon cellular stress, suggesting that this kinase may serve as an intermediate in the response to cellular stress.

Source: NCBI Gene 27347 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 71 total
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_013233

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17717
Approved symbol	STK39
Name	serine/threonine kinase 39
Location	2q24.3
Locus type	gene with protein product
Status	Approved
Aliases	DCHT, SPAK
Ensembl gene	ENSG00000198648
Ensembl biotype	protein_coding
OMIM	607648
Entrez	27347

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000355999, ENST00000461000, ENST00000487143, ENST00000697205, ENST00000940691, ENST00000940692, ENST00000940693, ENST00000940694, ENST00000952313, ENST00000952314, ENST00000952315

RefSeq mRNA: 2 — MANE Select: NM_013233 NM_001410961, NM_013233

CCDS: CCDS42770, CCDS92893

Canonical transcript exons

ENST00000355999 — 18 exons

Exon	Start	End
ENSE00001132252	168140289	168140390
ENSE00001187639	168247228	168247595
ENSE00001650003	168161787	168161842
ENSE00001698332	168163739	168163880
ENSE00001700708	168138088	168138221
ENSE00001715756	168129710	168129758
ENSE00001727466	168181978	168182090
ENSE00001769928	168167299	168167407
ENSE00001797557	168129541	168129606
ENSE00001799196	168140649	168140758
ENSE00003472433	168065319	168065381
ENSE00003526959	168074982	168075011
ENSE00003582963	167954022	167955570
ENSE00003597547	168063500	168063570
ENSE00003625002	168017043	168017095
ENSE00003642410	168012634	168012702
ENSE00003670074	168075109	168075231
ENSE00003684701	167964662	167964726

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.7986 / max 315.7795, expressed in 1675 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31708	4.9808	1534
31707	3.2782	1242
31709	1.8854	1031
31706	1.1116	578
31710	0.6656	309
31705	0.5094	181
31713	0.1494	63
31712	0.1416	50
31711	0.0766	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.84	gold quality
choroid plexus epithelium	UBERON:0003911	98.25	gold quality
pons	UBERON:0000988	97.95	gold quality
parotid gland	UBERON:0001831	97.89	gold quality
palpebral conjunctiva	UBERON:0001812	97.80	gold quality
substantia nigra pars compacta	UBERON:0001965	97.65	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.53	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.52	gold quality
inferior vagus X ganglion	UBERON:0005363	97.45	gold quality
tibia	UBERON:0000979	97.34	gold quality
subthalamic nucleus	UBERON:0001906	96.97	gold quality
superior vestibular nucleus	UBERON:0007227	96.63	gold quality
corpus callosum	UBERON:0002336	96.62	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.56	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.06	gold quality
spinal cord	UBERON:0002240	96.02	gold quality
medulla oblongata	UBERON:0001896	95.99	gold quality
ventricular zone	UBERON:0003053	95.98	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.97	gold quality
lateral globus pallidus	UBERON:0002476	95.91	gold quality
sperm	CL:0000019	95.81	gold quality
esophagus squamous epithelium	UBERON:0006920	95.79	gold quality
orbitofrontal cortex	UBERON:0004167	95.73	gold quality
CA1 field of hippocampus	UBERON:0003881	95.71	gold quality
trachea	UBERON:0003126	95.58	gold quality
postcentral gyrus	UBERON:0002581	95.57	gold quality
parietal lobe	UBERON:0001872	95.50	gold quality
saliva-secreting gland	UBERON:0001044	95.49	gold quality
ventral tegmental area	UBERON:0002691	95.45	gold quality
dorsal root ganglion	UBERON:0000044	95.43	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	1974.91
E-CURD-119	yes	46.75
E-ANND-3	yes	6.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, NFKB1, NFKB, RELA

miRNA regulators (miRDB)

217 targeting STK39, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955

Literature-anchored findings (GeneRIF, showing 40)

• roles in phosphorylation and activation of the Na-K-Cl cotransporter (NKCC1) (PMID:12740379)
• WNK1 and SPAK/OSR1 mediate the hypotonic stress signaling pathway to cation-chloride-coupled cotransporters (PMID:16263722)
• data establish that the CCT domain functions as a multipurpose docking site, enabling SPAK/OSR1 to interact with substrates (NKCC1) and activators (WNK1/WNK4) (PMID:16669787)
• TNF-related apoptosis-inducing ligand down-regulation of SPAK is an important event that enhances its apoptotic effects (PMID:16950202)
• The WNK1-SPAK/OSR1 signalling pathway plays a key role in controlling the phosphorylation and activity of NCC. (PMID:18270262)
• evidence for linkage and association between autism and loci within the 2q24-q33 region, including at STK39 (PMID:18348195)
• PKCdelta acts upstream of SPAK to increase activity of NKCC1 during hyperosmotic stress (PMID:18550547)
• During inflammatory conditions, TNF-alpha is a key regulator of SPAK expression. (PMID:18787102)
• variants in STK39 may influence blood pressure by increasing STK39 expression and consequently altering renal Na(+) excretion (PMID:19114657)
• data suggest that SPAK, the transcription of which is regulated by hyperosmolarity, plays an important role in epithelial barrier function (PMID:19343169)
• Brain WNK3 acts in tandem with SPAK, whereas renal WNK3 seems to upregulate NCCT through a SPAK-independent pathway. (PMID:19470686)
• SPAK loss in B-cell lymphomas promotes increased cell survival with DNA damage and provides a potential mechanism for increased resistance to genotoxic stress in cancer. (PMID:19717643)
• STK39 expression is modified by polymorphisms acting in cis and the typed SNPs are associated with allelic expression of this gene, but there is no evidence for an association with blood pressure in a British Caucasian cohort (PMID:20003416)
• phosphorylation-induced activation of NKCC1 by osmotic shrinkage does not involve AMP-activated protein kinase and is likely to be due to STE20/SPS1-related proline/alanine-rich kinase activation (PMID:20442269)
• STK39 is an independent risk factor for hypertension in men and its intragenic single nucleotide polymorphisms can interact and function in the control of blood pressure. (PMID:20889219)
• Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women. (PMID:21178783)
• IRBIT opposes the effects of WNKs and SPAK by recruiting PP1 to the complex to dephosphorylate CFTR and NBCe1-B, restoring their cell surface expression, in addition to stimulating their activities (PMID:21317537)
• Data demonstrate that hypotonic low-chloride conditions that activate the WNK1-SPAK and OSR1 pathway promote phosphorylation of NKCC2 isoforms. (PMID:21321328)
• our results suggest no significant assocation between any of the core autism symptom domains or the four additional previously identified familial features and the rs1807984 SNP on the STK39 gene. (PMID:21442361)
• SPAK increases intestinal epithelial permeability; both SPAK-transfected Caco2-cells and SPAK transgenic mice exhibit loss of intestinal barrier function and homeostasis in inflammatory bowel disease. (PMID:21705622)
• SPAK and OSR1, which are oftencoexpressed in cells can form functional heterodimers. (PMID:23034389)
• study found no evidence that STK39 was associated with hypertension in the Chinese population (PMID:23151749)
• A significant association between STK39 genetic variant rs6749447 and hypertension was found in a Finnish cohort. (PMID:23235358)
• The present meta-analysis confirms the significant association of STK39 polymorphism with susceptibility to hypertension in Europeans and East Asians. (PMID:23527223)
• In Chinese children, no association of CSK rs1378942, MTHFR rs1801133, CYP17A1 rs1004467, STK39 rs3754777 and FGF5 rs16998073 with BP/risk of hypertension. (PMID:23759979)
• Essential hypertension risk conferred by STK39 rs35929607 polymorphism *A/G) was different from that previously reported in a European population. (PMID:23894895)
• SPAK isoforms both inhibit NKCC1 and NKCC2 activity (cation cotransporter)that may be important in renal physiology. (PMID:24133122)
• OSR1 and SPAK integrate signals from osmosensing and survival pathways. (PMID:24191005)
• STK39 (rs2102808) and CCDC62/HIP1R (rs12817488) do not appear to influence PD risk. (PMID:24312176)
• the association of the loci rs11711441 near STK39 and sporadic Parkinson disease in the Chinese Han population is confirmed (PMID:24631562)
• SPAK may promote KCC3-mediated cervix tumor aggressiveness via the NF-kappaB/p38 MAPK/MMP2 axis. (PMID:24655550)
• Taken together, our findings suggest the potential interactive role of STK39 gene multiple polymorphisms in the development of hypertension among northeastern Han Chinese. (PMID:24873805)
• SPAK short forms in the kidney are created by aspartyl aminopeptidase (Dnpep)-mediated proteolytic cleavage (PMID:25164821)
• SPAK and OSR1 are powerful negative regulators of the cell volume regulatory Cl- channel ClC-2 (PMID:25323061)
• study identifies a separation of functions for the WNK1-activated protein kinases OSR1 and SPAK in mediating proliferation, invasion, and gene expression in endothelial cells (PMID:25362046)
• WNK 1, 3, 4, OSR1, and SPAK signaling system known to play a role in regulating the phosphorylation status, and hence activity of the CCCs in other tissues, is also present in the rat and human lenses. (PMID:25515571)
• Both, SPAK and OSR1, are negative regulators of the creatine transporter SLC6A8 (PMID:25531585)
• These observations establish that the CCT domain plays a crucial role in controlling SPAK activity and BP. (PMID:25994507)
• SPAK and OSR1 are negative regulators of EAAT3 activity (PMID:26112741)
• SPAK and OSR1 are powerful negative regulators of the excitatory glutamate transporters EAAT1 and EAAT2. (PMID:26233565)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stk39	ENSDARG00000087203
mus_musculus	Stk39	ENSMUSG00000027030
rattus_norvegicus	Stk39	ENSRNOG00000024808
drosophila_melanogaster	fray	FBGN0023083
caenorhabditis_elegans		WBGENE00013355

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), PAK3 (ENSG00000077264), STRADB (ENSG00000082146), MAP3K1 (ENSG00000095015), STK4 (ENSG00000101109), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), STK25 (ENSG00000115694), NRK (ENSG00000123572), PAK4 (ENSG00000130669), 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), STRADA (ENSG00000266173)

Protein

Protein identifiers

STE20/SPS1-related proline-alanine-rich protein kinase — Q9UEW8 (reviewed: Q9UEW8)

Alternative names: DCHT, Serine/threonine-protein kinase 39

All UniProt accessions (2): A0A8V8TKT5, Q9UEW8

UniProt curated annotations — full annotation on UniProt →

Function. Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure. Specifically recognizes and binds proteins with a RFXV motif. Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity. Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases. Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux. Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4. Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities. Phosphorylates RELT.

Subunit / interactions. The phosphorylated form forms a complex with WNK2. Interacts with SORL1 (via cytosolic C-terminus).

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Predominantly expressed in brain and pancreas followed by heart, lung, kidney, skeletal muscle, liver, placenta and testis.

Post-translational modifications. Phosphorylation at Thr-231 by WNK kinases (WNK1, WNK2, WNK3 or WNK4) is required for activation. Autophosphorylation at Thr-231 positively regulates its activity. Phosphorylated at Ser-309 by PRKCQ.

Activity regulation. Activated following phosphorylation at Thr-231 by WNK kinases (WNK1, WNK2, WNK3 or WNK4). Specifically inhibited by YU239252 (YU252).

Domain organisation. PAPA box (proline-alanine repeats) may target the kinase to a specific subcellular location by facilitating interaction with intracellular proteins such as actin or actin-like proteins.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UEW8-1	1	yes
Q9UEW8-2	2, A

RefSeq proteins (2): NP_001397890, NP_037365* (*=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
IPR024678	Kinase_OSR1/WNK_CCT	Domain
IPR050629	STE20/SPS1-PAK	Family

Pfam: PF00069, PF12202

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 (49 total): mutagenesis site 13, modified residue 9, strand 6, sequence conflict 3, turn 3, helix 3, binding site 2, region of interest 2, short sequence motif 2, compositionally biased region 2, chain 1, domain 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7O86	X-RAY DIFFRACTION	1.73

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UEW8-F1	75.98	0.41

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): 192 (proton acceptor)

Ligand- & substrate-binding residues (2): 92; 69–77

Post-translational modifications (9): 231, 235, 309, 349, 354, 370, 371, 385, 393

Mutagenesis-validated functional residues (13):

Position	Phenotype
92	abolished serine/threonine-protein kinase activity.
231	prevents phosphorylation and activation by wnk kinases.
231	mimics phosphorylation; promoting kinase activity independently of wnk kinases.
371	does not affect activation by wnk kinases.
371	does not greatly affect the kinase activity.
477	abolished binding to wnk1 and slc12a2/nkcc1.
478	decreased binding to slc12a2/nkcc1.
482	decreased binding to slc12a2/nkcc1.
485	decreased binding to slc12a2/nkcc1.
491	abolished binding to wnk1 and slc12a2/nkcc1.
492	decreased binding to slc12a2/nkcc1.
496	decreased binding to slc12a2/nkcc1.
500	decreased binding to slc12a2/nkcc1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 451 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_DIGESTION, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_REGULATION_OF_T_CELL_CHEMOTAXIS, GOBP_NEGATIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_RESPONSE_TO_DIETARY_EXCESS, GOBP_PEPTIDYL_SERINE_MODIFICATION, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_MIGRATION

GO Biological Process (34): response to dietary excess (GO:0002021), protein phosphorylation (GO:0006468), cell volume homeostasis (GO:0006884), inflammatory response (GO:0006954), signal transduction (GO:0007165), regulation of blood pressure (GO:0008217), positive regulation of T cell chemotaxis (GO:0010820), peptidyl-serine phosphorylation (GO:0018105), peptidyl-threonine phosphorylation (GO:0018107), intracellular chloride ion homeostasis (GO:0030644), negative regulation of transmembrane transport (GO:0034763), intracellular signal transduction (GO:0035556), sodium ion transmembrane transport (GO:0035725), cellular response to potassium ion (GO:0035865), maintenance of lens transparency (GO:0036438), chemokine (C-X-C motif) ligand 12 signaling pathway (GO:0038146), macrophage activation (GO:0042116), protein autophosphorylation (GO:0046777), regulation of inflammatory response (GO:0050727), renal sodium ion absorption (GO:0070294), cellular hyperosmotic response (GO:0071474), cellular hypotonic response (GO:0071476), negative regulation of pancreatic juice secretion (GO:0090188), positive regulation of p38MAPK cascade (GO:1900745), negative regulation of potassium ion transmembrane transport (GO:1901380), negative regulation of sodium ion transmembrane transport (GO:1902306), positive regulation of potassium ion import across plasma membrane (GO:1903288), positive regulation of sodium ion import across plasma membrane (GO:1903784), response to aldosterone (GO:1904044), regulation of monoatomic cation transmembrane transport (GO:1904062), cellular response to chemokine (GO:1990869), positive regulation of potassium ion transport (GO:0043268), monoatomic ion homeostasis (GO:0050801), potassium ion transmembrane transport (GO:0071805)

GO Molecular Function (14): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), kinase activity (GO:0016301), potassium channel inhibitor activity (GO:0019870), protein kinase binding (GO:0019901), transmembrane transporter binding (GO:0044325), ion channel regulator activity (GO:0099106), protein serine kinase activity (GO:0106310), transporter activator activity (GO:0141109), transporter inhibitor activity (GO:0141110), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (9): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cell cortex (GO:0005938), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), cell body (GO:0044297), nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein phosphorylation	3
intracellular anatomical structure	2
protein kinase activity	2
transporter activity	2
transporter regulator activity	2
cytoplasm	2
plasma membrane region	2
response to nutrient levels	1
energy homeostasis	1
phosphorylation	1
protein modification process	1
regulation of cell size	1
cellular homeostasis	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
blood circulation	1
regulation of biological quality	1
T cell chemotaxis	1
regulation of T cell chemotaxis	1
positive regulation of lymphocyte chemotaxis	1
positive regulation of T cell migration	1
peptidyl-serine modification	1
peptidyl-threonine modification	1
intracellular monoatomic anion homeostasis	1
chloride ion homeostasis	1
regulation of transmembrane transport	1
negative regulation of cellular process	1
negative regulation of transport	1
transmembrane transport	1
signal transduction	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
response to potassium ion	1
cellular response to metal ion	1
tissue homeostasis	1

Protein interactions and networks

STRING

1030 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK39	SLC12A1	Q13621	930
STK39	SLC12A2	P55011	918
STK39	SLC12A3	P55017	904
STK39	SLC12A6	Q9UHW9	885
STK39	KCNJ1	P48048	846
STK39	CAB39	Q9Y376	790
STK39	PHF12	Q96QT6	780
STK39	KLHL3	Q9UH77	779
STK39	SLC12A5	Q9H2X9	736
STK39	WNK1	P54963	710
STK39	KCNMA1	Q12791	704
STK39	CCDC62	Q6P9F0	693
STK39	SLC12A4	Q9UP95	657
STK39	SLC12A7	Q9Y666	655
STK39	ACMSD	Q8TDX5	653

IntAct

82 interactions, top by confidence:

A	B	Type	Score
RELL2	OXSR1	psi-mi:“MI:0914”(association)	0.830
EIF4E	EIF4G3	psi-mi:“MI:0914”(association)	0.810
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TOMM22	XRCC3	psi-mi:“MI:0914”(association)	0.640
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
RELT	OXSR1	psi-mi:“MI:0914”(association)	0.640
SLC12A2	CLGN	psi-mi:“MI:0914”(association)	0.640
SLC12A6	STK39	psi-mi:“MI:0915”(physical association)	0.560
STK39	CAB39	psi-mi:“MI:0407”(direct interaction)	0.540
CAB39	STK39	psi-mi:“MI:0407”(direct interaction)	0.540
CAB39	STK39	psi-mi:“MI:0915”(physical association)	0.540
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
RELL1	TCAF2	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
CHCHD4	ENSA	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
STK39	C2orf49	psi-mi:“MI:0915”(physical association)	0.400
CD46	STK39	psi-mi:“MI:0915”(physical association)	0.400
RHOA	SYNPO2	psi-mi:“MI:0914”(association)	0.350
ARX	MIGA1	psi-mi:“MI:0914”(association)	0.350
ATL2	ACRBP	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
LAMP2	HSPA12A	psi-mi:“MI:0914”(association)	0.350
ST8SIA4	NRP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (121): STK39 (Affinity Capture-MS), STK39 (Affinity Capture-MS), STK39 (Affinity Capture-MS), STK39 (Affinity Capture-MS), STK39 (Affinity Capture-MS), STK39 (Affinity Capture-MS), STK39 (Affinity Capture-MS), STK39 (Two-hybrid), STK39 (Affinity Capture-MS), STK39 (Affinity Capture-MS), STK39 (Affinity Capture-MS), STK39 (Affinity Capture-MS), STK39 (Affinity Capture-MS), STK39 (Affinity Capture-MS), STK39 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C0TYJ0, A0A8I5ZNK2, A2AWA9, A6QQZ7, A8KBF6, O55047, O88506, O95747, P20936, P23727, P26450, P27986, P31016, P78352, Q08CW1, Q08E27, Q12959, Q15139, Q15700, Q1ECX4, Q28C55, Q5PYH5, Q5PYH6, Q5PYH7, Q5R372, Q5R495, Q5R685, Q5R6Y5, Q5RAN1, Q5RCW6, Q5SRX1, Q5T2T1, Q5U2Y3, Q5ZIL4, Q5ZMW5, Q62101, Q62108, Q62696, Q63622, Q68FK8

Diamond homologs: A0A8I5ZNK2, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A8XJW8, B0LT89, F1LP90, F1NBT0, G5EEN4, G5EFU0, G5EGQ3, H2L099, O00506, O14047, O14305, O23304, O24527, O54748, O61122, O61125, O75011, O75914, O88506, O88643, O95747, O95819, O96013, P08458, P35465, P83510, Q03497, Q08E52, Q0IHQ8, Q12851, Q13043, Q13153

SIGNOR signaling

28 interactions.

A	Effect	B	Mechanism
STK39	up-regulates	MAPK14	binding
WNK1	up-regulates	STK39	phosphorylation
AATK	down-regulates	STK39
STK39	“up-regulates activity”	SLC12A1	phosphorylation
STK39	“down-regulates activity”	SLC4A4	phosphorylation
STK39	“down-regulates activity”	CFTR	phosphorylation
STK39	“up-regulates activity”	SNAI1	phosphorylation
STK39	“down-regulates activity”	SLC12A3	phosphorylation
WNK4	“up-regulates activity”	STK39	phosphorylation
STK39	“up-regulates activity”	SLC12A2	phosphorylation
PRKCQ	“up-regulates activity”	STK39	phosphorylation
STK39	“down-regulates activity”	SLC12A6	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
cell volume homeostasis	5	29.2×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4582 predictions. Top by Δscore:

Variant	Effect	Δscore
2:167964478:T:TA	donor_gain	1.0000
2:168012707:CCAAA:C	acceptor_gain	1.0000
2:168012708:C:CT	acceptor_gain	1.0000
2:168012708:C:T	acceptor_gain	1.0000
2:168012711:A:AC	acceptor_gain	1.0000
2:168012711:A:C	acceptor_gain	1.0000
2:168017036:AACTT:A	donor_loss	1.0000
2:168017037:ACTT:A	donor_loss	1.0000
2:168017038:CTT:C	donor_loss	1.0000
2:168017039:TTA:T	donor_loss	1.0000
2:168017040:TA:T	donor_loss	1.0000
2:168017041:A:AC	donor_gain	1.0000
2:168017042:C:CC	donor_gain	1.0000
2:168017042:C:CG	donor_loss	1.0000
2:168017042:CCT:C	donor_gain	1.0000
2:168017093:TTT:T	acceptor_gain	1.0000
2:168017094:TT:T	acceptor_gain	1.0000
2:168017095:TCTG:T	acceptor_loss	1.0000
2:168017096:C:CC	acceptor_gain	1.0000
2:168017096:C:T	acceptor_loss	1.0000
2:168017097:TGAAA:T	acceptor_loss	1.0000
2:168037783:ATT:A	donor_gain	1.0000
2:168063495:TTTA:T	donor_loss	1.0000
2:168063496:TTA:T	donor_loss	1.0000
2:168063497:TAC:T	donor_loss	1.0000
2:168063498:A:T	donor_loss	1.0000
2:168063499:C:CA	donor_loss	1.0000
2:168063566:GGGCC:G	acceptor_gain	1.0000
2:168063567:GGCC:G	acceptor_gain	1.0000
2:168063568:GCC:G	acceptor_gain	1.0000

AlphaMissense

3573 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:167955515:G:T	A540D	1.000
2:167955517:A:C	F539L	1.000
2:167955517:A:T	F539L	1.000
2:167955519:A:G	F539L	1.000
2:167955527:A:G	L536P	1.000
2:167964668:A:C	F519L	1.000
2:167964668:A:T	F519L	1.000
2:167964669:A:G	F519S	1.000
2:167964670:A:G	F519L	1.000
2:167964724:C:G	A501P	1.000
2:168012660:A:G	L491S	1.000
2:168012675:A:G	L486P	1.000
2:168012675:A:T	L486H	1.000
2:168017057:A:G	F472S	1.000
2:168017062:A:C	F470L	1.000
2:168017062:A:T	F470L	1.000
2:168017063:A:G	F470S	1.000
2:168017064:A:G	F470L	1.000
2:168017069:A:T	I468K	1.000
2:168075169:C:A	W384C	1.000
2:168075169:C:G	W384C	1.000
2:168075171:A:G	W384R	1.000
2:168075171:A:T	W384R	1.000
2:168075175:C:A	W382C	1.000
2:168075175:C:G	W382C	1.000
2:168075177:A:G	W382R	1.000
2:168075177:A:T	W382R	1.000
2:168129741:A:G	L331P	1.000
2:168129758:C:A	R325S	1.000
2:168129758:C:G	R325S	1.000

dbSNP variants (sampled 300 via entrez): RS1000002797 (2:168101286 C>G), RS1000005247 (2:168080139 A>G), RS1000007473 (2:168039295 T>C), RS1000008918 (2:168086038 T>A), RS1000015068 (2:167981049 G>GT), RS1000030306 (2:168005248 T>C), RS1000040230 (2:168005008 T>C,G), RS1000044112 (2:168127682 A>T), RS1000044315 (2:168045450 A>C), RS1000070093 (2:168248810 C>T), RS1000075006 (2:168225225 C>T), RS1000085557 (2:167958346 C>T), RS1000092355 (2:168169510 T>C), RS1000106824 (2:168086702 T>C), RS1000114676 (2:168145875 C>G,T)

Disease associations

OMIM: gene MIM:607648 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000306_1	Blood pressure	2.000000e-07
GCST000959_8	Parkinson’s disease	4.000000e-10
GCST002544_14	Parkinson’s disease	1.000000e-20
GCST003984_5	Parkinson’s disease	3.000000e-16
GCST004902_43	Parkinson’s disease	6.000000e-26
GCST004904_225	Body mass index	6.000000e-10
GCST004904_253	Body mass index	2.000000e-10
GCST006976_26	Macular thickness	3.000000e-20
GCST008152_164	Weight	7.000000e-06
GCST008158_123	Body mass index	8.000000e-06
GCST009325_38	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	3.000000e-39
GCST009391_715	Metabolite levels	2.000000e-06
GCST010681_4	Type 1 diabetes	3.000000e-09
GCST010991_5	Parkinson’s disease	4.000000e-13
GCST011494_16	Daytime nap	6.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004338	body weight
EFO:0010532	salicylurate measurement
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1163108 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 121,301 (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
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL1908397	KW-2449	1	622
CHEMBL574738	AST-487	1	451

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6749447	Efficacy	3	losartan

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6749447	STK39	3	3.00	1	losartan
rs10497338	STK39		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — FRAY subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
aplithianine A	Inhibition	7.46	pIC50

ChEMBL bioactivities

48 potent at pChembl≥5 of 49 total, top 46 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.84	IC50	14.4	nM	STAUROSPORINE
7.76	IC50	17.2	nM	STAUROSPORINE
7.46	IC50	35	nM	CHEMBL5433617
7.45	IC50	35.4	nM	STAUROSPORINE
7.30	IC50	50	nM	CHEMBL4792789
6.96	IC50	110	nM	CHEMBL4762099
6.89	Kd	130	nM	STAUROSPORINE
6.85	Kd	140	nM	SUNITINIB
6.82	Kd	150	nM	TAE-684
6.62	IC50	240	nM	CHEMBL4759888
6.58	IC50	260	nM	CHEMBL4797256
6.37	Kd	430	nM	SU-014813
6.28	Kd	520	nM	NINTEDANIB
6.28	Kd	530	nM	DOVITINIB
6.19	IC50	650	nM	CHEMBL4751500
6.05	Kd	890	nM	KW-2449
6.00	IC50	1000	nM	CHEMBL4759820
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
5.96	IC50	1100	nM	CHEMBL4753158
5.96	Kd	1100	nM	LESTAURTINIB
5.85	IC50	1400	nM	CHEMBL4750439
5.85	IC50	1400	nM	CHEMBL5205578
5.82	IC50	1500	nM	CHEMBL4783530
5.82	IC50	1500	nM	CHEMBL4758154
5.82	Kd	1500	nM	AST-487
5.80	Kd	1600	nM	FEDRATINIB
5.75	IC50	1800	nM	CHEMBL4747390
5.72	Kd	1900	nM	RUXOLITINIB
5.70	IC50	2000	nM	CHEMBL4793138
5.68	IC50	2100	nM	CHEMBL4744527
5.68	IC50	2100	nM	CHEMBL4748104
5.64	IC50	2300	nM	CHEMBL4795291
5.62	IC50	2400	nM	CHEMBL4757952
5.57	IC50	2700	nM	CHEMBL4748683
5.55	IC50	2800	nM	CHEMBL4757062
5.50	IC50	3200	nM	CHEMBL4796271
5.46	IC50	3500	nM	CHEMBL4762871
5.43	Kd	3700	nM	BOSUTINIB
5.36	IC50	4400	nM	CHEMBL4783506
5.35	IC50	4500	nM	CHEMBL1814047
5.31	IC50	4900	nM	CHEMBL4641560
5.29	IC50	5100	nM	CHEMBL4796688
5.25	IC50	5600	nM	CHEMBL4793886
5.24	IC50	5700	nM	CHEMBL4758811
5.00	Kd	1e+04	nM	CHEMBL4848254

PubChem BioAssay actives

46 with measured affinity, of 211 total; 41 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	1531897: Inhibition of human STK39 using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.0144	uM
6-(3-methylimidazol-4-yl)-4-(7H-purin-6-yl)-2,3-dihydro-1,4-thiazine	2019962: Inhibition of STLK3 (unknown origin)	ic50	0.0350	uM
N-[4-(1-bromonaphthalen-2-yl)oxy-3-chlorophenyl]-2,3-dihydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	0.0500	uM
N-[4-(1-bromonaphthalen-2-yl)oxy-3-chlorophenyl]-2-hydroxy-5-nitrobenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	0.1100	uM
Sunitinib	508098: Binding affinity to STK39	kd	0.1400	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	625071: Binding constant for STK39 kinase domain	kd	0.1500	uM
N-[4-(1-bromonaphthalen-2-yl)oxy-3-chlorophenyl]-2,6-dihydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	0.2400	uM
N-[4-(1-bromonaphthalen-2-yl)oxy-3-chlorophenyl]-3,5-dichloro-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	0.2600	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	625071: Binding constant for STK39 kinase domain	kd	0.4300	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625071: Binding constant for STK39 kinase domain	kd	0.5200	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	625071: Binding constant for STK39 kinase domain	kd	0.5300	uM
3,5-dichloro-N-[3-chloro-4-(3,5-dihydroxyphenoxy)phenyl]-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	0.6500	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625071: Binding constant for STK39 kinase domain	kd	0.8900	uM
3,5-dichloro-N-[3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl]-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	1.0000	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	508098: Binding affinity to STK39	kd	1.1000	uM
3,5-dichloro-N-[3-chloro-4-[2-(trifluoromethyl)phenoxy]phenyl]-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	1.1000	uM
methyl N-[4-[5-[(2S)-2-amino-2,4-dimethylpentoxy]-6-chloro-2-pyridinyl]-2-pyridinyl]carbamate	1904677: Inhibition of STLK3 (unknown origin)	ic50	1.4000	uM
3,5-dichloro-N-[3-chloro-4-(2,4-dichlorophenoxy)phenyl]-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	1.4000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	625071: Binding constant for STK39 kinase domain	kd	1.5000	uM
N-(3-bromo-4-phenoxyphenyl)-3,5-dichloro-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	1.5000	uM
3,5-dichloro-N-(2-chloro-4-phenoxyphenyl)-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	1.5000	uM
Fedratinib	625071: Binding constant for STK39 kinase domain	kd	1.6000	uM
3,5-dichloro-N-(3,5-dichloro-4-phenoxyphenyl)-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	1.8000	uM
Ruxolitinib	625071: Binding constant for STK39 kinase domain	kd	1.9000	uM
3,5-dichloro-N-[3-chloro-4-(2-hydroxyphenoxy)phenyl]-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	2.0000	uM
3,5-dichloro-2-hydroxy-N-(2-hydroxy-4-phenoxyphenyl)benzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	2.1000	uM
N-[4-(1-bromonaphthalen-2-yl)oxy-3-chlorophenyl]-4-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	2.1000	uM
N-[4-(1-bromonaphthalen-2-yl)oxy-3-chlorophenyl]-2-hydroxy-4-(trifluoromethyl)benzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	2.3000	uM
3,5-dichloro-2-hydroxy-N-[4-phenoxy-3-(trifluoromethyl)phenyl]benzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	2.4000	uM
3,5-dichloro-N-[3-chloro-4-(3,5-dichlorophenoxy)phenyl]-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	2.7000	uM
3,5-dichloro-N-[3-chloro-4-(5,6,7,8-tetrahydronaphthalen-2-yloxy)phenyl]-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	2.8000	uM
N-[4-(1-bromonaphthalen-2-yl)oxy-3-chlorophenyl]-2,6-dimethoxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	3.2000	uM
3,5-dichloro-N-[3-chloro-4-(3-hydroxyphenoxy)phenyl]-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	3.5000	uM
Bosutinib	625071: Binding constant for STK39 kinase domain	kd	3.7000	uM
N-[4-(1-bromonaphthalen-2-yl)oxy-3-chlorophenyl]-3-hydroxy-4-methylbenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	4.4000	uM
3,5-dichloro-N-(3-chloro-4-phenoxyphenyl)-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	4.5000	uM
3,5-dichloro-N-[3-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	4.9000	uM
3,5-dichloro-N-[3-chloro-4-(7-hydroxynaphthalen-2-yl)oxyphenyl]-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	5.1000	uM
3,5-dichloro-N-[3-chloro-4-(4-hydroxyphenoxy)phenyl]-2-hydroxybenzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	5.6000	uM
3,5-dichloro-2-hydroxy-N-(4-phenoxyphenyl)benzamide	1722045: Inhibition of SPAK (unknown origin) by ELISA	ic50	5.7000	uM
N,N-dimethyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine	1752108: Binding affinity to wild-type human partial length STK39 (P43 to I357 residues) expressed in mammalian expression system measured after 1 hr by competitive binding assay	kd	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	5
bisphenol A	increases expression, decreases expression	2
sodium arsenite	affects methylation, affects cotreatment, increases abundance, increases expression	2
cobaltous chloride	decreases expression	2
Arsenic	increases expression, affects methylation, affects cotreatment, increases abundance	2
Cisplatin	decreases expression, affects cotreatment, increases expression	2
Doxorubicin	affects cotreatment, affects expression, decreases expression	2
Estradiol	increases expression, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Dihydrotestosterone	decreases reaction, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Valproic Acid	affects expression, increases expression	2
Metribolone	increases expression, decreases reaction	2
Genistein	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
daidzein	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
salinomycin	decreases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1

ChEMBL screening assays

136 unique, capped per target: 136 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1167713	Binding	Inhibition of STK39 at 1 uM	Synthesis and structure-activity relationships of 1,2,3,4-tetrahydropyrido[2,3-b]pyrazines as potent and selective inhibitors of the anaplastic lymphoma kinase. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D6C7	HyCyte MDA-MB-231 KO-hSTK39	Cancer cell line	Female
CVCL_E1NA	HyCyte U-251MG KO-hSTK39	Cancer cell line	Male
CVCL_TQ92	HAP1 STK39 (-) 1	Cancer cell line	Male
CVCL_TQ93	HAP1 STK39 (-) 2	Cancer cell line	Male
CVCL_TQ94	HAP1 STK39 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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