TAOK3

Summary

TAOK3 (TAO kinase 3, HGNC:18133) is a protein-coding gene on chromosome 12q24.23, encoding Serine/threonine-protein kinase TAO3 (Q9H2K8). Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade.

The protein encoded by this gene is a serine/threonine protein kinase that activates the p38/MAPK14 stress-activated MAPK cascade but inhibits the basal activity of the MAPK8/JNK cascade. The encoded protein is a member of the GCK subfamily of STE20-like kinases.

Source: NCBI Gene 51347 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 115 total
• Druggable target: yes — 44 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016281

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18133
Approved symbol	TAOK3
Name	TAO kinase 3
Location	12q24.23
Locus type	gene with protein product
Status	Approved
Aliases	JIK, DPK, MAP3K18
Ensembl gene	ENSG00000135090
Ensembl biotype	protein_coding
OMIM	616711
Entrez	51347

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 22 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000392533, ENST00000419821, ENST00000535570, ENST00000536584, ENST00000536979, ENST00000537305, ENST00000537569, ENST00000537822, ENST00000537952, ENST00000538601, ENST00000539872, ENST00000540561, ENST00000541186, ENST00000541786, ENST00000541878, ENST00000542532, ENST00000542692, ENST00000542902, ENST00000543709, ENST00000894342, ENST00000894343, ENST00000894344, ENST00000967759, ENST00000967760, ENST00000967761, ENST00000967762, ENST00000967763

RefSeq mRNA: 12 — MANE Select: NM_016281 NM_001346487, NM_001346488, NM_001346489, NM_001346490, NM_001346491, NM_001346492, NM_001346493, NM_001346494, NM_001346495, NM_001346496, NM_001346497, NM_016281

CCDS: CCDS86334, CCDS9188

Canonical transcript exons

ENST00000392533 — 21 exons

Exon	Start	End
ENSE00001428454	118266655	118266759
ENSE00001429115	118372648	118372907
ENSE00001512311	118149801	118151158
ENSE00002337841	118244894	118244965
ENSE00002415025	118243415	118243516
ENSE00002726077	118255448	118255655
ENSE00003491768	118152227	118152409
ENSE00003494060	118239227	118239272
ENSE00003514710	118235558	118235671
ENSE00003536445	118161788	118162027
ENSE00003561954	118177201	118177329
ENSE00003565970	118214017	118214110
ENSE00003573233	118181371	118181607
ENSE00003593999	118189807	118189941
ENSE00003623573	118212914	118212995
ENSE00003642384	118238073	118238169
ENSE00003652364	118233674	118233765
ENSE00003656723	118172457	118172660
ENSE00003659146	118160146	118160358
ENSE00003665112	118201296	118201463
ENSE00003686461	118199051	118199257

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.5643 / max 1279.2337, expressed in 1811 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133557	24.5433	1805
133553	4.0243	609
133556	2.8914	283
133550	1.2417	389
133545	1.0238	347
133552	0.5325	219
133554	0.4521	66
133551	0.4519	170
133546	0.3823	139
133555	0.3433	170

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.64	gold quality
oocyte	CL:0000023	97.78	gold quality
monocyte	CL:0000576	96.14	gold quality
mononuclear cell	CL:0000842	96.12	gold quality
leukocyte	CL:0000738	95.82	gold quality
jejunal mucosa	UBERON:0000399	95.75	gold quality
colonic epithelium	UBERON:0000397	95.57	gold quality
bone marrow cell	CL:0002092	95.17	gold quality
superior vestibular nucleus	UBERON:0007227	94.98	gold quality
middle temporal gyrus	UBERON:0002771	94.91	gold quality
lateral globus pallidus	UBERON:0002476	94.76	gold quality
globus pallidus	UBERON:0001875	94.59	gold quality
medial globus pallidus	UBERON:0002477	94.55	gold quality
corpus callosum	UBERON:0002336	94.54	gold quality
inferior vagus X ganglion	UBERON:0005363	94.40	gold quality
cerebellar hemisphere	UBERON:0002245	94.33	gold quality
cerebellar cortex	UBERON:0002129	94.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.23	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.22	gold quality
lower lobe of lung	UBERON:0008949	94.18	gold quality
subthalamic nucleus	UBERON:0001906	93.95	gold quality
ventral tegmental area	UBERON:0002691	93.83	gold quality
cerebellum	UBERON:0002037	93.71	gold quality
substantia nigra pars compacta	UBERON:0001965	93.59	gold quality
medulla oblongata	UBERON:0001896	93.50	gold quality
sural nerve	UBERON:0015488	93.26	gold quality
blood	UBERON:0000178	93.21	gold quality
tendon of biceps brachii	UBERON:0008188	93.21	gold quality
amygdala	UBERON:0001876	93.16	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.07	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	290.18
E-HCAD-4	yes	61.93
E-MTAB-9067	yes	26.99
E-ANND-3	yes	17.10
E-CURD-112	yes	5.53
E-MTAB-7606	no	926.47
E-GEOD-99795	no	170.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

131 targeting TAOK3, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-9983-3P	99.94	71.48	3631

Literature-anchored findings (GeneRIF, showing 10)

• Results show that three CpG loci within FYN were hypermethylated in obese individuals, while obesity was associated with lower methylation of CpG loci within PIWIL4 and TAOK3. (PMID:26646899)
• TAOK3 SNPs (rs1277441 and rs795484) were associated with opioid doses in advanced cancer patients receiving palliative care. The proportions of variant homozygotes (8.2% of patients) and their requirement for higher doses of opioids would appear potentially clinically important and should be validated in further studies. (PMID:30031856)
• TAOK3 is a positive regulator of TCR signaling by preventing premature SHP-1-mediated inactivation of LCK (PMID:30373850)
• TAOK3 is a MAP3K contributing to osteoblast differentiation and skeletal mineralization. (PMID:32807497)
• Kinase shRNA screening reveals that TAOK3 enhances microtubule-targeted drug resistance of breast cancer cells via the NF-kappaB signaling pathway. (PMID:33087151)
• Serine-Threonine Kinase TAO3-Mediated Trafficking of Endosomes Containing the Invadopodia Scaffold TKS5alpha Promotes Cancer Invasion and Tumor Growth. (PMID:33414172)
• The STE20 kinase TAOK3 controls the development of house dust mite-induced asthma in mice. (PMID:34506849)
• STE20-type kinase TAOK3 regulates hepatic lipid partitioning. (PMID:34634521)
• TAOK3 Facilitates Esophageal Squamous Cell Carcinoma Progression and Cisplatin Resistance Through Augmenting Autophagy Mediated by IRGM. (PMID:37705061)
• The induction of SHP-1 degradation by TAOK3 ensures the responsiveness of T cells to TCR stimulation. (PMID:38166031)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	taok3a	ENSDARG00000060751
danio_rerio	taok3b	ENSDARG00000094052
mus_musculus	Taok3	ENSMUSG00000061288
rattus_norvegicus	Taok3	ENSRNOG00000001138

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), 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 TAO3 — Q9H2K8 (reviewed: Q9H2K8)

Alternative names: Cutaneous T-cell lymphoma-associated antigen HD-CL-09, Dendritic cell-derived protein kinase, JNK/SAPK-inhibitory kinase, Jun kinase-inhibitory kinase, Kinase from chicken homolog A, Thousand and one amino acid protein 3

All UniProt accessions (13): Q9H2K8, F5GWV8, F5GX96, F5GY38, F5H005, F5H0M3, F5H1I2, F5H3L7, F5H5C7, F5H5E0, F5H7G4, G3V1Q8, H0YF68

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Inhibits basal activity of the MAPK8/JNK cascade and diminishes its activation in response to epidermal growth factor (EGF). Positively regulates canonical T cell receptor (TCR) signaling by preventing early PTPN6/SHP1-mediated inactivation of LCK, ensuring sustained TCR signaling that is required for optimal activation and differentiation of T cells. Phosphorylates PTPN6/SHP1 on ‘Thr-394’, leading to its polyubiquitination and subsequent proteasomal degradation. Required for cell surface expression of metalloprotease ADAM10 on type 1 transitional B cells which is necessary for their NOTCH-mediated development into marginal zone B cells. Also required for the NOTCH-mediated terminal differentiation of splenic conventional type 2 dendritic cells. Positively regulates osteoblast differentiation by acting as an upstream activator of the JNK pathway. Promotes JNK signaling in hepatocytes and positively regulates hepatocyte lipid storage by inhibiting beta-oxidation and triacylglycerol secretion while enhancing lipid synthesis. Restricts age-associated inflammation by negatively regulating differentiation of macrophages and their production of pro-inflammatory cytokines. Plays a role in negatively regulating the abundance of regulatory T cells in white adipose tissue.

Subunit / interactions. Self-associates. Interacts with ERN1 and TRAF2. Interaction with TRAF2 is facilitated under ER stress conditions, such as treatment with tunicamycin, and may promote TRAF2 phosphorylation. Interacts (via N-terminus) with STK25; the interaction promotes STK25 abundance at the level of protein expression and/or stability. (Microbial infection) Interacts with herpes simplex virus 1 UL37 protein.

Subcellular location. Cytoplasm. Cell membrane. Membrane raft. Lipid droplet.

Tissue specificity. Ubiquitously expressed at a low level, and highly expressed in peripheral blood leukocytes (PBLs), thymus, spleen, kidney, skeletal muscle, heart and liver.

Post-translational modifications. Autophosphorylated. Phosphorylation at Ser-324 by ATM following DNA damage is required for activation of the p38/MAPK14 stress-activated MAPK cascade. Phosphorylated at Ser-324 and on Tyr residues during T cell activation. Phosphorylated by LRRK2.

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

RefSeq proteins (12): NP_001333416, NP_001333417, NP_001333418, NP_001333419, NP_001333420, NP_001333421, NP_001333422, NP_001333423, NP_001333424, NP_001333425, NP_001333426, NP_057365* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR051234	TAO_STE20_kinase	Family

Pfam: PF00069

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 (67 total): helix 18, modified residue 9, strand 9, mutagenesis site 6, sequence variant 4, sequence conflict 4, compositionally biased region 3, region of interest 3, turn 3, coiled-coil region 3, binding site 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6BDN	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2K8-F1	81.12	0.59

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): 147 (proton acceptor)

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

Post-translational modifications (9): 324, 331, 343, 346, 349, 357, 359, 442, 830

Mutagenesis-validated functional residues (6):

Position	Phenotype
165	loss of serine/threonine-protein kinase activity.
181	no autophosphorylation, no kinase activity and reduced il2 production by t cells; when associated with f-183.
183	no autophosphorylation, no kinase activity and reduced il2 production by t cells; when associated with a-181.
256	enhances il2 production by t cells and increases jnk phosphorylation.
305	enhances il2 production by t cells and increases jnk phosphorylation.
324	inhibits activation of the p38/mapk14 stress-activated mapk cascade in response to dna damage. enhances il2 production b

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 318 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, TGCACTT_MIR519C_MIR519B_MIR519A, KEGG_MAPK_SIGNALING_PATHWAY, VICENT_METASTASIS_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GOBP_POSITIVE_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, COUP_01

GO Biological Process (11): MAPK cascade (GO:0000165), DNA repair (GO:0006281), protein phosphorylation (GO:0006468), DNA damage response (GO:0006974), mitotic G2 DNA damage checkpoint signaling (GO:0007095), positive regulation of stress-activated MAPK cascade (GO:0032874), regulation of MAPK cascade (GO:0043408), positive regulation of JUN kinase activity (GO:0043507), negative regulation of JNK cascade (GO:0046329), positive regulation of JNK cascade (GO:0046330), neuron projection morphogenesis (GO:0048812)

GO Molecular Function (9): protein serine/threonine kinase activity (GO:0004674), protein kinase inhibitor activity (GO:0004860), ATP binding (GO:0005524), transferase activity (GO:0016740), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301)

GO Cellular Component (5): cytoplasm (GO:0005737), lipid droplet (GO:0005811), plasma membrane (GO:0005886), membrane raft (GO:0045121), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	3
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	3
positive regulation of MAPK cascade	2
JNK cascade	2
regulation of JNK cascade	2
cellular anatomical structure	2
intracellular signaling cassette	1
DNA metabolic process	1
DNA damage response	1
phosphorylation	1
protein modification process	1
cellular response to stress	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
regulation of stress-activated MAPK cascade	1
stress-activated MAPK cascade	1
positive regulation of stress-activated protein kinase signaling cascade	1
MAPK cascade	1
regulation of intracellular signal transduction	1
JUN kinase activity	1
positive regulation of MAP kinase activity	1
regulation of JUN kinase activity	1
negative regulation of MAPK cascade	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
kinase inhibitor activity	1
protein kinase regulator activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
catalytic activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1

Protein interactions and networks

STRING

632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAOK3	EPS8	Q12929	454
TAOK3	MAPDA	Q6DHV7	439
TAOK3	APIP	Q96GX9	389
TAOK3	PHRF1	Q9P1Y6	385
TAOK3	TRIB3	Q96RU7	376
TAOK3	FLNC	Q14315	353
TAOK3	MAP4K4	O95819	353
TAOK3	SVIP	Q8NHG7	321
TAOK3	WSB2	Q9NYS7	321
TAOK3	ADA	P00813	303
TAOK3	SLC67A1-AS	Q8N1D0	301
TAOK3	SPPL3	Q8TCT6	299
TAOK3	SAV1	Q9H4B6	298
TAOK3	PAK1IP1	Q9NWT1	277
TAOK3	WWC1	Q8IX03	266

IntAct

32 interactions, top by confidence:

A	B	Type	Score
HTT	TAOK3	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	TAOK3	psi-mi:“MI:0915”(physical association)	0.520
ERN1	TAOK3	psi-mi:“MI:0915”(physical association)	0.510
TAOK3	MANF	psi-mi:“MI:0915”(physical association)	0.400
TAOK3	SEPTIN9	psi-mi:“MI:0915”(physical association)	0.400
TAOK3	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
CTR9	POLR2B	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AHRR	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
	ZNF316	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
STK25	ACACB	psi-mi:“MI:0914”(association)	0.350
TAOK3	STATH	psi-mi:“MI:0914”(association)	0.350
TAOK2	AIP	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
BTN3A1	PIK3CA	psi-mi:“MI:0914”(association)	0.350
FASTKD2	MED19	psi-mi:“MI:2364”(proximity)	0.270
SBDS	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
SMNDC1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
TAF15	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
TAOK3	ATF7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (61): TAOK3 (Affinity Capture-MS), TAOK3 (Biochemical Activity), TAOK3 (Affinity Capture-RNA), TAOK3 (Affinity Capture-MS), TAOK3 (Proximity Label-MS), TAOK3 (Proximity Label-MS), TAOK3 (Proximity Label-MS), TAOK3 (Affinity Capture-MS), TAOK3 (Affinity Capture-RNA), TAOK3 (Affinity Capture-MS), TAOK3 (Affinity Capture-MS), TAOK3 (Co-fractionation), TAOK3 (Co-fractionation), TAOK3 (Co-fractionation), TAOK3 (Proximity Label-MS)

ESM2 similar proteins: A0JMA8, A5WW21, A8WVU9, B0S6J3, B7ZR30, E1BK52, E7F187, E9PTG8, F1NBT0, G5EFD2, O01583, O08815, O43150, O54874, O54988, O55092, O55098, O88664, O94804, P46549, Q08CX1, Q0IHQ8, Q22908, Q3UU96, Q4G3H4, Q53UA7, Q5F2E8, Q5R4F3, Q5U245, Q5VT25, Q5ZJB4, Q619T5, Q6DD27, Q6GPK9, Q6NU21, Q7L7X3, Q7SIG6, Q7SY52, Q7TT49, Q7TT50

Diamond homologs: A0A078CGE6, A0A194W8T8, A2AQW0, A2QHV0, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A7A1P0, A8XJW8, A9RVK2, A9SY39, B0XXN8, B5VNQ3, E9Q3S4, F4HRJ4, G4N7X0, G4NDR3, O08648, O14047, O14299, O22040, O22042, O35099, O54748, O61122, O74304, O81472, O95382, P23561, P25390, P28829, P41892, P53349, P53599, Q01389, Q03497

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
TAOK3	up-regulates	STK4	phosphorylation
TAOK3	up-regulates	STK3	phosphorylation
TAOK3	up-regulates	STK3/4	phosphorylation
TAOK3	“up-regulates activity”	TAOK3	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3367 predictions. Top by Δscore:

Variant	Effect	Δscore
12:118151158:TC:T	acceptor_loss	1.0000
12:118151159:C:CC	acceptor_gain	1.0000
12:118151159:CTGA:C	acceptor_loss	1.0000
12:118152222:CTTA:C	donor_loss	1.0000
12:118152223:TTA:T	donor_loss	1.0000
12:118152225:A:AC	donor_gain	1.0000
12:118152225:AC:A	donor_gain	1.0000
12:118152225:ACCT:A	donor_loss	1.0000
12:118152225:ACCTT:A	donor_gain	1.0000
12:118152226:C:CC	donor_gain	1.0000
12:118152226:CC:C	donor_gain	1.0000
12:118152226:CCT:C	donor_gain	1.0000
12:118152226:CCTT:C	donor_gain	1.0000
12:118152226:CCTTC:C	donor_gain	1.0000
12:118152405:CGTAA:C	acceptor_gain	1.0000
12:118152406:GTAA:G	acceptor_gain	1.0000
12:118152406:GTAAC:G	acceptor_gain	1.0000
12:118152407:TAA:T	acceptor_gain	1.0000
12:118152407:TAACT:T	acceptor_gain	1.0000
12:118152408:AA:A	acceptor_gain	1.0000
12:118152408:AAC:A	acceptor_loss	1.0000
12:118152408:AACTG:A	acceptor_gain	1.0000
12:118152409:ACTGC:A	acceptor_gain	1.0000
12:118152410:C:CC	acceptor_gain	1.0000
12:118152410:C:T	acceptor_loss	1.0000
12:118152410:CTGC:C	acceptor_gain	1.0000
12:118152419:C:CT	acceptor_gain	1.0000
12:118160355:TGGC:T	acceptor_gain	1.0000
12:118160356:GGCC:G	acceptor_loss	1.0000
12:118160357:GCCTG:G	acceptor_loss	1.0000

AlphaMissense

6024 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:118152324:T:G	Q813P	1.000
12:118152328:A:C	Y812D	1.000
12:118152336:A:G	L809P	1.000
12:118152339:A:G	L808P	1.000
12:118152357:A:G	L802P	1.000
12:118161891:T:G	H679P	1.000
12:118161906:A:G	L674P	1.000
12:118161915:C:G	R671P	1.000
12:118181492:A:G	L482P	1.000
12:118181513:A:G	L475P	1.000
12:118181540:C:G	R466P	1.000
12:118181542:C:A	K465N	1.000
12:118181542:C:G	K465N	1.000
12:118201390:C:G	R298P	1.000
12:118201393:A:T	V297D	1.000
12:118201397:C:G	A296P	1.000
12:118201417:A:G	L289P	1.000
12:118212938:C:A	R265S	1.000
12:118212938:C:G	R265S	1.000
12:118214053:G:T	A234D	1.000
12:118214056:A:T	I233N	1.000
12:118214063:A:C	Y231D	1.000
12:118214063:A:G	Y231H	1.000
12:118214065:A:G	L230S	1.000
12:118214068:G:T	A229D	1.000
12:118214098:G:T	P219Q	1.000
12:118233694:C:T	G208D	1.000
12:118233695:C:G	G208R	1.000
12:118233702:C:A	W205C	1.000
12:118233702:C:G	W205C	1.000

dbSNP variants (sampled 300 via entrez): RS1000027846 (12:118322158 T>C), RS1000029236 (12:118287109 G>T), RS1000034913 (12:118275652 C>T), RS1000048550 (12:118362612 G>C), RS1000062344 (12:118225174 G>A,T), RS1000067310 (12:118350853 T>C), RS1000069599 (12:118368740 A>C,G), RS1000075956 (12:118217488 C>T), RS1000108525 (12:118183717 T>C), RS1000112317 (12:118316669 C>A), RS1000134834 (12:118183308 C>G,T), RS1000138080 (12:118308973 T>C), RS1000149080 (12:118297094 T>C), RS1000172911 (12:118362295 A>T), RS1000180028 (12:118150369 C>G,T)

Disease associations

OMIM: gene MIM:616711 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): neurodevelopmental disorder (MONDO:0700092), prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002472_1	Morphine dose requirement in tonsillectomy and adenoidectomy surgery	3.000000e-07
GCST002726_17	Glucose homeostasis traits	2.000000e-06
GCST002726_30	Glucose homeostasis traits	5.000000e-06
GCST003263_100	Post bronchodilator FEV1 in COPD	5.000000e-06
GCST003263_17	Post bronchodilator FEV1 in COPD	2.000000e-06
GCST004621_58	Red cell distribution width	3.000000e-13
GCST004867_18	Systemic lupus erythematosus	8.000000e-07
GCST008162_42	Hip circumference	5.000000e-06
GCST009463_15	Loneliness	2.000000e-08
GCST012355_11	Depression	3.000000e-07
GCST90002404_144	Red cell distribution width	6.000000e-21

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004471	insulin sensitivity measurement
EFO:0004314	forced expiratory volume
EFO:0009188	Red cell distribution width
EFO:0007865	loneliness measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5701 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

44 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 349,951 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL180022	NERATINIB	4	9,404
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL3301612	ENCORAFENIB	4	4,624
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL3426621	RIPASUDIL	3	870
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL1721885	SU-014813	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL230011	TG100-115	2
CHEMBL3039513	DECERNOTINIB	2
CHEMBL384304	RG-547	2
CHEMBL445813	AT-7519	2
CHEMBL475251	R-406	2

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

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1277441	Dosage,Efficacy	3	morphine	Pain;Postoperative
rs1277441	Efficacy	3	opioids	Pain
rs1277441	Dosage	3	opioids	Pain
rs795484	Dosage,Efficacy	3	morphine	Pain;Postoperative
rs795484	Efficacy	3	opioids	Pain
rs795484	Dosage	3	opioids	Pain

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs795484	TAOK3	3	3.25	3	morphine;opioids
rs1277441	TAOK3	3	3.25	3	opioids;morphine

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — TAO subfamily

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
AMG28	Inhibition	7.35	pIC50
compound 89S [PMID: 19115845]	Inhibition	6.9	pIC50

ChEMBL bioactivities

120 potent at pChembl≥5 of 127 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.66	Kd	0.22	nM	STAUROSPORINE
8.96	IC50	1.09	nM	STAUROSPORINE
8.90	IC50	1.25	nM	STAUROSPORINE
8.68	IC50	2.11	nM	STAUROSPORINE
8.24	Kd	5.8	nM	AST-487
7.68	Kd	21	nM	CHEMBL3688339
7.37	Kd	43	nM	PHA-665752
7.36	Kd	44	nM	TAE-684
7.35	IC50	45	nM	CHEMBL2334586
7.35	Kd	45	nM	PAZOPANIB
7.30	IC50	50	nM	CHEMBL3715872
7.30	IC50	50	nM	CHEMBL3716788
7.30	IC50	50	nM	CHEMBL3717287
7.30	IC50	50	nM	CHEMBL3717391
7.30	IC50	50	nM	CHEMBL3716597
7.30	IC50	50	nM	CHEMBL3715806
7.30	IC50	50	nM	CHEMBL3715987
7.30	IC50	50	nM	CHEMBL3717452
7.30	IC50	50	nM	CHEMBL3716744
7.30	IC50	50	nM	CHEMBL3716968
7.30	IC50	50	nM	CHEMBL3718066
7.30	IC50	50	nM	CHEMBL3715589
7.30	IC50	50	nM	CHEMBL3719326
7.30	IC50	50	nM	CHEMBL3717193
7.30	IC50	50	nM	CHEMBL3717484
7.30	IC50	50	nM	CHEMBL3718166
7.30	IC50	50	nM	CHEMBL3715005
7.30	IC50	50	nM	CHEMBL3718736
7.30	IC50	50	nM	CHEMBL3718891
7.30	IC50	50	nM	CHEMBL3717584
7.30	IC50	50	nM	CHEMBL3717111
7.30	IC50	50	nM	CHEMBL3716318
7.30	IC50	50	nM	CHEMBL3715362
7.30	IC50	50	nM	CHEMBL3718473
7.30	IC50	50	nM	CHEMBL3718965
7.30	IC50	50	nM	CHEMBL3717468
7.30	IC50	50	nM	CHEMBL3719286
7.30	IC50	50	nM	CHEMBL3716849
7.30	IC50	50	nM	CHEMBL3719051
7.30	IC50	50	nM	CHEMBL3718164
7.30	IC50	50	nM	CHEMBL3717373
7.30	IC50	50	nM	CHEMBL3715956
7.30	IC50	50	nM	CHEMBL3718940
7.30	IC50	50	nM	CHEMBL3715942
7.30	IC50	50	nM	CHEMBL3716416
7.30	IC50	50	nM	CHEMBL3717713
7.30	IC50	50	nM	CHEMBL3716774
7.30	IC50	50	nM	CHEMBL3716742
7.30	Kd	49.6	nM	CHEMBL5653589
7.24	Kd	57	nM	AT-7519

PubChem BioAssay actives

70 with measured affinity, of 824 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	625101: Binding constant for TAOK3 kinase domain	kd	0.0002	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	625101: Binding constant for TAOK3 kinase domain	kd	0.0058	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425191: 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	0.0210	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	625101: Binding constant for TAOK3 kinase domain	kd	0.0430	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	625101: Binding constant for TAOK3 kinase domain	kd	0.0440	uM
Pazopanib	625101: Binding constant for TAOK3 kinase domain	kd	0.0450	uM
4-(4-amino-3,5,12-triazatetracyclo[9.7.0.02,7.013,18]octadeca-1(11),2,4,6,13(18),14,16-heptaen-16-yl)-2-methylbut-3-yn-2-ol	1856571: Inhibition of human wild type partial length TAOK3 (M1 to T316 residues) expressed in mammalian expression system by Kinomescan assay	ic50	0.0450	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149543: Binding affinity to human TAOK3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0496	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	625101: Binding constant for TAOK3 kinase domain	kd	0.0570	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	625101: Binding constant for TAOK3 kinase domain	kd	0.0810	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	508103: Binding affinity to TAOK3	kd	0.0860	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	625101: Binding constant for TAOK3 kinase domain	kd	0.0970	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	625101: Binding constant for TAOK3 kinase domain	kd	0.0990	uM
(7S)-2-(2-aminopyrimidin-4-yl)-7-(2-fluoroethyl)-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	412046: Inhibition of TAO3	ic50	0.1260	uM
Sunitinib	508103: Binding affinity to TAOK3	kd	0.2100	uM
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	625101: Binding constant for TAOK3 kinase domain	kd	0.2100	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	2189183: Inhibition of TAOK3 (unknown origin) in presence of ATP by enzymatic assay	ic50	0.2540	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	625101: Binding constant for TAOK3 kinase domain	kd	0.2600	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	1526264: Binding affinity to recombinant human full length N-terminal GST-tagged TAOK3 expressed in baculovirus expression system using PKC-epsilon peptide as substrate incubated for 1 hr by TR-FRET assay	kd	0.2930	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	625101: Binding constant for TAOK3 kinase domain	kd	0.3100	uM
Bosutinib	625101: Binding constant for TAOK3 kinase domain	kd	0.3400	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	1526264: Binding affinity to recombinant human full length N-terminal GST-tagged TAOK3 expressed in baculovirus expression system using PKC-epsilon peptide as substrate incubated for 1 hr by TR-FRET assay	kd	0.3600	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625101: Binding constant for TAOK3 kinase domain	kd	0.3900	uM
Crizotinib	625101: Binding constant for TAOK3 kinase domain	kd	0.4900	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625101: Binding constant for TAOK3 kinase domain	kd	0.4900	uM
Ruxolitinib	625101: Binding constant for TAOK3 kinase domain	kd	0.5900	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	625101: Binding constant for TAOK3 kinase domain	kd	0.6200	uM
1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	625101: Binding constant for TAOK3 kinase domain	kd	0.7200	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625101: Binding constant for TAOK3 kinase domain	kd	1.0000	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625101: Binding constant for TAOK3 kinase domain	kd	1.1000	uM
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	625101: Binding constant for TAOK3 kinase domain	kd	1.4000	uM
2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide	625101: Binding constant for TAOK3 kinase domain	kd	1.4000	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	1425191: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.4110	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	625101: Binding constant for TAOK3 kinase domain	kd	1.7000	uM
Nilotinib	625101: Binding constant for TAOK3 kinase domain	kd	1.7000	uM
Abemaciclib	1425191: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.7210	uM
N-[4-[[3-(2-aminopyrimidin-4-yl)-2-pyridinyl]oxy]phenyl]-4-(4-methylthiophen-2-yl)phthalazin-1-amine	1425191: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.7660	uM
Fedratinib	625101: Binding constant for TAOK3 kinase domain	kd	1.9000	uM
Ponatinib	1425191: 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	2.1360	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2R)-1-methoxy-4-methylpentan-2-yl]iminoimidazolidin-4-one	2024514: Inhibition of human TAO3 assessed as remaining activity by eurofins-cerep kinase profiler analysis	ic50	2.2000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625101: Binding constant for TAOK3 kinase domain	kd	2.2000	uM
8-chloro-2-pyrrolidin-2-yl-3H-[1]benzofuro[3,2-d]pyrimidin-4-one	1425191: 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	2.2920	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	625101: Binding constant for TAOK3 kinase domain	kd	2.3000	uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol	625101: Binding constant for TAOK3 kinase domain	kd	2.4000	uM
N-[2-[4-[[4-(cyclobutylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-11-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-11-yl]-2-oxoethyl]acetamide	1425191: 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	2.4020	uM
2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol	1425191: 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	2.4390	uM
Sorafenib	508103: Binding affinity to TAOK3	kd	2.7000	uM
(16E)-14-methyl-20-oxa-5,7,14,27-tetrazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8,10,12(26),16,21,23-decaene	1425191: 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	2.8560	uM
Encorafenib	1425191: 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	3.3250	uM
Neratinib	625101: Binding constant for TAOK3 kinase domain	kd	4.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression	9
Benzo(a)pyrene	affects methylation, decreases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
trichostatin A	affects expression, increases expression	2
Acetaminophen	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
titanium dioxide	decreases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
evodiamine	decreases expression	1
celastrol	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
gedunin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
asparanin A	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cadmium	increases expression, increases abundance	1

ChEMBL screening assays

205 unique, capped per target: 205 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1022462	Binding	Inhibition of TAO3	First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery. — J 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_B2I5	Abcam HeLa TAOK3 KO	Cancer cell line	Female
CVCL_D8C2	Ubigene A-549 TAOK3 KO	Cancer cell line	Male
CVCL_E0QI	Ubigene HeLa TAOK3 KO	Cancer cell line	Female
CVCL_TR58	HAP1 TAOK3 (-) 1	Cancer cell line	Male
CVCL_TR59	HAP1 TAOK3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery