TAOK2

Summary

TAOK2 (TAO kinase 2, HGNC:16835) is a protein-coding gene on chromosome 16p11.2, encoding Serine/threonine-protein kinase TAO2 (Q9UL54). Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade.

Enables mitogen-activated protein kinase kinase binding activity; neuropilin binding activity; and protein serine/threonine kinase activity. Involved in several processes, including focal adhesion assembly; intracellular signal transduction; and positive regulation of MAPK cascade. Located in cytoplasmic vesicle; cytosol; and nuclear lumen. Part of receptor complex.

Source: NCBI Gene 9344 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 19
• Clinical variants (ClinVar): 979 total — 1 pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 29 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016151

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16835
Approved symbol	TAOK2
Name	TAO kinase 2
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	TAO1, KIAA0881, PSK, PSK1, TAO2, MAP3K17, hKFC-C, PSK-1, PSK1-BETA, Tao2beta
Ensembl gene	ENSG00000149930
Ensembl biotype	protein_coding
OMIM	613199
Entrez	9344

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 retained_intron

ENST00000279394, ENST00000308893, ENST00000416441, ENST00000543033, ENST00000566552, ENST00000570844, ENST00000904630, ENST00000904631, ENST00000912380

RefSeq mRNA: 3 — MANE Select: NM_016151 NM_001252043, NM_004783, NM_016151

CCDS: CCDS10662, CCDS10663, CCDS58448

Canonical transcript exons

ENST00000308893 — 16 exons

Exon	Start	End
ENSE00000993031	29979195	29979308
ENSE00000993033	29977738	29977904
ENSE00000993034	29983072	29983332
ENSE00000993035	29983503	29983664
ENSE00000993037	29978799	29978844
ENSE00000993038	29985213	29985578
ENSE00000993039	29978974	29979070
ENSE00000993040	29982734	29982901
ENSE00000993041	29981661	29981754
ENSE00000993042	29978252	29978353
ENSE00000993048	29979417	29979508
ENSE00001178762	29973868	29974648
ENSE00001702128	29981859	29981940
ENSE00001703381	29978089	29978160
ENSE00003581795	29985658	29985861
ENSE00003846650	29986265	29988393

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 95.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.0791 / max 88.6392, expressed in 1794 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153570	7.9193	1769
153571	3.6288	1588
153569	0.4278	201
153572	0.1031	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	95.09	gold quality
apex of heart	UBERON:0002098	94.90	gold quality
cerebellar hemisphere	UBERON:0002245	94.43	gold quality
cerebellar cortex	UBERON:0002129	94.33	gold quality
right adrenal gland cortex	UBERON:0035827	94.06	gold quality
right adrenal gland	UBERON:0001233	93.73	gold quality
right lung	UBERON:0002167	93.44	gold quality
right frontal lobe	UBERON:0002810	93.41	gold quality
adenohypophysis	UBERON:0002196	93.24	gold quality
right testis	UBERON:0004534	93.19	gold quality
endometrium epithelium	UBERON:0004811	93.17	gold quality
left testis	UBERON:0004533	93.07	gold quality
left adrenal gland cortex	UBERON:0035825	93.06	gold quality
upper lobe of left lung	UBERON:0008952	93.00	gold quality
metanephros cortex	UBERON:0010533	92.84	gold quality
left adrenal gland	UBERON:0001234	92.80	gold quality
cerebellum	UBERON:0002037	92.54	gold quality
right lobe of thyroid gland	UBERON:0001119	92.50	gold quality
cingulate cortex	UBERON:0003027	92.44	gold quality
body of uterus	UBERON:0009853	92.42	gold quality
anterior cingulate cortex	UBERON:0009835	92.41	gold quality
adrenal cortex	UBERON:0001235	92.16	gold quality
spleen	UBERON:0002106	91.93	gold quality
right ovary	UBERON:0002118	91.90	gold quality
omental fat pad	UBERON:0010414	91.82	gold quality
peritoneum	UBERON:0002358	91.77	gold quality
pituitary gland	UBERON:0000007	91.69	gold quality
left lobe of thyroid gland	UBERON:0001120	91.64	gold quality
right uterine tube	UBERON:0001302	91.53	gold quality
lower esophagus mucosa	UBERON:0035834	91.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.66
E-GEOD-99795	no	24.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting TAOK2, 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-6748-5P	100.00	65.81	1057
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-4701-3P	98.17	66.25	788
HSA-MIR-6736-5P	98.17	66.43	760
HSA-MIR-1301-5P	98.09	66.62	495
HSA-MIR-6502-5P	98.09	66.73	495

Literature-anchored findings (GeneRIF, showing 10)

• PSK interacts with microtubules and affects their organization and stability independently of PSK kinase activity (PMID:12639963)
• mediates signaling from carbachol to p38 mitogen-activated protein kinase and ternary complex factors (PMID:12665513)
• the TAK1-JNK pathway is activated by osmotic stress, while blocking TAK1-mediated NF-kappaB activation; TAO2 regulates TAK1 pathways (PMID:16893890)
• PSK1-alpha is a bifunctional kinase that associates with microtubules, and JNK- and caspase-mediated removal of its C-terminal microtubule-binding domain permits nuclear translocation of the N-terminal region of PSK1-alpha and its induction of apoptosis (PMID:17158878)
• TAOK2 is essential for dendrite morphogenesis; TAOK2 downregulation impairs basal dendrite formation without affecting apical dendrites. (PMID:22683681)
• tau is a good substrate for PSK1 and PSK2 phosphorylation with mass spectrometric analysis of phosphorylated tau revealing more than 40 tau residues as targets of these kinases. (PMID:23585562)
• we characterize a compound that inhibits TAOK1 and TAOK2 activity with IC50 values of 11 to 15 nmol/L, is ATP-competitive, and targets these kinases selectively. TAOK inhibition or depletion in centrosome-amplified SKBR3 or BT549 breast cancer cell models increases the mitotic population, the percentages of mitotic cells displaying amplified centrosomes and multipolar spindles, induces cell death, and inhibits cell growt (PMID:28830982)
• TAOK2 is an ER-localized kinase that catalyzes the dynamic tethering of ER to microtubules. (PMID:34879262)
• The circRNA circSIAE Inhibits Replication of Coxsackie Virus B3 by Targeting miR-331-3p and Thousand and One Amino-Acid Kinase 2. (PMID:35141166)
• Comprehensive split TEV based protein-protein interaction screening reveals TAOK2 as a key modulator of Hippo signalling to limit growth. (PMID:37813295)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Taok2	ENSMUSG00000059981
rattus_norvegicus	Taok2	ENSRNOG00000019964

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), 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 TAO2 — Q9UL54 (reviewed: Q9UL54)

Alternative names: Kinase from chicken homolog C, Prostate-derived sterile 20-like kinase 1, Thousand and one amino acid protein kinase 2

All UniProt accessions (1): Q9UL54

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. 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. Isoform 1, but not isoform 2, plays a role in apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation. This function, which requires the activation of MAPK8/JNK and nuclear localization of C-terminally truncated isoform 1, may be linked to the mitochondrial CASP9-associated death pathway. Isoform 1 binds to microtubules and affects their organization and stability independently of its kinase activity. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation, but not that of MAPK8/JNK. May play a role in the osmotic stress-MAPK8 pathway. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14 phosphorylation.

Subunit / interactions. Interacts with MAP2K3 and MAP2K6. Self-associates. Interacts with tubulins through the C-terminal domain. Interacts with MAP3K7 and interferes with MAP3K7-binding to CHUK and thus prevents NF-kappa-B activation. Isoform 2 interacts with PCDH8; this complex may also include CDH2.

Subcellular location. Cytoplasmic vesicle membrane. Cytoplasm. Cytoskeleton. Nucleus Cell projection. Dendrite.

Tissue specificity. Ubiquitously expressed, with a higher level of expression in testis and brain.

Post-translational modifications. Isoforms 1 and 2 are autophosphorylated. C-terminal cleavage of isoform 1 and subsequent nuclear localization requires CASP9 activity. Autophosphorylated. Phosphorylated by ATM. Phosphorylated on Ser-1031 by MAPK14. This phosphorylation is required PCDH8 for endocytosis.

Activity regulation. Selectively inhibited by the enantiopure organoruthenium inhibitor 9E1. Activated following arsenic trioxide (As(2)O(3)) treatment.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UL54-1	1, PSK1-alpha, TAO2	yes
Q9UL54-2	2, PSK1-beta
Q9UL54-3	3
Q9UL54-4	4

RefSeq proteins (3): NP_001238972, NP_004774, NP_057235* (*=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 (43 total): modified residue 9, compositionally biased region 6, transmembrane region 5, region of interest 5, splice variant 5, coiled-coil region 3, mutagenesis site 3, binding site 2, sequence conflict 2, chain 1, active site 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UL54-F1	67.17	0.32

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): 151 (proton acceptor)

Ligand- & substrate-binding residues (2): 34–42; 57

Post-translational modifications (9): 9, 181, 414, 656, 777, 825, 827, 1011, 1031

Mutagenesis-validated functional residues (3):

Position	Phenotype
57	loss of kinase activity. in isoform 1, excluded from the nucleus. no effect on microtubule-binding.
169	loss of kinase activity; no effect on map3k7-mediated activation of nf-kappa-b.
919	no effect on kinase activity, nor on jnk activation, but severe reduction in nuclear localization and apoptotic membrane

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 270 (showing top): ATF_B, GOBP_DENDRITE_DEVELOPMENT, RNGTGGGC_UNKNOWN, E2F_Q4, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, E2F4DP1_01, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, RORA1_01, LFA1_Q6, KEGG_MAPK_SIGNALING_PATHWAY, CMYB_01, SP3_Q3, GOBP_FOCAL_ADHESION_ASSEMBLY, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_GROWTH

GO Biological Process (20): regulation of cell growth (GO:0001558), protein targeting to membrane (GO:0006612), apoptotic process (GO:0006915), DNA damage response (GO:0006974), mitotic G2 DNA damage checkpoint signaling (GO:0007095), axonogenesis (GO:0007409), regulation of cell shape (GO:0008360), cell migration (GO:0016477), actin cytoskeleton organization (GO:0030036), positive regulation of stress-activated MAPK cascade (GO:0032874), regulation of actin cytoskeleton organization (GO:0032956), positive regulation of MAPK cascade (GO:0043410), positive regulation of JNK cascade (GO:0046330), focal adhesion assembly (GO:0048041), stress-activated MAPK cascade (GO:0051403), basal dendrite morphogenesis (GO:0150019), basal dendrite arborization (GO:0150020), protein phosphorylation (GO:0006468), cell morphogenesis involved in neuron differentiation (GO:0048667), neuron projection morphogenesis (GO:0048812)

GO Molecular Function (14): protein serine/threonine kinase activity (GO:0004674), MAP kinase kinase kinase activity (GO:0004709), ATP binding (GO:0005524), mitogen-activated protein kinase kinase binding (GO:0031434), neuropilin binding (GO:0038191), protein serine/threonine kinase activator activity (GO:0043539), tau protein binding (GO:0048156), tau-protein kinase activity (GO:0050321), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (17): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), axon (GO:0030424), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), neuron projection (GO:0043005), signaling receptor complex (GO:0043235), dendritic growth cone (GO:0044294), axonal growth cone (GO:0044295), nucleus (GO:0005634), cytoskeleton (GO:0005856), membrane (GO:0016020), dendrite (GO:0030425), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
MAPK cascade	3
protein serine/threonine kinase activity	3
positive regulation of MAPK cascade	2
protein kinase activity	2
nuclear lumen	2
intracellular membraneless organelle	2
cytoplasm	2
neuron projection	2
growth cone	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
protein targeting	1
establishment of protein localization to membrane	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
regulation of cell morphogenesis	1
regulation of biological quality	1
cell motility	1
cytoskeleton organization	1
actin filament-based process	1
regulation of stress-activated MAPK cascade	1
stress-activated MAPK cascade	1
positive regulation of stress-activated protein kinase signaling cascade	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
JNK cascade	1
regulation of JNK cascade	1

Protein interactions and networks

STRING

1272 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAOK2	KCTD13	Q8WZ19	779
TAOK2	F8WDG0	F8WDG0	754
TAOK2	IQCJ-SCHIP1	B3KU38	734
TAOK2	INO80E	Q8NBZ0	647
TAOK2	TBX6	O95947	639
TAOK2	SEZ6L2	Q6UXD5	633
TAOK2	MAP2K3	P46734	628
TAOK2	DOC2A	Q14183	606
TAOK2	HIRIP3	Q9BW71	602
TAOK2	ASPHD1	Q5U4P2	590
TAOK2	C16orf54	Q6UWD8	585
TAOK2	PCDH8	O95206	582
TAOK2	QPRT	Q15274	567
TAOK2	KIF22	Q14807	538
TAOK2	TAB1	Q15750	532

IntAct

67 interactions, top by confidence:

A	B	Type	Score
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
STK26	STRN	psi-mi:“MI:0914”(association)	0.860
TAOK2	MAPRE3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	TAOK2	psi-mi:“MI:0915”(physical association)	0.560
CIDEB	TAOK2	psi-mi:“MI:0915”(physical association)	0.560
ABITRAM	POTEF	psi-mi:“MI:0914”(association)	0.530
LTBR	ZNF724	psi-mi:“MI:0914”(association)	0.530
KCNS3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PCDHB16	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
ZDHHC1	PIK3CA	psi-mi:“MI:0914”(association)	0.530
TAOK2	TNKS2	psi-mi:“MI:0407”(direct interaction)	0.440
PKM	TAOK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
TAOK2	KLHL12	psi-mi:“MI:0915”(physical association)	0.370
TAOK2	RCHY1	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	TAOK2	psi-mi:“MI:0915”(physical association)	0.370
MAPRE1	CTNNB1	psi-mi:“MI:0914”(association)	0.350
BCAR1	PSMD11	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TH	MAP3K7	psi-mi:“MI:0914”(association)	0.350
ZDHHC1	MTA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (115): TAOK2 (Affinity Capture-MS), TAOK2 (Affinity Capture-MS), TAOK2 (Affinity Capture-MS), TAOK2 (Co-localization), TAOK2 (Co-localization), TAOK2 (Affinity Capture-MS), TAOK2 (Affinity Capture-MS), TAOK2 (Affinity Capture-MS), TAOK2 (Affinity Capture-MS), TAOK2 (Affinity Capture-MS), TAOK2 (Affinity Capture-MS), TAOK2 (Affinity Capture-MS), TAOK2 (Affinity Capture-MS), TAOK2 (Affinity Capture-MS), TAOK2 (Affinity Capture-MS)

ESM2 similar proteins: A0JNG4, A1L3T7, B1AVH7, B5DFA1, D2H0G5, E1U8D0, E9QHE3, I1VZH0, O08629, O60826, O75052, O94964, P58660, P86182, P98171, Q13263, Q149G0, Q1LWB0, Q1RMI8, Q3ULW6, Q3V3A7, Q571B6, Q58D79, Q5JV73, Q5R8S0, Q62318, Q6P4K6, Q6PGG2, Q6ZQ29, Q6ZRF8, Q768S4, Q7TSI1, Q80TQ5, Q8BL43, Q8C7B8, Q8IWE5, Q8K1S6, Q8N163, Q8TF30, Q8VDP4

Diamond homologs: A0A7J6K7I9, A0A7J6K7Y0, A0A7J6KD88, A8X775, B1WAR9, C4YRB7, D2HXI8, E1C2I2, E9PSL7, G1X456, G5EGQ3, M3TYT0, O00506, O01583, O01700, O14578, O54874, O61267, O75116, O77819, O80902, O88643, O97627, P05131, P0CY23, P0CY24, P13677, P21146, P25098, P26817, P26818, P32865, P34100, P35465, P38070, P48562, P49025, P49673, P54265, P70335

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
TAOK2	“up-regulates activity”	MAP2K3	phosphorylation
TAOK2	“up-regulates activity”	MAP2K6	phosphorylation
TAOK2	up-regulates	STK3	phosphorylation
TAOK2	up-regulates	STK4	phosphorylation
DNA_damage	up-regulates	TAOK2
GNAO1	up-regulates	TAOK2
TAOK2	“up-regulates activity”	ELK1	phosphorylation
TAOK2	up-regulates	STK3/4	phosphorylation
TAOK2	“up-regulates activity”	MAP2K6	binding
TAOK2	“up-regulates activity”	MAP2K4	binding
TAOK2	up-regulates	MAP2K7	binding
TAOK2	“up-regulates activity”	MAP2K3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	540
Likely benign	378
Benign	28

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3778749	NM_004783.4(TAOK2):c.2529C>A (p.Tyr843Ter)	Pathogenic

SpliceAI

2657 predictions. Top by Δscore:

Variant	Effect	Δscore
16:29977284:GGGT:G	donor_gain	1.0000
16:29977285:GGTG:G	donor_gain	1.0000
16:29977905:G:GG	donor_gain	1.0000
16:29978317:G:GG	donor_gain	1.0000
16:29978338:G:GT	donor_gain	1.0000
16:29978793:CCTTA:C	acceptor_loss	1.0000
16:29978794:CTTAG:C	acceptor_loss	1.0000
16:29978797:A:AG	acceptor_gain	1.0000
16:29978797:AGCT:A	acceptor_gain	1.0000
16:29978798:G:GG	acceptor_gain	1.0000
16:29978798:GCT:G	acceptor_gain	1.0000
16:29978798:GCTG:G	acceptor_gain	1.0000
16:29978844:GGT:G	donor_loss	1.0000
16:29978845:GTA:G	donor_loss	1.0000
16:29978846:T:A	donor_loss	1.0000
16:29978972:A:AG	acceptor_gain	1.0000
16:29978973:G:GA	acceptor_gain	1.0000
16:29979101:G:GT	donor_gain	1.0000
16:29979101:G:T	donor_gain	1.0000
16:29979189:T:TA	acceptor_gain	1.0000
16:29979190:G:A	acceptor_gain	1.0000
16:29979191:GCA:G	acceptor_loss	1.0000
16:29979192:CA:C	acceptor_loss	1.0000
16:29979193:A:AG	acceptor_gain	1.0000
16:29979193:AG:A	acceptor_gain	1.0000
16:29979193:AGG:A	acceptor_gain	1.0000
16:29979194:G:GT	acceptor_gain	1.0000
16:29979194:GG:G	acceptor_gain	1.0000
16:29979194:GGG:G	acceptor_gain	1.0000
16:29979194:GGGAT:G	acceptor_gain	1.0000

AlphaMissense

7906 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:29977827:T:C	F19L	1.000
16:29977828:T:C	F19S	1.000
16:29977829:C:A	F19L	1.000
16:29977829:C:G	F19L	1.000
16:29977842:C:T	P24S	1.000
16:29977843:C:A	P24Q	1.000
16:29977843:C:G	P24R	1.000
16:29977854:T:C	F28L	1.000
16:29977855:T:C	F28S	1.000
16:29977855:T:G	F28C	1.000
16:29977856:C:A	F28L	1.000
16:29977856:C:G	F28L	1.000
16:29977873:T:A	I34N	1.000
16:29977873:T:G	I34S	1.000
16:29977875:G:C	G35R	1.000
16:29977875:G:T	G35C	1.000
16:29977876:G:A	G35D	1.000
16:29977876:G:T	G35V	1.000
16:29977878:C:G	H36D	1.000
16:29977881:G:C	G37R	1.000
16:29977881:G:T	G37C	1.000
16:29977882:G:A	G37D	1.000
16:29977882:G:C	G37A	1.000
16:29977882:G:T	G37V	1.000
16:29977884:A:C	S38R	1.000
16:29977886:C:A	S38R	1.000
16:29977886:C:G	S38R	1.000
16:29977887:T:A	F39I	1.000
16:29977887:T:C	F39L	1.000
16:29977887:T:G	F39V	1.000

dbSNP variants (sampled 300 via entrez): RS1000137586 (16:29981830 C>G), RS1000300527 (16:29975312 G>A), RS1000554434 (16:29977102 G>T), RS1000650947 (16:29975104 G>A,T), RS1000767856 (16:29988137 GCCT>G), RS1000878010 (16:29982750 G>A), RS1001159193 (16:29975469 G>T), RS1001202775 (16:29988620 C>G,T), RS1001279316 (16:29975225 T>C), RS1001427113 (16:29976756 A>T), RS1001529539 (16:29975692 C>T), RS1001733004 (16:29977602 C>A,T), RS1001923831 (16:29989102 G>A), RS1002269754 (16:29989370 C>T), RS1002324490 (16:29975876 C>T)

Disease associations

OMIM: gene MIM:613199 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant
autism spectrum disorder	Limited	Autosomal dominant
immunodeficiency disease	Limited	Autosomal recessive
inborn error of immunity	Limited	Autosomal recessive

Mondo (5): autism (MONDO:0005260), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258), immunodeficiency disease (MONDO:0021094), inborn error of immunity (MONDO:0003778)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST002539_82	Schizophrenia	5.000000e-11
GCST004521_236	Autism spectrum disorder or schizophrenia	4.000000e-10
GCST004946_142	Schizophrenia	8.000000e-13
GCST006803_23	Schizophrenia	6.000000e-13
GCST007201_202	Schizophrenia	4.000000e-12
GCST007293_15	Body fat distribution (arm fat ratio)	6.000000e-06
GCST007293_81	Body fat distribution (arm fat ratio)	4.000000e-08
GCST007611_22	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	7.000000e-09
GCST008129_85	Body mass index	2.000000e-21
GCST008595_205	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-09
GCST009602_58	Metabolic syndrome	2.000000e-09
GCST010173_141	Triglyceride levels	1.000000e-09
GCST010241_393	Apolipoprotein A1 levels	8.000000e-11
GCST010242_32	HDL cholesterol levels	7.000000e-16
GCST010244_128	Triglyceride levels	1.000000e-13
GCST010658_18	High density lipoprotein cholesterol levels	3.000000e-08
GCST010659_20	Waist circumference	8.000000e-09
GCST010703_269	Brain morphology (MOSTest)	4.000000e-13
GCST010988_42	Adult body size	8.000000e-27

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004340	body mass index
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0000195	metabolic syndrome
EFO:0004530	triglyceride measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D007153	Immunologic Deficiency Syndromes	C20.673
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075195 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

29 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 211,322 (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
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1944698	ZOTIRACICLIB	2	2,915
CHEMBL3039525	GOLVATINIB	2	535
CHEMBL384304	RG-547	2	93
CHEMBL445813	AT-7519	2	2,614
CHEMBL475251	R-406	2
CHEMBL558752	RAF-265	2
CHEMBL564829	MILCICLIB	2
CHEMBL572878	TOZASERTIB	2
CHEMBL296468	BMS-387032	1
CHEMBL4068509	PRN-1371	1
CHEMBL4289017	PF-03814735	1
CHEMBL494089	GSK-690693	1
CHEMBL574738	AST-487	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — TAO subfamily

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

Ligand	Action	Affinity	Parameter
AMG28	Inhibition	7.04	pIC50

ChEMBL bioactivities

60 potent at pChembl≥5 of 67 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.45	IC50	3.54	nM	STAUROSPORINE
8.36	IC50	4.35	nM	STAUROSPORINE
8.00	Kd	10	nM	CHEMBL3688339
7.93	IC50	11.7	nM	STAUROSPORINE
7.92	Kd	12	nM	STAUROSPORINE
7.36	Kd	44	nM	AST-487
7.30	Kd	50	nM	AT-7519
7.08	IC50	84	nM	CHEMBL4063500
7.05	IC50	89	nM	CHEMBL2334586
7.00	Kd	100	nM	CHEMBL4554938
6.87	IC50	134	nM	CHEMBL4554938
6.85	Kd	140	nM	RAF-265
6.60	Kd	250	nM	ALVOCIDIB
6.51	Kd	310	nM	RUXOLITINIB
6.41	Kd	390	nM	CHEMBL1241674
6.38	IC50	420	nM	CHEMBL4568087
6.37	Kd	430	nM	TOZASERTIB
6.36	Kd	440	nM	CHEMBL386051
6.30	Kd	500	nM	LESTAURTINIB
6.28	IC50	529	nM	CHEMBL2006765
6.27	Kd	540	nM	SORAFENIB
6.19	Kd	640	nM	R-406
6.16	IC50	689	nM	CHEMBL5437375
6.13	Kd	737	nM	AT-7519
6.13	Kd	740	nM	TAE-684
6.12	Kd	760	nM	FEDRATINIB
6.12	Kd	750	nM	RG-547
6.05	Kd	900	nM	CRIZOTINIB
6.04	IC50	903	nM	CHEMBL4793380
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.97	Kd	1070	nM	ZOTIRACICLIB
5.93	IC50	1175	nM	PRN-1371
5.92	Kd	1200	nM	PHA-665752
5.85	Kd	1400	nM	GSK-690693
5.76	Kd	1734	nM	CHEMBL3991933
5.75	Kd	1800	nM	BMS-387032
5.75	Kd	1800	nM	PAZOPANIB
5.72	Kd	1900	nM	BOSUTINIB
5.69	Kd	2046	nM	PF-03814735
5.68	Kd	2092	nM	GILTERITINIB
5.67	Kd	2121	nM	GOLVATINIB
5.65	Kd	2233	nM	DINACICLIB
5.65	Kd	2221	nM	Cerdulatinib Hydrochloride
5.62	Kd	2425	nM	RAF-265
5.60	Kd	2515	nM	CHEMBL5653589
5.57	IC50	2700	nM	CHEMBL4569508
5.47	Kd	3375	nM	PACRITINIB
5.41	Kd	3900	nM	RUBOXISTAURIN

PubChem BioAssay actives

55 with measured affinity, of 891 total; 48 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	1715148: Inhibition of human TAOK2 using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.0035	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425190: 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	0.0100	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	625099: Binding constant for TAOK2 kinase domain	kd	0.0440	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	625099: Binding constant for TAOK2 kinase domain	kd	0.0500	uM
N-[4-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]-N’-hydroxyoctanediamide	1469365: Inhibition of recombinant human N-terminal His6-tagged TAO2 expressed in sf21 cells	ic50	0.0840	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	1856573: Inhibition of human wild type partial length TAOK2 (M1 to A320 residues) expressed in mammalian expression system by Kinomescan assay	ic50	0.0890	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	2189159: Binding affinity to TAOK2 (unknown origin) assessed as dissociation constant	kd	0.1000	uM
1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	625099: Binding constant for TAOK2 kinase domain	kd	0.1400	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	625099: Binding constant for TAOK2 kinase domain	kd	0.2500	uM
Ruxolitinib	625099: Binding constant for TAOK2 kinase domain	kd	0.3100	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625099: Binding constant for TAOK2 kinase domain	kd	0.3900	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637141: Inhibition of recombinant human GST-tagged TAOK2 catalytic domain expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.4200	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	625099: Binding constant for TAOK2 kinase domain	kd	0.4300	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625099: Binding constant for TAOK2 kinase domain	kd	0.4400	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	625099: Binding constant for TAOK2 kinase domain	kd	0.5000	uM
N-propyl-4-[[4-(2,2,2-trifluoroethylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]benzamide	1440161: Inhibition of TAOK2 (unknown origin) after 60 mins by TR-FRET assay	ic50	0.5290	uM
Sorafenib	625099: Binding constant for TAOK2 kinase domain	kd	0.5400	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	625099: Binding constant for TAOK2 kinase domain	kd	0.6400	uM
2-[5-[[4-[(2,3-dimethylindazol-6-yl)-methylamino]pyrimidin-2-yl]amino]-2-methylphenyl]-1H-benzimidazole-4-carboxamide	1972175: Inhibition of TAO2 (unknown origin) by Z’-Lyte kinase assay	ic50	0.6890	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	625099: Binding constant for TAOK2 kinase domain	kd	0.7400	uM
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	625099: Binding constant for TAOK2 kinase domain	kd	0.7500	uM
Fedratinib	625099: Binding constant for TAOK2 kinase domain	kd	0.7600	uM
Crizotinib	625099: Binding constant for TAOK2 kinase domain	kd	0.9000	uM
1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[4-(6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-ylamino)phenyl]urea	1735616: Inhibition of recombinant human TAO2 (1 to 320 residues) using myelin basic protein as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay	ic50	0.9030	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	1425190: 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	1.0700	uM
6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)-8-[3-(4-prop-2-enoylpiperazin-1-yl)propyl]pyrido[2,3-d]pyrimidin-7-one	1446158: Inhibition of human TAOK2 preincubated for 15 mins followed by peptide substrate addition measured after 3 hrs by caliper capillary electrophoresis method	ic50	1.1750	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	625099: Binding constant for TAOK2 kinase domain	kd	1.2000	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	625099: Binding constant for TAOK2 kinase domain	kd	1.4000	uM
3-(2-methyl-1,3-benzoxazol-5-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine	1425190: 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	1.7340	uM
Pazopanib	625099: Binding constant for TAOK2 kinase domain	kd	1.8000	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	625099: Binding constant for TAOK2 kinase domain	kd	1.8000	uM
Bosutinib	625099: Binding constant for TAOK2 kinase domain	kd	1.9000	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	1425190: 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	2.0460	uM
Gilteritinib	1425190: 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	2.0920	uM
1-N’-[2-fluoro-4-[[2-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]-4-pyridinyl]oxy]phenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	1425190: 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	2.1210	uM
4-(cyclopropylamino)-2-[4-(4-ethylsulfonylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide;hydrochloride	1425190: 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	2.2210	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	1425190: 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	2.2330	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149542: Binding affinity to human TAOK2 incubated for 45 mins by Kinobead based pull down assay	kd	2.5155	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637141: Inhibition of recombinant human GST-tagged TAOK2 catalytic domain expressed in baculovirus expression system by Z’-LYTE assay	ic50	2.7000	uM
Pacritinib	1425190: 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	3.3750	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	625099: Binding constant for TAOK2 kinase domain	kd	3.9000	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625099: Binding constant for TAOK2 kinase domain	kd	4.9000	uM
N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide	1425190: 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	5.2460	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	625099: Binding constant for TAOK2 kinase domain	kd	5.4000	uM
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline	625099: Binding constant for TAOK2 kinase domain	kd	5.9000	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	625099: Binding constant for TAOK2 kinase domain	kd	6.9000	uM
5,5-dimethyl-8-[[4-(2,2,2-trifluoroethylamino)furo[3,2-d]pyrimidin-2-yl]amino]-1H-4,1-benzoxazepin-2-one	1440161: Inhibition of TAOK2 (unknown origin) after 60 mins by TR-FRET assay	ic50	8.5200	uM
2-anilino-7-[(1S)-4-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethylpyrrolo[2,3-d]pyrimidin-6-one	1336096: Inhibition of human recombinant GST-tagged TAOK2 cytoplasmic domain (1 to 314 residues) expressed in baculovirus expression system	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Glyphosate	decreases expression	1
Acrolein	decreases expression, increases abundance, affects cotreatment	1
Air Pollutants, Occupational	affects expression	1
Arsenicals	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Chelating Agents	decreases expression, affects binding	1
Clozapine	increases expression	1
Copper	decreases expression, affects binding	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1

ChEMBL screening assays

232 unique, capped per target: 232 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1043824	Binding	Residual activity of TAOK2 at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3J1	Abcam HEK293T TAOK2 KO	Transformed cell line	Female
CVCL_D8C1	Ubigene A-549 TAOK2 KO	Cancer cell line	Male
CVCL_E0QH	Ubigene HeLa TAOK2 KO	Cancer cell line	Female
CVCL_TR56	HAP1 TAOK2 (-) 1	Cancer cell line	Male
CVCL_TR57	HAP1 TAOK2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder