TAOK1

Summary

TAOK1 (TAO kinase 1, HGNC:29259) is a protein-coding gene on chromosome 17q11.2, encoding Serine/threonine-protein kinase TAO1 (Q7L7X3). Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability. It is haploinsufficient (ClinGen: sufficient evidence).

Enables alpha-tubulin binding activity; beta-tubulin binding activity; and kinase activity. Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; negative regulation of microtubule depolymerization; and positive regulation of MAPK cascade. Located in several cellular components, including microtubule cytoskeleton; nuclear body; and perinuclear region of cytoplasm.

Source: NCBI Gene 57551 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 22
• Clinical variants (ClinVar): 330 total — 31 pathogenic, 39 likely-pathogenic
• Phenotypes (HPO): 52
• Druggable target: yes — 58 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_020791

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29259
Approved symbol	TAOK1
Name	TAO kinase 1
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1361, MARKK, PSK2, MAP3K16, FLJ14314, TAO1, hTAOK1, hKFC-B
Ensembl gene	ENSG00000160551
Ensembl biotype	protein_coding
OMIM	610266
Entrez	57551

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 retained_intron

ENST00000261716, ENST00000536202, ENST00000577583, ENST00000578653, ENST00000583121, ENST00000587277, ENST00000867620, ENST00000867621, ENST00000916641

RefSeq mRNA: 2 — MANE Select: NM_020791 NM_020791, NM_025142

CCDS: CCDS32601, CCDS56024

Canonical transcript exons

ENST00000261716 — 20 exons

Exon	Start	End
ENSE00001052948	29522280	29522519
ENSE00001052963	29517453	29517656
ENSE00001052969	29534118	29534300
ENSE00001052976	29530407	29530619
ENSE00001053061	29480368	29480481
ENSE00001114300	29510864	29510992
ENSE00001114306	29477661	29477706
ENSE00001126418	29478251	29478347
ENSE00001254227	29475670	29475771
ENSE00001254249	29451455	29451680
ENSE00001659445	29467145	29467216
ENSE00002584590	29542561	29551903
ENSE00002699698	29390363	29391024
ENSE00003461530	29491784	29491865
ENSE00003512739	29495560	29495727
ENSE00003525765	29498318	29498521
ENSE00003527197	29502589	29502723
ENSE00003625064	29482197	29482288
ENSE00003630700	29507896	29508132
ENSE00003647478	29489664	29489757

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6454 / max 271.3708, expressed in 1783 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160090	11.1086	1773
160091	1.0382	576
160095	0.4987	253

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	97.61	gold quality
globus pallidus	UBERON:0001875	96.98	gold quality
medial globus pallidus	UBERON:0002477	96.98	gold quality
ventral tegmental area	UBERON:0002691	96.85	gold quality
subthalamic nucleus	UBERON:0001906	96.80	gold quality
sural nerve	UBERON:0015488	96.68	gold quality
substantia nigra pars compacta	UBERON:0001965	96.65	gold quality
inferior vagus X ganglion	UBERON:0005363	96.65	gold quality
pons	UBERON:0000988	96.64	gold quality
lateral globus pallidus	UBERON:0002476	96.49	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.41	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.36	gold quality
parietal pleura	UBERON:0002400	96.30	gold quality
cerebellar vermis	UBERON:0004720	96.28	gold quality
skin of hip	UBERON:0001554	96.24	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.19	gold quality
superior vestibular nucleus	UBERON:0007227	96.18	gold quality
parietal lobe	UBERON:0001872	96.17	gold quality
visceral pleura	UBERON:0002401	96.12	gold quality
entorhinal cortex	UBERON:0002728	96.10	gold quality
pigmented layer of retina	UBERON:0001782	95.97	gold quality
postcentral gyrus	UBERON:0002581	95.97	gold quality
nipple	UBERON:0002030	95.96	gold quality
endothelial cell	CL:0000115	95.86	gold quality
trabecular bone tissue	UBERON:0002483	95.66	gold quality
renal medulla	UBERON:0000362	95.59	gold quality
cauda epididymis	UBERON:0004360	95.57	gold quality
dorsal root ganglion	UBERON:0000044	95.50	gold quality
upper leg skin	UBERON:0004262	95.47	gold quality
pleura	UBERON:0000977	95.45	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	343.04
E-ANND-3	yes	7.92
E-MTAB-6524	no	84.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

586 targeting TAOK1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4668-3P	100.00	68.74	2635

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 21)

• Prostate-derived sterile 20-like kinase 2 (PSK2) regulates apoptotic morphology via C-Jun N-terminal kinase and Rho kinase-1 (PMID:16407310)
• TAO kinases are regulators of p38-mediated responses to DNA damage and are intermediates in the activation of p38 by ATM. (PMID:17396146)
• Dual functions of TAO1 in regulating microtubule dynamics and checkpoint signalling may help to coordinate the establishment and monitoring of correct congression of chromosomes, thereby protecting genomic stability in human cells. (PMID:17417629)
• It is concluded that human TAO kinase 1 induces apoptosis in SH-SY5Y cells and the kinase domain is essential, but its catalytic activity seems to be dispensable in this case. (PMID:17900936)
• Spred1-MARKK binding has no effect on the activity of MARKK; therefore, it does not change microtubule (MT) stability. (PMID:18216281)
• the apparent role of the Tao1 kinase in spindle checkpoing signaling might in reality reflect an off-target effect produced by particular Tao1-directed siRNA oligonucleotides on Mad2 (PMID:19904549)
• Data do not support the notion that Tao1 is a component of the spindle checkpoint. (PMID:20162290)
• Human TAO1 can phosphorylate and activate human MST2 (PMID:22075148)
• 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)
• The TAO1 kinase is required for ensuring the normal congression of chromosomes. Depletion of TAO1 reduces the density of growing interphase and mitotic microtubules in human cells, showing TAO1’s role in controlling microtubule dynamics. (PMID:24898139)
• This study reports a novel set of Dengue virus (DENV) NS1-interacting host cell proteins in the HepG2 cell line and proposes possible roles for human NEK2, TAO1, and COG1 in DENV infection. (PMID:27108190)
• this study reveals a protective role for miR-706 by blocking the oxidative stress-induced activation of PKCalpha/TAOK1. Our results further identify a major implication for miR-706 in preventing hepatic fibrogenesis and suggest that miR-706 may be a suitable molecular target for anti-fibrosis therapy. (PMID:27876854)
• 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)
• These results demonstrate that TAOK1 is a negative regulator of IL-17 signaling and that it may have therapeutic utility as a target for the treatment of IL-17-associated inflammatory disorders. (PMID:29400705)
• Variants in TAOK1 Cause Neurodevelopmental Disorders. (PMID:31230721)
• miR-381-abundant small extracellular vesicles derived from kartogenin-preconditioned mesenchymal stem cells promote chondrogenesis of MSCs by targeting TAOK1. (PMID:31864017)
• Inherited and de novo variants extend the etiology of TAOK1-associated neurodevelopmental disorder. (PMID:35091509)
• Exosomal circTAOK1 contributes to diabetic kidney disease progression through regulating SMAD3 expression by sponging miR-520h. (PMID:35142978)
• [The role and mechanism of lncRNA C9ORF139 targeting miR-24-3P/TAOK1 in regulating the proliferation of acute myeloid leukemia cells]. (PMID:35196780)
• Silencing of STE20-type kinase TAOK1 confers protection against hepatocellular lipotoxicity through metabolic rewiring. (PMID:36930872)
• lincRNA00907 promotes NASH progression by targeting miRNA-942-5p/TAOK1. (PMID:38613803)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	taok1a	ENSDARG00000069603
danio_rerio	taok1b	ENSDARG00000098304
mus_musculus	Taok1	ENSMUSG00000017291
rattus_norvegicus	Taok1	ENSRNOG00000015692

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), PAK3 (ENSG00000077264), STRADB (ENSG00000082146), MAP3K1 (ENSG00000095015), STK4 (ENSG00000101109), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), STK25 (ENSG00000115694), NRK (ENSG00000123572), PAK4 (ENSG00000130669), STK26 (ENSG00000134602), TAOK3 (ENSG00000135090), PAK6 (ENSG00000137843), MINK1 (ENSG00000141503), PAK1 (ENSG00000149269), TAOK2 (ENSG00000149930), TNIK (ENSG00000154310), MAP4K2 (ENSG00000168067), OXSR1 (ENSG00000172939), MAP3K19 (ENSG00000176601), PAK2 (ENSG00000180370), SBK2 (ENSG00000187550), STK39 (ENSG00000198648), STRADA (ENSG00000266173)

Protein

Protein identifiers

Serine/threonine-protein kinase TAO1 — Q7L7X3 (reviewed: Q7L7X3)

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

All UniProt accessions (3): Q7L7X3, A0A994J797, J3QS76

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability. Phosphorylates MAP2K3, MAP2K6 and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade by mediating phosphorylation and subsequent activation of the upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled receptor signaling to p38/MAPK14. 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 MAP2K3 and MAP2K6. Acts as a regulator of cytoskeleton stability by phosphorylating ‘Thr-208’ of MARK2, leading to activate MARK2 kinase activity and subsequent phosphorylation and detachment of MAPT/TAU from microtubules. Also acts as a regulator of apoptosis: regulates apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation via activation of the MAPK8/JNK cascade. Plays an essential role in the regulation of neuronal development in the central nervous system. Also plays a role in the regulation of neuronal migration to the cortical plate.

Subunit / interactions. Self-associates. Interacts with MAP2K3. Interacts with SPRED1. Interacts with TESK1; the interaction inhibits TAOK1 kinase activity. Interacts with MAP3K7.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in the testis, and to a lower extent also expressed in brain, placenta, colon and skeletal muscle.

Post-translational modifications. Proteolytically processed by caspase-3 (CASP3). Autophosphorylated. Phosphorylated by ATM in response to DNA damage. Phosphorylated by LRRK2.

Disease relevance. Developmental delay with or without intellectual impairment or behavioral abnormalities (DDIB) [MIM:619575] An autosomal dominant disorder characterized by a highly variable phenotype of developmental delay, intellectual disability, learning or behavioral problems, muscular hypotonia, and neonatal feeding difficulties. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Serine/threonine-protein kinase activity is inhibited by SPRED1.

Induction. In response to DNA damage.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q7L7X3-1	1	yes
Q7L7X3-2	2
Q7L7X3-3	3

RefSeq proteins (2): NP_065842, NP_079418 (=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 (52 total): sequence variant 19, mutagenesis site 6, compositionally biased region 5, modified residue 5, splice variant 4, region of interest 3, sequence conflict 3, binding site 2, coiled-coil region 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L7X3-F1	77.36	0.56

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 (5): 9, 421, 445, 669, 965

Mutagenesis-validated functional residues (6):

Position	Phenotype
57	abolishes kinase activity, ability to activate the mapk8/jnk cascade and cleavage by caspase-3 (casp3).
169	loss of serine/threonine-protein kinase activity.
376	does not abolish cleavage by caspase-3 (casp3).
643	abolishes phosphorylation by atm; when associated with a-785 and a-990.
785	abolishes phosphorylation by atm; when associated with a-643 and a-990.
990	abolishes phosphorylation by atm; when associated with a-643 and a-785.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-9920951	Dengue virus modulates apoptosis
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 536 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, TAATAAT_MIR126, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, KEGG_MAPK_SIGNALING_PATHWAY, GCANCTGNY_MYOD_Q6, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEUROGENESIS, GGGTGGRR_PAX4_03, chr17q11, GOBP_POSITIVE_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT

GO Biological Process (15): microtubule cytoskeleton organization (GO:0000226), DNA repair (GO:0006281), DNA damage response (GO:0006974), negative regulation of microtubule depolymerization (GO:0007026), mitotic G2 DNA damage checkpoint signaling (GO:0007095), central nervous system neuron development (GO:0021954), positive regulation of stress-activated MAPK cascade (GO:0032874), regulation of actin cytoskeleton organization (GO:0032956), positive regulation of JNK cascade (GO:0046330), regulation of cytoskeleton organization (GO:0051493), neuron cellular homeostasis (GO:0070050), regulation of microtubule cytoskeleton organization (GO:0070507), execution phase of apoptosis (GO:0097194), protein phosphorylation (GO:0006468), apoptotic process (GO:0006915)

GO Molecular Function (13): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), kinase activity (GO:0016301), transferase activity (GO:0016740), alpha-tubulin binding (GO:0043014), protein serine/threonine kinase activator activity (GO:0043539), tau protein binding (GO:0048156), beta-tubulin binding (GO:0048487), tau-protein kinase activity (GO:0050321), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), microtubule cytoskeleton (GO:0015630), nuclear body (GO:0016604), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Cell Cycle	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Dengue Virus-Host Interactions	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle Checkpoints	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoskeleton organization	2
positive regulation of MAPK cascade	2
regulation of cytoskeleton organization	2
protein kinase activity	2
tubulin binding	2
protein serine/threonine kinase activity	2
cytoplasm	2
microtubule-based process	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
central nervous system neuron differentiation	1
neuron development	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
JNK cascade	1
regulation of JNK cascade	1
regulation of organelle organization	1
cellular homeostasis	1
microtubule cytoskeleton organization	1
regulation of microtubule-based process	1
apoptotic process	1
cellular process	1
bleb assembly	1
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1

Protein interactions and networks

STRING

1178 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAOK1	S100A8	P05109	888
TAOK1	F8WDG0	F8WDG0	743
TAOK1	IQCJ-SCHIP1	B3KU38	722
TAOK1	BUB1B	O60566	637
TAOK1	PTPN11	Q06124	614
TAOK1	MARK2	Q7KZI7	573
TAOK1	SAV1	Q9H4B6	527
TAOK1	TESK1	Q15569	510
TAOK1	TP53	P04637	507
TAOK1	BUB1	O43683	502
TAOK1	CAB39	Q9Y376	482
TAOK1	BUB3	O43684	480
TAOK1	GFER	P55789	479
TAOK1	ZW10	O43264	475
TAOK1	DIAPH1	O60610	467
TAOK1	MYO5A	Q9Y4I1	467

IntAct

71 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
STK26	STK25	psi-mi:“MI:0914”(association)	0.790
LDHA	LDHC	psi-mi:“MI:0914”(association)	0.770
STK4	MAP1B	psi-mi:“MI:0914”(association)	0.730
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
ABITRAM	POTEF	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
PLEKHN1	ELP1	psi-mi:“MI:0914”(association)	0.530
TRPC4AP	SMCHD1	psi-mi:“MI:0914”(association)	0.530
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
MARK2	TAOK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
TAOK1	OCIAD2	psi-mi:“MI:0915”(physical association)	0.400
C8orf33	TAOK1	psi-mi:“MI:0915”(physical association)	0.370
TAOK1	CSNK1E	psi-mi:“MI:0915”(physical association)	0.370
TAOK1	DYNC1I1	psi-mi:“MI:0915”(physical association)	0.370
GEMIN7	TAOK1	psi-mi:“MI:0915”(physical association)	0.370
WT1	TAOK1	psi-mi:“MI:0915”(physical association)	0.370
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
	ZNF316	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
HTRA4	ATOX1	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): TAOK1 (Affinity Capture-MS), TAOK1 (Affinity Capture-MS), TAOK1 (Affinity Capture-MS), TAOK1 (Affinity Capture-MS), TAOK1 (Affinity Capture-MS), TAOK1 (Affinity Capture-MS), TAOK1 (Affinity Capture-RNA), TAOK1 (Affinity Capture-MS), TAOK1 (Affinity Capture-MS), TAOK1 (Affinity Capture-MS), TAOK1 (Proximity Label-MS), TAOK1 (Affinity Capture-RNA), TAOK1 (Affinity Capture-MS), TAOK1 (Affinity Capture-MS), TAOK1 (Affinity Capture-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: A0A7J6K7I9, A0A7J6K7Y0, A0A7J6KD88, A2QHV0, A8XJQ6, C4YRB7, O13839, O14047, O34507, O75011, O80888, O88664, P0CY23, P0CY24, P16912, P27636, P28829, P34722, P41892, P50527, P51956, P51957, P92199, P93025, P9WI62, P9WI63, Q0CL79, Q0KHQ5, Q0WPH8, Q12851, Q12852, Q19192, Q1DB00, Q4P5N0, Q53UA7, Q55CA6, Q55D99, Q55DD4, Q55GV3, Q5AP97

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
ATM	up-regulates	TAOK1	phosphorylation
TAOK1	up-regulates	STK3	phosphorylation
TAOK1	up-regulates	STK4	phosphorylation
DNA_damage	up-regulates	TAOK1
GNAO1	up-regulates	TAOK1
TAOK1	up-regulates	STK3/4	phosphorylation
STK24	“up-regulates activity”	TAOK1	phosphorylation
TAOK1	“up-regulates activity”	MAP2K3	phosphorylation
TAOK1	“up-regulates activity”	MARK2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Apoptosis	6	18.0×	9e-05
Programmed Cell Death	6	15.7×	1e-04
G2/M Checkpoints	5	12.0×	2e-03
mRNA Splicing	5	9.8×	5e-03
Transcriptional Regulation by TP53	6	6.7×	8e-03
Metabolism of RNA	8	6.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein autophosphorylation	6	11.3×	5e-03
protein phosphorylation	8	7.1×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	31
Likely pathogenic	39
Uncertain significance	191
Likely benign	27
Benign	11

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1064776	NM_020791.4(TAOK1):c.2161C>T (p.Gln721Ter)	Pathogenic
1300170	NM_020791.4(TAOK1):c.2366_2367insC (p.Leu790fs)	Pathogenic
1300172	NM_020791.4(TAOK1):c.1643T>C (p.Leu548Pro)	Pathogenic
1309471	NM_020791.4(TAOK1):c.2503G>T (p.Glu835Ter)	Pathogenic
1310669	NM_020791.4(TAOK1):c.2253_2256del (p.Glu752fs)	Pathogenic
1319697	NM_020791.4(TAOK1):c.2488G>T (p.Glu830Ter)	Pathogenic
1343153	NM_020791.4(TAOK1):c.1823del (p.Arg608fs)	Pathogenic
1686248	NM_020791.4(TAOK1):c.626G>A (p.Trp209Ter)	Pathogenic
1710010	NM_020791.4(TAOK1):c.2563del (p.Ala855fs)	Pathogenic
1712256	NM_020791.4(TAOK1):c.18_19del (p.Arg6fs)	Pathogenic
1879365	NM_020791.4(TAOK1):c.1813C>T (p.Arg605Ter)	Pathogenic
2579186	GRCh38/hg38 17q11.2(chr17:29461486-29495582)x1	Pathogenic
2579940	NM_020791.4(TAOK1):c.928C>T (p.Arg310Ter)	Pathogenic
2584442	NM_020791.4(TAOK1):c.204+1G>A	Pathogenic
3048845	NM_020791.4(TAOK1):c.2485C>T (p.Arg829Ter)	Pathogenic
3173777	NM_020791.4(TAOK1):c.1390dup (p.Met464fs)	Pathogenic
3251938	NM_020791.4(TAOK1):c.1850del (p.Arg617fs)	Pathogenic
3359008	NM_020791.4(TAOK1):c.1576-2A>T	Pathogenic
3359054	NM_020791.4(TAOK1):c.1507C>T (p.Gln503Ter)	Pathogenic
3377100	NM_020791.4(TAOK1):c.728del (p.Pro243fs)	Pathogenic
3452872	NM_020791.4(TAOK1):c.1673_1674del (p.Glu558fs)	Pathogenic
3677155	NM_020791.4(TAOK1):c.1819C>T (p.Gln607Ter)	Pathogenic
3778705	NM_020791.4(TAOK1):c.307-14A>G	Pathogenic
3900664	NM_020791.4(TAOK1):c.920del (p.Leu307fs)	Pathogenic
4072009	NM_020791.4(TAOK1):c.952del (p.Gln318fs)	Pathogenic
4072331	NM_020791.4(TAOK1):c.1684C>T (p.Arg562Ter)	Pathogenic
4537893	NM_020791.4(TAOK1):c.1501G>T (p.Glu501Ter)	Pathogenic
4632643	NM_020791.4(TAOK1):c.352+1G>A	Pathogenic
4819150	NM_020791.4(TAOK1):c.749G>A (p.Trp250Ter)	Pathogenic
4845404	NM_020791.4(TAOK1):c.2191A>T (p.Lys731Ter)	Pathogenic

SpliceAI

3917 predictions. Top by Δscore:

Variant	Effect	Δscore
17:29391022:AGGG:A	donor_loss	1.0000
17:29391023:GG:G	donor_gain	1.0000
17:29391023:GGGT:G	donor_loss	1.0000
17:29391024:GG:G	donor_gain	1.0000
17:29391024:GGTA:G	donor_loss	1.0000
17:29391025:GTA:G	donor_loss	1.0000
17:29436901:G:T	donor_gain	1.0000
17:29436934:G:GT	donor_gain	1.0000
17:29451453:A:AG	acceptor_gain	1.0000
17:29451454:G:GA	acceptor_gain	1.0000
17:29451454:GT:G	acceptor_gain	1.0000
17:29451454:GTA:G	acceptor_gain	1.0000
17:29451454:GTAGT:G	acceptor_gain	1.0000
17:29451658:G:GT	donor_gain	1.0000
17:29451658:G:T	donor_gain	1.0000
17:29451676:ATTTT:A	donor_gain	1.0000
17:29451677:TTTT:T	donor_gain	1.0000
17:29451678:TTT:T	donor_gain	1.0000
17:29451679:TT:T	donor_gain	1.0000
17:29451680:TGT:T	donor_loss	1.0000
17:29451681:G:GG	donor_gain	1.0000
17:29451681:GTA:G	donor_loss	1.0000
17:29451685:GT:G	donor_gain	1.0000
17:29467140:TTTA:T	acceptor_loss	1.0000
17:29467141:TTAG:T	acceptor_loss	1.0000
17:29467142:TA:T	acceptor_loss	1.0000
17:29467143:A:AG	acceptor_gain	1.0000
17:29467143:AG:A	acceptor_gain	1.0000
17:29467144:G:GA	acceptor_gain	1.0000
17:29467144:GG:G	acceptor_gain	1.0000

AlphaMissense

6653 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:29451619:C:A	P24Q	1.000
17:29451631:T:C	F28S	1.000
17:29451651:G:C	G35R	1.000
17:29451652:G:A	G35D	1.000
17:29451657:G:A	G37R	1.000
17:29451657:G:C	G37R	1.000
17:29451658:G:A	G37E	1.000
17:29451658:G:T	G37V	1.000
17:29451660:A:C	S38R	1.000
17:29451662:C:A	S38R	1.000
17:29451662:C:G	S38R	1.000
17:29451663:T:A	F39I	1.000
17:29451663:T:C	F39L	1.000
17:29451664:T:G	F39C	1.000
17:29451665:T:A	F39L	1.000
17:29451665:T:G	F39L	1.000
17:29451666:G:A	G40R	1.000
17:29451666:G:C	G40R	1.000
17:29451667:G:A	G40E	1.000
17:29451673:T:A	V42E	1.000
17:29451675:T:G	Y43D	1.000
17:29467146:C:A	A45E	1.000
17:29467176:C:A	A55D	1.000
17:29467181:A:G	K57E	1.000
17:29467183:G:C	K57N	1.000
17:29467183:G:T	K57N	1.000
17:29467188:T:C	M59T	1.000
17:29475691:G:A	E76K	1.000
17:29475704:T:C	L80P	1.000
17:29475769:T:A	W102R	1.000

dbSNP variants (sampled 300 via entrez): RS1000013501 (17:29418288 A>G), RS1000047173 (17:29425133 G>A), RS1000050318 (17:29525381 GATTAC>G), RS1000065096 (17:29437932 T>C), RS1000068118 (17:29410524 A>G), RS1000069127 (17:29498808 C>A,T), RS1000113999 (17:29544531 C>T), RS1000119137 (17:29471194 A>C,G), RS1000125218 (17:29411939 GT>G), RS1000134934 (17:29404118 C>G), RS1000163380 (17:29528300 A>G), RS1000164173 (17:29434270 G>A), RS1000217450 (17:29390014 T>C), RS1000233768 (17:29404437 C>T), RS1000267356 (17:29395848 T>G)

Disease associations

OMIM: gene MIM:610266 | disease phenotypes: MIM:619575, MIM:618330, MIM:156200

GenCC curated gene-disease

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	Autosomal dominant
developmental delay with or without intellectual impairment or behavioral abnormalities	Definitive	Autosomal dominant
complex neurodevelopmental disorder	Moderate	Autosomal dominant
autosomal dominant non-syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Mondo (8): neurodevelopmental disorder (MONDO:0700092), developmental delay with or without intellectual impairment or behavioral abnormalities (MONDO:0859199), macroglossia (MONDO:0015496), global developmental delay with or without impaired intellectual development (MONDO:0032680), intellectual disability, autosomal dominant 1 (MONDO:0007974), complex neurodevelopmental disorder (MONDO:0100038), syndromic intellectual disability (MONDO:0000508), autosomal dominant non-syndromic intellectual disability (MONDO:0015802)

Orphanet (2): Macroglossia (Orphanet:156207), 2q23.1 microdeletion syndrome (Orphanet:228402)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000540	Hypermetropia
HP:0000639	Nystagmus
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000736	Short attention span
HP:0000750	Delayed speech and language development
HP:0001134	Anterior polar cataract
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001382	Joint hypermobility
HP:0001508	Failure to thrive
HP:0001629	Ventricular septal defect
HP:0001763	Pes planus

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST000305_1	Mean platelet volume	7.000000e-28
GCST000497_9	Mean platelet volume	1.000000e-22
GCST001335_28	Mean platelet volume	5.000000e-38
GCST001337_50	Platelet count	3.000000e-18
GCST001439_2	Mean platelet volume	4.000000e-08
GCST002184_11	Mean platelet volume	1.000000e-10
GCST004599_117	Mean platelet volume	2.000000e-298
GCST004599_118	Mean platelet volume	2.000000e-26
GCST004599_119	Mean platelet volume	2.000000e-139
GCST005054_2	Platelet count	6.000000e-06
GCST90002395_247	Mean platelet volume	2.000000e-39
GCST90002395_248	Mean platelet volume	3.000000e-59
GCST90002395_249	Mean platelet volume	0.000000e+00
GCST90002402_444	Platelet count	3.000000e-18
GCST90002402_445	Platelet count	3.000000e-19
GCST90002402_446	Platelet count	1.000000e-66
GCST90002404_154	Red cell distribution width	3.000000e-09
GCST90020024_516	A body shape index	1.000000e-09
GCST90020025_1409	Waist-to-hip ratio adjusted for BMI	9.000000e-13
GCST90020027_456	Waist-hip index	8.000000e-13
GCST90020029_478	Waist circumference adjusted for body mass index	4.000000e-09
GCST90020029_479	Waist circumference adjusted for body mass index	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0009188	Red cell distribution width
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008260	Macroglossia	C07.465.910.460
D065886	Neurodevelopmental Disorders	F03.625
C566947	Mental Retardation, Autosomal Dominant 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5261 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

58 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 443,267 (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
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL941	IMATINIB	4	111,611
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL491473	CEDIRANIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL1230165	SILMITASERTIB	2
CHEMBL1230609	FORETINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL1967878	CENISERTIB	2
CHEMBL1976040	ADAVOSERTIB	2
CHEMBL1980297	ILORASERTIB	2

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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
AMG28	Inhibition	7.7	pIC50
compound 18 [PMID: 20873740]	Inhibition	6.38	pIC50

ChEMBL bioactivities

539 potent at pChembl≥5 of 554 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.35	Kd	0.45	nM	STAUROSPORINE
9.33	IC50	0.469	nM	STAUROSPORINE
9.14	IC50	0.723	nM	STAUROSPORINE
8.92	IC50	1.21	nM	STAUROSPORINE
8.70	Kd	2	nM	GSK-1059615
8.20	Ki	6.31	nM	PD-0166285
8.00	Ki	10	nM	CHEMBL1980995
7.93	Kd	11.86	nM	CHEMBL5653589
7.82	Kd	15	nM	CHEMBL4576489
7.80	Ki	15.85	nM	CHEMBL2006715
7.77	Kd	17	nM	CHEMBL3688339
7.75	ED50	17.84	nM	CHEMBL5653589
7.70	IC50	20	nM	CHEMBL2334586
7.70	IC50	20	nM	CHEMBL5409039
7.70	Ki	19.95	nM	CHEMBL1987034
7.62	IC50	23.7	nM	CHEMBL6190046
7.60	Kd	25	nM	CHEMBL4465866
7.60	Kd	25	nM	TAE-684
7.60	Ki	25.12	nM	CHEMBL1967998
7.60	Ki	25.12	nM	CHEMBL1984847
7.60	Ki	25.12	nM	JNJ-7706621
7.60	Ki	25.12	nM	CHEMBL1993661
7.54	Kd	29	nM	AST-487
7.50	Ki	31.62	nM	CHEMBL1998159
7.40	Ki	39.81	nM	CHEMBL1981725
7.30	IC50	50	nM	CHEMBL3718523
7.30	IC50	50	nM	CHEMBL3715956
7.30	IC50	50	nM	CHEMBL3716416
7.30	IC50	50	nM	CHEMBL3716849
7.30	IC50	50	nM	CHEMBL3719286
7.30	IC50	50	nM	CHEMBL3717468
7.30	IC50	50	nM	CHEMBL3718453
7.30	IC50	50	nM	CHEMBL3718473
7.30	IC50	50	nM	CHEMBL3715362
7.30	IC50	50	nM	CHEMBL3718166
7.30	IC50	50	nM	CHEMBL3717484
7.30	IC50	50	nM	CHEMBL3717193
7.30	IC50	50	nM	CHEMBL3719326
7.30	IC50	50	nM	CHEMBL3715589
7.30	IC50	50	nM	CHEMBL3718066
7.30	IC50	50	nM	CHEMBL3716968
7.30	IC50	50	nM	CHEMBL3716744
7.30	IC50	50	nM	CHEMBL3717452
7.30	IC50	50	nM	CHEMBL3715987
7.30	IC50	50	nM	CHEMBL3718397
7.30	IC50	50	nM	CHEMBL3715806
7.30	IC50	50	nM	CHEMBL3717236
7.30	IC50	50	nM	CHEMBL3716597
7.30	IC50	50	nM	CHEMBL3717391
7.30	IC50	50	nM	CHEMBL3717287

PubChem BioAssay actives

75 with measured affinity, of 1766 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	625126: Binding constant for TAOK1 kinase domain	kd	0.0004	uM
(5Z)-5-[(4-pyridin-4-ylquinolin-6-yl)methylidene]-1,3-thiazolidine-2,4-dione	1425189: 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	0.0020	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149541: Binding affinity to human TAOK1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0119	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	1526297: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged TAOK1 (unknown origin) (1 to 314 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0150	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425189: 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	0.0170	uM
(9S)-9-(hydroxymethyl)-6-[1-(2-hydroxy-2-methylpropyl)pyrazol-4-yl]-16-oxa-2,4,8,26-tetrazatetracyclo[19.3.1.13,7.010,15]hexacosa-1(25),3,5,7(26),10,12,14,21,23-nonaene-22-carbonitrile	1964765: Inhibition of TAO1 (unknown origin) by Kinase assay	ic50	0.0200	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	1856570: Inhibition of human wild type TAOK1 (M1 to A320 residues) expressed in mammalian expression system by Kinomescan assay	ic50	0.0200	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	1526297: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged TAOK1 (unknown origin) (1 to 314 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0250	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	625126: Binding constant for TAOK1 kinase domain	kd	0.0250	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	625126: Binding constant for TAOK1 kinase domain	kd	0.0290	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	508102: Binding affinity to TAOK1	kd	0.0700	uM
Abemaciclib	1425189: 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	0.1070	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	625126: Binding constant for TAOK1 kinase domain	kd	0.1300	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625126: Binding constant for TAOK1 kinase domain	kd	0.1300	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	625126: Binding constant for TAOK1 kinase domain	kd	0.1400	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	2189181: Inhibition of TAOK1 (unknown origin) in presence of ATP by enzymatic assay	ic50	0.1650	uM
1-[(1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-4-[2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]pyridin-2-one	1425189: 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	0.2300	uM
Pazopanib	625126: Binding constant for TAOK1 kinase domain	kd	0.2400	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	625126: Binding constant for TAOK1 kinase domain	kd	0.2900	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	625126: Binding constant for TAOK1 kinase domain	kd	0.3200	uM
N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide	1425189: 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	0.3420	uM
N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-4-[5-chloro-2-(propan-2-ylamino)-4-pyridinyl]-1H-pyrrole-2-carboxamide	1425189: 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	0.3880	uM
5-(2-aminopyrimidin-4-yl)-2-phenyl-1H-pyrrole-3-carboxamide	526160: Inhibition of TAO1	ic50	0.4200	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	625126: Binding constant for TAOK1 kinase domain	kd	0.4600	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625126: Binding constant for TAOK1 kinase domain	kd	0.4700	uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol	625126: Binding constant for TAOK1 kinase domain	kd	0.4800	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	625126: Binding constant for TAOK1 kinase domain	kd	0.4900	uM
6-imidazo[4,5-b]pyridin-1-yl-N-[5-(2-piperidin-1-ylethoxy)-2-pyridinyl]pyrimidin-4-amine	1533153: Inhibition recombinant human TAOK1 (1 to 356 residues) after 5 mins in presence of [33P] ATP by Topcount method	ic50	0.4900	uM
Brigatinib	2182860: Inhibition of human TAOK1 using MBP as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.4930	uM
Sorafenib	508101: Binding affinity to TAO1	kd	0.5400	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2R)-1-methoxy-4-methylpentan-2-yl]iminoimidazolidin-4-one	2024512: Inhibition of human TAO1 assessed as remaining activity by eurofins-cerep kinase profiler analysis	ic50	0.5960	uM
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	625126: Binding constant for TAOK1 kinase domain	kd	0.6000	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	625126: Binding constant for TAOK1 kinase domain	kd	0.6200	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625126: Binding constant for TAOK1 kinase domain	kd	0.8100	uM
Sunitinib	508102: Binding affinity to TAOK1	kd	0.8900	uM
3-(2-methyl-1,3-benzoxazol-5-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine	1425189: 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	1.0940	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	625126: Binding constant for TAOK1 kinase domain	kd	1.2000	uM
Crizotinib	625126: Binding constant for TAOK1 kinase domain	kd	1.2000	uM
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine	1425189: 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	1.2390	uM
Fedratinib	625126: Binding constant for TAOK1 kinase domain	kd	1.3000	uM
Ruxolitinib	625126: Binding constant for TAOK1 kinase domain	kd	1.3000	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	625126: Binding constant for TAOK1 kinase domain	kd	1.3000	uM
Bosutinib	625126: Binding constant for TAOK1 kinase domain	kd	1.3000	uM
(4Z)-2-anilino-4-(1,3-benzodioxol-5-ylmethylidene)-1H-imidazol-5-one	707475: Binding affinity to TAOK1	kd	1.7000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625126: Binding constant for TAOK1 kinase domain	kd	1.7000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625126: Binding constant for TAOK1 kinase domain	kd	1.8000	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	625126: Binding constant for TAOK1 kinase domain	kd	1.8000	uM
N-[4-[[3-(2-aminopyrimidin-4-yl)-2-pyridinyl]oxy]phenyl]-4-(4-methylthiophen-2-yl)phthalazin-1-amine	1425189: 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	1.8960	uM
4-[(1R)-1-aminoethyl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzamide	1425189: 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	2.0300	uM
5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid	1425189: 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	2.0800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation, increases methylation	1
coumarin	decreases phosphorylation	1
evodiamine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Vorinostat	decreases expression	1
Cidofovir	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Cannabinoids	affects methylation, increases abundance	1
Chelating Agents	increases expression, affects binding	1
Cisplatin	increases expression	1

ChEMBL screening assays

231 unique, capped per target: 230 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1020556	Binding	Inhibition of TAOK1 assessed as enzyme activity relative to control	Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem
CHEMBL1963750	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: TAO1	PubChem BioAssay data set

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1661	ZR-75-30	Cancer cell line	Female
CVCL_D8C0	Ubigene A-549 TAOK1 KO	Cancer cell line	Male
CVCL_D8WU	Ubigene HCT 116 TAOK1 KO	Cancer cell line	Male
CVCL_D9TV	Ubigene HEK293 TAOK1 KO	Transformed cell line	Female
CVCL_E0QG	Ubigene HeLa TAOK1 KO	Cancer cell line	Female
CVCL_TR54	HAP1 TAOK1 (-) 1	Cancer cell line	Male
CVCL_TR55	HAP1 TAOK1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

204 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,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism