TNIK

Summary

TNIK (TRAF2 and NCK interacting kinase, HGNC:30765) is a protein-coding gene on chromosome 3q26.2-q26.31, encoding TRAF2 and NCK-interacting protein kinase (Q9UKE5). Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway.

Wnt signaling plays important roles in carcinogenesis and embryonic development. The protein encoded by this gene is a serine/threonine kinase that functions as an activator of the Wnt signaling pathway. Mutations in this gene are associated with an autosomal recessive form of cognitive disability. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 23043 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, autosomal recessive 54 (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 22
• Clinical variants (ClinVar): 207 total — 1 pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes — 46 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_015028

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30765
Approved symbol	TNIK
Name	TRAF2 and NCK interacting kinase
Location	3q26.2-q26.31
Locus type	gene with protein product
Status	Approved
Aliases	MAP4K7, KIAA0551
Ensembl gene	ENSG00000154310
Ensembl biotype	protein_coding
OMIM	610005
Entrez	23043

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000284483, ENST00000341852, ENST00000357327, ENST00000436636, ENST00000459881, ENST00000460047, ENST00000464785, ENST00000465393, ENST00000468757, ENST00000470834, ENST00000475336, ENST00000484051, ENST00000487846, ENST00000488470, ENST00000496492, ENST00000928917, ENST00000948115

RefSeq mRNA: 8 — MANE Select: NM_015028 NM_001161560, NM_001161561, NM_001161562, NM_001161563, NM_001161564, NM_001161565, NM_001161566, NM_015028

CCDS: CCDS46956, CCDS54673, CCDS54674, CCDS54675, CCDS54676, CCDS54677, CCDS54678, CCDS54679

Canonical transcript exons

ENST00000436636 — 33 exons

Exon	Start	End
ENSE00001015207	171123596	171123702
ENSE00001015214	171125912	171126151
ENSE00001015215	171128714	171128878
ENSE00001015217	171110714	171110877
ENSE00001015234	171101449	171101633
ENSE00001212557	171369620	171369685
ENSE00001213123	171058414	171063964
ENSE00001291573	171167095	171167270
ENSE00001294850	171157460	171157664
ENSE00001303049	171211116	171211241
ENSE00001309385	171190697	171190787
ENSE00001309481	171161270	171161336
ENSE00001318580	171140399	171140509
ENSE00001327321	171194525	171194635
ENSE00001391432	171138191	171138379
ENSE00001411240	171108065	171108162
ENSE00001689233	171107183	171107206
ENSE00001845352	171460007	171460405
ENSE00002336461	171188702	171188832
ENSE00002474257	171139470	171139556
ENSE00002485455	171175252	171175330
ENSE00002492895	171228165	171228221
ENSE00002508686	171177326	171177380
ENSE00003465692	171084155	171084325
ENSE00003467289	171071223	171071323
ENSE00003506698	171085118	171085229
ENSE00003520374	171066187	171066326
ENSE00003526003	171087342	171087506
ENSE00003590637	171079518	171079652
ENSE00003591440	171066576	171066735
ENSE00003598222	171068848	171068997
ENSE00003603217	171093839	171093968
ENSE00003614861	171082251	171082394

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 96.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.3608 / max 932.8405, expressed in 1500 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45593	15.0223	1390
45592	3.1442	823
45591	2.3241	643
45594	0.8610	455
45590	0.3604	151
45595	0.3029	178
45589	0.2025	87
45588	0.1310	54
45575	0.0123	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.40	gold quality
oocyte	CL:0000023	95.71	gold quality
caudate nucleus	UBERON:0001873	93.03	gold quality
jejunal mucosa	UBERON:0000399	92.61	gold quality
secondary oocyte	CL:0000655	92.58	gold quality
nucleus accumbens	UBERON:0001882	92.02	gold quality
putamen	UBERON:0001874	91.96	gold quality
corpus callosum	UBERON:0002336	91.46	gold quality
medial globus pallidus	UBERON:0002477	90.74	gold quality
duodenum	UBERON:0002114	90.64	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.51	gold quality
postcentral gyrus	UBERON:0002581	90.07	gold quality
amygdala	UBERON:0001876	90.06	gold quality
globus pallidus	UBERON:0001875	90.05	gold quality
entorhinal cortex	UBERON:0002728	89.91	gold quality
temporal lobe	UBERON:0001871	89.72	gold quality
tibia	UBERON:0000979	89.53	gold quality
telencephalon	UBERON:0001893	89.30	gold quality
orbitofrontal cortex	UBERON:0004167	89.04	gold quality
parietal lobe	UBERON:0001872	88.99	gold quality
forebrain	UBERON:0001890	88.70	gold quality
cingulate cortex	UBERON:0003027	88.47	gold quality
superior frontal gyrus	UBERON:0002661	88.41	gold quality
anterior cingulate cortex	UBERON:0009835	88.39	gold quality
right frontal lobe	UBERON:0002810	88.35	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.35	gold quality
prefrontal cortex	UBERON:0000451	88.25	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.25	gold quality
adrenal tissue	UBERON:0018303	88.18	gold quality
apex of heart	UBERON:0002098	88.13	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	946.19
E-HCAD-35	yes	89.90
E-CURD-112	yes	32.90
E-HCAD-25	yes	24.19
E-CURD-119	yes	16.85
E-ANND-3	yes	15.15
E-GEOD-84465	yes	12.06
E-MTAB-6678	no	3.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

180 targeting TNIK, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642

Literature-anchored findings (GeneRIF, showing 20)

• TNIK is a specific effector of Rap2 to regulate actin cytoskeleton (PMID:15342639)
• TNIK is essential for the activation of both the canonical Wnt pathway and the JNK pathway, and serves as a pro-survival factor. (PMID:21710359)
• TNIK mediates proliferation and survival of EBV-transformed B-cells. (PMID:22904686)
• Dynamic change of TNIK offers a way to protect cells from outside stimulus. (PMID:23355318)
• nuclear p-TNIK expression was studied in hepatocellular carcinoma, and p-TNIK nuclear expression was associated with poor prognosis and is a candidate prognostic marker for hepatocellular carcinoma (PMID:25160513)
• Our results demonstrated that TNIK might play a crucial role in pancreatic carcinogenesis and serve as a novel therapeutic target of pancreatic cancer. (PMID:26269113)
• High expression of TNIK in colorectal cancer was associated with recurrence in stage II and III colorectal cancer patients. (PMID:26499327)
• Endogenous substrates of TNIK were identified in neurons, along with consensus sequences for TNIK. (PMID:26645429)
• results provide new evidence that TNIK may be involved in the proliferation of multiple myeloma IM-9 cells and in the anti-cancer activity of dovitinib via inhibition of the endogenous Wnt signaling pathway. (PMID:26995282)
• Exome sequencing of the index in each family revealed the same homozygous truncating mutation in TNIK that results in complete loss of the protein. TNIK is a kinase with a well-established role in dendrite development and synaptic transmission. The phenotype we observe in human patients who lack TNIK is consistent with the previously published Tnik (-/-) phenotype in the murine model (PMID:27106596)
• TNIK is required for the tumour-initiating function of colorectal cancer stem cells. Its inhibition is a promising therapeutic approach. (PMID:27562646)
• Here we present the result of a 4-stage genome-wide association study composed of 5,953 adolescent idiopathic scoliosis patients and 8,137 controls. Overall, we identified three novel susceptible loci including rs7593846 at 2p14 near MEIS1 , rs7633294 at 3p14.1 near MAGI1 and rs9810566 at 3q26.2 near TNIK (PMID:28334814)
• Results indicate that Traf2- and Nck-interacting kinase (TNIK) is involved in the interleukin-6-dependent proliferation of multiple myeloma cells. (PMID:28467797)
• Genome-wide association study on the etiology of adolescent idiopathic scoliosis using samples from more than 5 000 patients and 6 000 normal controls showed two genes: LBX1-AS1 on 10q24.32 and TNIK on 3q26.2 highly related to AIS initiation and progression [review] (PMID:30107698)
• We also show that the TNIK protein isoforms including/excluding exon 15 differently regulate cell spreading in non-neuronal cells and neuritogenesis in primary cortical neurons. Our data suggest a complex regulation between the ubiquitous TDP-43 and the neuron-specific NOVA-1 splicing factors in the brain that may help better understand the pathobiology of both neurodegenerative diseases and schizophrenia. (PMID:31382054)
• Effect of TNIK upregulation on JQ1-resistant human colorectal cancer HCT116 cells. (PMID:32828291)
• Methylome-wide association study of first-episode schizophrenia reveals a hypermethylated CpG site in the promoter region of the TNIK susceptibility gene. (PMID:32853717)
• TNIK influence the effects of antipsychotics on Wnt/beta-catenin signaling pathway. (PMID:34350475)
• The influence of TNIK gene polymorphisms on risperidone response in a Chinese Han population. (PMID:35698907)
• MiR-5590-3p inhibits the proliferation and invasion of ovarian cancer cells through mediating the Wnt/beta-catenin signaling pathway by targeting TNIK. (PMID:37318197)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tnika	ENSDARG00000056218
mus_musculus	Tnik	ENSMUSG00000027692
rattus_norvegicus	Tnik	ENSRNOG00000012422
drosophila_melanogaster	msn	FBGN0010909
caenorhabditis_elegans		WBGENE00003247

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), TAOK1 (ENSG00000160551), MAP4K2 (ENSG00000168067), OXSR1 (ENSG00000172939), MAP3K19 (ENSG00000176601), PAK2 (ENSG00000180370), SBK2 (ENSG00000187550), STK39 (ENSG00000198648), STRADA (ENSG00000266173)

Protein

Protein identifiers

TRAF2 and NCK-interacting protein kinase — Q9UKE5 (reviewed: Q9UKE5)

All UniProt accessions (3): Q9UKE5, C9J338, C9JVV1

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway.

Subunit / interactions. Interacts (via the CNH domain) with RAP2A (GTP-bound form preferentially); the interaction is direct and required for the activation of TNIK by RAP2A. Interacts with NEDD4; recruits RAP2A to NEDD4. Interacts with TRAF2 and NCK. Interacts with TCF7L2/TCF4 and CTNNB1; the interaction is direct. Interacts with TANC1.

Subcellular location. Nucleus. Cytoplasm. Recycling endosome. Cytoskeleton.

Tissue specificity. Expressed ubiquitously. Highest levels observed in heart, brain and skeletal muscle. Expressed in normal colonic epithelia and colorectal cancer tissues.

Post-translational modifications. Autophosphorylated. Autophosphorylation is activated by RAP2A and induces association to the cytoskeletal fraction.

Disease relevance. Intellectual developmental disorder, autosomal recessive 54 (MRT54) [MIM:617028] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT54 patients manifest intellectual disability, delayed speech and hyperactivity. The disease may be caused by variants affecting the gene represented in this entry.

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

Isoforms (8)

UniProt ID	Names	Canonical?
Q9UKE5-1	1	yes
Q9UKE5-2	2
Q9UKE5-3	3
Q9UKE5-4	4
Q9UKE5-5	5
Q9UKE5-6	6
Q9UKE5-7	7
Q9UKE5-8	8

RefSeq proteins (8): NP_001155032, NP_001155033, NP_001155034, NP_001155035, NP_001155036, NP_001155037, NP_001155038, NP_055843* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001180	CNH_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR051700	STE20_Ser-Thr_kinase	Family

Pfam: PF00069, PF00780

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 (85 total): modified residue 20, helix 17, strand 10, compositionally biased region 9, region of interest 8, turn 6, splice variant 3, sequence variant 3, mutagenesis site 3, domain 2, binding site 2, chain 1, active site 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
6RA7	X-RAY DIFFRACTION	1.2
7XZQ	X-RAY DIFFRACTION	2.09
7XZR	X-RAY DIFFRACTION	2.26
5AX9	X-RAY DIFFRACTION	2.4
8ZML	X-RAY DIFFRACTION	2.49
8X88	X-RAY DIFFRACTION	2.7
2X7F	X-RAY DIFFRACTION	2.8
8WM0	X-RAY DIFFRACTION	2.8
5CWZ	X-RAY DIFFRACTION	2.9
5D7A	X-RAY DIFFRACTION	2.9
6RA5	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKE5-F1	64.60	0.22

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): 153 (proton acceptor)

Ligand- & substrate-binding residues (2): 31–39; 54

Post-translational modifications (20): 187, 324, 326, 560, 570, 581, 600, 608, 610, 640, 678, 680, 688, 701, 707, 720, 764, 766, 769, 959

Mutagenesis-validated functional residues (3):

Position	Phenotype
54	kinase dead. loss of autophosphorylation and loss of function in cytoskeleton regulation.
152–153	loss of autophosphorylation.
171–172	loss of autophosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2559580	Oxidative Stress Induced Senescence

MSigDB gene sets: 272 (showing top): GOBP_DENDRITE_DEVELOPMENT, GCM_MAP4K4, LOPEZ_MESOTHELIOMA_SURVIVAL_DN, MORF_MSH3, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, chr3q26, MORF_RAD51L3, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, PID_TNF_PATHWAY

GO Biological Process (15): MAPK cascade (GO:0000165), protein phosphorylation (GO:0006468), cytoskeleton organization (GO:0007010), Wnt signaling pathway (GO:0016055), actin cytoskeleton organization (GO:0030036), intracellular signal transduction (GO:0035556), regulation of MAPK cascade (GO:0043408), positive regulation of JNK cascade (GO:0046330), protein autophosphorylation (GO:0046777), neuron projection morphogenesis (GO:0048812), regulation of dendrite morphogenesis (GO:0048814), positive regulation of microvillus assembly (GO:1903698), nervous system development (GO:0007399), regulation of JNK cascade (GO:0046328), positive regulation of intracellular signal transduction (GO:1902533)

GO Molecular Function (8): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), apical plasma membrane (GO:0016324), recycling endosome (GO:0055037), extracellular exosome (GO:0070062), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), postsynaptic density, intracellular component (GO:0099092), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cellular Senescence	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular anatomical structure	2
regulation of intracellular signal transduction	2
JNK cascade	2
protein kinase activity	2
synapse	2
intracellular signaling cassette	1
phosphorylation	1
protein modification process	1
organelle organization	1
cell surface receptor signaling pathway	1
cytoskeleton organization	1
actin filament-based process	1
signal transduction	1
MAPK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
protein phosphorylation	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
regulation of anatomical structure morphogenesis	1
dendrite morphogenesis	1
regulation of dendrite development	1
microvillus assembly	1
regulation of microvillus assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
system development	1
regulation of MAPK cascade	1
positive regulation of signal transduction	1
intracellular signal transduction	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1

Protein interactions and networks

STRING

1186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNIK	NCK1	P16333	980
TNIK	RAP2A	P10114	976
TNIK	STRN4	Q9NRL3	857
TNIK	CTNNB1	P35222	805
TNIK	DISC1	Q9NRI5	759
TNIK	GSN	P06396	676
TNIK	STRN	O43815	562
TNIK	TRAF2	Q12933	506
TNIK	PANK4	Q9NVE7	476
TNIK	TANC1	Q9C0D5	472
TNIK	NDEL1	Q9GZM8	452
TNIK	PDE4A	P27815	433
TNIK	MAP3K7	O43318	426
TNIK	CEP170	Q5SW79	425
TNIK	PDE4DIP	Q5VU43	424

IntAct

305 interactions, top by confidence:

A	B	Type	Score
TNIK	NCK1	psi-mi:“MI:0915”(physical association)	0.670
LMP1	TNIK	psi-mi:“MI:0915”(physical association)	0.610
TNIK	LMP1	psi-mi:“MI:0914”(association)	0.610
TNIK	TRAF6	psi-mi:“MI:0407”(direct interaction)	0.590
TNIK	TRAF6	psi-mi:“MI:0915”(physical association)	0.590
TNIK	TAB2	psi-mi:“MI:0915”(physical association)	0.560
TNIK	TRAF2	psi-mi:“MI:0407”(direct interaction)	0.540
TNIK	TRAF2	psi-mi:“MI:0915”(physical association)	0.540
TNIK	MAP3K7	psi-mi:“MI:0915”(physical association)	0.500
TNIK	IKBKB	psi-mi:“MI:0915”(physical association)	0.500
TNIK	IKBKB	psi-mi:“MI:0914”(association)	0.500
TNIK	STK26	psi-mi:“MI:0915”(physical association)	0.400
TNIK	ERO1A	psi-mi:“MI:0915”(physical association)	0.400
Tanc1	TNIK	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
TMEM17	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
EZR	EEF2K	psi-mi:“MI:2364”(proximity)	0.270
LAMP1	TRAPPC13	psi-mi:“MI:2364”(proximity)	0.270
LAMP1	PIPSL	psi-mi:“MI:2364”(proximity)	0.270
TNIK	RANBP1	psi-mi:“MI:0915”(physical association)	0.000
TNIK		psi-mi:“MI:0915”(physical association)	0.000
BUB3	TNIK	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (197): TNIK (Affinity Capture-MS), TNIK (Affinity Capture-MS), TNIK (Proximity Label-MS), TNIK (Proximity Label-MS), TNIK (Affinity Capture-MS), TNIK (Biochemical Activity), TNIK (Affinity Capture-MS), TNIK (Affinity Capture-MS), TNIK (Affinity Capture-MS), TNIK (Affinity Capture-MS), TNIK (Affinity Capture-MS), TNIK (Affinity Capture-MS), TNIK (Reconstituted Complex), TNIK (Affinity Capture-Western), TNIK (Affinity Capture-MS)

ESM2 similar proteins: A0A0K3AV08, A7J1T0, A7J1T2, A7KAX9, A8X775, A8XU52, A9SY39, B4K6T8, G5EBZ8, G5ECQ3, G5EDE9, G5EEK3, G5EEW9, G5EGK6, O01700, O13839, O17862, O43283, O44757, O45797, O61366, O62090, O95835, P03949, P83510, Q03345, Q09314, Q09446, Q09994, Q11100, Q11181, Q17353, Q21341, Q3LRZ3, Q5R8X7, Q60JJ0, Q60LV7, Q61DP2, Q6E3D4, Q6GPD0

Diamond homologs: A0A194VNL2, A0A1S4CGX4, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A8XJW8, A9RWC9, A9S5R3, A9SR33, B0XPE4, C4YLK8, E1BK52, F1NBT0, G4N6Z6, G4NEB8, G5EDF7, O00506, O09110, O14733, O54748, O80396, O94804, O95819, P06784, P08018, P0CY25, P10506, P29678, P31938, P32490, P32491, P33886, P36506, P36507, P45985, P46734

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
TNIK	up-regulates	TCF7L2	phosphorylation
TNIK	“down-regulates activity”	SMAD1	phosphorylation
TNIK	“up-regulates activity”	NF2	phosphorylation
TNIK	“up-regulates activity”	GSN	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 177 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
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	9	16.8×	3e-07
Regulation of activated PAK-2p34 by proteasome mediated degradation	8	16.8×	2e-06
Regulation of ornithine decarboxylase (ODC)	8	16.4×	2e-06
Vpu mediated degradation of CD4	8	16.0×	2e-06
Autodegradation of the E3 ubiquitin ligase COP1	8	16.0×	2e-06
Ubiquitin-dependent degradation of Cyclin D	8	16.0×	2e-06
Cross-presentation of soluble exogenous antigens (endosomes)	8	15.3×	2e-06
Vif-mediated degradation of APOBEC3G	8	15.3×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
nuclear migration	5	21.7×	1e-03
positive regulation of axon extension	5	15.1×	5e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	14	4.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	112
Likely benign	40
Benign	14

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
243022	NM_015028.4(TNIK):c.538C>T (p.Arg180Ter)	Pathogenic

SpliceAI

6533 predictions. Top by Δscore:

Variant	Effect	Δscore
3:171066571:CCTA:C	donor_loss	1.0000
3:171066572:CTACC:C	donor_loss	1.0000
3:171066573:TA:T	donor_loss	1.0000
3:171066574:A:AT	donor_loss	1.0000
3:171066575:C:A	donor_loss	1.0000
3:171066575:CCCA:C	donor_gain	1.0000
3:171066614:T:TA	donor_gain	1.0000
3:171066731:TGAAT:T	acceptor_gain	1.0000
3:171066736:C:CC	acceptor_gain	1.0000
3:171066736:C:CG	acceptor_loss	1.0000
3:171066737:T:C	acceptor_loss	1.0000
3:171068840:GTACT:G	donor_loss	1.0000
3:171068841:TACTT:T	donor_loss	1.0000
3:171068842:ACTT:A	donor_loss	1.0000
3:171068843:CTTA:C	donor_loss	1.0000
3:171068844:TTACA:T	donor_loss	1.0000
3:171068845:T:TG	donor_loss	1.0000
3:171068846:A:AC	donor_gain	1.0000
3:171068846:ACAT:A	donor_loss	1.0000
3:171068847:C:CC	donor_gain	1.0000
3:171071319:TTTAA:T	acceptor_gain	1.0000
3:171071324:C:CC	acceptor_gain	1.0000
3:171079517:CCAA:C	donor_gain	1.0000
3:171082246:CATA:C	donor_loss	1.0000
3:171082247:ATACC:A	donor_loss	1.0000
3:171082248:TACC:T	donor_loss	1.0000
3:171082249:ACC:A	donor_loss	1.0000
3:171082250:C:A	donor_loss	1.0000
3:171082391:ACACC:A	acceptor_loss	1.0000
3:171082393:ACCT:A	acceptor_loss	1.0000

AlphaMissense

8933 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:171063929:G:C	S1345R	1.000
3:171063929:G:T	S1345R	1.000
3:171063931:T:G	S1345R	1.000
3:171063957:A:G	F1336S	1.000
3:171066215:A:G	L1324S	1.000
3:171066224:G:T	A1321D	1.000
3:171066229:C:A	K1319N	1.000
3:171066229:C:G	K1319N	1.000
3:171066230:T:A	K1319M	1.000
3:171066231:T:C	K1319E	1.000
3:171066238:A:C	F1316L	1.000
3:171066238:A:T	F1316L	1.000
3:171066239:A:C	F1316C	1.000
3:171066239:A:G	F1316S	1.000
3:171066240:A:G	F1316L	1.000
3:171066245:C:T	G1314E	1.000
3:171066246:C:G	G1314R	1.000
3:171066246:C:T	G1314R	1.000
3:171066272:C:G	R1305P	1.000
3:171066275:A:C	I1304S	1.000
3:171066287:T:A	K1300I	1.000
3:171066295:C:A	W1297C	1.000
3:171066295:C:G	W1297C	1.000
3:171066297:A:G	W1297R	1.000
3:171066297:A:T	W1297R	1.000
3:171066587:G:C	P1283R	1.000
3:171066587:G:T	P1283H	1.000
3:171066597:C:G	G1280R	1.000
3:171066597:C:T	G1280R	1.000
3:171066598:C:A	W1279C	1.000

dbSNP variants (sampled 300 via entrez): RS1000001564 (3:171363776 T>C), RS1000003069 (3:171280284 C>G,T), RS1000004649 (3:171194800 C>T), RS1000011901 (3:171384419 T>C), RS1000019425 (3:171114587 G>A), RS1000022822 (3:171405772 C>A,G), RS1000023002 (3:171305854 C>G), RS1000026717 (3:171264652 C>G,T), RS1000049166 (3:171101335 A>C,G), RS1000049325 (3:171225836 T>G), RS1000059376 (3:171432365 G>T), RS1000063995 (3:171390378 T>A,C), RS1000067053 (3:171426041 C>T), RS1000072208 (3:171221970 T>C), RS1000083494 (3:171215266 C>T)

Disease associations

OMIM: gene MIM:610005 | disease phenotypes: MIM:617028

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal recessive 54	Moderate	Autosomal recessive
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
non-syndromic intellectual disability	Limited	AR

Mondo (2): intellectual disability, autosomal recessive 54 (MONDO:0014876), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (1): Autosomal recessive non-syndromic intellectual disability (Orphanet:88616)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000712	Emotional lability
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0002267	Exaggerated startle response
HP:0003593	Infantile onset
HP:0007018	Attention deficit hyperactivity disorder

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST000271_4	Brain imaging in schizophrenia (dorsolateral prefrontal cortex interaction)	6.000000e-06
GCST000975_13	LDL cholesterol	4.000000e-06
GCST003542_33	Night sleep phenotypes	1.000000e-06
GCST004288_2	Adolescent idiopathic scoliosis	1.000000e-11
GCST004627_51	Lymphocyte count	8.000000e-09
GCST006147_1	Frontotemporal dementia (age at onset)	1.000000e-06
GCST006292_5	Response to antipsychotic treatment in schizophrenia	5.000000e-08
GCST006867_27	Type 2 diabetes	2.000000e-08
GCST007012_1	Cerebrospinal fluid AB1-42 levels	5.000000e-07
GCST007645_5	Estimated glomerular filtration rate after 1 year in renal transplantation (recipient effect)	5.000000e-06
GCST008156_86	Hip circumference adjusted for BMI	6.000000e-06
GCST009239_5	Change in serum metabolite levels (CMS)	3.000000e-08
GCST009241_4	Change in serum metabolite levels	3.000000e-08
GCST010173_172	Triglyceride levels	3.000000e-08
GCST010396_317	Gut microbiota (bacterial taxa, hurdle binary method)	6.000000e-06
GCST010699_57	Brain morphology (min-P)	1.000000e-35
GCST010701_104	Cortical surface area (MOSTest)	2.000000e-12
GCST010702_135	Subcortical volume (MOSTest)	2.000000e-14
GCST010703_59	Brain morphology (MOSTest)	2.000000e-08
GCST90002388_202	Lymphocyte count	1.000000e-11
GCST90002388_203	Lymphocyte count	5.000000e-09
GCST90002389_35	Lymphocyte percentage of white cells	3.000000e-10

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004587	lymphocyte count
EFO:0004847	age at onset
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0005199	renal transplant outcome measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004530	triglyceride measurement
EFO:0007874	gut microbiome measurement
EFO:0004346	neuroimaging measurement
EFO:0007993	lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4527 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

46 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 542,000 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1289601	LENVATINIB	4	8,784
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL180022	NERATINIB	4	9,404
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL274654	ORANTINIB	3	3,596
CHEMBL31965	CANERTINIB	3
CHEMBL377300	BRIVANIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL1614713	CC-401	2
CHEMBL1721885	SU-014813	2

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2088885	TNIK		0.00	0
rs7627954	TNIK		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — MSN subfamily

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
staurosporine	Inhibition	8.85	pIC50
compound 5 [PMID: 23232060]	Inhibition	8.52	pIC50
PF06260933	Inhibition	7.82	pIC50
compound 21k [PMID: 34985886]	Inhibition	7.59	pIC50
rentosertib	Inhibition	7.51	pIC50
compound 25c [PMID: 36649216]	Inhibition	6.44	pIC50

Binding affinities (BindingDB)

109 measured of 109 human assays (109 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
5-[[4-[(4-aminopiperidin-1-yl)methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	1.3 nM	US-9102637: Bicyclic thiazole compounds
2-[[6-(hydroxymethyl)naphthalen-2-yl]amino]-5-(3-methylbut-2-enoylamino)-1,3-thiazole-4-carboxamide	IC50	1.6 nM	US-9102637: Bicyclic thiazole compounds
Staurosporine	KD	1.7 nM
5-[[4-[(2-methylimidazol-1-yl)methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	2.3 nM	US-9102637: Bicyclic thiazole compounds
2-(naphthalen-2-ylamino)-5-[[4-(1,2,4-triazol-1-ylmethyl)benzoyl]amino]-1,3-thiazole-4-carboxamide	IC50	2.5 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	2.6 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	2.7 nM	US-9102637: Bicyclic thiazole compounds
2-(naphthalen-2-ylamino)-5-[[4-(2H-tetrazol-5-ylmethyl)benzoyl]amino]-1,3-thiazole-4-carboxamide	IC50	2.9 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-(imidazol-1-ylmethyl)benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	3 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[[(3S)-3-aminopyrrolidin-1-yl]methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	3 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-(imidazol-1-ylmethyl)benzoyl]amino]-2-(quinolin-6-ylamino)-1,3-thiazole-4-carboxamide	IC50	3 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[(4-methylimidazol-1-yl)methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	3.1 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[(4-methyl-1,4-diazepan-1-yl)methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	3.2 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[(4-hydroxypiperidin-1-yl)methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	3.4 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[[4-(hydroxymethyl)imidazol-1-yl]methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	3.5 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[(2-hydroxyethylamino)methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	3.7 nM	US-9102637: Bicyclic thiazole compounds
5-(5-hydroxypent-2-ynoylamino)-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	4 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-(4-methylpiperazin-1-yl)benzoyl]amino]-2-(quinolin-6-ylamino)-1,3-thiazole-4-carboxamide	IC50	4.1 nM	US-9102637: Bicyclic thiazole compounds
2-(naphthalen-2-ylamino)-5-[[4-[(3-oxopiperazin-1-yl)methyl]benzoyl]amino]-1,3-thiazole-4-carboxamide	IC50	4.2 nM	US-9102637: Bicyclic thiazole compounds
5-(but-2-ynoylamino)-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	4.4 nM	US-9102637: Bicyclic thiazole compounds
5-(4-hydroxybut-2-ynoylamino)-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	4.5 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-(imidazol-1-ylmethyl)benzoyl]amino]-2-(quinolin-5-ylamino)-1,3-thiazole-4-carboxamide	IC50	4.8 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[[(3S)-3-hydroxypyrrolidin-1-yl]methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	5 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	5.1 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-(aminomethyl)benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	5.3 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[[4-(hydroxymethyl)triazol-1-yl]methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	5.3 nM	US-9102637: Bicyclic thiazole compounds
2-[[6-(hydroxymethyl)naphthalen-2-yl]amino]-5-(thiophene-3-carbonylamino)-1,3-thiazole-4-carboxamide	IC50	5.5 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[[(3R)-3-hydroxypyrrolidin-1-yl]methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	5.5 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-(imidazol-1-ylmethyl)benzoyl]amino]-2-(quinolin-8-ylamino)-1,3-thiazole-4-carboxamide	IC50	5.5 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[(3-hydroxyazetidin-1-yl)methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	5.6 nM	US-9102637: Bicyclic thiazole compounds
2-[methyl(quinolin-6-yl)amino]-5-[[5-(morpholin-4-ylmethyl)thiophene-3-carbonyl]amino]-1,3-thiazole-4-carboxamide	IC50	5.7 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-(2-hydroxyethyl)benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	5.8 nM	US-9102637: Bicyclic thiazole compounds
5-(cyclopropanecarbonylamino)-2-[[6-(hydroxymethyl)naphthalen-2-yl]amino]-1,3-thiazole-4-carboxamide	IC50	5.8 nM	US-9102637: Bicyclic thiazole compounds
2-(naphthalen-2-ylamino)-5-[[4-(tetrazol-1-ylmethyl)benzoyl]amino]-1,3-thiazole-4-carboxamide	IC50	5.9 nM	US-9102637: Bicyclic thiazole compounds
2-(naphthalen-2-ylamino)-5-[[4-[(4-nitroimidazol-1-yl)methyl]benzoyl]amino]-1,3-thiazole-4-carboxamide	IC50	5.9 nM	US-9102637: Bicyclic thiazole compounds
2-(naphthalen-2-ylamino)-5-(prop-2-ynoylamino)-1,3-thiazole-4-carboxamide	IC50	6 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-(imidazol-1-ylmethyl)benzoyl]amino]-2-[(6-methoxynaphthalen-2-yl)amino]-1,3-thiazole-4-carboxamide	IC50	6.1 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	6.2 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[[2-(hydroxymethyl)piperidin-1-yl]methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	6.8 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[(5-methyltetrazol-1-yl)methyl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	7.1 nM	US-9102637: Bicyclic thiazole compounds
2-[(7-fluoronaphthalen-2-yl)amino]-5-(3-methylbut-2-enoylamino)-1,3-thiazole-4-carboxamide	IC50	7.2 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[4-(2-hydroxyethyl)piperazin-1-yl]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	7.2 nM	US-9102637: Bicyclic thiazole compounds
2-(naphthalen-2-ylamino)-5-(1H-pyrrole-2-carbonylamino)-1,3-thiazole-4-carboxamide	IC50	7.5 nM	US-9102637: Bicyclic thiazole compounds
5-[[5-(imidazol-1-ylmethyl)thiophene-2-carbonyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	7.7 nM	US-9102637: Bicyclic thiazole compounds
2-(naphthalen-2-ylamino)-5-[[4-(2-piperidin-1-ylethylamino)benzoyl]amino]-1,3-thiazole-4-carboxamide	IC50	8 nM	US-9102637: Bicyclic thiazole compounds
5-[[5-[(4-methylpiperazin-1-yl)methyl]thiophene-3-carbonyl]amino]-2-(quinolin-5-ylamino)-1,3-thiazole-4-carboxamide	IC50	8.2 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-(2-aminoethylamino)benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	8.4 nM	US-9102637: Bicyclic thiazole compounds
2-[(7-fluoronaphthalen-2-yl)amino]-5-[[4-(imidazol-1-ylmethyl)benzoyl]amino]-1,3-thiazole-4-carboxamide	IC50	8.4 nM	US-9102637: Bicyclic thiazole compounds
5-[[4-[2-(dimethylamino)ethylamino]benzoyl]amino]-2-(naphthalen-2-ylamino)-1,3-thiazole-4-carboxamide	IC50	8.6 nM	US-9102637: Bicyclic thiazole compounds

ChEMBL bioactivities

670 potent at pChembl≥5 of 681 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.92	IC50	0.12	nM	CHEMBL4760558
9.89	IC50	0.13	nM	CHEMBL4749291
9.74	IC50	0.18	nM	CHEMBL4762464
9.72	IC50	0.19	nM	CHEMBL4759123
9.68	IC50	0.21	nM	CHEMBL4744045
9.68	IC50	0.21	nM	CHEMBL4751494
9.66	IC50	0.22	nM	CHEMBL4788405
9.66	IC50	0.22	nM	CHEMBL4788976
9.64	IC50	0.23	nM	CHEMBL4797452
9.60	IC50	0.25	nM	CHEMBL4791330
9.52	IC50	0.3	nM	CHEMBL4756005
9.50	IC50	0.314	nM	STAUROSPORINE
9.48	IC50	0.33	nM	CHEMBL4788688
9.37	IC50	0.43	nM	CHEMBL4760435
9.36	IC50	0.44	nM	CHEMBL4754003
9.33	IC50	0.47	nM	CHEMBL4797770
9.26	IC50	0.551	nM	STAUROSPORINE
9.25	IC50	0.559	nM	STAUROSPORINE
9.17	IC50	0.68	nM	CHEMBL4780310
9.15	IC50	0.7	nM	CHEMBL214253
9.10	IC50	0.8	nM	CHEMBL4781043
9.04	IC50	0.91	nM	CHEMBL4743105
9.00	IC50	1	nM	CHEMBL5776440
9.00	IC50	1	nM	CHEMBL5931952
9.00	IC50	1	nM	CHEMBL5897460
9.00	IC50	1	nM	CHEMBL5752994
9.00	IC50	1	nM	CHEMBL5927842
9.00	IC50	1	nM	CHEMBL5973418
9.00	IC50	1	nM	CHEMBL5821868
8.89	IC50	1.3	nM	CHEMBL3684049
8.89	IC50	1.3	nM	CHEMBL6169506
8.85	IC50	1.4	nM	STAUROSPORINE
8.80	IC50	1.6	nM	CHEMBL3684025
8.70	IC50	2	nM	DOVITINIB
8.70	IC50	2	nM	CHEMBL5784722
8.70	IC50	2	nM	CHEMBL6165365
8.64	IC50	2.3	nM	CHEMBL3684056
8.64	IC50	2.3	nM	CHEMBL5999390
8.60	IC50	2.5	nM	CHEMBL3684039
8.59	IC50	2.6	nM	CHEMBL3684048
8.57	IC50	2.7	nM	CHEMBL3684034
8.55	IC50	2.8	nM	CHEMBL6167068
8.54	IC50	2.9	nM	CHEMBL3684051
8.52	IC50	3	nM	CHEMBL2312144
8.52	IC50	3	nM	CHEMBL3684045
8.52	IC50	3	nM	CHEMBL3684047
8.52	IC50	3	nM	CHEMBL3684063
8.52	IC50	3	nM	CHEMBL5595897
8.52	Kd	3	nM	CHEMBL5816387
8.52	IC50	3	nM	CHEMBL5905836

PubChem BioAssay actives

279 with measured affinity, of 1038 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
N-[3-cyano-5-[5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]methanesulfonamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0001	uM
3-[3-[3-cyano-5-(methanesulfonamido)phenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-cyclopropylbenzamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0001	uM
N-[3-cyano-5-[5-[3-(pyrrolidine-1-carbonyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]methanesulfonamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0002	uM
N-[3-cyano-5-[5-[4-(4-methylpiperazine-1-carbonyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]methanesulfonamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0002	uM
N-[3-cyano-5-[5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]cyclopropanesulfonamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0002	uM
3-[3-[3-cyano-5-(methanesulfonamido)phenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-methylbenzamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0002	uM
N-[3-cyano-5-[5-[3-[3-(dimethylamino)pyrrolidine-1-carbonyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]methanesulfonamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0002	uM
N-[3-cyano-5-[5-[3-(piperidine-1-carbonyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]methanesulfonamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0002	uM
5-[5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-indazole-7-carbonitrile	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0002	uM
3-[3-[4-chloro-3-cyano-5-(methanesulfonamido)phenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-methylbenzamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0003	uM
2-[4-[3-[3-cyano-5-(methanesulfonamido)phenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]phenoxy]-2-methylpropanoic acid	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0003	uM
N-[3-cyano-5-[5-[3-(4-methylpiperazine-1-carbonyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]methanesulfonamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0003	uM
(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	1715142: Inhibition of human TNIK using RLGRDKYKTLRQIRQ as substrate by [gamma-33P]-ATP assay	ic50	0.0003	uM
N-[2-chloro-3-cyano-5-[5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]methanesulfonamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0004	uM
3-(1H-indazol-5-yl)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridine	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0004	uM
2-[4-[3-[3-cyano-5-(methanesulfonamido)phenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]phenyl]-2-methylpropanoic acid	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0005	uM
2-[4-[6-amino-5-(4-chlorophenyl)-3-pyridinyl]phenoxy]-2-methylpropanoic acid	1686957: Inhibition of TNIK (unknown origin) in presence of 10 uM ATP	ic50	0.0006	uM
N-[2-chloro-3-cyano-5-[5-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]methanesulfonamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0007	uM
9-hydroxy-4-phenyl-6H-pyrrolo[3,4-c]carbazole-1,3-dione	2102332: Inhibition of TNIK (unknown origin)	ic50	0.0007	uM
N-[3-cyano-5-[5-[4-(1-methylpyrazol-4-yl)phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]methanesulfonamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0008	uM
3-[5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]benzonitrile	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0009	uM
4-[6-[5-(4-fluorophenyl)-1H-imidazol-4-yl]quinolin-3-yl]-2-methylbut-3-yn-2-ol	2102280: Inhibition of recombinant human TNIK (1 to 367 residues) using RLGRDKYKTLRQI as substrate incubated for 40 mins in presence of ATP at Km concentration by radiometric scintillation counting analysis	ic50	0.0030	uM
4-methoxy-3-[2-[3-methoxy-4-(4-methylpiperazin-1-yl)anilino]-4-pyridinyl]benzonitrile	721050: Inhibition of TNIK (unknown origin) by ADP glo luminescent assay	ic50	0.0030	uM
3-(3H-benzimidazol-5-yl)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridine	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0038	uM
2-methyl-4-[6-(3-methyl-5-phenylimidazol-4-yl)quinolin-3-yl]but-3-yn-2-ol	2102280: Inhibition of recombinant human TNIK (1 to 367 residues) using RLGRDKYKTLRQI as substrate incubated for 40 mins in presence of ATP at Km concentration by radiometric scintillation counting analysis	ic50	0.0040	uM
4-(5-chloro-2-methoxyphenyl)-N-[3-methoxy-4-(4-methylpiperazin-1-yl)phenyl]pyridin-2-amine	721050: Inhibition of TNIK (unknown origin) by ADP glo luminescent assay	ic50	0.0040	uM
(2Z)-6-[(2,6-dichlorophenyl)sulfonylmethyl]-2-[(4-hydroxy-3-nitrophenyl)methylidene]-4H-1,4-benzothiazin-3-one	2028074: Inhibition of TNIK (unknown origin)	ic50	0.0050	uM
4-methoxy-3-[2-[4-(4-methylpiperazin-1-yl)anilino]-4-pyridinyl]benzonitrile	721050: Inhibition of TNIK (unknown origin) by ADP glo luminescent assay	ic50	0.0050	uM
3-(1H-indol-5-yl)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridine	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0052	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	508113: Binding affinity to TNIK	kd	0.0054	uM
2-[3-[5-chloro-2-[3-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]phenyl]acetonitrile	721047: Inhibition of TNIK-mediated TCF4/beta-casein transcription in human HCT116 cells by beta-lactamase reporter gene assay	ic50	0.0054	uM
4-[5-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1779139: Inhibition of N-terminal GST-tagged TNIK (1 to 314 residues) (unknown origin) cytoplasmic domain expressed in Sf21 cells	ic50	0.0058	uM
4-[6-[5-(4-fluorophenyl)-3-methylimidazol-4-yl]quinolin-3-yl]-2-methylbut-3-yn-2-ol	2102280: Inhibition of recombinant human TNIK (1 to 367 residues) using RLGRDKYKTLRQI as substrate incubated for 40 mins in presence of ATP at Km concentration by radiometric scintillation counting analysis	ic50	0.0060	uM
3-[2-[3-methoxy-4-(4-methylpiperazin-1-yl)anilino]-4-pyridinyl]benzonitrile	721050: Inhibition of TNIK (unknown origin) by ADP glo luminescent assay	ic50	0.0060	uM
N-[3-[5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]methanesulfonamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0071	uM
5-bromo-2-(2-fluoro-4-pyridinyl)-1,7-naphthyridin-8-amine	1633851: Inhibition of human full length TNIK(1-1360)-G5-Avi-6His-Flag expressed in baculovirus-infected sf21 cells using His6-SMAD1 as substrate preincubated for 30 mins followed by substrate addition and measured after 120 mins by ADP-Glo Reagent based method	ic50	0.0079	uM
5-[5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-pyrazolo[3,4-b]pyridine	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0079	uM
4-methoxy-3-[2-(3-methoxy-4-morpholin-4-ylanilino)-4-pyridinyl]benzonitrile	2102332: Inhibition of TNIK (unknown origin)	ic50	0.0080	uM
N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)-6-(pyrazolo[1,5-a]pyrimidin-5-ylamino)pyridine-3-carboxamide	1664780: Inhibition of human wild type partial length TNIK (D4-K311 residues) expressed in bacterial expression system	ic50	0.0080	uM
3,5-diphenyl-1H-pyrrolo[2,3-b]pyridine	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0092	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	256566: Average Binding Constant for TNIK; NA=Not Active at 10 uM	kd	0.0099	uM
4-[6-amino-5-(4-methylsulfonylphenyl)-3-pyridinyl]phenol	1633849: Inhibition of human 6His-TEV-TNIK(1 to 325) expressed in baculovirus-infected sf21 cells using LRRKtide as substrate preincubated for 30 mins followed by substrate addition and measured after 75 to 90 mins by ADP-Glo Reagent based method	ic50	0.0100	uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-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-nonaene-16-carboxylate	1425199: 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
4-methoxy-3-[2-(4-morpholin-4-ylanilino)-4-pyridinyl]benzonitrile	721050: Inhibition of TNIK (unknown origin) by ADP glo luminescent assay	ic50	0.0110	uM
3-[2-[4-[4-(dimethylamino)piperidin-1-yl]-3-fluoroanilino]-4-pyridinyl]-4-methoxybenzonitrile	721050: Inhibition of TNIK (unknown origin) by ADP glo luminescent assay	ic50	0.0110	uM
N-[3-[5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]acetamide	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0120	uM
3-[2,4-dimethyl-5-[(Z)-(2-oxo-1H-indol-3-ylidene)methyl]-1H-pyrrol-3-yl]propanoic acid	1425199: 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	0.0120	uM
5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-3-phenyl-1H-pyrrolo[2,3-b]pyridine	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0140	uM
3-(4-chlorophenyl)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridine	1684760: Inhibition of TNIK (unknown origin)	ic50	0.0140	uM
4-[6-[3-ethyl-5-(4-fluorophenyl)imidazol-4-yl]quinolin-3-yl]-2-methylbut-3-yn-2-ol	2102280: Inhibition of recombinant human TNIK (1 to 367 residues) using RLGRDKYKTLRQI as substrate incubated for 40 mins in presence of ATP at Km concentration by radiometric scintillation counting analysis	ic50	0.0140	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	9
trichostatin A	affects cotreatment, increases expression	4
Estradiol	decreases expression, increases expression, affects cotreatment	4
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Aflatoxin B1	affects expression, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
multi-kinase inhibitor 108600	decreases activity	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
2-butenal	decreases expression	1
arsenite	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
nickel sulfate	decreases expression	1
hydroquinone	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

257 unique, capped per target: 257 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1059381	Binding	Inhibition of TNIK assessed as enzyme activity at 1 uM relative to untreated control	Selective inhibitors of the mutant B-Raf pathway: discovery of a potent and orally bioavailable aminoisoquinoline. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TT13	HAP1 TNIK (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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