TESK1

Summary

TESK1 (testis associated actin remodelling kinase 1, HGNC:11731) is a protein-coding gene on chromosome 9p13.3, encoding Dual specificity testis-specific protein kinase 1 (Q15569). Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues.

This gene product is a serine/threonine protein kinase that contains an N-terminal protein kinase domain and a C-terminal proline-rich domain. Its protein kinase domain is most closely related to those of the LIM motif-containing protein kinases (LIMKs). The encoded protein can phosphorylate myelin basic protein and histone in vitro. The testicular germ cell-specific expression and developmental pattern of expression of the mouse gene suggests that this gene plays an important role at and after the meiotic phase of spermatogenesis. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 7016 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 86 total
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006285

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11731
Approved symbol	TESK1
Name	testis associated actin remodelling kinase 1
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000107140
Ensembl biotype	protein_coding
OMIM	601782
Entrez	7016

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000336395, ENST00000463897, ENST00000467424, ENST00000480077, ENST00000498522, ENST00000970553, ENST00000970554, ENST00000970555

RefSeq mRNA: 2 — MANE Select: NM_006285 NM_001318230, NM_006285

CCDS: CCDS6580

Canonical transcript exons

ENST00000336395 — 10 exons

Exon	Start	End
ENSE00000698882	35607327	35607409
ENSE00001423309	35605262	35605838
ENSE00003531970	35608160	35608249
ENSE00003539288	35607582	35607672
ENSE00003553419	35607928	35608011
ENSE00003599059	35605984	35606105
ENSE00003653244	35606237	35606285
ENSE00003660959	35608395	35608509
ENSE00003690306	35606837	35606983
ENSE00003849244	35608862	35610033

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 96.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.8936 / max 53.8943, expressed in 1784 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96604	5.9955	1729
96603	5.4991	1711
96606	0.3990	199

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	96.23	gold quality
popliteal artery	UBERON:0002250	96.14	gold quality
left testis	UBERON:0004533	96.14	gold quality
tibial artery	UBERON:0007610	96.14	gold quality
aorta	UBERON:0000947	95.37	gold quality
right adrenal gland cortex	UBERON:0035827	94.94	gold quality
right coronary artery	UBERON:0001625	94.92	gold quality
left coronary artery	UBERON:0001626	94.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.90	gold quality
ascending aorta	UBERON:0001496	94.77	gold quality
thoracic aorta	UBERON:0001515	94.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.75	gold quality
lower esophagus	UBERON:0013473	94.73	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.71	gold quality
adenohypophysis	UBERON:0002196	94.63	gold quality
gastrocnemius	UBERON:0001388	94.56	gold quality
left adrenal gland cortex	UBERON:0035825	94.45	gold quality
mucosa of stomach	UBERON:0001199	94.35	gold quality
right adrenal gland	UBERON:0001233	94.32	gold quality
adrenal tissue	UBERON:0018303	94.30	gold quality
descending thoracic aorta	UBERON:0002345	94.08	gold quality
omental fat pad	UBERON:0010414	93.99	gold quality
left adrenal gland	UBERON:0001234	93.95	gold quality
peritoneum	UBERON:0002358	93.90	gold quality
muscle of leg	UBERON:0001383	93.76	gold quality
granulocyte	CL:0000094	93.71	gold quality
body of uterus	UBERON:0009853	93.68	gold quality
endocervix	UBERON:0000458	93.64	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.54	gold quality
right frontal lobe	UBERON:0002810	93.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CREM

miRNA regulators (miRDB)

31 targeting TESK1, 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-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-597-5P	96.82	67.57	732
HSA-MIR-3194-5P	96.80	64.90	1027

Literature-anchored findings (GeneRIF, showing 4)

• the association between actopaxin and TESK1, which is likely regulated by phosphorylation of actopaxin, regulates TESK1 activity and subsequent cellular spreading on fibronectin (PMID:15817463)
• enhanced TESK1 activity results in increased stress fibers (via phospho-cofilin), but this can be blocked by elevating Spred1 (PMID:18216281)
• Actin remodelling factor TESK1 is a key player in the ciliogenesis control network in which YAP/TAZ and directional vesicle trafficking are integral components. (PMID:25849865)
• In conclusion, deregulation of cytoskeleton dynamics through TESK1/CFL1 pathway underlies epithelial intestinal dysfunction in the small bowel mucosa of diarrhea-predominant irritable bowel syndrome, particularly in female patients. (PMID:29396473)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tesk1a	ENSDARG00000078251
danio_rerio	tesk1b	ENSDARG00000079281
mus_musculus	Tesk1	ENSMUSG00000028458
rattus_norvegicus	Tesk1	ENSRNOG00000053729

Paralogs (23): MAP3K9 (ENSG00000006432), TESK2 (ENSG00000070759), MAP3K13 (ENSG00000073803), ARAF (ENSG00000078061), MAP3K20 (ENSG00000091436), RIPK2 (ENSG00000104312), LIMK1 (ENSG00000106683), TNNI3K (ENSG00000116783), RIPK3 (ENSG00000129465), MAP3K10 (ENSG00000130758), RAF1 (ENSG00000132155), RIPK1 (ENSG00000137275), MAP3K12 (ENSG00000139625), KSR1 (ENSG00000141068), MAP3K21 (ENSG00000143674), BRAF (ENSG00000157764), ILK (ENSG00000166333), MLKL (ENSG00000168404), KSR2 (ENSG00000171435), MOS (ENSG00000172680), MAP3K11 (ENSG00000173327), LIMK2 (ENSG00000182541), LRRK2 (ENSG00000188906)

Protein

Protein identifiers

Dual specificity testis-specific protein kinase 1 — Q15569 (reviewed: Q15569)

Alternative names: Testicular protein kinase 1

All UniProt accessions (1): Q15569

UniProt curated annotations — full annotation on UniProt →

Function. Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues. Regulates the cellular cytoskeleton by enhancing actin stress fiber formation via phosphorylation of cofilin and by preventing microtubule breakdown via inhibition of TAOK1/MARKK kinase activity. Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1. Positively regulates integrin-mediated cell spreading, via phosphorylation of cofilin. Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of ciliary vesicle directional trafficking to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1. Probably plays a central role at and after the meiotic phase of spermatogenesis.

Subunit / interactions. Interacts (via both C- and N-termini) with SPRY4 (via C-terminus); the interaction inhibits TESK1 kinase activity. Interacts with TAOK1; the interaction inhibits TAOK1 kinase activity. Interacts (via C-terminus) with SPRED1 (via C-terminus); the interaction inhibits TESK1 kinase activity. Interacts (via C-terminus) with PARVA/PARVIN (via C-terminus); the interaction inhibits TESK1 kinase activity. Interacts with YWHAB/14-3-3 beta; the interaction is dependent on the phosphorylation of TESK1 Ser-437 and inhibits TESK1 kinase activity. Interacts with SPRY1, SPRY3 and SPRED2. Interacts (via C-terminus) with SPRY2 (via C-terminus); the interaction disrupts SPRY2 interaction with PPP2CA/PP2A-C, possibly by vesicular sequestration of SPRY2. Therefore dephosphorylation of SPRY2 by the serine/threonine-protein phosphatase 2A (PP2A) holoenzyme is lost, inhibiting its interaction with GRB2.

Subcellular location. Cytoplasm. Perinuclear region. Cytoskeleton. Microtubule organizing center. Centrosome. Cell projection. Lamellipodium.

Tissue specificity. Expressed in podocytes and renal tubular cells in the kidney (at protein level).

Post-translational modifications. Autophosphorylated on serine and tyrosine residues.

Activity regulation. Activated by autophosphorylation on Ser-220. Kinase activity is inhibited by SPRED1.

Domain organisation. The extracatalytic C-terminal part is highly rich in proline residues.

Similarity. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

RefSeq proteins (2): NP_001305159, NP_006276* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR050940	Actin_reg-Ser/Thr_kinase	Family

Pfam: PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 3 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
• 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 (21 total): region of interest 7, compositionally biased region 3, binding site 2, modified residue 2, sequence variant 2, chain 1, domain 1, active site 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15569-F1	62.98	0.33

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): 175 (proton acceptor)

Ligand- & substrate-binding residues (2): 63–71; 86

Post-translational modifications (2): 220, 338

Mutagenesis-validated functional residues (1):

Position	Phenotype
175	abolishes inhibition of spry4-mediated repression of cell spreading. no effect on interaction with spry4 or colocalizati

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-446388	Regulation of cytoskeletal remodeling and cell spreading by IPP complex components
R-HSA-1500931	Cell-Cell communication
R-HSA-446353	Cell-extracellular matrix interactions
R-HSA-446728	Cell junction organization

MSigDB gene sets: 213 (showing top): GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_VESICLE_LOCALIZATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_POSITIVE_REGULATION_OF_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ASSEMBLY, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

GO Biological Process (12): spermatogenesis (GO:0007283), actin cytoskeleton organization (GO:0030036), regulation of protein localization (GO:0032880), regulation of actin cytoskeleton organization (GO:0032956), positive regulation of stress fiber assembly (GO:0051496), establishment of vesicle localization (GO:0051650), nuclear-transcribed mRNA catabolic process, no-go decay (GO:0070966), podocyte cell migration (GO:0090521), positive regulation of substrate adhesion-dependent cell spreading (GO:1900026), positive regulation of protein localization to nucleus (GO:1900182), negative regulation of cilium assembly (GO:1902018), protein phosphorylation (GO:0006468)

GO Molecular Function (13): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein serine/threonine/tyrosine kinase activity (GO:0004712), protein tyrosine kinase activity (GO:0004713), ATP binding (GO:0005524), protein kinase binding (GO:0019901), protein serine/threonine kinase inhibitor activity (GO:0030291), metal ion binding (GO:0046872), 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 (9): nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), lamellipodium (GO:0030027), cytoplasmic vesicle (GO:0031410), perinuclear region of cytoplasm (GO:0048471), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cell-extracellular matrix interactions	1
Cell junction organization	1
Cell-Cell communication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	4
cellular anatomical structure	4
cytoplasm	3
developmental process involved in reproduction	1
male gamete generation	1
cytoskeleton organization	1
actin filament-based process	1
intracellular protein localization	1
regulation of localization	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
vesicle localization	1
establishment of localization in cell	1
establishment of organelle localization	1
nuclear-transcribed mRNA catabolic process	1
epithelial cell migration	1
positive regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
protein localization to nucleus	1
regulation of protein localization to nucleus	1
positive regulation of protein localization	1
cilium assembly	1
negative regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
negative regulation of organelle assembly	1
phosphorylation	1
protein modification process	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
kinase binding	1
protein serine/threonine kinase activity	1
protein kinase inhibitor activity	1

Protein interactions and networks

STRING

1352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TESK1	SPRY4	Q9C004	751
TESK1	PARVA	Q9NVD7	605
TESK1	CFL1	P23528	588
TESK1	PDXP	Q96GD0	571
TESK1	CFL2	Q9Y281	538
TESK1	SSH3	Q8TE77	520
TESK1	SSH1	Q8WYL5	516
TESK1	TAOK1	Q7L7X3	510
TESK1	SPRY2	O43597	490
TESK1	YWHAB	P31946	467
TESK1	SSH2	Q76I76	463
TESK1	RUSC2	Q8N2Y8	426
TESK1	TEX26	Q8N6G2	348
TESK1	PDGFRB	P09619	341
TESK1	TEX53	A0A1B0GU33	317

IntAct

25 interactions, top by confidence:

A	B	Type	Score
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
PFDN2	POLR3A	psi-mi:“MI:0914”(association)	0.670
YWHAB	TESK1	psi-mi:“MI:0407”(direct interaction)	0.610
TESK1	YWHAB	psi-mi:“MI:0915”(physical association)	0.610
TESK1	YWHAB	psi-mi:“MI:0403”(colocalization)	0.610
GRK7	HSP90AA1	psi-mi:“MI:0914”(association)	0.530
SPRY4	TESK1	psi-mi:“MI:0915”(physical association)	0.510
TESK1	SPRY4	psi-mi:“MI:0915”(physical association)	0.510
TESK1	YWHAE	psi-mi:“MI:0915”(physical association)	0.400
SFN	TESK1	psi-mi:“MI:0915”(physical association)	0.400
TESK1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
TESK1	ARAF	psi-mi:“MI:0915”(physical association)	0.370
TESK1	PFKL	psi-mi:“MI:0915”(physical association)	0.370
TESK1	ABCB4	psi-mi:“MI:0915”(physical association)	0.370
YY1	TESK1	psi-mi:“MI:0915”(physical association)	0.370
TESK1	ACACB	psi-mi:“MI:0914”(association)	0.350
TESK2	ILVBL	psi-mi:“MI:0914”(association)	0.350
RABEPK	ST3GAL3	psi-mi:“MI:0914”(association)	0.350
RABEPK	ZSWIM8	psi-mi:“MI:0914”(association)	0.350

BioGRID (40): TESK1 (Affinity Capture-MS), YWHAB (Two-hybrid), YWHAB (Affinity Capture-Western), TESK1 (Affinity Capture-Western), TESK1 (Reconstituted Complex), TESK1 (Affinity Capture-MS), TESK1 (Two-hybrid), TESK1 (Affinity Capture-Western), SPRY4 (Affinity Capture-Western), TESK1 (Affinity Capture-Western), TESK1 (Affinity Capture-Western), TESK1 (Affinity Capture-Western), TESK1 (Affinity Capture-Western), TESK1 (Affinity Capture-Western), TESK1 (Affinity Capture-Western)

ESM2 similar proteins: A1YGK1, A2T7E6, A8K8V0, B1WBS3, B2RXF5, C9JTQ0, O14559, O43918, O70146, O88282, P10074, Q15569, Q2QGD7, Q5FWU5, Q5R633, Q5RJR4, Q5T619, Q5XJV6, Q63572, Q6IQX8, Q6PD29, Q6XYB7, Q80VM4, Q80YF9, Q811H0, Q8BI69, Q8BXX2, Q8JZL0, Q8N143, Q8N8E2, Q8NCA9, Q8WUU4, Q90850, Q91X45, Q96C55, Q96H86, Q96Q04, Q96SL8, Q96SZ4, Q9BV97

Diamond homologs: A1Z9X0, A2CI34, A2CI35, A8KBH6, A8XW88, F1M7Y5, O70146, P00542, P00543, P04409, P05126, P05128, P05129, P05696, P05771, P05772, P07332, P09215, P0CD62, P10102, P10829, P13678, P14238, P16054, P16879, P17252, P20444, P21137, P22612, P23298, P24723, P28867, P32866, P41743, P43057, P48562, P50527, P57078, P63318, P63319

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
TESK1	“down-regulates activity”	CFL1	phosphorylation
TESK1	“up-regulates activity”	TESK1	phosphorylation
TESK1	“down-regulates activity”	CFL2	phosphorylation
SPRY4	“down-regulates activity”	TESK1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1125 predictions. Top by Δscore:

Variant	Effect	Δscore
9:35606062:G:T	donor_gain	1.0000
9:35606102:TAAGG:T	donor_loss	1.0000
9:35606103:AAGGT:A	donor_loss	1.0000
9:35606104:AG:A	donor_gain	1.0000
9:35606104:AGGT:A	donor_loss	1.0000
9:35606105:GG:G	donor_gain	1.0000
9:35606106:G:GG	donor_gain	1.0000
9:35606828:A:AG	acceptor_gain	1.0000
9:35606828:AT:A	acceptor_gain	1.0000
9:35606829:T:G	acceptor_gain	1.0000
9:35606829:T:TA	acceptor_gain	1.0000
9:35606832:A:AG	acceptor_gain	1.0000
9:35606833:CCAGT:C	acceptor_loss	1.0000
9:35606835:A:AG	acceptor_gain	1.0000
9:35606835:AGTAT:A	acceptor_loss	1.0000
9:35606836:G:GC	acceptor_gain	1.0000
9:35606836:GT:G	acceptor_gain	1.0000
9:35606836:GTAT:G	acceptor_gain	1.0000
9:35606836:GTATA:G	acceptor_gain	1.0000
9:35606981:AAG:A	donor_loss	1.0000
9:35606982:AGGT:A	donor_loss	1.0000
9:35606984:G:T	donor_loss	1.0000
9:35607580:AG:A	acceptor_gain	1.0000
9:35607581:GG:G	acceptor_gain	1.0000
9:35608154:CCACA:C	acceptor_loss	1.0000
9:35608155:CACA:C	acceptor_loss	1.0000
9:35608157:CA:C	acceptor_loss	1.0000
9:35608158:A:AG	acceptor_gain	1.0000
9:35608158:AG:A	acceptor_gain	1.0000
9:35608159:G:GA	acceptor_loss	1.0000

AlphaMissense

3960 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:35605789:T:C	F57S	1.000
9:35606018:T:C	L85P	1.000
9:35606022:G:C	K86N	1.000
9:35606022:G:T	K86N	1.000
9:35606970:A:C	D175A	1.000
9:35607376:A:C	D196A	1.000
9:35607376:A:T	D196V	1.000
9:35607937:T:C	F241L	1.000
9:35607939:T:A	F241L	1.000
9:35607939:T:G	F241L	1.000
9:35607946:G:T	G244W	1.000
9:35607947:G:A	G244E	1.000
9:35605750:T:A	L44H	0.999
9:35605788:T:C	F57L	0.999
9:35605789:T:G	F57C	0.999
9:35605790:T:A	F57L	0.999
9:35605790:T:G	F57L	0.999
9:35605818:T:C	F67L	0.999
9:35605820:C:A	F67L	0.999
9:35605820:C:G	F67L	0.999
9:35605821:T:C	F68L	0.999
9:35605823:C:A	F68L	0.999
9:35605823:C:G	F68L	0.999
9:35605824:T:C	S69P	0.999
9:35606020:A:G	K86E	0.999
9:35606072:T:C	L103P	0.999
9:35606244:G:A	G117R	0.999
9:35606244:G:C	G117R	0.999
9:35606245:G:A	G117E	0.999
9:35606250:T:C	C119R	0.999

dbSNP variants (sampled 300 via entrez): RS1000160337 (9:35606114 C>A,T), RS1000208275 (9:35605028 G>A), RS1000513122 (9:35610046 G>A,T), RS1000566923 (9:35610234 G>A,C,T), RS1000724288 (9:35604555 G>A), RS1001073434 (9:35604231 C>A), RS1001417894 (9:35610288 T>C), RS1001908302 (9:35603993 G>A), RS1002067089 (9:35609902 G>A,T), RS1003682762 (9:35608237 C>A), RS1004394518 (9:35606490 T>A,G), RS1004530294 (9:35604799 C>G), RS1005450268 (9:35604219 T>G), RS1005495653 (9:35610322 G>A,C,T), RS1005801012 (9:35608100 G>C)

Disease associations

OMIM: gene MIM:601782 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5604 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 93,649 (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
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL253969	OSI-632	2	1,150
CHEMBL3039525	GOLVATINIB	2	535
CHEMBL475251	R-406	2	762
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL574738	AST-487	1	451

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — TESK subfamily

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 31 [PMID: 22902653]	Inhibition	6.34	pIC50
compound 30 [PMID: 22902653]	Inhibition	5.95	pIC50
compound 35 [PMID: 22902653]	Inhibition	4.52	pIC50

Binding affinities (BindingDB)

7 measured of 7 human assays (7 total across all organisms); most potent 7 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
BMS-354825	KD	27 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CI-1033	KD	1700 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM

ChEMBL bioactivities

37 potent at pChembl≥5 of 38 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.07	Kd	0.086	nM	CHEMBL3752910
9.93	ED50	0.117	nM	CHEMBL3752910
7.48	Kd	33	nM	DASATINIB
7.19	Kd	65	nM	DASATINIB
7.10	Kd	79	nM	CHEMBL386051
6.86	IC50	138	nM	STAUROSPORINE
6.58	IC50	261	nM	STAUROSPORINE
6.58	Kd	260	nM	FORETINIB
6.57	IC50	268	nM	STAUROSPORINE
6.54	Kd	286	nM	GOLVATINIB
6.54	Kd	290	nM	LESTAURTINIB
6.52	Kd	300	nM	CHEMBL1241674
6.50	Kd	320	nM	STAUROSPORINE
6.44	Kd	360	nM	R-406
6.42	Kd	380	nM	CRIZOTINIB
6.34	IC50	455	nM	CHEMBL2070615
6.00	IC50	1000	nM	TP-030n
5.96	Kd	1100	nM	CHEMBL1908396
5.95	IC50	1133	nM	CHEMBL2070614
5.85	Kd	1417	nM	OSI-632
5.82	Kd	1500	nM	PLX-4720
5.66	IC50	2198	nM	CHEMBL2070613
5.64	IC50	2265	nM	CHEMBL2070616
5.62	Kd	2400	nM	AST-487
5.51	Kd	3100	nM	JNJ-7706621
5.50	Kd	3200	nM	CANERTINIB
5.50	Kd	3200	nM	FEDRATINIB
5.43	Kd	3700	nM	VANDETANIB
5.37	Kd	4300	nM	AXITINIB
5.25	Kd	5600	nM	TOZASERTIB

PubChem BioAssay actives

35 with measured affinity, of 461 total; 24 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149950: Binding affinity to human TESK1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0001	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435937: Binding constant for TESK1 kinase domain	kd	0.0330	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625056: Binding constant for TESK1 kinase domain	kd	0.0790	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	1715146: Inhibition of human TESK1 using cofilin as substrate by [gamma-33P]-ATP assay	ic50	0.1380	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625056: Binding constant for TESK1 kinase domain	kd	0.2600	uM
1-N’-[2-fluoro-4-[[2-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]-4-pyridinyl]oxy]phenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	1425194: 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	0.2860	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	508106: Binding affinity to TESK1	kd	0.2900	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625056: Binding constant for TESK1 kinase domain	kd	0.3000	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	625056: Binding constant for TESK1 kinase domain	kd	0.3600	uM
Crizotinib	625056: Binding constant for TESK1 kinase domain	kd	0.3800	uM
1-ethyl-3-[5-[6-(4-methoxy-2,6-dimethylphenyl)-2-pyrazin-2-ylpyrimidin-4-yl]-1,3-thiazol-2-yl]urea	678592: Inhibition of TESK1	ic50	0.4550	uM
1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-methoxyphenyl]-3-[1-(1,3-thiazol-2-yl)ethyl]urea	625056: Binding constant for TESK1 kinase domain	kd	1.1000	uM
1-[5-[6-(4-methoxy-2,6-dimethylphenyl)-2-pyrazin-2-ylpyrimidin-4-yl]-1,3-thiazol-2-yl]-3-methylurea	678592: Inhibition of TESK1	ic50	1.1330	uM
3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide	1425194: 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	1.4170	uM
N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide	625056: Binding constant for TESK1 kinase domain	kd	1.5000	uM
1-[5-[6-(2,6-dimethyl-4-pentan-3-yloxyphenyl)-2-pyrazin-2-ylpyrimidin-4-yl]-1,3-thiazol-2-yl]-3-methylurea	678592: Inhibition of TESK1	ic50	2.1980	uM
N-[5-[6-(4-methoxy-2,6-dimethylphenyl)-2-pyrazin-2-ylpyrimidin-4-yl]-1,3-thiazol-2-yl]acetamide	678592: Inhibition of TESK1	ic50	2.2650	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435937: Binding constant for TESK1 kinase domain	kd	2.4000	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435937: Binding constant for TESK1 kinase domain	kd	3.1000	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	435937: Binding constant for TESK1 kinase domain	kd	3.2000	uM
Fedratinib	625056: Binding constant for TESK1 kinase domain	kd	3.2000	uM
Vandetanib	435937: Binding constant for TESK1 kinase domain	kd	3.7000	uM
Axitinib	625056: Binding constant for TESK1 kinase domain	kd	4.3000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435937: Binding constant for TESK1 kinase domain	kd	5.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
cobaltous chloride	increases expression	2
Acetaminophen	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
FR900359	increases phosphorylation	1
bufotalin	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tanshinone	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
ICG 001	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Theophylline	increases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

ChEMBL screening assays

104 unique, capped per target: 104 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1025746	Binding	Binding affinity to human TESK1 at 10 uM relative to control	Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TR99	HAP1 TESK1 (-) 1	Cancer cell line	Male
CVCL_TS00	HAP1 TESK1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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