TESK2

Summary

TESK2 (testis associated actin remodelling kinase 2, HGNC:11732) is a protein-coding gene on chromosome 1p34.1, encoding Dual specificity testis-specific protein kinase 2 (Q96S53). 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 that is structurally similar to the kinase domains of testis-specific protein kinase-1 and the LIM motif-containing protein kinases (LIMKs). Its overall structure is most related to the former, indicating that it belongs to the TESK subgroup of the LIMK/TESK family of protein kinases. This gene is predominantly expressed in testis and prostate. The developmental expression pattern of the rat gene in testis suggests an important role for this gene in meitoic stages and/or early stages of spermiogenesis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10420 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 108 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007170

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11732
Approved symbol	TESK2
Name	testis associated actin remodelling kinase 2
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000070759
Ensembl biotype	protein_coding
OMIM	604746
Entrez	10420

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 18 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000372084, ENST00000372086, ENST00000486676, ENST00000493974, ENST00000873857, ENST00000873858, ENST00000873859, ENST00000873860, ENST00000873861, ENST00000873862, ENST00000873863, ENST00000873864, ENST00000937751, ENST00000937752, ENST00000937753, ENST00000937754, ENST00000937755, ENST00000951681, ENST00000951682, ENST00000951683

RefSeq mRNA: 2 — MANE Select: NM_007170 NM_001320800, NM_007170

CCDS: CCDS41323

Canonical transcript exons

ENST00000372086 — 11 exons

Exon	Start	End
ENSE00001141205	45385912	45385960
ENSE00001145211	45343883	45345558
ENSE00001936285	45490852	45491163
ENSE00003466361	45345877	45345994
ENSE00003474024	45347918	45348000
ENSE00003527191	45355303	45355449
ENSE00003578287	45346979	45347062
ENSE00003600569	45457564	45457871
ENSE00003622052	45421725	45421846
ENSE00003636051	45347609	45347693
ENSE00003692424	45346693	45346779

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 87.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7304 / max 191.1177, expressed in 1588 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12118	5.5482	1514
12117	2.9664	804
12120	0.0842	22
12116	0.0713	24
12119	0.0602	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	87.70	gold quality
ileal mucosa	UBERON:0000331	84.90	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	84.50	gold quality
secondary oocyte	CL:0000655	84.48	gold quality
spinal cord	UBERON:0002240	83.09	gold quality
skin of abdomen	UBERON:0001416	82.41	gold quality
jejunal mucosa	UBERON:0000399	81.83	gold quality
skin of leg	UBERON:0001511	81.78	gold quality
duodenum	UBERON:0002114	81.08	gold quality
zone of skin	UBERON:0000014	80.93	gold quality
sperm	CL:0000019	80.67	silver quality
upper arm skin	UBERON:0004263	80.40	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.33	gold quality
oocyte	CL:0000023	80.06	gold quality
mucosa of transverse colon	UBERON:0004991	79.97	gold quality
upper leg skin	UBERON:0004262	79.94	gold quality
corpus callosum	UBERON:0002336	79.74	gold quality
prostate gland	UBERON:0002367	79.66	gold quality
lower esophagus mucosa	UBERON:0035834	79.56	gold quality
male germ cell	CL:0000015	79.24	silver quality
mucosa of stomach	UBERON:0001199	79.11	gold quality
hair follicle	UBERON:0002073	78.80	gold quality
rectum	UBERON:0001052	78.74	gold quality
leukocyte	CL:0000738	78.59	gold quality
monocyte	CL:0000576	78.57	gold quality
mononuclear cell	CL:0000842	78.44	gold quality
bone marrow cell	CL:0002092	78.25	gold quality
left ovary	UBERON:0002119	78.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.19	gold quality
blood	UBERON:0000178	77.99	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	65.27
E-ANND-3	no	3.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting TESK2, 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-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-1264	99.25	66.81	1317

Literature-anchored findings (GeneRIF, showing 1)

• Epimutations in both the TESK2 and MMACHC promoters in the Epi-cblC inherited disorder of intracellular metabolism of vitamin B12. (PMID:35440018)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tesk2	ENSDARG00000061450
mus_musculus	Tesk2	ENSMUSG00000033985
rattus_norvegicus	Tesk2	ENSRNOG00000017282

Paralogs (23): MAP3K9 (ENSG00000006432), MAP3K13 (ENSG00000073803), ARAF (ENSG00000078061), MAP3K20 (ENSG00000091436), RIPK2 (ENSG00000104312), LIMK1 (ENSG00000106683), TESK1 (ENSG00000107140), 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 2 — Q96S53 (reviewed: Q96S53)

Alternative names: Testicular protein kinase 2

All UniProt accessions (1): Q96S53

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. Phosphorylates cofilin at ‘Ser-3’. May play an important role in spermatogenesis.

Subcellular location. Nucleus.

Tissue specificity. Predominantly expressed in testis and prostate. Found predominantly in non-germinal Sertoli cells.

Activity regulation. Activated by autophosphorylation on Ser-219.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q96S53-1	1	yes
Q96S53-2	2
Q96S53-3	3

RefSeq proteins (2): NP_001307729, NP_009101* (*=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 (15 total): modified residue 4, splice variant 2, binding site 2, chain 1, domain 1, sequence variant 1, sequence conflict 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96S53-F1	66.52	0.35

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): 176 (proton acceptor)

Ligand- & substrate-binding residues (2): 64–72; 87

Post-translational modifications (4): 460, 219, 369, 456

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 196 (showing top): CCAWYNNGAAR_UNKNOWN, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_FOCAL_ADHESION_ASSEMBLY, GCAAGGA_MIR502, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_MALE_GAMETE_GENERATION, CTATGCA_MIR153, BROWNE_HCMV_INFECTION_12HR_UP, TTGGGAG_MIR150, AGTCTTA_MIR499, GOBP_CELL_JUNCTION_ORGANIZATION, MYCMAX_01, USF_01, chr1p34, GOBP_CELL_JUNCTION_ASSEMBLY

GO Biological Process (4): protein phosphorylation (GO:0006468), spermatogenesis (GO:0007283), actin cytoskeleton organization (GO:0030036), focal adhesion assembly (GO:0048041)

GO Molecular Function (11): 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), 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 (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear body (GO:0016604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	4
cellular anatomical structure	2
phosphorylation	1
protein modification process	1
developmental process involved in reproduction	1
male gamete generation	1
cytoskeleton organization	1
actin filament-based process	1
cell-substrate junction assembly	1
cell-matrix adhesion	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
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TESK2	TEX36	Q5VZQ5	572
TESK2	PDXP	Q96GD0	481
TESK2	TOE1	Q96GM8	458
TESK2	SSH3	Q8TE77	451
TESK2	SSH1	Q8WYL5	423
TESK2	CFL2	Q9Y281	397
TESK2	SSH2	Q76I76	394
TESK2	CFL1	P23528	392
TESK2	ALG1L2	C9J202	353
TESK2	DSTN	P18282	348
TESK2	CCDC163	A0A0D9SF12	336
TESK2	C10orf71	Q711Q0	312
TESK2	CYLC1	P35663	305
TESK2	LIMK2	P53671	302
TESK2	KIF16B	Q96L93	286

IntAct

94 interactions, top by confidence:

A	B	Type	Score
TESK2	YWHAH	psi-mi:“MI:0914”(association)	0.740
YWHAE	TESK2	psi-mi:“MI:0915”(physical association)	0.690
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
HSP90AB1	TESK2	psi-mi:“MI:0915”(physical association)	0.640
TESK2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
SFN	TESK2	psi-mi:“MI:0915”(physical association)	0.470
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AURKA	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
TESK2	ILVBL	psi-mi:“MI:0914”(association)	0.350
YWHAQ	MCRIP1	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAQ	FOXO6	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAE	PLEKHG3	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (115): TESK2 (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), TESK2 (Affinity Capture-MS), TESK2 (Affinity Capture-MS), TESK2 (Affinity Capture-MS), TESK2 (Affinity Capture-MS), TESK2 (Affinity Capture-MS), TESK2 (Affinity Capture-MS), TESK2 (Affinity Capture-MS), TESK2 (Affinity Capture-MS), TESK2 (Affinity Capture-MS), TESK2 (Affinity Capture-MS), TESK2 (Affinity Capture-MS), TESK2 (Affinity Capture-MS), MAGI1 (Affinity Capture-MS)

ESM2 similar proteins: A2VDZ4, A7MBB4, B1WAS2, B2GUY1, D3ZML2, O15021, O43283, O60285, O88866, P27704, P50526, P51956, P57058, Q0WPH8, Q12923, Q1HKZ5, Q5R8X7, Q5REX1, Q5VUJ6, Q5XHI9, Q60592, Q61532, Q63553, Q641K5, Q64702, Q66HE5, Q68UT7, Q6AX33, Q6IVY4, Q6P0Q8, Q6VZ17, Q6ZEZ5, Q7T2V3, Q7ZVS3, Q810W7, Q811L6, Q8CFH6, Q8IYT8, Q8RXT4, Q8VCT9

Diamond homologs: A0A0P0XII1, A0A0R0HPY5, A7J1T2, C0LGD6, C0LGD8, C0LGD9, C0LGG3, C0LGR6, C0LGV0, O00238, O00506, O04086, O35607, O46680, O64556, O65440, P04627, P09560, P0C5E2, P10398, P10533, P14056, P15056, P18161, P20792, P27037, P27038, P27039, P27040, P27041, P27966, P28028, P34908, P36894, P36895, P36896, P36897, P36898, P37023, P37172

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TESK2	“down-regulates activity”	CFL1	phosphorylation
TESK2	“down-regulates activity”	DSTN	phosphorylation
TESK2	“down-regulates activity”	CFL2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	94.3×	2e-12
Activation of BAD and translocation to mitochondria	7	93.5×	3e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	82.5×	8e-11
Activation of BH3-only proteins	7	61.0×	4e-10
RHO GTPases activate PKNs	8	44.5×	3e-10
Intrinsic Pathway for Apoptosis	7	36.0×	2e-08
FOXO-mediated transcription	5	29.5×	7e-06
SARS-CoV-1-host interactions	7	21.6×	5e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	28.9×	3e-05
intracellular protein localization	8	11.0×	2e-04
regulation of small GTPase mediated signal transduction	5	9.5×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3238 predictions. Top by Δscore:

Variant	Effect	Δscore
1:45345554:GAGTC:G	acceptor_gain	1.0000
1:45345556:GTC:G	acceptor_gain	1.0000
1:45345556:GTCC:G	acceptor_loss	1.0000
1:45345557:TC:T	acceptor_gain	1.0000
1:45345558:CC:C	acceptor_gain	1.0000
1:45345559:C:CC	acceptor_gain	1.0000
1:45345871:TCTTA:T	donor_loss	1.0000
1:45345872:CTTAC:C	donor_loss	1.0000
1:45345873:TTACC:T	donor_loss	1.0000
1:45345874:TACC:T	donor_loss	1.0000
1:45345875:A:AG	donor_loss	1.0000
1:45345875:AC:A	donor_gain	1.0000
1:45345875:ACC:A	donor_gain	1.0000
1:45345876:C:CT	donor_loss	1.0000
1:45345876:CC:C	donor_gain	1.0000
1:45345876:CCC:C	donor_gain	1.0000
1:45345898:T:TA	donor_gain	1.0000
1:45345909:T:A	donor_gain	1.0000
1:45345965:C:CT	acceptor_gain	1.0000
1:45345990:TCCAT:T	acceptor_gain	1.0000
1:45345991:CCAT:C	acceptor_gain	1.0000
1:45345991:CCATC:C	acceptor_gain	1.0000
1:45345992:CAT:C	acceptor_gain	1.0000
1:45345992:CATC:C	acceptor_gain	1.0000
1:45345993:ATCTG:A	acceptor_loss	1.0000
1:45345994:TCT:T	acceptor_loss	1.0000
1:45345995:C:CC	acceptor_gain	1.0000
1:45345996:T:C	acceptor_loss	1.0000
1:45346691:A:AC	donor_gain	1.0000
1:45346692:C:CT	donor_gain	1.0000

AlphaMissense

3736 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:45347951:T:A	D197V	1.000
1:45347998:G:C	N181K	1.000
1:45347998:G:T	N181K	1.000
1:45355313:A:G	L177P	1.000
1:45355316:T:A	D176V	1.000
1:45355316:T:G	D176A	1.000
1:45355319:C:G	R175P	1.000
1:45385919:A:G	L129P	1.000
1:45385919:A:T	L129H	1.000
1:45385943:A:T	V121D	1.000
1:45385945:A:C	C120W	1.000
1:45385946:C:T	C120Y	1.000
1:45385947:A:G	C120R	1.000
1:45385953:C:G	G118R	1.000
1:45421746:A:G	L108P	1.000
1:45421758:A:G	L104P	1.000
1:45421808:C:A	K87N	1.000
1:45421808:C:G	K87N	1.000
1:45421812:A:G	L86P	1.000
1:45457610:A:G	F59S	1.000
1:45345979:G:T	R299S	0.999
1:45346699:G:C	C291W	0.999
1:45346987:G:T	R262S	0.999
1:45347043:C:T	G243D	0.999
1:45347044:C:G	G243R	0.999
1:45347051:G:C	F240L	0.999
1:45347051:G:T	F240L	0.999
1:45347053:A:G	F240L	0.999
1:45347059:C:G	D238H	0.999
1:45347653:A:G	W222R	0.999

dbSNP variants (sampled 300 via entrez): RS1000009900 (1:45382529 A>G), RS1000047057 (1:45394163 C>A,T), RS1000056021 (1:45382227 T>C), RS1000076558 (1:45380833 A>G), RS1000115116 (1:45387311 T>C), RS1000131640 (1:45434086 C>G,T), RS1000140171 (1:45439081 A>G), RS1000160679 (1:45358595 C>A,T), RS1000174913 (1:45369789 G>A), RS1000177360 (1:45375505 C>A,T), RS1000182135 (1:45454177 T>C), RS1000189301 (1:45465918 G>C,T), RS1000209049 (1:45437086 C>A,T), RS1000238386 (1:45388806 C>T), RS1000240158 (1:45438638 C>T)

Disease associations

OMIM: gene MIM:604746 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST004599_245	Mean platelet volume	6.000000e-15
GCST004603_164	Platelet count	4.000000e-19
GCST004607_201	Plateletcrit	2.000000e-15
GCST004612_196	High light scatter reticulocyte percentage of red cells	7.000000e-10
GCST004616_106	Platelet distribution width	3.000000e-12
GCST004628_7	Immature fraction of reticulocytes	1.000000e-14
GCST004628_8	Immature fraction of reticulocytes	1.000000e-11
GCST007692_79	Chronic obstructive pulmonary disease	4.000000e-08
GCST90002385_610	High light scatter reticulocyte count	2.000000e-15
GCST90002386_315	High light scatter reticulocyte percentage of red cells	1.000000e-33
GCST90002386_382	High light scatter reticulocyte percentage of red cells	3.000000e-16
GCST90002387_196	Immature fraction of reticulocytes	5.000000e-41
GCST90002387_197	Immature fraction of reticulocytes	2.000000e-21
GCST90002395_303	Mean platelet volume	3.000000e-18
GCST90002395_304	Mean platelet volume	3.000000e-12
GCST90002400_30	Plateletcrit	1.000000e-37
GCST90002401_18	Platelet distribution width	1.000000e-23
GCST90002402_548	Platelet count	1.000000e-51

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007986	reticulocyte count
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2069163 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,478 (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
CHEMBL1738757	REBASTINIB	2	1,478

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	6.6	pIC50
compound 30 [PMID: 22902653]	Inhibition	6.38	pIC50
compound 35 [PMID: 22902653]	Inhibition	4.52	pIC50

ChEMBL bioactivities

15 potent at pChembl≥5 of 15 total, top 15 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.11	Kd	0.772	nM	CHEMBL3752910
8.87	ED50	1.364	nM	CHEMBL3752910
8.70	Kd	2	nM	REBASTINIB
8.46	Kd	3.488	nM	CHEMBL5653589
8.21	ED50	6.162	nM	CHEMBL5653589
7.75	Kd	18	nM	CHEMBL3991933
6.60	IC50	252	nM	CHEMBL2070615
6.38	IC50	415	nM	CHEMBL2070613
6.38	IC50	415	nM	CHEMBL2070614
6.21	IC50	612	nM	CHEMBL2070616
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.70	IC50	2013	nM	CHEMBL2070611
5.56	IC50	2740	nM	CHEMBL2070617

PubChem BioAssay actives

10 with measured affinity, of 171 total; 10 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	2149572: Binding affinity to human TESK2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0008	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	1425195: 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	2149572: Binding affinity to human TESK2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0035	uM
3-(2-methyl-1,3-benzoxazol-5-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine	1425195: 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	0.0180	uM
1-ethyl-3-[5-[6-(4-methoxy-2,6-dimethylphenyl)-2-pyrazin-2-ylpyrimidin-4-yl]-1,3-thiazol-2-yl]urea	678593: Inhibition of TESK2	ic50	0.2520	uM
1-[5-[6-(4-methoxy-2,6-dimethylphenyl)-2-pyrazin-2-ylpyrimidin-4-yl]-1,3-thiazol-2-yl]-3-methylurea	678593: Inhibition of TESK2	ic50	0.4150	uM
1-[5-[6-(2,6-dimethyl-4-pentan-3-yloxyphenyl)-2-pyrazin-2-ylpyrimidin-4-yl]-1,3-thiazol-2-yl]-3-methylurea	678593: Inhibition of TESK2	ic50	0.4150	uM
N-[5-[6-(4-methoxy-2,6-dimethylphenyl)-2-pyrazin-2-ylpyrimidin-4-yl]-1,3-thiazol-2-yl]acetamide	678593: Inhibition of TESK2	ic50	0.6120	uM
N-[5-[6-(2,6-dimethyl-4-pentan-3-yloxyphenyl)-2-pyrazin-2-ylpyrimidin-4-yl]-1,3-thiazol-2-yl]acetamide	678593: Inhibition of TESK2	ic50	2.0130	uM
methyl N-[5-[6-(4-methoxy-2,6-dimethylphenyl)-2-pyrazin-2-ylpyrimidin-4-yl]-1,3-thiazol-2-yl]carbamate	678593: Inhibition of TESK2	ic50	2.7400	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Estradiol	affects binding, increases expression, decreases expression	2
FR900359	increases phosphorylation	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects expression	1
Rotenone	decreases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2071843	Binding	Inhibition of TESK2	Modulation of cofilin phosphorylation by inhibition of the Lim family kinases. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TS01	HAP1 TESK2 (-) 1	Cancer cell line	Male
CVCL_TS02	HAP1 TESK2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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