CLK3

Summary

CLK3 (CDC like kinase 3, HGNC:2071) is a protein-coding gene on chromosome 15q24.1, encoding Dual specificity protein kinase CLK3 (P49761). Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates.

This gene encodes a protein belonging to the serine/threonine type protein kinase family. This protein is a nuclear dual-specificity kinase that regulates the intranuclear distribution of the serine/arginine-rich (SR) family of splicing factors. Two transcript variants encoding different isoforms have been found for this gene. Related pseudogenes are located on chromosomes 1 and 9.

Source: NCBI Gene 1198 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 122 total
• Druggable target: yes — 23 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001130028

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2071
Approved symbol	CLK3
Name	CDC like kinase 3
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000179335
Ensembl biotype	protein_coding
OMIM	602990
Entrez	1198

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 21 protein_coding, 8 retained_intron, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000345005, ENST00000395066, ENST00000454830, ENST00000483723, ENST00000561673, ENST00000562078, ENST00000562389, ENST00000562626, ENST00000562670, ENST00000563112, ENST00000563297, ENST00000563418, ENST00000563842, ENST00000564096, ENST00000564353, ENST00000564468, ENST00000566126, ENST00000566926, ENST00000567805, ENST00000567992, ENST00000568139, ENST00000568232, ENST00000568488, ENST00000568605, ENST00000569063, ENST00000569406, ENST00000570296, ENST00000899326, ENST00000899327, ENST00000899328, ENST00000899329, ENST00000899330, ENST00000899331, ENST00000969919, ENST00000969920, ENST00000969921

RefSeq mRNA: 2 — MANE Select: NM_001130028 NM_001130028, NM_003992

CCDS: CCDS10265

Canonical transcript exons

ENST00000395066 — 13 exons

Exon	Start	End
ENSE00001257892	74622120	74622216
ENSE00002586582	74615836	74615898
ENSE00003463004	74629707	74630201
ENSE00003465044	74622494	74622560
ENSE00003485316	74628942	74629032
ENSE00003502025	74620009	74620225
ENSE00003505832	74627970	74628052
ENSE00003570280	74625802	74625968
ENSE00003577508	74627352	74627446
ENSE00003596709	74627539	74627668
ENSE00003609716	74624902	74625018
ENSE00003613810	74628604	74628683
ENSE00003760292	74619197	74619348

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 98.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6280 / max 182.7254, expressed in 1815 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147704	18.6945	1806
147703	3.2301	1105
147705	0.8380	535
147702	0.8100	441
147707	0.0461	23
147706	0.0093	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.14	gold quality
granulocyte	CL:0000094	97.69	gold quality
left testis	UBERON:0004533	97.32	gold quality
right testis	UBERON:0004534	97.31	gold quality
monocyte	CL:0000576	96.96	gold quality
mononuclear cell	CL:0000842	96.59	gold quality
adenohypophysis	UBERON:0002196	96.56	gold quality
leukocyte	CL:0000738	96.48	gold quality
left lobe of thyroid gland	UBERON:0001120	96.35	gold quality
mucosa of transverse colon	UBERON:0004991	96.32	gold quality
skin of leg	UBERON:0001511	96.27	gold quality
minor salivary gland	UBERON:0001830	96.21	gold quality
skin of abdomen	UBERON:0001416	96.17	gold quality
right lobe of thyroid gland	UBERON:0001119	96.10	gold quality
left ovary	UBERON:0002119	96.09	gold quality
transverse colon	UBERON:0001157	96.02	gold quality
right uterine tube	UBERON:0001302	96.02	gold quality
endocervix	UBERON:0000458	95.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.96	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.95	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.94	gold quality
ectocervix	UBERON:0012249	95.89	gold quality
right ovary	UBERON:0002118	95.88	gold quality
body of uterus	UBERON:0009853	95.82	gold quality
right lung	UBERON:0002167	95.77	gold quality
body of stomach	UBERON:0001161	95.68	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.66	gold quality
gall bladder	UBERON:0002110	95.64	gold quality
cerebellar hemisphere	UBERON:0002245	95.63	gold quality
lower esophagus	UBERON:0013473	95.63	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

miRNA regulators (miRDB)

30 targeting CLK3, 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-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-5581-5P	97.91	66.50	965
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-7703	97.64	67.00	965
HSA-MIR-3974	96.56	66.22	928
HSA-MIR-4453	95.61	65.84	436
HSA-MIR-4538	95.61	65.34	449

Literature-anchored findings (GeneRIF, showing 6)

• Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells. (PMID:19168442)
• regulated but the expression of CDK9, CDC20 and CLK3 was down- regulated in azoospermic testes. (PMID:19426592)
• The identified the splicing kinase CLK3 that, by regulating HMGA2 splicing, preserves HMGA2 function in the setting of an increase in let-7 miRNA levels, delineating how CLK3 and HMGA2 form a functional axis that influences HSC properties during development. (PMID:29625070)
• The novel circCLK3/miR-320a/FoxM1 axis promotes cervical cancer progression. (PMID:31831728)
• Targeting CLK3 inhibits the progression of cholangiocarcinoma by reprogramming nucleotide metabolism. (PMID:32453420)
• CLK3 positively promoted colorectal cancer proliferation by activating IL-6/STAT3 signaling. (PMID:38885806)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	clk4a	ENSDARG00000089372
mus_musculus	Clk3	ENSMUSG00000032316
rattus_norvegicus	Clk3	ENSRNOG00000030126
drosophila_melanogaster	mnb	FBGN0259168
caenorhabditis_elegans		WBGENE00001994
caenorhabditis_elegans		WBGENE00003149
caenorhabditis_elegans		WBGENE00013727
caenorhabditis_elegans		WBGENE00185089

Paralogs (12): DYRK4 (ENSG00000010219), CLK1 (ENSG00000013441), HIPK2 (ENSG00000064393), DYRK1B (ENSG00000105204), HIPK3 (ENSG00000110422), CLK4 (ENSG00000113240), DYRK2 (ENSG00000127334), DYRK3 (ENSG00000143479), DYRK1A (ENSG00000157540), HIPK4 (ENSG00000160396), HIPK1 (ENSG00000163349), CLK2 (ENSG00000176444)

Protein

Protein identifiers

Dual specificity protein kinase CLK3 — P49761 (reviewed: P49761)

Alternative names: CDC-like kinase 3

All UniProt accessions (13): P49761, H3BNC8, H3BNQ5, H3BQG1, H3BQR7, H3BRE4, H3BRK0, H3BRT8, H3BRW2, H3BTW9, H3BUL5, H3BV35, H3BVF8

UniProt curated annotations — full annotation on UniProt →

Function. Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.

Subcellular location. Nucleus. Cytoplasm. Cytoplasmic vesicle. Secretory vesicle. Acrosome Nucleus speckle.

Tissue specificity. Endothelial cells.

Post-translational modifications. Autophosphorylates on all three types of residues.

Activity regulation. Leucettine L41 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins.

Miscellaneous. Lacks the kinase domain. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P49761-1	1, Long	yes
P49761-2	2, Short
P49761-3	3

RefSeq proteins (2): NP_001123500, NP_003983 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR051175	CLK_kinases	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.12.1 — dual-specificity kinase (BRENDA: 51 organisms, 125 substrates, 188 inhibitors, 14 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.019–0.1185	7
HISTONE H1	0.006–0.012	5

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 (61 total): helix 18, strand 13, modified residue 8, turn 5, compositionally biased region 4, splice variant 3, sequence variant 3, binding site 2, chain 1, domain 1, region of interest 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
6FYR	X-RAY DIFFRACTION	1.42
2EU9	X-RAY DIFFRACTION	1.53
6Z53	X-RAY DIFFRACTION	1.65
6Z55	X-RAY DIFFRACTION	1.7
6Z54	X-RAY DIFFRACTION	1.73
6YTY	X-RAY DIFFRACTION	1.76
6YU1	X-RAY DIFFRACTION	1.9
2WU6	X-RAY DIFFRACTION	1.92
6Z51	X-RAY DIFFRACTION	1.92
6YTW	X-RAY DIFFRACTION	2
6FT7	X-RAY DIFFRACTION	2.02
3RAW	X-RAY DIFFRACTION	2.09
29MO	X-RAY DIFFRACTION	2.1
6Z52	X-RAY DIFFRACTION	2.12
2WU7	X-RAY DIFFRACTION	2.25
6FYP	X-RAY DIFFRACTION	2.29
6RCT	X-RAY DIFFRACTION	2.32
2EXE	X-RAY DIFFRACTION	2.35
29MP	X-RAY DIFFRACTION	2.5
6KHF	X-RAY DIFFRACTION	2.6
6Z2V	X-RAY DIFFRACTION	2.6
9EZ3	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49761-F1	78.27	0.67

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): 283 (proton acceptor)

Ligand- & substrate-binding residues (2): 162–170; 186

Post-translational modifications (8): 7, 9, 49, 51, 67, 76, 78, 135

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 176 (showing top): GOCC_SECRETORY_GRANULE, MENSE_HYPOXIA_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, CACCAGC_MIR138, RICKMAN_METASTASIS_DN, CCTGTGA_MIR513, GOBP_RNA_SPLICING, GGCAGTG_MIR3243P, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_UP, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, AGCTCCT_MIR28, GOBP_REGULATION_OF_RNA_SPLICING, GOCC_SECRETORY_VESICLE

GO Biological Process (2): protein phosphorylation (GO:0006468), regulation of RNA splicing (GO:0043484)

GO Molecular Function (12): RNA binding (GO:0003723), 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), identical protein binding (GO:0042802), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (8): acrosomal vesicle (GO:0001669), nucleus (GO:0005634), nucleoplasm (GO:0005654), membrane (GO:0016020), nuclear speck (GO:0016607), intermediate filament cytoskeleton (GO:0045111), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	4
cellular anatomical structure	3
phosphorylation	1
protein modification process	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
secretory granule	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear ribonucleoprotein granule	1
cytoskeleton	1
intracellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLK3	COQ7	Q99807	893
CLK3	TELO2	Q9Y4R8	767
CLK3	IMMT	Q16891	762
CLK3	PAFAH1B3	Q15102	550
CLK3	UBL7	Q96S82	496
CLK3	SRSF4	Q08170	492
CLK3	SCAMP5	Q8TAC9	482
CLK3	SRSF1	Q07955	472
CLK3	SRSF6	Q13247	411
CLK3	PDCD2	Q16342	403
CLK3	MBNL3	Q9NUK0	388
CLK3	TXLNA	P40222	385
CLK3	PPP1R10	Q96QC0	375
CLK3	CCDC33	Q8N5R6	366
CLK3	ADPGK	Q9BRR6	365

IntAct

246 interactions, top by confidence:

A	B	Type	Score
CLK2	CLK3	psi-mi:“MI:0915”(physical association)	0.870
CLK3	CLK2	psi-mi:“MI:0915”(physical association)	0.870
RSRP1	CLK3	psi-mi:“MI:0915”(physical association)	0.830
CLK3	RSRP1	psi-mi:“MI:0915”(physical association)	0.830
SRPK2	CLK3	psi-mi:“MI:0915”(physical association)	0.810
TRA2B	CLK3	psi-mi:“MI:0915”(physical association)	0.800
SNIP1	CLK3	psi-mi:“MI:0915”(physical association)	0.740
RNPS1	CLK3	psi-mi:“MI:0915”(physical association)	0.740
CLK3	PSME3	psi-mi:“MI:0914”(association)	0.730
CLK3	SDCBP	psi-mi:“MI:0915”(physical association)	0.720
CLK3	HOXB7	psi-mi:“MI:0915”(physical association)	0.720
HOXB6	CLK3	psi-mi:“MI:0915”(physical association)	0.720
SDCBP	CLK3	psi-mi:“MI:0915”(physical association)	0.720
HOXB7	CLK3	psi-mi:“MI:0915”(physical association)	0.720
CLK3	HOXB6	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (373): CLK3 (Two-hybrid), CLK3 (Two-hybrid), HOXB6 (Two-hybrid), HOXB7 (Two-hybrid), OAS2 (Two-hybrid), RBMY1A1 (Two-hybrid), SDCBP (Two-hybrid), SRPK2 (Two-hybrid), ZNF263 (Two-hybrid), RBMX (Two-hybrid), RSRP1 (Two-hybrid), RBMY1F (Two-hybrid), KRTAP10-3 (Two-hybrid), CLK3 (Affinity Capture-RNA), CLK3 (Affinity Capture-MS)

ESM2 similar proteins: A1CL96, A1D624, A2X0M1, A2Y4B6, O35491, O35492, O35493, O35831, O35832, O44514, P22518, P46551, P49759, P49760, P49761, P51566, P51567, P83099, Q00536, Q00537, Q04735, Q09437, Q0CQK1, Q0E459, Q11179, Q23357, Q3SX21, Q4FCZ5, Q4I5U9, Q4WYR6, Q53N72, Q5BAE1, Q5SN53, Q5VP69, Q5Z9J0, Q5ZCI1, Q5ZIU3, Q63117, Q63686, Q67C40

Diamond homologs: A1CAF0, A1CPG7, A1D2C9, A1DES4, A2QN07, A2QRF6, A3EZ55, A4L9P5, A8WJR8, A8X4H1, B0XR80, B0Y462, G1XJZ4, M1T7M3, O35491, O35492, O35493, O43781, O88850, O88904, P0C431, P0CP68, P0CP69, P14680, P22518, P49657, P49759, P49760, P49761, P49762, P50613, P51566, P51567, P51568, P83102, Q03147, Q07538, Q08DZ2, Q09690, Q09815

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
AR	“down-regulates quantity by repression”	CLK3	“transcriptional regulation”
CLK3	“up-regulates activity”	USP13	phosphorylation
MYC	“up-regulates quantity by expression”	CLK3	“transcriptional regulation”
CLK3	“up-regulates activity”	SRSF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 101 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
Activation of BAD and translocation to mitochondria	7	86.0×	2e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	75.8×	5e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	75.8×	5e-11
Activation of BH3-only proteins	7	56.1×	5e-10
Transport of Mature Transcript to Cytoplasm	8	49.1×	6e-11
RHO GTPases activate PKNs	7	35.8×	1e-08
RNA Polymerase II Transcription Termination	10	35.4×	6e-12
mRNA 3’-end processing	11	34.9×	5e-13

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	7	58.9×	2e-09
mRNA splice site recognition	6	52.9×	7e-08
regulation of alternative mRNA splicing, via spliceosome	14	37.6×	3e-16
positive regulation of mRNA splicing, via spliceosome	5	29.9×	4e-05
protein targeting	5	20.1×	2e-04
RNA splicing	16	15.5×	1e-12
mRNA processing	15	13.0×	7e-11
mRNA splicing, via spliceosome	12	12.1×	3e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	106
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2957 predictions. Top by Δscore:

Variant	Effect	Δscore
15:74620003:T:A	acceptor_gain	1.0000
15:74620007:A:AG	acceptor_gain	1.0000
15:74620008:G:GG	acceptor_gain	1.0000
15:74620008:GCC:G	acceptor_gain	1.0000
15:74622488:TCCTA:T	acceptor_loss	1.0000
15:74622490:CTA:C	acceptor_loss	1.0000
15:74622492:A:AG	acceptor_gain	1.0000
15:74622492:A:T	acceptor_loss	1.0000
15:74622492:AGAT:A	acceptor_gain	1.0000
15:74622493:G:GA	acceptor_gain	1.0000
15:74622493:GAT:G	acceptor_gain	1.0000
15:74622493:GATG:G	acceptor_gain	1.0000
15:74622493:GATGA:G	acceptor_gain	1.0000
15:74624892:C:A	acceptor_gain	1.0000
15:74624893:G:A	acceptor_gain	1.0000
15:74624897:A:AG	acceptor_gain	1.0000
15:74624900:A:AG	acceptor_gain	1.0000
15:74624900:AGAG:A	acceptor_gain	1.0000
15:74624900:AGAGG:A	acceptor_gain	1.0000
15:74624901:G:GA	acceptor_gain	1.0000
15:74624901:GA:G	acceptor_gain	1.0000
15:74624901:GAGG:G	acceptor_gain	1.0000
15:74624901:GAGGG:G	acceptor_gain	1.0000
15:74625014:AAGTT:A	donor_gain	1.0000
15:74625016:GTT:G	donor_gain	1.0000
15:74625017:TT:T	donor_gain	1.0000
15:74625017:TTGTG:T	donor_loss	1.0000
15:74625018:TG:T	donor_loss	1.0000
15:74625019:G:GG	donor_gain	1.0000
15:74625800:A:AG	acceptor_gain	1.0000

AlphaMissense

4151 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:74622174:G:C	G290R	1.000
15:74622181:T:C	L292P	1.000
15:74622205:T:C	L300P	1.000
15:74622520:G:C	G313R	1.000
15:74622520:G:T	G313C	1.000
15:74622526:T:A	F315I	1.000
15:74622526:T:C	F315L	1.000
15:74622526:T:G	F315V	1.000
15:74622527:T:G	F315C	1.000
15:74622528:T:A	F315L	1.000
15:74622528:T:G	F315L	1.000
15:74622529:G:C	G316R	1.000
15:74622530:G:A	G316D	1.000
15:74622530:G:T	G316V	1.000
15:74622544:T:C	C321R	1.000
15:74622545:G:A	C321Y	1.000
15:74622546:C:G	C321W	1.000
15:74624919:C:A	A332D	1.000
15:74624922:T:C	L333P	1.000
15:74624924:A:G	K334E	1.000
15:74624926:G:C	K334N	1.000
15:74624926:G:T	K334N	1.000
15:74624928:T:G	I335S	1.000
15:74624931:T:A	I336N	1.000
15:74624933:C:A	R337S	1.000
15:74624948:T:C	Y342H	1.000
15:74624957:G:C	A345P	1.000
15:74624960:G:C	A346P	1.000
15:74624961:C:A	A346D	1.000
15:74624967:T:C	L348P	1.000

dbSNP variants (sampled 300 via entrez): RS1000030976 (15:74626447 G>A), RS1000051165 (15:74619052 T>G), RS1000093008 (15:74609836 G>A), RS1000414350 (15:74609213 C>G), RS1000504685 (15:74614853 T>G), RS1000885726 (15:74607312 C>T), RS1000950004 (15:74615060 G>C), RS1000984660 (15:74614673 G>A,T), RS1001068821 (15:74619828 G>T), RS1001320312 (15:74614541 G>C), RS1001350759 (15:74624246 G>A), RS1001418290 (15:74607712 T>A,C), RS1001604184 (15:74618812 C>T), RS1001727171 (15:74613178 C>T), RS1001740129 (15:74630337 CCT>C)

Disease associations

OMIM: gene MIM:602990 | 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
GCST002645_1	Bladder cancer	4.000000e-09
GCST003846_10	Caffeine metabolism (plasma 1,3,7-trimethylxanthine (caffeine) level)	5.000000e-18
GCST003846_11	Caffeine metabolism (plasma 1,3,7-trimethylxanthine (caffeine) level)	1.000000e-20
GCST003846_7	Caffeine metabolism (plasma 1,3,7-trimethylxanthine (caffeine) level)	1.000000e-11
GCST003846_8	Caffeine metabolism (plasma 1,3,7-trimethylxanthine (caffeine) level)	2.000000e-16
GCST003846_9	Caffeine metabolism (plasma 1,3,7-trimethylxanthine (caffeine) level)	3.000000e-09
GCST003848_1	Caffeine metabolism (plasma 1,3-dimethylxanthine (theophylline) level)	1.000000e-07
GCST003848_2	Caffeine metabolism (plasma 1,3-dimethylxanthine (theophylline) level)	1.000000e-08
GCST003848_3	Caffeine metabolism (plasma 1,3-dimethylxanthine (theophylline) level)	2.000000e-07
GCST003848_4	Caffeine metabolism (plasma 1,3-dimethylxanthine (theophylline) level)	1.000000e-07
GCST003851_4	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-07
GCST003851_5	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-14
GCST003851_6	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-11
GCST003851_7	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	4.000000e-15
GCST003851_8	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-22
GCST004412_7	Craniofacial microsomia	1.000000e-23
GCST005523_34	Celiac disease	8.000000e-09
GCST010108_21	Coffee consumption (cups per day)	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007872	caffeine metabolite measurement
EFO:0006782	cups of coffee per day measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4226 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

23 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 109,105 (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
CHEMBL1738797	ALECTINIB	4	6,731
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL1241855	RIGOSERTIB	3	1,544
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL4297639	LORECIVIVINT	3	282
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL124660	TANDUTINIB	2	2,530
CHEMBL230011	TG100-115	2	1,504
CHEMBL384304	RG-547	2	93
CHEMBL445813	AT-7519	2	2,614
CHEMBL475251	R-406	2	762
CHEMBL513909	BI-2536	2	895
CHEMBL607707	PELITINIB	2	6,340
CHEMBL1908397	KW-2449	1	622
CHEMBL2140408	AMG-900	1	675
CHEMBL259084	MLN-8054	1	2,430
CHEMBL269538	HARMINE	1	4,346
CHEMBL4784318	CIRTUVIVINT	1
CHEMBL5426285	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-	1
CHEMBL574738	AST-487	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CLK family

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
leucettine L41	Inhibition	8.35	pIC50
cirtuvivint	Inhibition	7.92	pIC50
KH-CB19	Inhibition	6.28	pIC50
compound 3b [PMID: 23454515]	Inhibition	6.26	pIC50

Binding affinities (BindingDB)

8 measured of 8 human assays (8 total across all organisms); most potent 8 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
3A5	IC50	51 nM
5F4	IC50	273 nM
5E4	IC50	277 nM
NR9	IC50	390 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM

ChEMBL bioactivities

967 potent at pChembl≥5 of 969 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.66	IC50	2.2	nM	CIRTUVIVINT
8.54	IC50	2.9	nM	CHEMBL4284209
8.52	EC50	3	nM	CHEMBL4748515
8.22	EC50	6	nM	CHEMBL4761662
8.19	Kd	6.5	nM	CHEMBL4797564
8.19	IC50	6.5	nM	CHEMBL4797564
8.15	EC50	7	nM	CHEMBL4740064
8.15	EC50	7	nM	CHEMBL4746469
8.10	EC50	8	nM	CHEMBL4782826
8.10	IC50	8	nM	CHEMBL4083249
8.05	EC50	9	nM	CHEMBL4754110
8.05	EC50	9	nM	CHEMBL4741472
8.05	EC50	9	nM	CHEMBL4745584
8.00	Kd	10	nM	SILMITASERTIB
8.00	EC50	10	nM	CHEMBL4798969
8.00	IC50	10	nM	CHEMBL5441121
7.96	EC50	11	nM	CHEMBL4761354
7.96	EC50	11	nM	CHEMBL4779592
7.96	EC50	11	nM	CHEMBL4748995
7.96	EC50	11	nM	CHEMBL4780597
7.96	EC50	11	nM	CHEMBL4797241
7.96	EC50	11	nM	CHEMBL4780537
7.92	Kd	12	nM	AT-7519
7.92	EC50	12	nM	CHEMBL4752625
7.92	EC50	12	nM	CHEMBL4783783
7.92	EC50	12	nM	CHEMBL4786746
7.92	EC50	12	nM	CIRTUVIVINT
7.92	EC50	12	nM	CHEMBL4800068
7.92	EC50	12	nM	CHEMBL4741101
7.92	EC50	12	nM	CHEMBL4793171
7.92	IC50	11.9	nM	CHEMBL393525
7.89	EC50	13	nM	CHEMBL4742870
7.89	EC50	13	nM	CHEMBL4746668
7.89	EC50	13	nM	CHEMBL4755579
7.89	Kd	13	nM	RG-547
7.85	EC50	14	nM	CHEMBL4742725
7.85	EC50	14	nM	CHEMBL4788275
7.85	EC50	14	nM	CHEMBL4748484
7.85	EC50	14	nM	CHEMBL4799760
7.82	EC50	15	nM	CHEMBL4759361
7.82	EC50	15	nM	CHEMBL4740518
7.81	IC50	15.6	nM	CHEMBL5560595
7.80	EC50	16	nM	CHEMBL4747740
7.80	EC50	16	nM	CHEMBL4745415
7.80	EC50	16	nM	CHEMBL4748909
7.80	EC50	16	nM	CHEMBL4800405
7.77	EC50	17	nM	CHEMBL4786934
7.77	EC50	17	nM	CHEMBL4745260
7.77	EC50	17	nM	CHEMBL4786564
7.77	EC50	17	nM	CHEMBL4791409

PubChem BioAssay actives

362 with measured affinity, of 1479 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
2-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	1933968: Inhibition of human CLK3	ic50	0.0022	uM
2-N-(4-aminocyclohexyl)-8-propan-2-yl-4-N-[(4-pyridin-2-ylphenyl)methyl]pyrazolo[1,5-a][1,3,5]triazine-2,4-diamine	1933968: Inhibition of human CLK3	ic50	0.0029	uM
2-N-methyl-4-N-(pyrimidin-2-ylmethyl)-5-quinolin-6-yl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine	1851266: Binding affinity to CLK3 (unknown origin) assessed as dissociation constant	kd	0.0065	uM
5-[1-[(1S)-1-(4-fluorophenyl)ethyl]triazolo[4,5-c]quinolin-8-yl]-1,3-benzoxazole	1933968: Inhibition of human CLK3	ic50	0.0080	uM
(5Z)-2-[(1S)-2-amino-1-phenylethyl]imino-5-(1,3-benzothiazol-6-ylmethylidene)imidazolidin-4-one;dihydrochloride	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0100	uM
5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid	1424957: 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
N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide	1947680: Inhibition of recombinant human CLK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.0119	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	1424957: 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
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	624931: Binding constant for CLK3 kinase domain	kd	0.0130	uM
3-methyl-N-[5-[3-(2-pyridin-3-ylethynyl)-2H-indazol-5-yl]-3-pyridinyl]butanamide	2082332: Inhibition of CLK3 (unknown origin) incubated for 10 mins in presence of ATP	ic50	0.0156	uM
(5Z)-2-(2-amino-1-phenylethyl)imino-5-(1,3-benzothiazol-6-ylmethylidene)imidazolidin-4-one;dihydrochloride	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0230	uM
3-(3-chlorophenyl)-6,7-dihydro-1H-pyrrolo[3,4-g]indol-8-one	1933968: Inhibition of human CLK3	ic50	0.0280	uM
5-amino-N-(2,6-difluorophenyl)-3-(4-sulfamoylanilino)-1,2,4-triazole-1-carbothioamide	1436044: Inhibition of human CLK3 (275 to 632 residues) expressed in Escherichia coli BL21(DE3) preincubated for 10 mins followed by substrate addition by pyruvate kinase and lactate dehydrogenase coupled enzyme assay	ic50	0.0292	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[2-(methylamino)-1-phenylethyl]iminoimidazolidin-4-one;dihydrochloride	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0300	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2R)-2-hydroxy-2-phenylethyl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0380	uM
(2S)-2-[[6-(6-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-yl]amino]-2-phenylethanol	2110576: Inhibition of CLK3 (unknown origin) preincubated with enzyme for 10 mins followed by substrate and ATP addition measured after 60 mins by ADP-Glo reagent based assay	ic50	0.0389	uM
2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetic acid	1424957: 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	0.0400	uM
N-[5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-1H-indazol-5-yl]-3-pyridinyl]-3-methylbutanamide	2082332: Inhibition of CLK3 (unknown origin) incubated for 10 mins in presence of ATP	ic50	0.0443	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,2R)-2-methoxycyclopentyl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0490	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1S,2S)-2-methoxycyclopentyl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0530	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1S,3S)-3-methoxycyclohexyl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0730	uM
(5Z)-5-(quinolin-6-ylmethylidene)-2-sulfanylidene-1,3-thiazolidin-4-one	1284898: Inhibition of recombinant human GST-tagged CLK3 expressed in baculovirus expression system by lantha screen kinase binding assay	ic50	0.0866	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3,5,7-trifluoro-1-adamantyl)imino]imidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0900	uM
(5Z)-2-(2,6-dichlorophenyl)imino-5-(quinoxalin-6-ylmethylidene)-1,3-thiazolidin-4-one	1947680: Inhibition of recombinant human CLK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.0926	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3,3-difluorocycloheptyl)iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0960	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(thian-3-ylimino)imidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1070	uM
4-[2-methyl-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl]-N-(6-pyridin-4-ylimidazo[1,2-a]pyridin-2-yl)benzamide	1933968: Inhibition of human CLK3	ic50	0.1100	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3-tricyclo[3.3.1.03,7]nonanylimino)imidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1140	uM
(5Z)-5-(2,3-dihydro-1-benzofuran-5-ylmethylidene)-2-imino-1,3-thiazolidin-4-one	1851161: Inhibition of human full length recombinant CLK3 expressed in baculovirus by measuring substrate phosphorylation	ic50	0.1160	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3S)-oxan-3-yl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1190	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R)-2-methoxy-1-phenylethyl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1270	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(2,2-difluorocyclohexyl)iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1270	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,2R)-2-methoxycycloheptyl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1330	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[[2-(trifluoromethyl)phenyl]methylimino]imidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1350	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,2R)-2-hydroxycycloheptyl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1380	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(2-bicyclo[2.2.1]heptanylimino)imidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1430	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624931: Binding constant for CLK3 kinase domain	kd	0.1600	uM
methyl 2-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]adamantane-2-carboxylate	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1670	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3,3-difluorocyclopentyl)iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1730	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,2R)-2-hydroxycyclohexyl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1750	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3,3-difluorocyclohexyl)iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1750	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1S)-2-hydroxy-1-phenylethyl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1780	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R)-2-hydroxy-1-phenylethyl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1790	uM
10-methoxy-11H-pyrido[4,3-a]carbazole-6-carbonitrile	1335825: Inhibition of GST-tagged human recombinant CLK3 expressed in Escherichia coli using RS peptide as substrate incubated for 30 mins in presence of [gamma-33 P] ATP by liquid scintillation counting analysis	ic50	0.1800	uM
9-methoxy-11H-pyrido[4,3-a]carbazole-6-carbonitrile	1335825: Inhibition of GST-tagged human recombinant CLK3 expressed in Escherichia coli using RS peptide as substrate incubated for 30 mins in presence of [gamma-33 P] ATP by liquid scintillation counting analysis	ic50	0.1900	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2S)-2-hydroxy-2-phenylethyl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1940	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3-fluoro-1-adamantyl)imino]imidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1940	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,2S)-2-hydroxycycloheptyl]iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1950	uM
(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-2-(pyridin-3-ylamino)-1H-imidazol-5-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2010	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(1-methylpyrazol-3-yl)iminoimidazolidin-4-one	2010388: Inhibition of human full length CLK3 (1 to 490 residues) expressed in Sf9 cells using S6 peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2010	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases methylation	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
urushiol	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	affects cotreatment, increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
ferrous chloride	increases expression	1
coumarin	decreases phosphorylation	1
5-iodotubercidin	decreases activity	1
epigallocatechin gallate	increases expression, affects cotreatment	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases expression	1
pentabromodiphenyl ether	increases expression	1
monomethylarsonous acid	decreases expression	1
K 7174	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
PCI 5002	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Leflunomide	increases expression	1
Air Pollutants	increases expression, increases abundance	1

ChEMBL screening assays

294 unique, capped per target: 292 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1033252	Binding	Inhibition of CLK3 at 3 uM	Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem
CHEMBL1738045	Functional	PUBCHEM_BIOASSAY: Kinase Inhibition Study on Inhibitors of CDC-like Kinase 3 (Reaction Biology data). (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1459, AID1487, AID1498, AID1770, AID1970, AID1997, AID488872	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1NI	Abcam HeLa CLK3 KO	Cancer cell line	Female
CVCL_SJ23	HAP1 CLK3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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