CLK2

Summary

CLK2 (CDC like kinase 2, HGNC:2069) is a protein-coding gene on chromosome 1q22, encoding Dual specificity protein kinase CLK2 (P49760). Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. It is a selective cancer dependency (DepMap: 34.0% of cell lines).

This gene encodes a dual specificity protein kinase that phosphorylates serine/threonine and tyrosine-containing substrates. Activity of this protein regulates serine- and arginine-rich (SR) proteins of the spliceosomal complex, thereby influencing alternative transcript splicing. Chromosomal translocations have been characterized between this locus and the PAFAH1B3 (platelet-activating factor acetylhydrolase 1b, catalytic subunit 3 (29kDa)) gene on chromosome 19, resulting in the production of a fusion protein. Note that this gene is distinct from the TELO2 gene (GeneID:9894), which shares the CLK2 alias, but encodes a protein that is involved in telomere length regulation. There is a pseudogene for this gene on chromosome 7. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1196 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 105 total
• Druggable target: yes — 55 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 34.0% of screened cell lines
• MANE Select transcript: NM_001294338

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2069
Approved symbol	CLK2
Name	CDC like kinase 2
Location	1q22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176444
Ensembl biotype	protein_coding
OMIM	602989
Entrez	1196

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000355560, ENST00000361168, ENST00000368361, ENST00000471047, ENST00000476983, ENST00000484699, ENST00000497188, ENST00000715978

RefSeq mRNA: 4 — MANE Select: NM_001294338 NM_001294338, NM_001294339, NM_001363704, NM_003993

CCDS: CCDS1107, CCDS72939, CCDS86020

Canonical transcript exons

ENST00000368361 — 13 exons

Exon	Start	End
ENSE00001849557	155262868	155263400
ENSE00003509242	155265860	155265954
ENSE00003531363	155264221	155264300
ENSE00003557484	155268010	155268126
ENSE00003582083	155268293	155268359
ENSE00003594650	155266729	155266895
ENSE00003604029	155264645	155264774
ENSE00003613802	155263950	155264040
ENSE00003621689	155264468	155264550
ENSE00003632828	155270808	155270977
ENSE00003647022	155268708	155268795
ENSE00003662691	155269488	155269716
ENSE00004028504	155273201	155273504

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.5659 / max 108.8837, expressed in 1806 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14955	18.1757	1806
14956	0.3902	199

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.31	gold quality
right lobe of thyroid gland	UBERON:0001119	97.08	gold quality
pituitary gland	UBERON:0000007	96.97	gold quality
spleen	UBERON:0002106	96.96	gold quality
right adrenal gland cortex	UBERON:0035827	96.78	gold quality
left lobe of thyroid gland	UBERON:0001120	96.77	gold quality
right adrenal gland	UBERON:0001233	96.72	gold quality
metanephros cortex	UBERON:0010533	96.66	gold quality
adenohypophysis	UBERON:0002196	96.64	gold quality
thyroid gland	UBERON:0002046	96.56	gold quality
right ovary	UBERON:0002118	96.42	gold quality
left ovary	UBERON:0002119	96.27	gold quality
left adrenal gland cortex	UBERON:0035825	96.26	gold quality
body of uterus	UBERON:0009853	96.16	gold quality
granulocyte	CL:0000094	96.12	gold quality
left adrenal gland	UBERON:0001234	96.10	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.07	gold quality
endocervix	UBERON:0000458	95.77	gold quality
ovary	UBERON:0000992	95.71	gold quality
lymph node	UBERON:0000029	95.68	gold quality
left uterine tube	UBERON:0001303	95.59	gold quality
prostate gland	UBERON:0002367	95.55	gold quality
fundus of stomach	UBERON:0001160	95.45	gold quality
adrenal gland	UBERON:0002369	95.39	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.38	gold quality
vermiform appendix	UBERON:0001154	95.33	gold quality
body of pancreas	UBERON:0001150	95.27	gold quality
minor salivary gland	UBERON:0001830	95.27	gold quality
small intestine	UBERON:0002108	95.27	gold quality
body of stomach	UBERON:0001161	95.19	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2

miRNA regulators (miRDB)

35 targeting CLK2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-147A	98.33	66.40	795

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells. (PMID:19168442)
• AKT activation controls cell survival to ionizing radiation by phosphorylating CLK2, revealing an important regulatory mechanism required for promoting cell survival. (PMID:20682768)
• CLK1 Increases While CLK2 Decreases HIV-1 Gene Expression. (PMID:21682887)
• LAMMER/Cdc2-like kinase, represented by Doa and its mammalian homolog CLK2, is a critical and conserved component in the regulatory program of the mitosis-to-meiosis switch (PMID:23376537)
• Loss of CLK2 in luminal breast cancer cells leads to the upregulation of epithelial-to-mesenchymal transition (EMT)-related genes and a switch to mesenchymal splice variants of several genes. (PMID:25670169)
• These findings suggest that CLK2 plays a critical role in controlling the cell cycle and survival of glioblastoma (PMID:27050366)
• Clk1, Clk2 and Clk4 prevent chromatin breakage by regulating the Aurora B-dependent abscission checkpoint. (PMID:27126587)
• CLK2 promotes occurrence and development of non-small cell lung cancer. (PMID:33721432)
• CDC Like Kinase 2 plays an oncogenic role in colorectal cancer via modulating the Wnt/beta-catenin signaling. (PMID:35293765)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	clk2b	ENSDARG00000059870
danio_rerio	clk2a	ENSDARG00000062954
mus_musculus	Clk2	ENSMUSG00000068917
rattus_norvegicus	Clk2	ENSRNOG00000077782
drosophila_melanogaster	Doa	FBGN0265998
caenorhabditis_elegans		WBGENE00006517

Paralogs (12): DYRK4 (ENSG00000010219), CLK1 (ENSG00000013441), HIPK2 (ENSG00000064393), DYRK1B (ENSG00000105204), HIPK3 (ENSG00000110422), CLK4 (ENSG00000113240), DYRK2 (ENSG00000127334), DYRK3 (ENSG00000143479), DYRK1A (ENSG00000157540), HIPK4 (ENSG00000160396), HIPK1 (ENSG00000163349), CLK3 (ENSG00000179335)

Protein

Protein identifiers

Dual specificity protein kinase CLK2 — P49760 (reviewed: P49760)

Alternative names: CDC-like kinase 2

All UniProt accessions (3): P49760, A8K7I0, B1AVT0

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. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Phosphorylates PAGE4 at several serine and threonine residues and this phosphorylation attenuates the ability of PAGE4 to potentiate the transcriptional activator activity of JUN.

Subunit / interactions. Interacts with RBMX. Interacts with AKT1 and UBL5.

Subcellular location. Nucleus Nucleus. Nucleus speckle Nucleus speckle.

Tissue specificity. Endothelial cells. Expressed in androgen-dependent prostate cancer cells.

Post-translational modifications. Autophosphorylates on all three types of residues. Phosphorylation on Ser-34 and Thr-127 by AKT1 is induced by ionizing radiation or insulin. Phosphorylation plays a critical role in cell proliferation following low dose radiation and prevents cell death following high dose radiation. Phosphorylation at Thr-344 by PKB/AKT2 induces its kinase activity which is required for its stability. The phosphorylation status at Ser-142 influences its subnuclear localization; inhibition of phosphorylation at Ser-142 results in accumulation in the nuclear speckle.

Activity regulation. 5,6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) inhibits autophosphorylation. TG003 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?
P49760-1	1, Long	yes
P49760-2	2, Short
P49760-3	3

RefSeq proteins (4): NP_001281267, NP_001281268, NP_001350633, NP_003984 (=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 (57 total): helix 17, strand 13, modified residue 7, turn 6, compositionally biased region 4, splice variant 3, binding site 2, region of interest 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6FYL	X-RAY DIFFRACTION	1.95
6FYK	X-RAY DIFFRACTION	2.39
6FYI	X-RAY DIFFRACTION	2.6
6KHE	X-RAY DIFFRACTION	2.8
3NR9	X-RAY DIFFRACTION	2.89
5UNP	X-RAY DIFFRACTION	2.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49760-F1	76.61	0.64

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): 290 (proton acceptor)

Ligand- & substrate-binding residues (2): 193; 169–177

Post-translational modifications (7): 34, 98, 99, 127, 142, 153, 344

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): GCACCTT_MIR18A_MIR18B, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_RESPONSE_TO_IONIZING_RADIATION, ACTACCT_MIR196A_MIR196B, CACCAGC_MIR138, YY1_Q6, CCATCCA_MIR432, PATIL_LIVER_CANCER, NKX61_01, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_MONOSACCHARIDE_BIOSYNTHETIC_PROCESS, CCTGTGA_MIR513, GOBP_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (5): protein phosphorylation (GO:0006468), response to ionizing radiation (GO:0010212), regulation of RNA splicing (GO:0043484), negative regulation of gluconeogenesis (GO:0045721), protein autophosphorylation (GO:0046777)

GO Molecular Function (11): 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 (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), nuclear speck (GO:0016607)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	4
phosphorylation	1
protein modification process	1
response to radiation	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
gluconeogenesis	1
regulation of gluconeogenesis	1
negative regulation of biosynthetic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of small molecule metabolic process	1
protein phosphorylation	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
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLK2	PAFAH1B3	Q15102	770
CLK2	PAGE4	O60829	584
CLK2	PRKAG1	P54619	438
CLK2	PRKAB1	Q9Y478	428
CLK2	TLK1	Q9UKI8	385
CLK2	CAMKK2	Q96RR4	373
CLK2	PRKAA2	P54646	372
CLK2	TICAM1	Q8IUC6	350
CLK2	LY96	Q9Y6Y9	348
CLK2	CCDC90B	Q9GZT6	344
CLK2	TTC32	Q5I0X7	318
CLK2	ERICH6	Q7L0X2	304
CLK2	MIS12	Q9H081	287
CLK2	SRSF12	Q8WXF0	280
CLK2	TOR4A	Q9NXH8	272

IntAct

310 interactions, top by confidence:

A	B	Type	Score
CLK2	CLK3	psi-mi:“MI:0915”(physical association)	0.870
SNIP1	CLK2	psi-mi:“MI:0915”(physical association)	0.870
CLK3	CLK2	psi-mi:“MI:0915”(physical association)	0.870
CLK2	SNIP1	psi-mi:“MI:0915”(physical association)	0.870
RSRP1	CLK2	psi-mi:“MI:0915”(physical association)	0.840
CLK2	RSRP1	psi-mi:“MI:0915”(physical association)	0.840
CLK2	LNX1	psi-mi:“MI:0915”(physical association)	0.830
LNX1	CLK2	psi-mi:“MI:0915”(physical association)	0.830
RBM39	CLK2	psi-mi:“MI:0915”(physical association)	0.780
CLK2	YTHDC1	psi-mi:“MI:0915”(physical association)	0.780
CLK2	RBM39	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (331): CLK2 (Two-hybrid), CLK3 (Two-hybrid), ECE1 (Two-hybrid), TRIM27 (Two-hybrid), SDCBP (Two-hybrid), SRPK2 (Two-hybrid), U2AF1 (Two-hybrid), UBE2I (Two-hybrid), ZRSR2 (Two-hybrid), RBM39 (Two-hybrid), ZNF263 (Two-hybrid), SRRM1 (Two-hybrid), RNPS1 (Two-hybrid), KLHL2 (Two-hybrid), ZNF473 (Two-hybrid)

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

10 interactions.

A	Effect	B	Mechanism
AKT1	up-regulates	CLK2	phosphorylation
CLK2	up-regulates	CLK2	phosphorylation
AKT	up-regulates	CLK2	phosphorylation
CLK2	“down-regulates activity”	PPARGC1A	phosphorylation
CLK2	“up-regulates activity”	PTPN1	phosphorylation
CLK2	“up-regulates activity”	SRSF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	78.1×	6e-07
RNA Polymerase II Transcription Termination	6	30.6×	3e-06
mRNA 3’-end processing	6	27.5×	3e-06
Transport of Mature mRNA derived from an Intron-Containing Transcript	6	21.2×	8e-06
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	17.9×	1e-04
Programmed Cell Death	5	17.0×	1e-04
G2/M Checkpoints	5	15.6×	1e-04
mRNA Splicing	6	15.3×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
regulation of mRNA splicing, via spliceosome	5	83.7×	5e-07
mRNA splicing, via spliceosome	9	15.6×	5e-07
RNA splicing	8	13.3×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2054 predictions. Top by Δscore:

Variant	Effect	Δscore
1:155263396:TACCG:T	acceptor_gain	1.0000
1:155263398:CCG:C	acceptor_gain	1.0000
1:155263399:CG:C	acceptor_gain	1.0000
1:155263399:CGC:C	acceptor_gain	1.0000
1:155263401:C:CC	acceptor_gain	1.0000
1:155264041:C:CC	acceptor_gain	1.0000
1:155264296:TGGGT:T	acceptor_gain	1.0000
1:155264301:C:CC	acceptor_gain	1.0000
1:155264463:CTTA:C	donor_loss	1.0000
1:155264464:TTAC:T	donor_loss	1.0000
1:155264465:TACCT:T	donor_loss	1.0000
1:155264466:A:AC	donor_gain	1.0000
1:155264467:C:CA	donor_loss	1.0000
1:155264467:C:CC	donor_gain	1.0000
1:155264546:CAACT:C	acceptor_gain	1.0000
1:155264547:AACT:A	acceptor_gain	1.0000
1:155264549:CT:C	acceptor_gain	1.0000
1:155264551:C:CC	acceptor_gain	1.0000
1:155264551:C:T	acceptor_loss	1.0000
1:155264555:G:C	acceptor_gain	1.0000
1:155264555:G:GC	acceptor_gain	1.0000
1:155264561:A:AC	acceptor_gain	1.0000
1:155264561:A:C	acceptor_gain	1.0000
1:155264638:C:CA	donor_gain	1.0000
1:155264639:CCTTA:C	donor_loss	1.0000
1:155264640:CTTA:C	donor_loss	1.0000
1:155264641:TTAC:T	donor_loss	1.0000
1:155264642:TACC:T	donor_loss	1.0000
1:155264643:A:AC	donor_gain	1.0000
1:155264643:ACCA:A	donor_loss	1.0000

AlphaMissense

3287 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:155263975:A:T	V431D	1.000
1:155264006:A:G	W421R	1.000
1:155264006:A:T	W421R	1.000
1:155264271:C:A	M392I	1.000
1:155264271:C:G	M392I	1.000
1:155264271:C:T	M392I	1.000
1:155264278:A:G	L390P	1.000
1:155264281:T:C	H389R	1.000
1:155264484:C:A	G377V	1.000
1:155264484:C:T	G377E	1.000
1:155264497:C:T	E373K	1.000
1:155264507:G:C	C369W	1.000
1:155264508:C:T	C369Y	1.000
1:155264509:A:G	C369R	1.000
1:155264511:C:T	G368D	1.000
1:155264512:C:G	G368R	1.000
1:155264516:A:C	S366R	1.000
1:155264516:A:T	S366R	1.000
1:155264518:T:G	S366R	1.000
1:155264519:C:A	W365C	1.000
1:155264519:C:G	W365C	1.000
1:155264521:A:G	W365R	1.000
1:155264521:A:T	W365R	1.000
1:155264526:T:A	D363V	1.000
1:155264526:T:C	D363G	1.000
1:155264526:T:G	D363A	1.000
1:155264527:C:A	D363Y	1.000
1:155264527:C:G	D363H	1.000
1:155264528:A:C	C362W	1.000
1:155264529:C:T	C362Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000140263 (1:155273618 G>A), RS1000575136 (1:155265140 A>G,T), RS1001205723 (1:155271898 C>T), RS1001352514 (1:155269676 G>A,C,T), RS1001385232 (1:155269957 C>T), RS1001390686 (1:155270201 T>A,C), RS1001517739 (1:155263713 AGAATCCAG>A), RS1002216533 (1:155262872 G>A), RS1002866286 (1:155266019 C>T), RS1002924414 (1:155262397 C>A,T), RS1003306435 (1:155266365 T>C), RS1003660954 (1:155273928 A>C), RS1003697312 (1:155271167 C>G), RS1003725265 (1:155271431 G>A), RS1003818520 (1:155267343 G>A)

Disease associations

OMIM: gene MIM:602989 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST004131_70	Inflammatory bowel disease	6.000000e-08
GCST004132_44	Crohn’s disease	2.000000e-07
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28
GCST010696_19	Cortical thickness (min-P)	2.000000e-10
GCST010697_10	Cortical surface area (min-P)	3.000000e-10
GCST010698_59	Subcortical volume (min-P)	9.000000e-10
GCST010699_20	Brain morphology (min-P)	7.000000e-10
GCST010700_5	Cortical thickness (MOSTest)	8.000000e-17
GCST010701_66	Cortical surface area (MOSTest)	1.000000e-09
GCST010702_43	Subcortical volume (MOSTest)	3.000000e-10
GCST010703_253	Brain morphology (MOSTest)	4.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL4225 (SINGLE PROTEIN), CHEMBL5291951 (PROTEIN FAMILY), CHEMBL6066547 (PROTEIN FAMILY), CHEMBL6066578 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

55 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 329,243 (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
CHEMBL1738797	ALECTINIB	4	6,731
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2005186	BELUMOSUDIL	4	1,817
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL31	GATIFLOXACIN	4	25,151
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL790	CHLORHEXIDINE	4	85,053
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL4297639	LORECIVIVINT	3	282
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL1230165	SILMITASERTIB	2
CHEMBL124660	TANDUTINIB	2
CHEMBL14762	SELICICLIB	2
CHEMBL1614713	CC-401	2
CHEMBL1721885	SU-014813	2
CHEMBL1967878	CENISERTIB	2
CHEMBL230011	TG100-115	2
CHEMBL362558	LY-2090314	2
CHEMBL384304	RG-547	2

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 (11 total), top 11:

Ligand	Action	Affinity	Parameter
cirtuvivint	Inhibition	9.0	pIC50
rogocekib	Inhibition	8.85	pIC50
lorecivivint	Inhibition	8.24	pIC50
compound 17 [PMID: 23642479]	Inhibition	7.64	pIC50
Cdc2-like kinase inhibitor	Inhibition	6.7	pIC50
compound 3b [PMID: 23454515]	Inhibition	6.68	pIC50
ML315	Inhibition	6.64	pIC50
compound 20 [PMID: 30998356]	Inhibition	6.58	pIC50
MW01	Inhibition	6.44	pIC50
Takinib	Inhibition	6.37	pIC50
MW05	Inhibition	5.84	pIC50

Binding affinities (BindingDB)

45 measured of 47 human assays (47 total across all organisms); most potent 45 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
3-methoxy-4-[[4-methoxy-5-(6-methoxy-3-pyridinyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-N-methylbenzamide	IC50	2.29 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
QL-X-138	IC50	7 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
4-[[4-cyclopentyloxy-5-[4-(methylcarbamoyl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxy-N-methylbenzamide	IC50	34 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
4-[(4-methoxy-5-pyridin-4-yl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino]-N,N,3-trimethylbenzamide	IC50	41.5 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
3A5	IC50	51 nM
4-[[4-(4-hydroxy-4-methylcyclohexyl)oxy-5-[4-(methylcarbamoyl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxy-N-(1-methylazetidin-3-yl)benzamide	IC50	59.3 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
4-[[5-(4-hydroxyphenyl)-4-(oxan-4-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxy-N-methylbenzamide	IC50	82.4 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
3-cyano-N-methyl-4-[[5-(2-methyl-1,3-benzoxazol-6-yl)-4-(oxan-4-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]benzamide	IC50	82.8 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
3-chloro-N-methyl-4-[[5-[4-(methylcarbamoyl)phenyl]-4-(oxan-4-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]benzamide	IC50	84.6 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
3-chloro-N-methyl-4-[[5-(1-methylpyrazol-4-yl)-4-(oxan-4-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]benzamide	IC50	97.8 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
3-methoxy-N-methyl-4-[[5-(2-methyl-1,3-benzoxazol-6-yl)-4-(oxan-4-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]benzamide	IC50	124 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
3-chloro-N-methyl-4-[[5-(2-methyl-1,3-benzoxazol-6-yl)-4-[(3S)-oxolan-3-yl]oxy-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]benzamide	IC50	130 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
N-methyl-4-[[5-(2-methyl-1,3-benzoxazol-6-yl)-4-(oxan-4-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-(trifluoromethyl)benzamide	IC50	172 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
PKC-412	KD	190 nM
N,3-dimethyl-4-[[5-(2-methyl-1,3-benzoxazol-6-yl)-4-(oxan-4-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]benzamide	IC50	220 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
4-[[4-(cyclopentylamino)-5-(4-hydroxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxy-N-methylbenzamide	IC50	225 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
3-chloro-N-methyl-4-[[5-(2-methyl-1,3-benzoxazol-6-yl)-4-(oxan-4-yloxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]benzamide	IC50	226 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
6-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine	IC50	235 nM
4-[[4-cyclopentyloxy-5-(2-methyl-1,3-benzoxazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-2-fluoro-5-methoxy-N-methylbenzamide	IC50	237 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
(2R)-2-[[6-(benzylamino)-9-isopropyl-purin-2-yl]amino]butan-1-ol	KD	260 nM
5F4	IC50	273 nM
5E4	IC50	277 nM
4-[[4-cyclopentyloxy-5-(4-hydroxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-N-methyl-3-propan-2-ylbenzamide	IC50	299 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
4-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	KD	300 nM
NR9	IC50	390 nM
4-[[4-cyclopentyloxy-5-(2-methyl-1,3-benzoxazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-N-(2-hydroxyethyl)-3-methoxybenzamide	IC50	501 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
3-chloro-4-[[4-cyclopentyloxy-5-(2-methyl-1,3-benzoxazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-N-methylbenzamide	IC50	505 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
4-[[4-cyclobutyloxy-5-(2-methyl-1,3-benzoxazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxy-N-(oxetan-3-yl)benzamide	IC50	526 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
SCH772984	IC50	580 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
4-[[4-cyclopentyloxy-5-(2-methyl-1,3-benzoxazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxy-N-methylbenzamide	IC50	728 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
4-(6-(4-(piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline	IC50	1120 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
4-[[4-cyclopentyloxy-5-(4-hydroxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxy-N-methylbenzamide	IC50	1440 nM	US-9623028: Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
BMS-387072	KD	1800 nM
DMH3	IC50	1940 nM	US-9040694: Compounds and methods useful for directing stem cell differentiation
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 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
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM
4-(2-(4-(3-(quinolin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl)phenoxy)ethyl)morpholine	IC50	3530 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM
4-(2-(4-(3-phenylpyrazolo[1,5- a]pyrimidin-6-yl)phenoxy)ethyl)morpholine	IC50	8040 nM

ChEMBL bioactivities

1777 potent at pChembl≥5 of 1803 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.02	Kd	0.096	nM	CHEMBL4797564
10.02	IC50	0.096	nM	CHEMBL4797564
9.58	IC50	0.261	nM	CHEMBL4546504
9.40	Kd	0.4	nM	GSK-1059615
9.29	Kd	0.51	nM	CHEMBL379218
9.26	IC50	0.55	nM	SILMITASERTIB
9.22	IC50	0.6	nM	CHEMBL5091238
9.12	IC50	0.76	nM	T3-CLK
9.10	Ki	0.7943	nM	CHEMBL1980407
9.09	IC50	0.822	nM	CHEMBL4800084
9.09	IC50	0.822	nM	CHEMBL5269810
9.05	Kd	0.9	nM	CHEMBL5093650
9.00	EC50	1	nM	CHEMBL4743901
9.00	EC50	1	nM	CHEMBL4788267
9.00	EC50	1	nM	CHEMBL4755807
9.00	EC50	1	nM	CHEMBL4741792
9.00	EC50	1	nM	CHEMBL4791039
9.00	EC50	1	nM	CHEMBL4761714
9.00	EC50	1	nM	CHEMBL4785637
9.00	EC50	1	nM	CHEMBL4750147
9.00	EC50	1	nM	CHEMBL4742870
9.00	EC50	1	nM	CHEMBL4745311
9.00	EC50	1	nM	CHEMBL4760183
9.00	EC50	1	nM	CHEMBL4778412
9.00	EC50	1	nM	CHEMBL4746176
9.00	EC50	1	nM	CHEMBL4790477
9.00	EC50	1	nM	CHEMBL4788156
9.00	EC50	1	nM	CHEMBL4797346
9.00	EC50	1	nM	CHEMBL4800437
9.00	EC50	1	nM	CHEMBL4795039
9.00	EC50	1	nM	CHEMBL4761354
9.00	EC50	1	nM	CHEMBL4754606
9.00	EC50	1	nM	CHEMBL4776499
9.00	EC50	1	nM	CHEMBL4800084
9.00	EC50	1	nM	CHEMBL4742725
9.00	EC50	1	nM	CHEMBL4779592
9.00	EC50	1	nM	CHEMBL4752625
9.00	EC50	1	nM	CHEMBL4788275
9.00	EC50	1	nM	CHEMBL4782319
9.00	EC50	1	nM	CHEMBL4756030
9.00	EC50	1	nM	CHEMBL4794727
9.00	EC50	1	nM	CHEMBL4748995
9.00	EC50	1	nM	CHEMBL4743856
9.00	EC50	1	nM	CHEMBL4786934
9.00	EC50	1	nM	CHEMBL4758259
9.00	EC50	1	nM	CHEMBL4785547
9.00	EC50	1	nM	CHEMBL4764569
9.00	EC50	1	nM	CHEMBL4743240
9.00	EC50	1	nM	CHEMBL4762097
9.00	EC50	1	nM	CHEMBL4796085

PubChem BioAssay actives

663 with measured affinity, of 1859 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-N-methyl-4-N-(pyrimidin-2-ylmethyl)-5-quinolin-6-yl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine	1851162: Binding affinity to CLK2 (unknown origin) assessed as dissociation constant	kd	0.0001	uM
4-[[5-chloro-4-(4-hydroxy-4-methylcyclohexyl)oxy-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-N,N-dimethyl-3-[(2R)-1,1,1-trifluoropropan-2-yl]oxybenzamide	1551607: Inhibition of recombinant human GST-tagged CLK2 catalytic domain (137 to 498 residues) expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0003	uM
(5Z)-5-[(4-pyridin-4-ylquinolin-6-yl)methylidene]-1,3-thiazolidine-2,4-dione	1424956: 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	0.0004	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624932: Binding constant for CLK2 kinase domain	kd	0.0005	uM
(5Z)-2-(1-adamantylimino)-5-(1,3-benzothiazol-6-ylmethylidene)imidazolidin-4-one	1947679: Inhibition of recombinant human CLK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.0006	uM
5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid	1750391: Inhibition of human CLK2 incubated for 2 hrs	ic50	0.0006	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	2183567: Inhibition of N-terminal FLAG-tagged human CLK2 using ULight MBP peptide as substrate incubated for 10 mins in presence of 20 uM ATP incubated for 45 mins by LANCE Ultra kinase assay	ic50	0.0008	uM
N-(4-methoxyphenyl)-5-[5-(piperidin-1-ylmethyl)-3-pyridinyl]-1H-indazole-3-carboxamide	1933977: Inhibition of human CLK2	ic50	0.0008	uM
N-(6-methoxy-3-pyridinyl)-5-[5-(piperidin-1-ylmethyl)-3-pyridinyl]-1H-indazole-3-carboxamide	1851156: Inhibition of CLK2 (unknown origin)	ic50	0.0008	uM
5-(2-amino-4-pyridinyl)-N-[(2,6-difluorophenyl)methyl]-2-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1812181: Inhibition of human partial length CLK2 (D144/R498) expressed in bacterial system by DiscoveryX Kinomescan binding assay	kd	0.0009	uM
N-[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl]methanesulfonamide	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0010	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3-tricyclo[3.3.1.03,7]nonanylimino)imidazolidin-4-one	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0010	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	1799383: in vitro Kinase Assay from Article 10.1021/cb9002865: “In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors.”	ic50	0.0010	uM
N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide	1947679: Inhibition of recombinant human CLK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.0011	uM
2-fluoroethyl 5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylate	1750391: Inhibition of human CLK2 incubated for 2 hrs	ic50	0.0011	uM
2-[(1R)-1-fluoroethyl]-5-[[6-(4-methoxypyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-methylimidazo[4,5-b]pyridin-1-yl]methyl]-1,3,4-oxadiazole	1851156: Inhibition of CLK2 (unknown origin)	ic50	0.0014	uM
(2S)-4-methyl-1-[[5-[3-(2-thiophen-3-ylethynyl)-2H-indazol-5-yl]-3-pyridinyl]oxy]pentan-2-amine	2082331: Inhibition of CLK2 (unknown origin) incubated for 10 mins in presence of ATP	ic50	0.0014	uM
2,2-difluoroethyl 5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylate	1750391: Inhibition of human CLK2 incubated for 2 hrs	ic50	0.0015	uM
2-iodoethyl 5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylate	1750391: Inhibition of human CLK2 incubated for 2 hrs	ic50	0.0017	uM
2-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	1851157: Inhibition of CLK2 (unknown origin) by Z’-LYTE kinase assay	ic50	0.0020	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]imino]imidazolidin-4-one	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0020	uM
N-[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl]cyclopropanecarboxamide	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0020	uM
2-(1-adamantylamino)-5-[(E)-benzimidazol-5-ylidenemethyl]-1H-imidazol-4-ol	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0020	uM
(5Z)-2-(1-adamantylimino)-5-(1,3-benzoxazol-6-ylmethylidene)imidazolidin-4-one	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0020	uM
5-[(5S)-5-(4-chlorophenyl)-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-3-methyl-2H-indazole	2030649: Binding affinity to CLK2 (unknown origin) assessed as dissociation constant by competitive binding assay	kd	0.0021	uM
6-(1-hydroxy-2-methylpropan-2-yl)-N-[6-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-2-yl]pyridine-3-carboxamide	1933977: Inhibition of human CLK2	ic50	0.0021	uM
2-hydroxyethyl 5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylate	1750391: Inhibition of human CLK2 incubated for 2 hrs	ic50	0.0024	uM
6-tert-butyl-N-(6-pyridin-4-ylimidazo[1,2-a]pyridin-2-yl)pyridine-3-carboxamide	1933977: Inhibition of human CLK2	ic50	0.0024	uM
6-tert-butyl-N-[6-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-2-yl]pyridine-3-carboxamide	1861151: Inhibition of human recombinant GST-tagged Clk2 expressed in Baculovirus expression system using GRSRSRSRSRSRSRSR peptide as substrate preincubated for 10 mins followed by ATP addition measured after 30 mins by ADP-Glo assay	ic50	0.0024	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R)-2-hydroxy-1-phenylethyl]iminoimidazolidin-4-one	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0030	uM
N-[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl]acetamide	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0030	uM
(5Z)-2-(1-adamantylimino)-5-[(3-methylbenzimidazol-5-yl)methylidene]imidazolidin-4-one	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0030	uM
3-methyl-N-[5-[3-(2-pyridin-3-ylethynyl)-2H-indazol-5-yl]-3-pyridinyl]butanamide	2082331: Inhibition of CLK2 (unknown origin) incubated for 10 mins in presence of ATP	ic50	0.0037	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-spiro[2.5]octan-2-yliminoimidazolidin-4-one	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-cyclooctyliminoimidazolidin-4-one	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
4-(6-methoxypyrazolo[1,5-b]pyridazin-3-yl)-N-[3-methoxy-5-(trifluoromethyl)phenyl]pyrimidin-2-amine	1933977: Inhibition of human CLK2	ic50	0.0040	uM
N-(4-morpholin-4-ylcyclohexyl)-5-(oxan-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1471970: Inhibition of recombinant N-terminal GST-tagged human CLK2 (138 end residues) expressed in baculovirus infected Sf21 cells	ic50	0.0050	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3,3-difluorocycloheptyl)iminoimidazolidin-4-one	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0050	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[[3-(dimethylamino)-1-adamantyl]imino]imidazolidin-4-one	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0050	uM
methyl 2-(2-chloroanilino)-4-hydroxy-5-[(Z)-pyrrolo[2,3-b]pyridin-3-ylidenemethyl]furan-3-carboxylate	1444266: Inhibition of CLK2 (unknown origin) pretreated for 30 mins followed by substrate addition measured after 5 hrs in presence of 1 mM ATP	ic50	0.0053	uM
(2S)-1-[[5-[3-(2-cyclopropylethynyl)-2H-indazol-5-yl]-3-pyridinyl]oxy]-4-methylpentan-2-amine	2082331: Inhibition of CLK2 (unknown origin) incubated for 10 mins in presence of ATP	ic50	0.0056	uM
(3R)-1-[3-[[3-amino-6-(2-fluoro-5-propan-2-yloxyphenyl)pyrazine-2-carbonyl]amino]-4-pyridinyl]piperidine-3-carboxylic acid	1947679: Inhibition of recombinant human CLK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.0059	uM
4-[[4-cyclopentyloxy-5-(2-methyl-1,3-benzoxazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxy-N-methylbenzamide	1476573: Inhibition of human GST-tagged CLK2 expressed in baculovirus by Z’-LYTE assay	ic50	0.0060	uM
6-N-(3-amino-5-chlorophenyl)-2-N-[(1R,2S)-2-aminocyclohexyl]-9-propan-2-ylpurine-2,6-diamine	1436446: Inhibition of human CLK2 using YRRAAVPPSPSLSRHSSPHQS(p)EDEEE as substrate in presence of [gamma-33P]ATP after 40 mins by scintillation counter method	ic50	0.0060	uM
6-N-(3-amino-5-chlorophenyl)-2-N-(2-aminocyclohexyl)-9-propan-2-ylpurine-2,6-diamine	1933977: Inhibition of human CLK2	ic50	0.0060	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[[(1R,2R,3R,5S)-2,6,6-trimethyl-3-bicyclo[3.1.1]heptanyl]imino]imidazolidin-4-one	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0060	uM
3-methyl-N-[5-[3-(2-pyrimidin-2-ylethynyl)-2H-indazol-5-yl]-3-pyridinyl]butanamide	2082331: Inhibition of CLK2 (unknown origin) incubated for 10 mins in presence of ATP	ic50	0.0068	uM
N-[3-[[2-[[(1R,2S)-2-aminocyclohexyl]amino]-9-propan-2-ylpurin-6-yl]amino]-5-chlorophenyl]acetamide	1436446: Inhibition of human CLK2 using YRRAAVPPSPSLSRHSSPHQS(p)EDEEE as substrate in presence of [gamma-33P]ATP after 40 mins by scintillation counter method	ic50	0.0070	uM
(5Z)-2-(2-amino-1-phenylethyl)imino-5-(1,3-benzothiazol-6-ylmethylidene)imidazolidin-4-one;dihydrochloride	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0070	uM
(5Z)-2-[(1S)-2-amino-1-phenylethyl]imino-5-(1,3-benzothiazol-6-ylmethylidene)imidazolidin-4-one;dihydrochloride	2010387: Inhibition of human CLK2 using GSK3(14-27) peptide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0070	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
FR900359	affects phosphorylation	1
takinib	decreases activity	1
bisphenol A	decreases expression	1
cinnamaldehyde	decreases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
5-iodotubercidin	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
vanillin	increases expression	1
ICG 001	decreases expression	1
picoxystrobin	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Aspirin	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Daunorubicin	increases expression	1
Formaldehyde	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Polychlorinated Biphenyls	affects expression	1
Rifampin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Lithium Chloride	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

458 unique, capped per target: 452 binding, 6 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032274	Binding	Inhibition of CLK2 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
CHEMBL1738309	Functional	PUBCHEM_BIOASSAY: Kinase Inhibition Study on Inhibitors of CDC-like Kinase 2 (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

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SJ20	HAP1 CLK2 (-) 1	Cancer cell line	Male
CVCL_SJ21	HAP1 CLK2 (-) 2	Cancer cell line	Male
CVCL_SJ22	HAP1 CLK2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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