CDKL2

Summary

CDKL2 (cyclin dependent kinase like 2, HGNC:1782) is a protein-coding gene on chromosome 4q21.1, encoding Cyclin-dependent kinase-like 2 (Q92772).

This gene product is a member of a large family of CDC2-related serine/threonine protein kinases. It accumulates primarily in the cytoplasm, with lower levels in the nucleus.

Source: NCBI Gene 8999 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 85 total — 1 likely-pathogenic
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001330724

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1782
Approved symbol	CDKL2
Name	cyclin dependent kinase like 2
Location	4q21.1
Locus type	gene with protein product
Status	Approved
Aliases	P56, KKIAMRE
Ensembl gene	ENSG00000138769
Ensembl biotype	protein_coding
OMIM	603442
Entrez	8999

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000307465, ENST00000429927, ENST00000506234, ENST00000515793, ENST00000905143, ENST00000905144, ENST00000943251, ENST00000943252, ENST00000943253

RefSeq mRNA: 2 — MANE Select: NM_001330724 NM_001330724, NM_003948

CCDS: CCDS3570, CCDS82933

Canonical transcript exons

ENST00000307465 — 14 exons

Exon	Start	End
ENSE00000723456	75605522	75605634
ENSE00000723481	75607183	75607361
ENSE00001025066	75598077	75598212
ENSE00001025071	75596935	75597236
ENSE00001123655	75596247	75596340
ENSE00001123709	75614255	75614449
ENSE00001127491	75581810	75581898
ENSE00001193532	75630042	75630528
ENSE00001285092	75625821	75626017
ENSE00001630179	75592146	75592269
ENSE00001800703	75591819	75591925
ENSE00001826577	75576496	75579178
ENSE00003490247	75603817	75603956
ENSE00003556028	75600281	75600369

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 88.04.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9503 / max 143.5361, expressed in 440 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52585	1.7809	406
52584	0.1694	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	88.04	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.01	gold quality
middle temporal gyrus	UBERON:0002771	85.99	gold quality
cortical plate	UBERON:0005343	85.42	gold quality
postcentral gyrus	UBERON:0002581	83.11	gold quality
superior frontal gyrus	UBERON:0002661	82.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.81	gold quality
parietal lobe	UBERON:0001872	81.63	gold quality
primary visual cortex	UBERON:0002436	81.40	gold quality
entorhinal cortex	UBERON:0002728	80.55	gold quality
lower lobe of lung	UBERON:0008949	79.37	gold quality
prefrontal cortex	UBERON:0000451	79.24	gold quality
occipital lobe	UBERON:0002021	78.93	gold quality
renal medulla	UBERON:0000362	78.45	gold quality
metanephros cortex	UBERON:0010533	78.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.91	gold quality
pons	UBERON:0000988	77.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.37	gold quality
frontal cortex	UBERON:0001870	77.31	gold quality
frontal lobe	UBERON:0016525	77.29	gold quality
neocortex	UBERON:0001950	77.16	gold quality
cerebral cortex	UBERON:0000956	76.97	gold quality
caudate nucleus	UBERON:0001873	76.77	gold quality
ventricular zone	UBERON:0003053	76.50	gold quality
telencephalon	UBERON:0001893	76.37	gold quality
nucleus accumbens	UBERON:0001882	75.67	gold quality
right frontal lobe	UBERON:0002810	75.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	75.38	gold quality
forebrain	UBERON:0001890	75.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	19.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

126 targeting CDKL2, 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-656-3P	100.00	72.15	2788
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3617-3P	99.98	67.86	918
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-454-3P	99.91	74.01	1925

Literature-anchored findings (GeneRIF, showing 7)

• We hypothesized that LA might induce dissociation of p56(Lck) from CD4, thus leading to its downmodulation. (PMID:16631599)
• High CDKL2 promotes epithelial-mesenchymal transition and breast cancer progression. (PMID:25333262)
• Results showed that the methylation levels of CDKL2 were higher in hepatocellular carcinoma (HCC) cell lines and tissues but the mRNA expression levels decreased both in HCC tissues and cell lines. CDKL2 status seems to correlate with tumor size and may play an important role in hepatocarcinogenesis. (PMID:30292871)
• In HeLa cells infected with HSV-2, we detected significantly reduced expression of CDKN2A and CDKL2 and demonstrated the negative regulation effect of miRNA-H4-5p on these two target genes. (PMID:30953292)
• Decreased CDKL2 expression is correlated with the progression and poor prognosis of glioma. (PMID:32173142)
• Identification of a Set of Genes Improving Survival Prediction in Kidney Renal Clear Cell Carcinoma through Integrative Reanalysis of Transcriptomic Data. (PMID:33110456)
• CDKL2 Is Associated with HER2 Status and Overall Survival in Gastric Cancer: Comparative Analysis of CDKL2 Protein Expression and Gene Copy Number. (PMID:33178818)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cdkl2	ENSMUSG00000029403
rattus_norvegicus	Cdkl2	ENSRNOG00000002506

Paralogs (26): CDKL3 (ENSG00000006837), CDKL5 (ENSG00000008086), CDK11A (ENSG00000008128), CDK14 (ENSG00000058091), CDK17 (ENSG00000059758), CDK13 (ENSG00000065883), CDKL1 (ENSG00000100490), CDK16 (ENSG00000102225), CDK6 (ENSG00000105810), PRP4K (ENSG00000112739), CDK18 (ENSG00000117266), CDK2 (ENSG00000123374), CDK8 (ENSG00000132964), CDK7 (ENSG00000134058), CDK4 (ENSG00000135446), CDK9 (ENSG00000136807), CDK15 (ENSG00000138395), CDK19 (ENSG00000155111), CDK20 (ENSG00000156345), CDK5 (ENSG00000164885), CDK12 (ENSG00000167258), CDK1 (ENSG00000170312), CDK10 (ENSG00000185324), CDKL4 (ENSG00000205111), CDK11B (ENSG00000248333), CDK3 (ENSG00000250506)

Protein

Protein identifiers

Cyclin-dependent kinase-like 2 — Q92772 (reviewed: Q92772)

Alternative names: Protein kinase p56 KKIAMRE, Serine/threonine-protein kinase KKIAMRE

All UniProt accessions (4): A0A140VJG1, D6RBJ5, Q92772, J3KNE8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in testis and kidney, and at lower level in brain and lung.

Domain organisation. The [NKR]KIAxRE motif seems to be a cyclin-binding region.

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

RefSeq proteins (2): NP_001317653, NP_003939 (=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
IPR050108	CDK	Family

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (43 total): helix 21, strand 8, sequence variant 6, binding site 2, chain 1, domain 1, turn 1, region of interest 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4AAA	X-RAY DIFFRACTION	1.53
8S6I	X-RAY DIFFRACTION	1.72
4BBM	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92772-F1	71.38	0.50

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): 126 (proton acceptor)

Ligand- & substrate-binding residues (2): 10–18; 33

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 104 (showing top): CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_SEX_DIFFERENTIATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, RFX1_02, CUI_TCF21_TARGETS_2_DN, MCDOWELL_ACUTE_LUNG_INJURY_DN, chr4q21, TGGAAA_NFAT_Q4_01, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_CYCLIN_DEPENDENT_PROTEIN_KINASE_ACTIVITY, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (4): signal transduction (GO:0007165), sex differentiation (GO:0007548), protein phosphorylation (GO:0006468), regulation of cell cycle (GO:0051726)

GO Molecular Function (9): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), cyclin-dependent protein serine/threonine kinase activity (GO:0004693), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	2
protein kinase activity	2
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
developmental process involved in reproduction	1
phosphorylation	1
protein modification process	1
cell cycle	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein serine/threonine kinase activity	1
cyclin-dependent protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1

Protein interactions and networks

STRING

632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDKL2	EGF	P01133	503
CDKL2	ZNF154	Q13106	472
CDKL2	SOWAHB	A6NEL2	446
CDKL2	TMEM101	Q96IK0	445
CDKL2	NR4A1	P22736	425
CDKL2	COL1A2	P02464	421
CDKL2	SOCS3	O14543	418
CDKL2	IL17A	Q16552	407
CDKL2	PRAMEF19	Q5SWL8	391
CDKL2	COL1A1	P02452	376
CDKL2	RPP40	O75818	373
CDKL2	TSPYL5	Q86VY4	349
CDKL2	ZSCAN30	Q86W11	336
CDKL2	FGL1	Q08830	335
CDKL2	TMEM17	Q86X19	333

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CDKL2	HSP90AA5P	psi-mi:“MI:0915”(physical association)	0.620
CDKL2	CDK14	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CDKL2	MYO1C	psi-mi:“MI:0914”(association)	0.350
CDKL2	FKBP5	psi-mi:“MI:0914”(association)	0.350
CDKL2	FRY	psi-mi:“MI:0914”(association)	0.350

BioGRID (74): HSP90AA1 (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), CDC37 (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS), CDK14 (Affinity Capture-MS), CDKL2 (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), MYO1C (Affinity Capture-MS), MYO1F (Affinity Capture-MS), MYO1B (Affinity Capture-MS)

ESM2 similar proteins: B3WFY8, O35831, O43781, P20793, P20794, P23293, P39073, P83101, Q00537, Q03407, Q03957, Q04859, Q4R6S5, Q4R7T5, Q501Q9, Q5R754, Q5SN53, Q5U4C9, Q5VN19, Q5XIT0, Q5ZCI1, Q5ZIU3, Q62726, Q63686, Q67C40, Q6BV06, Q6CR51, Q6CRA9, Q6FKC6, Q6FQ83, Q6Z8C8, Q753D9, Q75D46, Q75KK8, Q8K0D0, Q8W4J2, Q922Y0, Q92630, Q92772, Q96WV9

Diamond homologs: A4L9P5, A8WJR8, A8X4H1, A8X5H5, B3WFY8, G5EDB2, O14132, O23145, O43781, O55076, O76039, O88850, O88904, P14680, P18265, P18431, P20911, P22518, P24941, P43288, P43289, P48963, P49657, P49759, P49840, P50613, P51136, P51567, P51568, P51952, P83102, Q00526, Q03147, Q04859, Q07538, Q08DZ2, Q09690, Q09815, Q0IJ08, Q10156

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	71
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3906935	NM_001330724.2(CDKL2):c.643A>T (p.Met215Leu)	Likely pathogenic

SpliceAI

2623 predictions. Top by Δscore:

Variant	Effect	Δscore
4:75596245:A:AC	donor_gain	1.0000
4:75596246:C:CC	donor_gain	1.0000
4:75598072:TTTA:T	donor_loss	1.0000
4:75598074:TA:T	donor_loss	1.0000
4:75598075:A:T	donor_loss	1.0000
4:75598076:CC:C	donor_loss	1.0000
4:75598208:AAAAC:A	acceptor_gain	1.0000
4:75598209:AAAC:A	acceptor_gain	1.0000
4:75598210:AAC:A	acceptor_gain	1.0000
4:75598210:AACC:A	acceptor_loss	1.0000
4:75598211:AC:A	acceptor_gain	1.0000
4:75598212:CC:C	acceptor_gain	1.0000
4:75598213:C:CC	acceptor_gain	1.0000
4:75598213:CTAC:C	acceptor_loss	1.0000
4:75598216:CA:C	acceptor_gain	1.0000
4:75598217:A:C	acceptor_gain	1.0000
4:75600365:CATTT:C	acceptor_gain	1.0000
4:75600367:TTT:T	acceptor_gain	1.0000
4:75603811:GATTA:G	donor_loss	1.0000
4:75603812:ATTAC:A	donor_loss	1.0000
4:75603813:TTAC:T	donor_loss	1.0000
4:75603814:TACC:T	donor_loss	1.0000
4:75603815:ACCTT:A	donor_loss	1.0000
4:75603816:C:CT	donor_loss	1.0000
4:75603830:A:AC	donor_gain	1.0000
4:75625818:CA:C	donor_loss	1.0000
4:75625819:A:T	donor_loss	1.0000
4:75625820:C:CA	donor_loss	1.0000
4:75626014:TTTG:T	acceptor_gain	1.0000
4:75626015:TTG:T	acceptor_gain	1.0000

AlphaMissense

3782 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:75607282:G:T	A148E	1.000
4:75607284:A:C	F147L	1.000
4:75607284:A:T	F147L	1.000
4:75607286:A:G	F147L	1.000
4:75607288:C:T	G146E	1.000
4:75607293:A:C	D144E	1.000
4:75607293:A:T	D144E	1.000
4:75607294:T:A	D144V	1.000
4:75607294:T:C	D144G	1.000
4:75607294:T:G	D144A	1.000
4:75607295:C:G	D144H	1.000
4:75607296:G:C	C143W	1.000
4:75607297:C:T	C143Y	1.000
4:75607332:A:C	N131K	1.000
4:75607332:A:T	N131K	1.000
4:75607333:T:C	N131S	1.000
4:75607334:T:C	N131D	1.000
4:75607334:T:G	N131H	1.000
4:75607341:C:A	K128N	1.000
4:75607341:C:G	K128N	1.000
4:75607347:A:C	D126E	1.000
4:75607347:A:T	D126E	1.000
4:75607348:T:A	D126V	1.000
4:75607348:T:C	D126G	1.000
4:75607348:T:G	D126A	1.000
4:75607349:C:G	D126H	1.000
4:75607351:C:A	R125I	1.000
4:75614385:A:G	L78P	1.000
4:75625837:T:A	E51V	1.000
4:75625840:C:G	R50P	1.000

dbSNP variants (sampled 300 via entrez): RS1000139440 (4:75610029 C>G), RS1000198732 (4:75603573 A>G), RS1000241296 (4:75612015 G>C), RS1000273088 (4:75578840 C>G,T), RS1000301119 (4:75619847 G>A), RS1000355058 (4:75605910 T>C), RS1000416530 (4:75589526 G>A), RS1000441511 (4:75617212 C>A,T), RS1000445274 (4:75596468 T>C,G), RS1000636989 (4:75618497 G>GC), RS1000643761 (4:75598149 T>A,C), RS1000686482 (4:75604485 C>A), RS1000696723 (4:75603981 T>A), RS1000738581 (4:75598744 G>A), RS1000778584 (4:75610789 C>G)

Disease associations

OMIM: gene MIM:603442 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003160_4	Subjective response to lithium treatment in bipolar disorder	7.000000e-07
GCST004635_8	Testicular germ cell tumor	2.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5728 (SINGLE PROTEIN), CHEMBL6195530 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

21 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 235,417 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL124660	TANDUTINIB	2	2,530
CHEMBL1721885	SU-014813	2	363
CHEMBL215152	DEFOSBARASERTIB	2	372
CHEMBL445813	AT-7519	2	2,614
CHEMBL475251	R-406	2	762
CHEMBL5083772	BIIB-091	2	86
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1908397	KW-2449	1	622
CHEMBL296468	BMS-387032	1	2,075
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 — Cyclin-dependent kinase-like (CDKL) family

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-methylsulfanyl-6-[4-[3-[3-(trifluoromethyl)anilino]-1H-1,2,4-triazol-5-yl]phenoxy]pyrimidin-4-amine	KD	7500 nM	US-9260417: Therapeutic methods and compositions involving allosteric kinase inhibition

ChEMBL bioactivities

40 potent at pChembl≥5 of 41 total, top 34 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.28	Kd	0.52	nM	AST-487
7.39	Kd	41	nM	BMS-387032
7.37	IC50	43	nM	CHEMBL4522276
7.37	Kd	43	nM	LESTAURTINIB
7.31	Kd	49	nM	TOZASERTIB
6.89	Kd	130	nM	SORAFENIB
6.78	IC50	165	nM	CHEMBL5190023
6.75	Kd	180	nM	DOVITINIB
6.64	IC50	230	nM	CHEMBL4522276
6.62	Kd	240	nM	BIIB-091
6.62	Kd	240	nM	FORETINIB
6.38	Kd	420	nM	CHEMBL4744041
6.35	IC50	450	nM	CHEMBL4542463
6.34	IC50	460	nM	CHEMBL4522276
6.29	Kd	510	nM	STAUROSPORINE
6.28	Kd	530	nM	AXITINIB
6.16	IC50	700	nM	CHEMBL4542463
6.16	Kd	700	nM	CHEMBL379218
6.06	Kd	880	nM	CHEMBL4452939
6.00	Kd	1000	nM	AT-7519
5.96	Kd	1100	nM	SUNITINIB
5.92	IC50	1200	nM	CHEMBL5614135
5.92	Kd	1200	nM	DEFOSBARASERTIB
5.89	Kd	1300	nM	NINTEDANIB
5.89	Kd	1300	nM	FEDRATINIB
5.85	Kd	1400	nM	KW-2449
5.82	EC50	1500	nM	CHEMBL6195031
5.68	Kd	2100	nM	CRIZOTINIB
5.62	Kd	2400	nM	PHA-665752
5.54	Kd	2900	nM	TANDUTINIB
5.47	Kd	3400	nM	ENZASTAURIN
5.41	Kd	3900	nM	SU-014813
5.29	Kd	5100	nM	CHEMBL3932957
5.23	Kd	5900	nM	R-406

PubChem BioAssay actives

35 with measured affinity, of 178 total; 28 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
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	624928: Binding constant for CDKL2 kinase domain	kd	0.0005	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	624928: Binding constant for CDKL2 kinase domain	kd	0.0410	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507871: Binding affinity to CDKL2	kd	0.0430	uM
N-[6-[3-[(2-methylpropylsulfonylamino)methyl]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide	2126447: Inhibition of FLAG-tagged full-length recombinant wild-type human CDKL2 expressed in HeLa cells using MBP as substrate incubated for 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0430	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	624928: Binding constant for CDKL2 kinase domain	kd	0.0490	uM
Sorafenib	507871: Binding affinity to CDKL2	kd	0.1300	uM
cis-(1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide	1856715: Inhibition of CDKL2 (unknown origin)	ic50	0.1650	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	624928: Binding constant for CDKL2 kinase domain	kd	0.1800	uM
1-tert-butyl-N-[(5R)-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-2-(oxetan-3-yl)-1,3,4,5-tetrahydro-2-benzazepin-5-yl]triazole-4-carboxamide	1820531: Binding affinity to wild-type human partial length CDKL2 (M1 to D327 residues) expressed in bacterial expression system by Kinomescan method	kd	0.2400	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	624928: Binding constant for CDKL2 kinase domain	kd	0.2400	uM
N-[[2-methyl-4-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]phenyl]methyl]-3-propan-2-yloxyazetidine-1-carboxamide	1696274: Binding affinity to wild-type human partial length CDKL2 (M1 to D327 residues) expressed in bacterial expression system by Kinomescan method	kd	0.4200	uM
N-[6-[3-[(cyclopropylmethylsulfonylamino)methyl]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide	2126418: Inhibition of CDKL2 (unknown origin) by radiometric assay	ic50	0.4500	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	624928: Binding constant for CDKL2 kinase domain	kd	0.5100	uM
Axitinib	624928: Binding constant for CDKL2 kinase domain	kd	0.5300	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624928: Binding constant for CDKL2 kinase domain	kd	0.7000	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	624928: Binding constant for CDKL2 kinase domain	kd	1.0000	uM
Sunitinib	507871: Binding affinity to CDKL2	kd	1.1000	uM
2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide	624928: Binding constant for CDKL2 kinase domain	kd	1.2000	uM
N-[6-[3-[(4-fluorophenyl)sulfonylamino]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide	2126419: Displacement of tracer K10 from N-terminal NLuc-fused full-length CDKL2 (unknown origin) expressed in HEK293 cells by NanoBRET assay	ic50	1.2000	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624928: Binding constant for CDKL2 kinase domain	kd	1.3000	uM
Fedratinib	624928: Binding constant for CDKL2 kinase domain	kd	1.3000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624928: Binding constant for CDKL2 kinase domain	kd	1.4000	uM
Crizotinib	624928: Binding constant for CDKL2 kinase domain	kd	2.1000	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	624928: Binding constant for CDKL2 kinase domain	kd	2.4000	uM
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide	507871: Binding affinity to CDKL2	kd	2.9000	uM
3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione	624928: Binding constant for CDKL2 kinase domain	kd	3.4000	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	624928: Binding constant for CDKL2 kinase domain	kd	3.9000	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624928: Binding constant for CDKL2 kinase domain	kd	5.9000	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
sodium arsenite	decreases expression, increases expression	3
entinostat	increases expression	2
Nickel	decreases expression	2
potassium chromate(VI)	decreases expression	1
nickel sulfate	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	decreases expression	1
Lead	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

108 unique, capped per target: 108 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032269	Binding	Inhibition of CDKL2 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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7MC	Ubigene A-549 CDKL2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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