CDKL3

Summary

CDKL3 (cyclin dependent kinase like 3, HGNC:15483) is a protein-coding gene on chromosome 5q31.1, encoding Cyclin-dependent kinase-like 3 (Q8IVW4).

The protein encoded by this gene is a member of cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This gene was identified as a gene absent in leukemic patients with chromosome 5q deletion. This loss may be an important determinant of dysmyelopoiesis. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 51265 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 100 total — 1 pathogenic
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001113575

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15483
Approved symbol	CDKL3
Name	cyclin dependent kinase like 3
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	NKIAMRE
Ensembl gene	ENSG00000006837
Ensembl biotype	protein_coding
OMIM	608459
Entrez	51265

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000265334, ENST00000518990, ENST00000519312, ENST00000520592, ENST00000520693, ENST00000521118, ENST00000521755, ENST00000522501, ENST00000523054, ENST00000523832

RefSeq mRNA: 6 — MANE Select: NM_001113575 NM_001113575, NM_001300853, NM_001349363, NM_001349364, NM_001349366, NM_016508

CCDS: CCDS47264, CCDS47265, CCDS75303

Canonical transcript exons

ENST00000265334 — 13 exons

Exon	Start	End
ENSE00001417607	134366977	134367171
ENSE00001632274	134298424	134298710
ENSE00002300468	134366359	134366544
ENSE00003471297	134308138	134308466
ENSE00003487216	134321791	134321903
ENSE00003523307	134319358	134319497
ENSE00003552998	134312292	134312380
ENSE00003557701	134302590	134302687
ENSE00003610964	134304405	134304567
ENSE00003618929	134306609	134306702
ENSE00003625884	134308574	134308727
ENSE00003650379	134359897	134360091
ENSE00003680254	134350249	134350427

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 88.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.6617 / max 211.4608, expressed in 1730 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63459	5.7819	1632
63458	2.7139	1255
63457	0.1660	70

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.41	gold quality
sperm	CL:0000019	86.79	silver quality
left testis	UBERON:0004533	86.78	gold quality
right testis	UBERON:0004534	86.20	gold quality
buccal mucosa cell	CL:0002336	85.19	gold quality
testis	UBERON:0000473	85.06	gold quality
cortical plate	UBERON:0005343	81.27	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.93	gold quality
calcaneal tendon	UBERON:0003701	79.56	gold quality
hypothalamus	UBERON:0001898	79.36	gold quality
spinal cord	UBERON:0002240	79.18	gold quality
gastrocnemius	UBERON:0001388	79.03	gold quality
muscle of leg	UBERON:0001383	78.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.97	gold quality
anterior cingulate cortex	UBERON:0009835	78.66	gold quality
ventricular zone	UBERON:0003053	78.40	gold quality
amygdala	UBERON:0001876	78.39	gold quality
prefrontal cortex	UBERON:0000451	78.34	gold quality
tendon	UBERON:0000043	77.92	gold quality
nucleus accumbens	UBERON:0001882	77.77	gold quality
right frontal lobe	UBERON:0002810	77.73	gold quality
tendon of biceps brachii	UBERON:0008188	77.33	gold quality
right adrenal gland cortex	UBERON:0035827	77.26	gold quality
putamen	UBERON:0001874	77.10	gold quality
caudate nucleus	UBERON:0001873	76.64	gold quality
tibial nerve	UBERON:0001323	76.61	gold quality
left adrenal gland cortex	UBERON:0035825	76.33	gold quality
right adrenal gland	UBERON:0001233	76.30	gold quality
left adrenal gland	UBERON:0001234	76.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting CDKL3, 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-432-3P	100.00	67.86	705
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-7850-5P	98.12	67.28	1111
HSA-MIR-924	97.78	66.21	681
HSA-MIR-320E	97.49	65.96	865
HSA-MIR-643	97.35	67.91	805
HSA-MIR-3674	97.01	68.86	1171
HSA-MIR-4529-3P	96.40	66.46	582
HSA-MIR-3935	96.33	66.79	797
HSA-MIR-10525-3P	96.32	68.04	699
HSA-MIR-4681	89.50	61.59	122

Literature-anchored findings (GeneRIF, showing 8)

• NKIAMRE is a member of a conserved family of kinases with homology to both MAP kinases and cyclin-dependent kinases (PMID:12927787)
• cdkl3 transfected in anchorage-independent (suspension) HeLa cells overexpressed relative to attached cells and lead to elevated proliferation and faster transition G0/G1 phases to S phase relative to controls. Same in two HEK-293 and a CHO cell lines. (PMID:17945021)
• data suggest that the CDKL3 gene is a strong candidate for nonsyndromal autosomal dominant mild mental retardation (PMID:18412109)
• CDKL3 promotes osteosarcoma progression by activating Akt/PKB. (PMID:32234750)
• CircTP53 promotes colorectal cancer by acting as a miR-876-3p sponge to increase cyclin-dependent kinase-like 3 expression. (PMID:33232736)
• Identification of CDKL3 as a critical regulator in development of glioma through regulating RRM2 and the JNK signaling pathway. (PMID:34097336)
• Cyclin-dependent kinase like 3 promotes triple-negative breast cancer progression via inhibiting the p53 signaling pathway. (PMID:34427098)
• CDKL3 Promotes Non-small Cell Lung Cancer by Suppressing Autophagy Via Activation of PI3K/Akt/mTOR Pathway. (PMID:36630073)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cdkl3	ENSMUSG00000020389
rattus_norvegicus	Cdkl3	ENSRNOG00000059485

Paralogs (26): 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), CDKL2 (ENSG00000138769), 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 3 — Q8IVW4 (reviewed: Q8IVW4)

Alternative names: Serine/threonine-protein kinase NKIAMRE

All UniProt accessions (8): Q8IVW4, B4DX41, E5RFT9, E5RGK4, E5RI54, E7ET86, H0YAP8, H0YB17

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IVW4-1	1	yes
Q8IVW4-2	2

RefSeq proteins (6): NP_001107047, NP_001287782, NP_001336292, NP_001336293, NP_001336295, NP_057592 (=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 (41 total): helix 16, strand 9, modified residue 2, region of interest 2, compositionally biased region 2, binding site 2, chain 1, domain 1, splice variant 1, sequence variant 1, sequence conflict 1, turn 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3ZDU	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVW4-F1	64.87	0.42

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): 125 (proton acceptor)

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

Post-translational modifications (2): 158, 160

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 196 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_GROWTH, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

GO Biological Process (6): negative regulation of axon extension (GO:0030517), protein modification process (GO:0036211), positive regulation of dendrite morphogenesis (GO:0050775), dendrite extension (GO:0097484), 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 (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
negative regulation of cell growth	1
regulation of axon extension	1
negative regulation of developmental growth	1
axon extension	1
negative regulation of axonogenesis	1
protein metabolic process	1
macromolecule modification	1
positive regulation of cell morphogenesis	1
positive regulation of cell projection organization	1
dendrite morphogenesis	1
regulation of dendrite morphogenesis	1
positive regulation of neurogenesis	1
neuron projection extension	1
phosphorylation	1
protein modification process	1
cell cycle	1
regulation of cellular process	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
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDKL3	MBD3L2	Q8NHZ7	432
CDKL3	ANKRD10	Q9NXR5	411
CDKL3	C19orf73	Q9NVV2	370
CDKL3	ADCK1	Q86TW2	364
CDKL3	TMEM17	Q86X19	343
CDKL3	CEP19	Q96LK0	340
CDKL3	ACRV1	P26436	328
CDKL3	CABLES1	Q8TDN4	318
CDKL3	SNX25	Q9H3E2	311
CDKL3	TMEM231	Q9H6L2	303
CDKL3	ZNF473	Q8WTR7	303
CDKL3	PVALEF	A0A1B0GWK0	300
CDKL3	SPHKAP	Q2M3C7	297
CDKL3	SAMD8	Q96LT4	292
CDKL3	DPM1	O60762	285

IntAct

100 interactions, top by confidence:

A	B	Type	Score
CDKL3	FXR2	psi-mi:“MI:0915”(physical association)	0.780
FXR2	CDKL3	psi-mi:“MI:0915”(physical association)	0.780
TRIM27	CDKL3	psi-mi:“MI:0915”(physical association)	0.720
ZBTB8A	CDKL3	psi-mi:“MI:0915”(physical association)	0.720
CDKL3	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.720
CDKL3	TRIM27	psi-mi:“MI:0915”(physical association)	0.720
CDKL3	MTUS2	psi-mi:“MI:0915”(physical association)	0.670
MTUS2	CDKL3	psi-mi:“MI:0915”(physical association)	0.670
CDKL3	ZBTB14	psi-mi:“MI:0915”(physical association)	0.560
CDKL3	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
CDKL3	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	CDKL3	psi-mi:“MI:0915”(physical association)	0.560
KASH5	CDKL3	psi-mi:“MI:0915”(physical association)	0.560
ATG4A	CDKL3	psi-mi:“MI:0915”(physical association)	0.560
MDFI	CDKL3	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	CDKL3	psi-mi:“MI:0915”(physical association)	0.560
CDKL3	DNAAF6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	CDKL3	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	CDKL3	psi-mi:“MI:0915”(physical association)	0.560
CDKL3	KASH5	psi-mi:“MI:0915”(physical association)	0.560
CDKL3	ATG4A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (74): CDKL3 (Two-hybrid), CDKL3 (Two-hybrid), CDKL3 (Two-hybrid), CDKL3 (Two-hybrid), CDKL3 (Two-hybrid), CDKL3 (Two-hybrid), LZTS2 (Two-hybrid), ATG4A (Two-hybrid), PIH1D3 (Two-hybrid), CCDC155 (Two-hybrid), KRTAP10-9 (Two-hybrid), ZBTB8A (Two-hybrid), STAMBP (Affinity Capture-MS), CDKL3 (Reconstituted Complex), CDKL3 (Synthetic Lethality)

ESM2 similar proteins: A6ZU08, A6ZZF6, B5X564, O14098, O14132, O43077, O59722, O60114, O74815, O94603, O94647, O94751, P20794, P28708, P28829, P32801, P38757, P38938, P43637, P50873, P83102, P87060, Q09690, Q09815, Q09872, Q10077, Q10407, Q10719, Q4R7T5, Q4R8T9, Q5AHA0, Q5R754, Q5XIT0, Q62726, Q6BV06, Q6NTJ3, Q8BLF2, Q8IVW4, Q8TFG6, Q92772

Diamond homologs: F4I313, Q4R8T9, Q6P3W7, Q8CFE4, Q8IVW4, Q8SRF5, Q8W490, Q9C9H8, A0A194WDG1, A0A1S3Z5Y0, A2QN07, A2XFC8, A3EZ55, A9S9Q8, A9T142, B0Y4X4, B3WFY8, G1XJZ4, G4N374, O13352, O14132, O43077, O55076, O61443, O93982, P0C431, P20793, P20794, P23111, P23437, P24100, P24788, P24941, P29618, P29619, P32485, P32581, P42525, P43063, P43294

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	78
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
58362	GRCh38/hg38 5q31.1(chr5:133531234-134847678)x1	Pathogenic

SpliceAI

2402 predictions. Top by Δscore:

Variant	Effect	Δscore
5:134302585:GTTA:G	donor_loss	1.0000
5:134302586:TTACC:T	donor_loss	1.0000
5:134302587:TAC:T	donor_loss	1.0000
5:134302588:A:C	donor_loss	1.0000
5:134302589:C:CA	donor_loss	1.0000
5:134302591:T:TA	donor_gain	1.0000
5:134302688:C:CC	acceptor_gain	1.0000
5:134302689:T:C	acceptor_gain	1.0000
5:134302690:T:C	acceptor_gain	1.0000
5:134302691:T:C	acceptor_gain	1.0000
5:134302691:T:TC	acceptor_gain	1.0000
5:134302694:C:CT	acceptor_gain	1.0000
5:134304412:T:A	donor_gain	1.0000
5:134304468:T:A	donor_gain	1.0000
5:134304566:CT:C	acceptor_gain	1.0000
5:134304568:C:CC	acceptor_gain	1.0000
5:134306607:A:AC	donor_gain	1.0000
5:134306608:C:CC	donor_gain	1.0000
5:134308597:G:C	donor_gain	1.0000
5:134312286:GCTT:G	donor_loss	1.0000
5:134312287:CTT:C	donor_loss	1.0000
5:134312288:TTA:T	donor_loss	1.0000
5:134312289:TACTT:T	donor_loss	1.0000
5:134312290:A:AC	donor_gain	1.0000
5:134312290:A:T	donor_loss	1.0000
5:134312291:C:CC	donor_gain	1.0000
5:134312291:CTTTT:C	donor_gain	1.0000
5:134312376:CAAGC:C	acceptor_gain	1.0000
5:134312378:AGCC:A	acceptor_loss	1.0000
5:134312379:GCC:G	acceptor_loss	1.0000

AlphaMissense

3950 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:134321880:C:T	G188D	1.000
5:134321890:A:G	W185R	1.000
5:134321890:A:T	W185R	1.000
5:134350292:A:G	Y166H	1.000
5:134350295:A:G	W165R	1.000
5:134350295:A:T	W165R	1.000
5:134350359:A:C	D143E	1.000
5:134350359:A:T	D143E	1.000
5:134350360:T:A	D143V	1.000
5:134350360:T:C	D143G	1.000
5:134350360:T:G	D143A	1.000
5:134350407:T:A	K127N	1.000
5:134350407:T:G	K127N	1.000
5:134350413:A:C	D125E	1.000
5:134350413:A:T	D125E	1.000
5:134350414:T:A	D125V	1.000
5:134350414:T:C	D125G	1.000
5:134350414:T:G	D125A	1.000
5:134350417:C:G	R124P	1.000
5:134366425:C:A	K33N	1.000
5:134366425:C:G	K33N	1.000
5:134312351:C:A	R274S	0.999
5:134312351:C:G	R274S	0.999
5:134312352:C:A	R274M	0.999
5:134312352:C:G	R274T	0.999
5:134312377:A:G	C266R	0.999
5:134321864:C:A	E193D	0.999
5:134321864:C:G	E193D	0.999
5:134321865:T:A	E193V	0.999
5:134321881:C:G	G188R	0.999

dbSNP variants (sampled 300 via entrez): RS1000025626 (5:134324074 G>T), RS1000047754 (5:134365872 A>G), RS1000050217 (5:134325240 C>G), RS1000073441 (5:134288172 G>T), RS1000090740 (5:134370530 C>A,T), RS1000111366 (5:134284939 C>T), RS1000129008 (5:134295866 G>A,C), RS1000173163 (5:134340345 C>A,G), RS1000191349 (5:134371377 C>G,T), RS1000199793 (5:134371197 C>T), RS1000238373 (5:134330230 A>G), RS1000270961 (5:134332349 T>C), RS1000293545 (5:134336680 C>A), RS1000331914 (5:134317378 C>T), RS1000356691 (5:134336401 G>C)

Disease associations

OMIM: gene MIM:608459 | 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
GCST004606_128	Eosinophil count	3.000000e-09
GCST008179_12	Moderate-to-late spontaneous preterm birth	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0006917	spontaneous preterm birth

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1163117 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 96,060 (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
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL495727	AT-9283	2	1,376
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL296468	BMS-387032	1	2,075
CHEMBL5426285	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-	1	4
CHEMBL574738	AST-487	1	451

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Cyclin-dependent kinase-like (CDKL) family

ChEMBL bioactivities

17 potent at pChembl≥5 of 17 total, top 15 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	IC50	0.5	nM	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-
8.41	Kd	3.9	nM	AST-487
8.15	IC50	7.1	nM	AST-487
6.84	IC50	143	nM	CHEMBL5190023
6.46	Kd	350	nM	TOZASERTIB
6.37	Kd	430	nM	LESTAURTINIB
6.31	Kd	490	nM	SORAFENIB
6.17	IC50	668.5	nM	CHEMBL5393904
5.96	IC50	1100	nM	AT-9283
5.96	IC50	1100	nM	STAUROSPORINE
5.96	Kd	1100	nM	CHEMBL379218
5.85	Kd	1400	nM	BMS-387032
5.36	Kd	4400	nM	FORETINIB
5.29	Kd	5100	nM	STAUROSPORINE
5.10	IC50	7900	nM	FORETINIB

PubChem BioAssay actives

17 with measured affinity, of 154 total; 12 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
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2R)-1-methoxy-4-methylpentan-2-yl]iminoimidazolidin-4-one	2024493: Inhibition of human CDKL3 assessed as remaining activity by eurofins-cerep kinase profiler analysis	ic50	0.0005	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	624822: Binding constant for CDKL3 kinase domain	kd	0.0039	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	1856716: Inhibition of CDKL3 (unknown origin)	ic50	0.1430	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	624822: Binding constant for CDKL3 kinase domain	kd	0.3500	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	507872: Binding affinity to CDKL3	kd	0.4300	uM
Sorafenib	507872: Binding affinity to CDKL3	kd	0.4900	uM
[4-[3-[[(4-chloro-1H-indazol-3-yl)amino]methyl]benzoyl]piperazin-1-yl]-(2,4-dichlorophenyl)methanone	1966717: Inhibition of CDKL3 (unknown origin) by kinase profiling assay	ic50	0.6685	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624822: Binding constant for CDKL3 kinase domain	kd	1.1000	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	1733107: Inhibition of CDKL3 (unknown origin) by NanoBRET cellular target engagement assay	ic50	1.1000	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	1733107: Inhibition of CDKL3 (unknown origin) by NanoBRET cellular target engagement assay	ic50	1.1000	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	624822: Binding constant for CDKL3 kinase domain	kd	1.4000	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	624822: Binding constant for CDKL3 kinase domain	kd	4.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
Air Pollutants	increases expression, affects expression, increases abundance	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	affects expression	1
cupric oxide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	increases expression	1
Sunitinib	increases expression	1
Atrazine	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Nickel	decreases expression	1
Niclosamide	increases expression	1
Ozone	affects expression, increases abundance	1
Tunicamycin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

94 unique, capped per target: 94 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1168827	Binding	Inhibition of CDKL3 at 1 uM	Synthesis and structure-activity relationships of 1,2,3,4-tetrahydropyrido[2,3-b]pyrazines as potent and selective inhibitors of the anaplastic lymphoma kinase. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SI46	HAP1 CDKL3 (-) 1	Cancer cell line	Male
CVCL_SI47	HAP1 CDKL3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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