CDKL5

Summary

CDKL5 (cyclin dependent kinase like 5, HGNC:11411) is a protein-coding gene on chromosome Xp22.13, encoding Cyclin-dependent kinase-like 5 (O76039). Mediates phosphorylation of MECP2. It is haploinsufficient (ClinGen: sufficient evidence).

This gene is a member of Ser/Thr protein kinase family and encodes a phosphorylated protein with protein kinase activity. Mutations in this gene have been associated with X-linked infantile spasm syndrome (ISSX), also known as X-linked West syndrome, and Rett syndrome (RTT). Alternate transcriptional splice variants have been characterized.

Source: NCBI Gene 6792 — RefSeq curated summary.

At a glance

• Gene–disease (curated): CDKL5 disorder (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 2,283 total — 557 pathogenic, 261 likely-pathogenic
• Phenotypes (HPO): 148
• Druggable target: yes — 14 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001323289

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11411
Approved symbol	CDKL5
Name	cyclin dependent kinase like 5
Location	Xp22.13
Locus type	gene with protein product
Status	Approved
Aliases	EIEE2, CFAP247
Ensembl gene	ENSG00000008086
Ensembl biotype	protein_coding
OMIM	300203
Entrez	6792

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000379989, ENST00000379996, ENST00000463994, ENST00000623364, ENST00000623535, ENST00000623610, ENST00000624700, ENST00000624953, ENST00000635828, ENST00000636046, ENST00000637881, ENST00000673617, ENST00000674046

RefSeq mRNA: 3 — MANE Select: NM_001323289 NM_001037343, NM_001323289, NM_003159

CCDS: CCDS14186, CCDS83458

Canonical transcript exons

ENST00000623535 — 18 exons

Exon	Start	End
ENSE00000666204	18575354	18575490
ENSE00000666205	18579848	18579968
ENSE00000666206	18581891	18581950
ENSE00000666207	18584263	18584353
ENSE00000666208	18587954	18588143
ENSE00000666209	18595348	18595428
ENSE00000666210	18598462	18598613
ENSE00000666211	18603902	18604868
ENSE00001049028	18510820	18510854
ENSE00001150105	18506935	18507160
ENSE00001280913	18564477	18564522
ENSE00001281269	18625128	18625247
ENSE00001281273	18619867	18619966
ENSE00001281279	18613152	18613275
ENSE00003754917	18608811	18608912
ENSE00003756261	18609465	18609570
ENSE00003760347	18628371	18640196
ENSE00003888970	18425608	18425695

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 95.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.9872 / max 473.6693, expressed in 1464 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195678	5.8480	1369
195679	1.5605	457
209618	0.1587	61
195686	0.0923	34
195684	0.0761	11
195683	0.0697	25
195687	0.0524	20
195685	0.0518	15
195680	0.0506	13
195688	0.0271	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	95.81	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.97	gold quality
cortical plate	UBERON:0005343	90.35	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.12	gold quality
middle temporal gyrus	UBERON:0002771	89.75	gold quality
esophagus squamous epithelium	UBERON:0006920	89.05	gold quality
endothelial cell	CL:0000115	88.23	gold quality
palpebral conjunctiva	UBERON:0001812	87.72	gold quality
primary visual cortex	UBERON:0002436	87.63	gold quality
superior frontal gyrus	UBERON:0002661	87.23	gold quality
occipital lobe	UBERON:0002021	85.94	gold quality
entorhinal cortex	UBERON:0002728	85.91	gold quality
visceral pleura	UBERON:0002401	85.79	gold quality
postcentral gyrus	UBERON:0002581	85.77	gold quality
parietal lobe	UBERON:0001872	85.75	gold quality
amniotic fluid	UBERON:0000173	85.74	gold quality
tibia	UBERON:0000979	85.64	gold quality
prefrontal cortex	UBERON:0000451	85.57	gold quality
Brodmann (1909) area 10	UBERON:0013541	85.22	gold quality
lower lobe of lung	UBERON:0008949	85.06	gold quality
calcaneal tendon	UBERON:0003701	83.83	gold quality
frontal cortex	UBERON:0001870	83.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.51	gold quality
neocortex	UBERON:0001950	82.90	gold quality
epithelium of esophagus	UBERON:0001976	82.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.18	gold quality
cerebral cortex	UBERON:0000956	81.49	gold quality
corpus callosum	UBERON:0002336	80.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.98	gold quality
telencephalon	UBERON:0001893	79.98	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.79
E-MTAB-10137	no	112.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, MECP2, MEF2C, MYCN, SSRP1

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• CDKL5 mutations are associated with epilepsy, X-linked mental retardation and a clinical phenotype that overlaps Rett syndrome. (PMID:15492925)
• A proportion of Rett syndrome atypical cases may result from mutations in CDKL5. (review) (PMID:15635068)
• demonstrate that MeCP2 and CDKL5 interact both in vivo and in vitro and that CDKL5 is indeed a kinase, which is able to phosphorylate itself and to mediate MeCP2 phosphorylation (PMID:15917271)
• novel pathogenic CDKL5 mutations were identified in three girls, two of whom had initially been diagnosed with the early onset seizure variant of Rett Syndrome (RTT) and the other with early onset seizures and some features of RTT (PMID:16015284)
• Patients with the CDKL5 mutation have an early onset, epileptic encephalopathy in infancy that evolves into myoclonic seizures in childhood with a unique EEG pattern. (PMID:16326141)
• CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder, irrespective of whether they have suspected Rett syndrome. (PMID:16611748)
• CDKL5 phosphorylation is required for its entrance into the nucleus whereas a portion of the COOH-terminal domain is responsible for a stable residency in this cellular compartment probably through protein-protein interactions (PMID:16935860)
• The observation of this study and review of the literature suggest that a broader polymorphic electroclinical pattern with both generalized and focal seizures may occur in patients with CDKL5 mutations. (PMID:17049193)
• CDKL5 mutations may a rare cause of Rett syndrome. (PMID:17089071)
• screened entire coding region of CDKL5 in 151 affected girls with a heterogeneous phenotype ranging from encephalopathy with epilepsy to atypical Rett syndrome, and identified 3 novel missense mutations in catalytic domain Ala40Val, Arg65Gln, Leu220Pro (PMID:17993579)
• clinical features & electroencephalographic findings of 2 patients affected by a previously unreported CDKL5 mutation; both manifest Hanefeld variant Rett syndrome & had early-onset seizures, hand stereotypies, congenital psychomotor delay & hypotonia (PMID:18063413)
• Epileptic phenotype in CDKL5 mutations, and a potential relationship between the phenotype and the genotype. (PMID:18266744)
• CDKL5 expression is modulated during neuronal development and its subcellular distribution is tightly regulated by the C-terminal tail (PMID:18701457)
• 18 different mutations (7 novel ones) were identified in 20 unrelated girls. These mutations were identified in eight patients with encephalopathy with RTT-like features, five with infantile spasms and seven with encephalopathy with refractory epilepsy. (PMID:18790821)
• CDKL5 gene mutations may represent a cause of severe or profound mental retardation and early-onset intractable seizures, also in boys. (PMID:18809835)
• Results describe the correlation of genotype and phenotype in CDKL5 mutated female carriers. (PMID:19241098)
• a novel p.Arg970X mutation in the last exon of the CDKL5 gene resulting in late onset seizure disorder. (PMID:19428276)
• Data demonstrate the first instance of genomic deletion as the molecular basis of CDKL5 deficiency in females. (PMID:19471977)
• We report CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy. (PMID:19564592)
• CDKL5 mutations are not responsible for early onset severe myoclonic epilepsy in infancy (PMID:19734009)
• CDKL5 is involved in pre-mRNA processing, by controlling splicing factor dynamics. (PMID:19740913)
• We found CDKL5 mutations in 8.2% (4 of 49) of patients and genomic deletions in 8.2% (4 of 49). Overall, abnormalities of the CDKL5 gene accounted for 16.3% (8 of 49) of patients. (PMID:19780792)
• The CDKL5 mutation rate is high (28%) in women with early-onset seizures and infantile spasms. (PMID:19793311)
• seven polymorphic variations and four de novo mutations of the CDKL5 gene were identified, and in all instances of the latter the clinical phenotype was that of an epileptic encephalopathy. (PMID:20397747)
• Two patients (one female, one male) with CDKL5 mutations have epileptic spasms after tonic seizures but never present infantile spasms as the main seizure type or hypsarrhythmia in electroencephalography. (PMID:20493745)
• Data indicate that MEF2C missense de novo mutations in severe mental retardation showed diminished MECP2 and CDKL5 expression. (PMID:20513142)
• CDKL5 mutation is associated with epileptic encephalopathy. (PMID:20602487)
• CDKL5 deficit may induce changes in synaptic plasticity in the patient’s brain. (PMID:21107515)
• CDKL5 exon 16b should now be considered in the genetic screening of patients presenting with a CDKL5-related disease profile. (PMID:21124335)
• We report the first case of an exonic deletion of CDKL5 in a male and emphasize the importance of underappreciated mosaic exonic copy number variation in patients with early-onset seizures and RTT-like features of both genders. (PMID:21293276)
• Infants with CDKL5-related early epileptic encephalopathy can present in the first year of life with an unusual. (PMID:21309761)
• A novel CDKL5 exon and pathogenic mutations in patients with severe mental retardation, early-onset seizures and Rett-like features. (PMID:21318334)
• the distinctive hypermotor-tonic-spasms sequence is a feature of CDKL5 epileptic encephalopathy. (PMID:21502606)
• female CDKL5-mutated iPSCs maintain X-chromosome inactivation and clones express either the mutant CDKL5 allele or the wild-type allele that serve as an ideal experimental control. (PMID:21750574)
• This study present clinical phenotype of 5 girls having a mutation in the CDKL5 gene (PMID:21765152)
• mutations in early onset epileptic encephalopathy (PMID:21770923)
• A novel CDKL5 mutation is identified in an ambulatory girl who had severe mental retardation and multiple types of seizures without Rett-like features. (PMID:21775177)
• sought to determine the historic, clinical, and prognostic features of epilepsy secondary to CDKL5 mutations. all children developed infantile spasms. All children demonstrated developmental delay and visual impairment. (PMID:22264704)
• The patients with clinical features of Rett syndrome, with epileptic encephalopathy before 6 months of age, regardless the presence of genetic abnormalities (mutations in MeCP2 or CDKL5 or both) or even in their absence. (PMID:22430159)
• Recurrent mutations in the CDKL5 gene in patients with epileptic encephalopathies can be associated with either a milder or a more severe phenotype. (PMID:22678952)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdkl5	ENSDARG00000015240
mus_musculus	Cdkl5	ENSMUSG00000031292
rattus_norvegicus	Cdkl5	ENSRNOG00000003742

Paralogs (26): CDKL3 (ENSG00000006837), 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 5 — O76039 (reviewed: O76039)

Alternative names: Serine/threonine-protein kinase 9

All UniProt accessions (8): O76039, A0A096LNR9, A0A096LP32, A0A096LPG3, A0A096LPI4, A0A1B0GTX4, A0A1B0GUM4, A0A669KBC2

UniProt curated annotations — full annotation on UniProt →

Function. Mediates phosphorylation of MECP2. May regulate ciliogenesis.

Subunit / interactions. Interacts with MECP2.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Cilium basal body. Microtubule organizing center. Centrosome.

Tissue specificity. Expressed in brain, lung, kidney, prostate, ovary, placenta, pancreas and testis. Predominant transcript in brain.

Post-translational modifications. Autophosphorylated.

Disease relevance. Chromosomal aberrations involving CDKL5 are found in patients manifesting early-onset seizures and spams and psychomotor impairment. Translocation t(X;6)(p22.3;q14); translocation t(X;7)(p22.3;p15). Developmental and epileptic encephalopathy 2 (DEE2) [MIM:300672] A severe form of epilepsy characterized by seizures or spasms beginning in infancy. Patients with epileptic encephalopathy early infantile type 2 manifest features resembling Rett syndrome such as microcephaly, lack of speech development, stereotypic hand movements. However, DEE2 and Rett syndrome are considered two distinct entities. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O76039-2	1	yes
O76039-1	2

RefSeq proteins (3): NP_001032420, NP_001310218, NP_003150 (=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

Enzyme classification (BRENDA):

• EC 2.7.11.22 — cyclin-dependent kinase (BRENDA: 49 organisms, 441 substrates, 555 inhibitors, 8 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ADAQHATPPKKKRKVEDPKDF	0.046–0.521	2
ATP	0.0052–0.017	2
FIN1	0.003	1
PKTPKKAKKL	0.0029	1

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 (94 total): sequence variant 35, compositionally biased region 15, helix 15, strand 9, region of interest 4, modified residue 4, sequence conflict 3, turn 3, binding site 2, chain 1, domain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4BGQ	X-RAY DIFFRACTION	2
8CIE	X-RAY DIFFRACTION	2.2
9EPU	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76039-F1	53.76	0.23

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): 135 (proton acceptor)

Ligand- & substrate-binding residues (2): 19–27; 42

Post-translational modifications (4): 407, 479, 720, 761

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 535 (showing top): GOBP_DENDRITE_DEVELOPMENT, RNGTGGGC_UNKNOWN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOZGIT_ESR1_TARGETS_DN, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_GROWTH, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEUROGENESIS, BROWNE_HCMV_INFECTION_16HR_UP, TGACCTY_ERR1_Q2, GOCC_RUFFLE, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (10): neuron migration (GO:0001764), positive regulation of Rac protein signal transduction (GO:0035022), positive regulation of axon extension (GO:0045773), regulation of dendrite development (GO:0050773), positive regulation of dendrite morphogenesis (GO:0050775), modulation of chemical synaptic transmission (GO:0050804), regulation of postsynapse organization (GO:0099175), regulation of cilium assembly (GO:1902017), protein phosphorylation (GO:0006468), regulation of cell cycle (GO:0051726)

GO Molecular Function (10): 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), kinase activity (GO:0016301), small GTPase binding (GO:0031267), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), dendrite cytoplasm (GO:0032839), ciliary basal body (GO:0036064), dendritic growth cone (GO:0044294), ciliary tip (GO:0097542), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), ruffle membrane (GO:0032587), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein kinase activity	2
microtubule organizing center	2
cilium	2
cell migration	1
generation of neurons	1
Rac protein signal transduction	1
regulation of Rac protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
positive regulation of cell growth	1
regulation of axon extension	1
positive regulation of developmental growth	1
axon extension	1
positive regulation of axonogenesis	1
regulation of neuron projection development	1
dendrite development	1
regulation of developmental process	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
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
regulation of synapse organization	1
postsynapse organization	1
cilium assembly	1
regulation of plasma membrane bounded cell projection assembly	1
regulation of organelle assembly	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

Protein interactions and networks

STRING

1294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDKL5	MECP2	P51608	963
CDKL5	PCDH19	Q8TAB3	893
CDKL5	FOXG1	P55315	866
CDKL5	STXBP1	P61764	866
CDKL5	SCN1A	P35498	853
CDKL5	NTNG1	Q9Y2I2	844
CDKL5	KCNQ2	O43526	837
CDKL5	PCDH10	Q9P2E7	830
CDKL5	SLC25A22	Q9H936	819
CDKL5	SCN2A	Q99250	813
CDKL5	ARX	Q96QS3	804
CDKL5	RAI2	Q9Y5P3	776
CDKL5	NTNG2	Q96CW9	739
CDKL5	DNMT1	P26358	738
CDKL5	PPEF1	O14829	738

IntAct

19 interactions, top by confidence:

A	B	Type	Score
CDKL5	MLH1	psi-mi:“MI:0915”(physical association)	0.670
MLH1	CDKL5	psi-mi:“MI:0915”(physical association)	0.670
CDKL5	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
CDKL5	SERPINB8	psi-mi:“MI:0915”(physical association)	0.560
Dlg4	CDKL5	psi-mi:“MI:0407”(direct interaction)	0.440
PRKG2	CDKL5	psi-mi:“MI:0915”(physical association)	0.400
SPTBN4	CDKL5	psi-mi:“MI:0915”(physical association)	0.370
TACC3	CDKL5	psi-mi:“MI:0915”(physical association)	0.370
SKIC2	CDKL5	psi-mi:“MI:0915”(physical association)	0.370
PB2	SEC15L3	psi-mi:“MI:0914”(association)	0.350
CDKL5	DHX16	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CDKL5	PTX3	psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
CDKL5	MLH1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (44): SERPINB8 (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), DHX16 (Affinity Capture-MS), MACF1 (Affinity Capture-MS), GPALPP1 (Affinity Capture-MS), KLHL20 (Affinity Capture-MS), SAR1B (Affinity Capture-MS), RABL6 (Affinity Capture-MS), UBAP2 (Affinity Capture-MS), DHX38 (Affinity Capture-MS), CDKL5 (Proximity Label-MS), DHX38 (Affinity Capture-MS), MACF1 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), DHX16 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LFM6, A0A1L8H8C0, A0A1L8HFX9, A0A2R6X6S3, A0JM08, A2ARZ3, A2RUV4, A5WUN7, A6QP06, D4AEC2, E9Q309, O76039, P51960, Q03898, Q05935, Q06190, Q08AD1, Q08D57, Q0WPH8, Q3KQW7, Q3UTQ8, Q498L0, Q5RAU1, Q5SW79, Q5T0W9, Q5T5U3, Q5VT06, Q62770, Q66J90, Q69Z38, Q6A065, Q6DFG0, Q6DFV3, Q6IRN6, Q71M21, Q80TN7, Q8AV28, Q8C1B1, Q8IVL0, Q8IZ21

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

7 interactions.

A	Effect	B	Mechanism
CDKL5	unknown	LRRC4C	phosphorylation
MEF2C	“up-regulates quantity by expression”	CDKL5	“transcriptional regulation”
CDKL5	“down-regulates activity”	SOX9	phosphorylation
CDKL5	“down-regulates activity”	AMPH	phosphorylation
CDKL5	“up-regulates activity”	CDKL5	phosphorylation
CDKL5	unknown	MECP2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

2283 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	557
Likely pathogenic	261
Uncertain significance	515
Likely benign	489
Benign	117

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1019831	NM_000330.4(RS1):c.311A>C (p.Asn104Thr)	Pathogenic
1020776	NM_001323289.2(CDKL5):c.554+5G>A	Pathogenic
1037382	NM_001323289.2(CDKL5):c.424T>G (p.Leu142Val)	Pathogenic
1038592	NM_001323289.2(CDKL5):c.412C>G (p.Pro138Ala)	Pathogenic
1052408	NM_001323289.2(CDKL5):c.217G>A (p.Val73Met)	Pathogenic
1066419	NM_000330.4(RS1):c.227T>A (p.Val76Asp)	Pathogenic
1066639	NM_000330.4(RS1):c.575C>A (p.Pro192His)	Pathogenic
1066892	NM_000330.4(RS1):c.327-2A>G	Pathogenic
1066910	NM_000330.4(RS1):c.274T>G (p.Trp92Gly)	Pathogenic
1068997	NC_000023.10:g.(?18662550)(18690188_?)del	Pathogenic
1070205	NM_001323289.2(CDKL5):c.2606del (p.Asn869fs)	Pathogenic
1070858	NC_000023.10:g.(?18582587)(18690188_?)del	Pathogenic
1070859	NC_000023.10:g.(?18525211)(18528980_?)dup	Pathogenic
1070860	NC_000023.10:g.(?18582587)(18627700_?)dup	Pathogenic
1070908	NM_001323289.2(CDKL5):c.1927C>T (p.Gln643Ter)	Pathogenic
1071237	NM_001323289.2(CDKL5):c.532C>G (p.Arg178Gly)	Pathogenic
1072615	NM_001323289.2(CDKL5):c.194G>C (p.Arg65Pro)	Pathogenic
1072616	NM_001323289.2(CDKL5):c.1976_1977del (p.Val659fs)	Pathogenic
1072660	NM_001323289.2(CDKL5):c.1053_1056dup (p.Leu353fs)	Pathogenic
1072862	NM_001323289.2(CDKL5):c.513C>G (p.Tyr171Ter)	Pathogenic
1072905	NM_001323289.2(CDKL5):c.1584dup (p.Ser529fs)	Pathogenic
1073273	NM_001323289.2(CDKL5):c.554+4A>G	Pathogenic
1073422	NM_000330.4(RS1):c.581dup (p.Ile195fs)	Pathogenic
1075877	NM_001323289.2(CDKL5):c.2579_2582dup (p.Leu862fs)	Pathogenic
11500	NM_001323289.2(CDKL5):c.2500C>T (p.Gln834Ter)	Pathogenic
11502	NM_001323289.2(CDKL5):c.119C>T (p.Ala40Val)	Pathogenic
11503	NM_001323289.2(CDKL5):c.215T>C (p.Ile72Thr)	Pathogenic
1184473	NM_000330.4(RS1):c.287G>A (p.Trp96Ter)	Pathogenic
1193529	NM_001323289.2(CDKL5):c.292G>T (p.Glu98Ter)	Pathogenic
1275772	NM_000330.4(RS1):c.372_373insTAGCCAGTGG (p.Ile125Ter)	Pathogenic

SpliceAI

3357 predictions. Top by Δscore:

Variant	Effect	Δscore
X:18517344:GGAC:G	donor_gain	1.0000
X:18548689:G:GT	donor_gain	1.0000
X:18564521:AG:A	donor_loss	1.0000
X:18564522:GGTAG:G	donor_loss	1.0000
X:18564523:G:GA	donor_loss	1.0000
X:18564524:T:A	donor_loss	1.0000
X:18575350:CTAG:C	acceptor_loss	1.0000
X:18575351:TA:T	acceptor_loss	1.0000
X:18575352:A:AG	acceptor_gain	1.0000
X:18575352:A:C	acceptor_loss	1.0000
X:18575353:G:A	acceptor_loss	1.0000
X:18575353:G:GA	acceptor_gain	1.0000
X:18575353:GAA:G	acceptor_gain	1.0000
X:18575353:GAAA:G	acceptor_gain	1.0000
X:18575437:G:GT	donor_gain	1.0000
X:18575457:A:T	donor_gain	1.0000
X:18575470:GTGTT:G	donor_gain	1.0000
X:18575471:TGTTT:T	donor_gain	1.0000
X:18575472:GTTTG:G	donor_gain	1.0000
X:18575478:G:GG	donor_gain	1.0000
X:18575487:AAAA:A	donor_gain	1.0000
X:18575488:AAA:A	donor_gain	1.0000
X:18575488:AAAGT:A	donor_loss	1.0000
X:18575489:AA:A	donor_gain	1.0000
X:18575490:AG:A	donor_loss	1.0000
X:18575491:G:C	donor_loss	1.0000
X:18575491:G:GG	donor_gain	1.0000
X:18575492:TAA:T	donor_loss	1.0000
X:18579844:TTAG:T	acceptor_loss	1.0000
X:18579846:A:AG	acceptor_gain	1.0000

AlphaMissense

6332 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:18507133:T:A	F13I	1.000
X:18507133:T:C	F13L	1.000
X:18507134:T:C	F13S	1.000
X:18507134:T:G	F13C	1.000
X:18507135:T:A	F13L	1.000
X:18507135:T:G	F13L	1.000
X:18507143:T:C	L16P	1.000
X:18507145:G:T	G17W	1.000
X:18507154:G:A	G20S	1.000
X:18507154:G:C	G20R	1.000
X:18507154:G:T	G20C	1.000
X:18507155:G:A	G20D	1.000
X:18507155:G:T	G20V	1.000
X:18507160:G:A	G22R	1.000
X:18507160:G:C	G22R	1.000
X:18510820:G:A	G22E	1.000
X:18510820:G:T	G22V	1.000
X:18510825:T:C	Y24H	1.000
X:18510828:G:A	G25R	1.000
X:18510828:G:C	G25R	1.000
X:18510829:G:A	G25E	1.000
X:18510829:G:T	G25V	1.000
X:18510835:T:A	V27E	1.000
X:18510838:T:C	L28P	1.000
X:18510843:T:C	C30R	1.000
X:18510844:G:A	C30Y	1.000
X:18510845:C:G	C30W	1.000
X:18564493:T:A	V39E	1.000
X:18564495:G:C	A40P	1.000
X:18564496:C:A	A40E	1.000

dbSNP variants (sampled 300 via entrez): RS1000008451 (X:18424569 A>G), RS1000036592 (X:18555304 A>G), RS1000041857 (X:18652644 G>A), RS1000047274 (X:18542932 G>C,T), RS1000063721 (X:18556988 C>G,T), RS1000072804 (X:18653211 T>C), RS1000099137 (X:18493333 C>A,T), RS1000108263 (X:18555602 T>C), RS1000108656 (X:18433256 A>G), RS1000110080 (X:18562730 G>A), RS1000140353 (X:18523950 C>A), RS1000150383 (X:18460482 T>TTTTA), RS1000150845 (X:18625030 G>C,T), RS1000154659 (X:18619449 T>C), RS1000156113 (X:18536779 T>C)

Disease associations

OMIM: gene MIM:300203 | disease phenotypes: MIM:300672, MIM:312700, MIM:312750, MIM:308350, MIM:123100, MIM:209850, MIM:105830, MIM:601358, MIM:612164

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 2	Definitive	X-linked
CDKL5 disorder	Definitive	X-linked
genetic developmental and epileptic encephalopathy	Supportive	Autosomal dominant
atypical Rett syndrome	Supportive	Autosomal dominant
infantile spasms	Supportive	Autosomal dominant
precocious puberty	Limited	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
CDKL5 disorder	Definitive	XL

Mondo (23): developmental and epileptic encephalopathy, 2 (MONDO:0010396), CDKL5 disorder (MONDO:0100039), X-linked retinoschisis (MONDO:0010725), inherited retinal dystrophy (MONDO:0019118), atypical Rett syndrome (MONDO:0017746), Rett syndrome (MONDO:0010726), developmental and epileptic encephalopathy, 1 (MONDO:0010632), craniosynostosis (MONDO:0015469), autism (MONDO:0005260), intellectual disability (MONDO:0001071), Angelman syndrome (MONDO:0007113), retinal disorder (MONDO:0005283), infantile spasms (MONDO:0018097), stereotypic movement disorder (MONDO:0002265), bruxism (MONDO:0002443)

Orphanet (14): Early infantile developmental and epileptic encephalopathy (Orphanet:1934), West syndrome (Orphanet:3451), CDKL5-deficiency disorder (Orphanet:505652), X-linked retinoschisis (Orphanet:792), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Atypical Rett syndrome (Orphanet:3095), Rett syndrome (Orphanet:778), Craniosynostosis (Orphanet:1531), Angelman syndrome (Orphanet:72), Infantile epileptic spasms syndrome (Orphanet:697160), Nicolaides-Baraitser syndrome (Orphanet:3051), Dravet syndrome (Orphanet:33069), STXBP1-related encephalopathy (Orphanet:599373), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

148 total (30 of 148 shown, HPO-id order):

HPO	Term
HP:0000054	Micropenis
HP:0000070	Ureterocele
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000179	Thick lower lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000337	Broad forehead
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000348	High forehead
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000565	Esotropia
HP:0000577	Exotropia
HP:0000664	Synophrys
HP:0000707	Abnormality of the nervous system
HP:0000713	Agitation
HP:0000723	Restrictive behavior
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000748	Inappropriate laughter
HP:0000749	Paroxysmal bursts of laughter
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000817	Reduced eye contact
HP:0000826	Precocious puberty
HP:0001182	Tapered finger

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007876_133	Estimated glomerular filtration rate	1.000000e-09

MeSH disease descriptors (16)

Descriptor	Name	Tree numbers
D017204	Angelman Syndrome	C10.228.662.075; C16.131.077.095; C16.131.260.040; C16.320.180.040; C16.320.447.250
D001321	Autistic Disorder	F03.625.164.113.500
D002012	Bruxism	C07.793.099; F01.145.466.132; F01.470.315.500
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D004828	Epilepsies, Partial	C10.228.140.490.360
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D011629	Puberty, Precocious	C19.391.693
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D041441	Retinoschisis	C11.768.585.865
D015518	Rett Syndrome	C10.597.606.360.455.937; C16.320.322.500.937; C16.320.400.525.937
D019956	Stereotypic Movement Disorder	F03.625.984
C564064	CDKL5 deficiency disorder (supp.)
C567404	Epileptic Encephalopathy, Early Infantile, 4 (supp.)
C531619	Happy puppet syndrome (formerly) (supp.)
C536116	Nicolaides Baraitser syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1163112 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

14 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 47,089 (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
CHEMBL3188267	CAPMATINIB	4	2,884
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL384304	RG-547	2	93
CHEMBL445813	AT-7519	2	2,614
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL296468	BMS-387032	1	2,075
CHEMBL3128043	PF-03758309	1	233
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

23 potent at pChembl≥5 of 24 total, top 22 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.84	Kd	1.44	nM	CHEMBL3752910
8.79	ED50	1.62	nM	CHEMBL3752910
8.77	Kd	1.7	nM	BMS-387032
8.59	Kd	2.6	nM	AT-7519
8.18	Kd	6.6	nM	AST-487
8.15	Kd	7.1	nM	ALVOCIDIB
8.00	Kd	10	nM	LESTAURTINIB
7.80	Kd	16	nM	DEFACTINIB
7.70	Kd	20	nM	CHEMBL3699142
7.62	Kd	24	nM	CHEMBL3991935
6.70	Kd	200	nM	CHEMBL379218
6.47	Kd	340	nM	STAUROSPORINE
6.32	Kd	482.9	nM	CHEMBL5653589
6.26	ED50	543	nM	CHEMBL5653589
5.85	IC50	1420	nM	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-
5.71	Kd	1930	nM	PF-03758309
5.69	Kd	2042	nM	CAPMATINIB
5.57	Kd	2700	nM	FORETINIB
5.55	Kd	2800	nM	TOZASERTIB
5.40	Kd	4000	nM	RG-547
5.39	Kd	4100	nM	RUBOXISTAURIN
5.14	Kd	7300	nM	FEDRATINIB

PubChem BioAssay actives

21 with measured affinity, of 288 total; 20 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148054: Binding affinity to human CDKL5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0014	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	624905: Binding constant for CDKL5 kinase domain	kd	0.0017	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	624905: Binding constant for CDKL5 kinase domain	kd	0.0026	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	624905: Binding constant for CDKL5 kinase domain	kd	0.0066	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	624905: Binding constant for CDKL5 kinase domain	kd	0.0071	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	507873: Binding affinity to CDKL5	kd	0.0100	uM
N-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide	1424951: 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	0.0160	uM
3-[3-[N-[4-[(dimethylamino)methyl]phenyl]-C-phenylcarbonimidoyl]-2-hydroxy-1H-indol-6-yl]-N-ethylprop-2-ynamide	1424951: 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	0.0200	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]chromen-4-one;hydrochloride	1424951: 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	0.0240	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624905: Binding constant for CDKL5 kinase domain	kd	0.2000	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	624905: Binding constant for CDKL5 kinase domain	kd	0.3400	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148054: Binding affinity to human CDKL5 incubated for 45 mins by Kinobead based pull down assay	kd	0.4829	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2R)-1-methoxy-4-methylpentan-2-yl]iminoimidazolidin-4-one	2024495: Inhibition of human CDKL5 assessed as remaining activity by eurofins-cerep kinase profiler analysis	ic50	1.4200	uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	1424951: 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	1.9300	uM
Capmatinib	1424951: 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	2.0420	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	624905: Binding constant for CDKL5 kinase domain	kd	2.7000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	624905: Binding constant for CDKL5 kinase domain	kd	2.8000	uM
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	624905: Binding constant for CDKL5 kinase domain	kd	4.0000	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	624905: Binding constant for CDKL5 kinase domain	kd	4.1000	uM
Fedratinib	624905: Binding constant for CDKL5 kinase domain	kd	7.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, increases methylation	3
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol A	increases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
aflatoxin B2	decreases methylation	1
nickel sulfate	decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Leflunomide	increases expression	1
Amphotericin B	increases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Vehicle Emissions	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Coumestrol	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1

ChEMBL screening assays

74 unique, capped per target: 74 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1168828	Binding	Inhibition of CDKL5 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

14 cell lines: 9 induced pluripotent stem cell, 3 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7JZ	BCHi001-A	Induced pluripotent stem cell	Male
CVCL_A7KB	BCHi002-A	Induced pluripotent stem cell	Female
CVCL_A7KC	BCHi002-B	Induced pluripotent stem cell	Female
CVCL_A7KE	BCHi003-B	Induced pluripotent stem cell	Male
CVCL_A7KG	BCHi004-B	Induced pluripotent stem cell	Male
CVCL_A7KH	BCHi005-A	Induced pluripotent stem cell	Female
CVCL_A7KI	BCHi005-B	Induced pluripotent stem cell	Female
CVCL_A7KJ	BCHi006-A	Induced pluripotent stem cell	Female
CVCL_A7KK	BCHi006-B	Induced pluripotent stem cell	Female
CVCL_D9BQ	Ubigene HEK293 CDKL5 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03963752	PHASE4	COMPLETED	Clinical Trial of Rapid Progressive Central Precocious Puberty With Integrative Chinese and Western Medicine
NCT01413711	PHASE4	WITHDRAWN	An Open-Label, Single and Multiple Oral Dose Pharmacokinetic Study of Vigabatrin in Infants With Infantile Spasms
NCT02092883	PHASE4	COMPLETED	Evaluation of Neuroinflammation in Children With Infantile Spasms
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
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