KCNQ2

Summary

KCNQ2 (potassium voltage-gated channel subfamily Q member 2, HGNC:6296) is a protein-coding gene on chromosome 20q13.33, encoding Potassium voltage-gated channel subfamily KQT member 2 (O43526). Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability. It is haploinsufficient (ClinGen: sufficient evidence).

The M channel is a slowly activating and deactivating potassium channel that plays a critical role in the regulation of neuronal excitability. The M channel is formed by the association of the protein encoded by this gene and a related protein encoded by the KCNQ3 gene, both integral membrane proteins. M channel currents are inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 1 (BFNC), also known as epilepsy, benign neonatal type 1 (EBN1). At least five transcript variants encoding five different isoforms have been found for this gene.

Source: NCBI Gene 3785 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neonatal-onset developmental and epileptic encephalopathy (Definitive, ClinGen) — +9 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 2,462 total — 492 pathogenic, 231 likely-pathogenic
• Phenotypes (HPO): 94
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_172107

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6296
Approved symbol	KCNQ2
Name	potassium voltage-gated channel subfamily Q member 2
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	Kv7.2, ENB1, BFNC, KCNA11, HNSPC
Ensembl gene	ENSG00000075043
Ensembl biotype	protein_coding
OMIM	602235
Entrez	3785

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 25 protein_coding, 24 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000344425, ENST00000344462, ENST00000357249, ENST00000359125, ENST00000360480, ENST00000370221, ENST00000370224, ENST00000482957, ENST00000625514, ENST00000626313, ENST00000626684, ENST00000626717, ENST00000626839, ENST00000627221, ENST00000629241, ENST00000629318, ENST00000629498, ENST00000629676, ENST00000630274, ENST00000635864, ENST00000636042, ENST00000636065, ENST00000636255, ENST00000636499, ENST00000636591, ENST00000636614, ENST00000636623, ENST00000636638, ENST00000636846, ENST00000636858, ENST00000636873, ENST00000636959, ENST00000637063, ENST00000637193, ENST00000637338, ENST00000637573, ENST00000637584, ENST00000637632, ENST00000637639, ENST00000637656, ENST00000637704, ENST00000637772, ENST00000637803, ENST00000637890, ENST00000706989, ENST00000713605, ENST00000713606, ENST00000713658, ENST00000852159, ENST00000852160, ENST00000921678, ENST00000921679, ENST00000921680

RefSeq mRNA: 6 — MANE Select: NM_172107 NM_001382235, NM_004518, NM_172106, NM_172107, NM_172108, NM_172109

CCDS: CCDS13518, CCDS13519, CCDS13520, CCDS13521, CCDS46629

Canonical transcript exons

ENST00000359125 — 17 exons

Exon	Start	End
ENSE00000896770	63408413	63408536
ENSE00000896774	63413450	63413581
ENSE00000896779	63419619	63419672
ENSE00001173651	63414088	63414193
ENSE00001173654	63414903	63415126
ENSE00001173657	63424177	63424206
ENSE00001372803	63400208	63407375
ENSE00003703343	63446747	63446837
ENSE00003704337	63433809	63433903
ENSE00003705696	63428367	63428435
ENSE00003705905	63445238	63445364
ENSE00003706485	63439598	63439708
ENSE00003707888	63444659	63444834
ENSE00003709085	63438625	63438720
ENSE00003709503	63442406	63442531
ENSE00003768310	63472168	63472655
ENSE00003997833	63431340	63431369

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 99.50.

FANTOM5 (CAGE): breadth broad, TPM avg 7.1890 / max 200.6999, expressed in 384 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188348	6.7574	381
188345	0.2097	34
188347	0.1143	41
188346	0.0445	28
188341	0.0256	9
188344	0.0183	6
188342	0.0141	2
188343	0.0050	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.50	gold quality
cerebellar hemisphere	UBERON:0002245	99.35	gold quality
cerebellar cortex	UBERON:0002129	99.26	gold quality
cerebellum	UBERON:0002037	98.87	gold quality
right frontal lobe	UBERON:0002810	97.74	gold quality
right testis	UBERON:0004534	97.70	gold quality
ganglionic eminence	UBERON:0004023	97.59	gold quality
amygdala	UBERON:0001876	97.46	gold quality
left testis	UBERON:0004533	97.37	gold quality
nucleus accumbens	UBERON:0001882	97.34	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.23	gold quality
superior frontal gyrus	UBERON:0002661	96.93	gold quality
caudate nucleus	UBERON:0001873	96.89	gold quality
cingulate cortex	UBERON:0003027	96.86	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.86	gold quality
anterior cingulate cortex	UBERON:0009835	96.83	gold quality
temporal lobe	UBERON:0001871	96.81	gold quality
Ammon’s horn	UBERON:0001954	96.80	gold quality
postcentral gyrus	UBERON:0002581	96.62	gold quality
middle temporal gyrus	UBERON:0002771	96.62	gold quality
putamen	UBERON:0001874	96.52	gold quality
entorhinal cortex	UBERON:0002728	96.47	gold quality
cerebral cortex	UBERON:0000956	96.41	gold quality
parietal lobe	UBERON:0001872	96.23	gold quality
telencephalon	UBERON:0001893	96.16	gold quality
neocortex	UBERON:0001950	96.11	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.09	gold quality
cerebellar vermis	UBERON:0004720	96.07	gold quality
frontal cortex	UBERON:0001870	96.03	gold quality
forebrain	UBERON:0001890	95.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.59
E-MTAB-7303	no	1402.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): REST, SP1

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• Benign familial neonatal convulsions (BFNC) have been previously found to be associated with mutations within the coding region of KCNQ2 (PMID:11726784)
• We investigated whether KCNQ2 gene polymorphisms can be used as markers of susceptibility to febrile convulsions. We found that the KCNQ2 gene might not be a useful marker for prediction of the susceptibility of febrile convulsions. (PMID:12395102)
• A chimaera (KCNQ1-sid(Q3)) carrying the si domain of KCNQ3 within the KCNQ1 backbone interacted with KCNQ2. as shown by enhancement of KCNQ2 currents. (PMID:12524525)
• specific parts of the C-terminus enable the interaction between KCNQ2 and KCNQ3 channels and that different parts of the KCNQ3 C-terminus are important for regulating current amplitude (PMID:12640002)
• Coexpressed KCNQ2 plus KCNQ3 cDNAs generate channels with 1:1 (KCNQ2:KCNQ3) stoichiometry in CHO cells and that native M channels in SCG neurons adopt the same conformation during development (PMID:12832524)
• A heterozygous 1-base pair deletion (2043DeltaT) in the KCNQ2 gene encoding for K+ channel subunits was found in a patient with benign familial neonatal convulsions (PMID:12847176)
• defect in calmodulin binding to mutant KCNQ2 may be one of the pathogenic mechanisms associated with benign familial neonatal seizures (PMID:14985406)
• A novel 2-base pair deletion within the coding sequence of the KCNQ2 gene is detected in patients from a large and heterogeneous family with benign neonatal familial convulsions (BNFCs) or non-BNFC seizures. (PMID:15030501)
• Frameshift mutation in a Chinese family causes benign familial neonatal convulsions. (PMID:15178210)
• The KCNQ2 K526N mutation may affect M-channel function by disrupting the complex biochemical signaling involving KCNQ2 C-terminus. (PMID:15249611)
• Src associates with KCNQ2-5 subunits but phosphorylates only KCNQ3-5. (PMID:15304482)
• After KCNQ2/3 heteromerization, current levels can augment as much as 10-fold, and we have discovered that there are three processes underlying this potentiation. (PMID:15483133)
• 2 heterozygous deletion mutations (c.232delC in EP 70 and c.314_316delCCT in EP 65) & a heterozygous splice site mutation (c.1118 + 1G>A in EP 69)were identified in patients with benign neonatal convulsions. (PMID:15596769)
• the KCNQ2 mutation is responsible for the benign familial neonatal convulsion phenotype, possibly because of haplo-insufficiency, whereas the KCNQ3 variant is functionally silent (PMID:16235065)
• mutation-induced reduced stability of KCNQ2 subunits may cause epilepsy in neonates (PMID:16260777)
• Mutagenesis and electrophysiological studies of the second site, located in the S4-S5 intracellular loop of all KCNQ subunits, reveal a mechanism of channel inhibition (PMID:16319223)
• Genetic interaction between the combined mild alleles of monogenic epilepsy genes KCNQ2 and SCN2A1 results in severe epilepsy in transgenic mice. (PMID:16464983)
• A novel KCNQ2 missense mutation, G271V, in 17 members of a Chinese family with the benign familial infantile seizure phenotype . (PMID:16691402)
• the diacylglycerol produced during activation of phospholipase c, any activation of protein kinase C that it may stimulate, and downstream products of its metabolism are not essential players in the acute muscarinic modulation of KCNQ2/3 channels (PMID:16721610)
• depletion of phosphatidylinositol 4,5-bisphosphate suffices to suppress KCNQ current fully, and other second messengers are not needed (PMID:16990515)
• KCNQ2 mutation exists in patients with benign familial infantile convulsions. (PMID:17044971)
• These data suggest a crucial role of coiled-coil motifs in tetrameric KCNQ channel assembly. (PMID:17382933)
• Gating changes caused by mutations of the noncharged residues at the N-terminal end of KCNQ2 may decrease the slow neuronal potassium M-currents, thus causing neuronal hyperexcitability, ultimately leading to neonatal convulsions. (PMID:17475800)
• 3 deletions & 1 duplication were found in benign familial neonatal seizure cases. Pathogenic intragenic submicroscopic deletions or duplications segregate with the phenotype. (PMID:17675531)
• Intracellular Mg/polyamines inhibit KCNQ2 by electrostatic binding to the negative charges of PIP(2), competitively reducing the amount of free PIP(2) available for interaction with channels. (PMID:17724161)
• mutations in KCNQ2 can cause idiopathic peripheral nerve hyperexcitability (PNH) alone; both K(V)7.2 mutants produce PNH by changing voltage-dependent activation with a dominant negative effect on the wild type channel (PMID:17872363)
• trafficking of KCNQ2(potassium voltage-gated channel, KQT-like subfamily, member 2 protein) potassium channels by calmodulin. (PMID:17993630)
• A novel BFNC-causing mutation (E119G) in the S1-S2 region of KV7.2 (KCNQ2) is identified. (PMID:18006581)
• ICA-27243 is a novel and selective KCNQ2 potassium channel activator. (PMID:18089837)
• high expression of KCNQ2 was identified in the hippocampus, temporal cortex, cerebellar cortex and medulla oblongata in fetal life, but such expression decreased after birth. (PMID:18166285)
• This study reveals a novel missense mutation (N258S) in the KCNQ2 gene between the S5 domain and the pore of the potassium channel in two patients in a Turkish family with benign familial neonatal convulsions. (PMID:18246739)
• Two siblings with BFNC had a novel heterozygous missense mutation, p.R213W, in KCNQ2 (PMID:18353052)
• the inhibition of KCNQ/M currents by histamine in HEK293 cells and SCG neurons is due to the consumption of membrane PIP(2) by PLC. (PMID:18448631)
• Schizophrenia-linked mutation of the kinase results in reduced KCNQ channel function and thereby might explain the loss of dopaminergic control in schizophrenic patients. (PMID:18545987)
• Sequence variations of the KCNQ3 (and KCNQ2)genes may contribute to the etiology of common idiopathic epilepsy syndromes. (PMID:18625963)
• mutations in the SCN1A gene are differentially involved in the pathogenesis of and sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of rare and common idiopathic epilepsy syndromes [review] (PMID:19464834)
• CaM bound to KCNQ2 acts as a Ca2+ sensor, conferring Ca2+ dependence to the trafficking of the channel to the plasma membrane and fully explaining the requirement of CaM binding for KCNQ2 function. (PMID:19494108)
• functionally characterized three Benign Familial Neonatal Convulsions mutations that all show very similar electrophysiological aberrations, although these are due to different biochemical defects (PMID:19559753)
• a novel KCNQ2 mutation c.63-66delGGTG (p.K21fsX40), causing a framework shift and early chain termination, was identified in family members affectd with benign familial neonatal seizures (PMID:19818940)
• KCNQ2 mutation in a family with benign familial neonatal convulsions. (PMID:20119593)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnq2a	ENSDARG00000075307
danio_rerio	kcnq2b	ENSDARG00000091130
mus_musculus	Kcnq2	ENSMUSG00000016346
rattus_norvegicus	Kcnq2	ENSRNOG00000011624

Paralogs (31): KCNG1 (ENSG00000026559), KCNQ1 (ENSG00000053918), KCND1 (ENSG00000102057), KCNA7 (ENSG00000104848), KCNA1 (ENSG00000111262), KCNC4 (ENSG00000116396), KCNQ4 (ENSG00000117013), KCNS1 (ENSG00000124134), KCNC1 (ENSG00000129159), KCNA5 (ENSG00000130037), KCNC3 (ENSG00000131398), KCNA10 (ENSG00000143105), KCNA6 (ENSG00000151079), KCNS2 (ENSG00000156486), KCNB1 (ENSG00000158445), KCNF1 (ENSG00000162975), KCNV1 (ENSG00000164794), KCNC2 (ENSG00000166006), KCNV2 (ENSG00000168263), KCNG4 (ENSG00000168418), KCNS3 (ENSG00000170745), KCNG3 (ENSG00000171126), KCND3 (ENSG00000171385), KCNA3 (ENSG00000177272), KCNA2 (ENSG00000177301), KCNG2 (ENSG00000178342), KCNA4 (ENSG00000182255), KCNB2 (ENSG00000182674), KCNQ3 (ENSG00000184156), KCND2 (ENSG00000184408), KCNQ5 (ENSG00000185760)

Protein

Protein identifiers

Potassium voltage-gated channel subfamily KQT member 2 — O43526 (reviewed: O43526)

Alternative names: KQT-like 2, Neuroblastoma-specific potassium channel subunit alpha KvLQT2, Voltage-gated potassium channel subunit Kv7.2

All UniProt accessions (19): O43526, A0A0D9SEV1, A0A0D9SF10, A0A0D9SFE0, A0A0D9SG49, A0A0D9SGD4, A0A0D9SGG3, A0A0D9SGJ7, A0A0G2JH35, A0A1B0GUK1, A0A1B0GW14, A0A9L9PXL0, A0AAQ5BGD3, A0AAQ5BGE9, A0AAQ5BGF6, A0AAQ5BGI0, A0AAQ5BGK9, Q4VXP6, Q53Y30

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability. M-channel is composed of pore-forming subunits KCNQ2 and KCNQ3 assembled as heterotetramers. The native M-current has a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. KCNQ2-KCNQ3 M-channel is selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+). M-channel association with SLC5A3/SMIT1 alters channel ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+). Suppressed by activation of the muscarinic acetylcholine receptor CHRM1.

Subunit / interactions. Heterotetramer with KCNQ3; forms heterotetrameric M-channel responsible for the native M-current. Homotetrameric; forms a functional homotetrameric channel resulting in the expression of a small M-current. Interacts with calmodulin; the interaction is calcium-independent, constitutive and participates in the proper assembly of a functional M-channel. May associate with KCNE2. Interacts with IQCJ-SCHIP1. Interacts (via the pore module) with SLC5A3/SMIT1; forms a coregulatory complex that alters ion selectivity, voltage dependence and gating kinetics of the channel. Interacts with AKAP5; the interaction may help KCNQ2 channel complex to retain calcium-bound calmodulin.

Subcellular location. Cell membrane.

Tissue specificity. In adult and fetal brain. Highly expressed in areas containing neuronal cell bodies, low in spinal cord and corpus callosum. Isoform 2 is preferentially expressed in differentiated neurons. Isoform 6 is prominent in fetal brain, undifferentiated neuroblastoma cells and brain tumors.

Post-translational modifications. KCNQ2/KCNQ3 heteromeric current can be increased by intracellular cyclic AMP, an effect that depends on phosphorylation of Ser-52 in the N-terminal region. KCNQ2/KCNQ3 are ubiquitinated by NEDD4L. Ubiquitination leads to protein degradation. Degradation induced by NEDD4L is inhibited by USP36.

Disease relevance. Seizures, benign familial neonatal 1 (BFNS1) [MIM:121200] A disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age and show normal psychomotor development. Some rare cases manifest an atypical severe phenotype associated with epileptic encephalopathy and psychomotor retardation. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset. In some patients, neonatal convulsions are followed later in life by myokymia, a benign condition characterized by spontaneous involuntary contractions of skeletal muscles fiber groups that can be observed as vermiform movement of the overlying skin. Electromyography typically shows continuous motor unit activity with spontaneous oligo- and multiplet-discharges of high intraburst frequency (myokymic discharges). Some patients may have isolated myokymia. The disease is caused by variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 7 (DEE7) [MIM:613720] An autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Phosphatidylinositol-4,5-bisphosphate (PIP2) potentiates the activation of KCNQ channels by enhancing the electro-mechanical coupling of the voltage-sensing domain (VSD) and the pore-forming domain (PD). In the closed state of the channel, PIP2 is anchored at the S2-S3 loop; upon channel activation, PIP2 interacts with the S4-S5 linker and is involved in channel gating. Calcium suppresses KCNQ2 and KCNQ2-KCNQ3 channel currents, with calcium-bound calmodulin inducing a change in channel configuration which leads to the reduction of channel affinity for PIP2 and subsequent current suppression. M-channel is blocked by linopirdine and XE991, and activated by the anticonvulsants ztz240 and retigabine.

Domain organisation. Each subunit contains six transmembrane segments (S1-S6) with S1-S4 forming one voltage sensing domain (VSD) and S5-S6 contributing to form one quarter of an interlocking pore-forming domain (PD). The S4-S5 linker preferentially interacts with PIP2 in the open-state KCNQ2 channel, whereas the S2-S3 loop interacts with PIP2 in the closed state. The intracellular C-terminal domain is bound constitutively by calmodulin (CaM). This domain plays key functions in channel tetramerization, trafficking, and gating.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Inclusion of isoform 6 in heteromultimers results in attenuation of potassium current. Prominent expression of isoform 6 in the developing brain may alter firing repertoires of immature neurons excitability to provide cues for proliferation rather than differentiation.

Similarity. Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.2/KCNQ2 sub-subfamily.

Isoforms (6)

UniProt ID	Names	Canonical?
O43526-1	1	yes
O43526-2	2
O43526-3	3
O43526-4	4
O43526-5	5
O43526-6	6, HNSPC

RefSeq proteins (6): NP_001369164, NP_004509, NP_742104, NP_742105, NP_742106, NP_742107 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003937	K_chnl_volt-dep_KCNQ	Family
IPR003947	K_chnl_volt-dep_KCNQ2	Family
IPR005821	Ion_trans_dom	Domain
IPR013821	K_chnl_volt-dep_KCNQ_C	Domain
IPR020969	Ankyrin-G_BS	Binding_site

Pfam: PF00520, PF03520, PF11956, PF16642

Catalyzed reactions (Rhea), 4 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• Rb(+)(in) = Rb(+)(out) (RHEA:78547)
• Cs(+)(in) = Cs(+)(out) (RHEA:78555)

UniProt features (127 total): sequence variant 42, helix 16, mutagenesis site 11, modified residue 11, topological domain 8, region of interest 8, splice variant 7, transmembrane region 6, strand 5, compositionally biased region 3, binding site 3, sequence conflict 2, turn 2, chain 1, intramembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

39 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5J03	X-RAY DIFFRACTION	2
22AY	ELECTRON MICROSCOPY	2.3
22BJ	ELECTRON MICROSCOPY	2.4
22BF	ELECTRON MICROSCOPY	2.5
22BG	ELECTRON MICROSCOPY	2.5
8IZY	ELECTRON MICROSCOPY	2.5
22BE	ELECTRON MICROSCOPY	2.6
22BI	ELECTRON MICROSCOPY	2.6
22AZ	ELECTRON MICROSCOPY	2.7
22BK	ELECTRON MICROSCOPY	2.7
8J03	ELECTRON MICROSCOPY	2.7
8J04	ELECTRON MICROSCOPY	2.7
8J05	ELECTRON MICROSCOPY	2.7
22BC	ELECTRON MICROSCOPY	2.8
22BH	ELECTRON MICROSCOPY	2.8
22BA	ELECTRON MICROSCOPY	2.9
9L8W	ELECTRON MICROSCOPY	2.9
22BD	ELECTRON MICROSCOPY	3
8J00	ELECTRON MICROSCOPY	3
8X43	ELECTRON MICROSCOPY	3
9X5J	ELECTRON MICROSCOPY	3.05
7CR0	ELECTRON MICROSCOPY	3.1
8J01	ELECTRON MICROSCOPY	3.1
9IXY	ELECTRON MICROSCOPY	3.1
9XB9	ELECTRON MICROSCOPY	3.1
9X65	ELECTRON MICROSCOPY	3.19
7CR2	ELECTRON MICROSCOPY	3.2
9IXZ	ELECTRON MICROSCOPY	3.2
8W4U	ELECTRON MICROSCOPY	3.3
7CR1	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43526-F1	59.27	0.22

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 214; 230; 327

Post-translational modifications (11): 52, 217, 466, 468, 472, 476, 478, 507, 672, 801, 803

Mutagenesis-validated functional residues (11):

Position	Phenotype
327	decreased voltage sensitivity of kncq2 channel. no difference in pip2 sensitivity.
331	no difference in pip2 sensitivity.
52	40% increase in potassium current amplitude. ratio of 1:1.
52	decrease of pka stimulation. ratio of 1:1.
87	no change in voltage activation of kncq2 channel.
89	increased voltage sensitivity of kncq2 channel.
162	decreased current amplitude; reduced sensitivity to pip2. does not alter the voltage sensitivity of the channel.
214	no change in voltage activation of kncq2 channel.
217	abolishes currents without reducing channel protein expression.
230	reduced sensitivity to pip2 and voltage sensitivity of kcnq2 channel.
279	more than 50% reduction of wt heteromeric current. ratio of 1:1 and 1:1:2.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1296072	Voltage gated Potassium channels
R-HSA-445095	Interaction between L1 and Ankyrins
R-HSA-112316	Neuronal System
R-HSA-1266738	Developmental Biology
R-HSA-1296071	Potassium Channels
R-HSA-373760	L1CAM interactions
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 299 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GNF2_RTN1, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, TGCACTT_MIR519C_MIR519B_MIR519A, REACTOME_POTASSIUM_CHANNELS, PRAMOONJAGO_SOX4_TARGETS_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, MODULE_213, GOBP_SYNAPTIC_SIGNALING, FONTAINE_PAPILLARY_THYROID_CARCINOMA_DN, GOCC_NEURON_PROJECTION, ULE_SPLICING_VIA_NOVA2, GNF2_RAB3A, TGCCTTA_MIR124A

GO Biological Process (8): action potential (GO:0001508), chemical synaptic transmission (GO:0007268), nervous system development (GO:0007399), potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (7): voltage-gated potassium channel activity (GO:0005249), calmodulin binding (GO:0005516), voltage-gated monoatomic cation channel activity (GO:0022843), ankyrin binding (GO:0030506), monoatomic ion channel activity (GO:0005216), potassium channel activity (GO:0005267), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020), node of Ranvier (GO:0033268), axon initial segment (GO:0043194), synapse (GO:0045202), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Potassium Channels	1
L1CAM interactions	1
Neuronal System	1
Axon guidance	1
Nervous system development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
transport	2
monoatomic cation channel activity	2
main axon	2
regulation of membrane potential	1
anterograde trans-synaptic signaling	1
system development	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
potassium channel activity	1
voltage-gated monoatomic cation channel activity	1
protein binding	1
voltage-gated monoatomic ion channel activity	1
cytoskeletal protein binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
potassium ion transmembrane transporter activity	1
binding	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
cell junction	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

3354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNQ2	KCNQ3	O43525	984
KCNQ2	KCNQ5	Q9NR82	966
KCNQ2	CALML3	P27482	953
KCNQ2	CALML5	Q9NZT1	953
KCNQ2	CALML6	Q8TD86	951
KCNQ2	CALML4	Q96GE6	951
KCNQ2	ANK3	Q12955	910
KCNQ2	SCN8A	Q9UQD0	906
KCNQ2	CHRNA4	P43681	899
KCNQ2	CALM1	P02593	891
KCNQ2	SCN2A	Q99250	887
KCNQ2	SCN1A	P35498	882
KCNQ2	PCDH19	Q8TAB3	869
KCNQ2	KCNE1	P15382	849
KCNQ2	STXBP1	P61764	845

IntAct

7 interactions, top by confidence:

A	B	Type	Score
KCNQ2	GOLM1	psi-mi:“MI:0915”(physical association)	0.400
GIGYF1	DYNC1I1	psi-mi:“MI:0914”(association)	0.350
GRIK1	KCNQ2	psi-mi:“MI:0915”(physical association)	0.000
BTG3	KCNQ2	psi-mi:“MI:0915”(physical association)	0.000
ARIH2	KCNQ2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): GOLM1 (Affinity Capture-MS), GOLM1 (Affinity Capture-MS), KCNQ2 (Affinity Capture-RNA), KCNQ2 (Affinity Capture-Western), KCNQ2 (Two-hybrid), P4HB (Proximity Label-MS), KCNQ2 (Affinity Capture-Western), CALM2 (Two-hybrid), CALM3 (Two-hybrid), GOLM1 (Affinity Capture-MS), KCNQ2 (PCA), KCNQ2 (Affinity Capture-RNA), KCNQ2 (Two-hybrid), KCNQ2 (Two-hybrid), CALM1 (Reconstituted Complex)

ESM2 similar proteins: A6H8H5, B1WAZ8, O18868, O43525, O43526, O54928, O70344, O75159, O88866, O88943, O88944, O95279, P15385, P15387, P19024, P22462, P51787, P56696, P57058, Q03717, Q14721, Q14B80, Q3UUF8, Q4ZHA6, Q5JV73, Q61762, Q62897, Q63099, Q68UT7, Q76N89, Q8K3F6, Q8K4P8, Q92831, Q92953, Q95167, Q95L11, Q96PR1, Q9JHD1, Q9JK45, Q9JK96

Diamond homologs: A4K2M4, A4K2P6, A4K2T1, A4K2Y2, A6H8H5, B2RQA1, G5EFC3, O18868, O35174, O43526, O88759, O88943, O97531, P08510, P10499, P15384, P15385, P15387, P15388, P16388, P16389, P16390, P17658, P17659, P17970, P17971, P17972, P19024, P22001, P22459, P22460, P22462, P22739, P25122, P48547, P50638, P56696, P59994, P59995, P63141

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
ezogabine	up-regulates	KCNQ2	“chemical activation”
KCNQ2	“up-regulates quantity”	potassium(1+)	relocalization
KCNQ3	“up-regulates activity”	KCNQ2	binding
KCNQ2	“up-regulates activity”	KCNQ3	binding
PRKCA	“up-regulates activity”	KCNQ2	phosphorylation
PRKCA	“up-regulates quantity”	KCNQ2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

2462 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	492
Likely pathogenic	231
Uncertain significance	669
Likely benign	626
Benign	124

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1020770	NM_172107.4(KCNQ2):c.560C>T (p.Ser187Phe)	Pathogenic
1022833	NC_000020.10:g.(?_62081939)_62119720del	Pathogenic
1029260	NM_172107.4(KCNQ2):c.1420G>T (p.Glu474Ter)	Pathogenic
1034352	NM_172107.4(KCNQ2):c.1160dup (p.Leu388fs)	Pathogenic
1066163	NM_172107.4(KCNQ2):c.1024-2A>C	Pathogenic
1069867	NC_000020.10:g.(?_61952107)_62044936del	Pathogenic
1069870	NC_000020.10:g.(?62069968)(62078200_?)del	Pathogenic
1069909	NM_172107.4(KCNQ2):c.2568_2574del (p.Thr857fs)	Pathogenic
1070673	NM_172107.4(KCNQ2):c.1006_1009dup (p.Ala337fs)	Pathogenic
1071234	NM_172107.4(KCNQ2):c.1966del (p.Glu656fs)	Pathogenic
1071549	NM_172107.4(KCNQ2):c.1114dup (p.Tyr372fs)	Pathogenic
1071682	NM_172107.4(KCNQ2):c.699_709del (p.Thr234fs)	Pathogenic
1072506	NM_172107.4(KCNQ2):c.653G>A (p.Trp218Ter)	Pathogenic
1073519	NM_172107.4(KCNQ2):c.1118+2T>G	Pathogenic
1073750	NC_000020.10:g.(?62046246)(62055569_?)del	Pathogenic
1073751	NC_000020.10:g.(?62037977)(62051045_?)del	Pathogenic
1073752	NC_000020.10:g.(?62037997)(62046489_?)del	Pathogenic
1073802	NM_172107.4(KCNQ2):c.2305G>T (p.Glu769Ter)	Pathogenic
1074100	NM_172107.4(KCNQ2):c.437G>A (p.Trp146Ter)	Pathogenic
1074630	NM_172107.4(KCNQ2):c.1064A>G (p.Asp355Gly)	Pathogenic
1074752	NM_172107.4(KCNQ2):c.734T>C (p.Leu245Pro)	Pathogenic
1074881	NM_172107.4(KCNQ2):c.1056_1057delinsCG (p.Arg353Gly)	Pathogenic
1075006	NM_172107.4(KCNQ2):c.195_196del (p.Lys66fs)	Pathogenic
1076179	NM_172107.4(KCNQ2):c.1217+2_1217+3delinsAG	Pathogenic
1076431	NM_172107.4(KCNQ2):c.1113del (p.Met371fs)	Pathogenic
1076678	NM_172107.4(KCNQ2):c.792C>A (p.Tyr264Ter)	Pathogenic
1076681	NM_172107.4(KCNQ2):c.493dup (p.Arg165fs)	Pathogenic
1164059	NM_172107.4(KCNQ2):c.878T>C (p.Leu293Pro)	Pathogenic
1175996	NM_172107.4(KCNQ2):c.2403del (p.Phe802fs)	Pathogenic
1175998	NM_172107.4(KCNQ2):c.816+1G>T	Pathogenic

SpliceAI

5153 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63408408:CGCAC:C	donor_loss	1.0000
20:63408412:C:G	donor_loss	1.0000
20:63408412:CCTG:C	donor_gain	1.0000
20:63408542:G:T	acceptor_gain	1.0000
20:63413577:TGACA:T	acceptor_gain	1.0000
20:63413578:GACA:G	acceptor_gain	1.0000
20:63413579:ACA:A	acceptor_gain	1.0000
20:63413579:ACAC:A	acceptor_loss	1.0000
20:63413580:CA:C	acceptor_gain	1.0000
20:63413580:CAC:C	acceptor_gain	1.0000
20:63413582:C:CA	acceptor_loss	1.0000
20:63413582:C:CC	acceptor_gain	1.0000
20:63413583:T:G	acceptor_loss	1.0000
20:63414087:CCACA:C	donor_gain	1.0000
20:63414189:TGCTT:T	acceptor_gain	1.0000
20:63414191:CTT:C	acceptor_gain	1.0000
20:63414192:TT:T	acceptor_gain	1.0000
20:63414192:TTCT:T	acceptor_loss	1.0000
20:63414193:TCTG:T	acceptor_loss	1.0000
20:63414194:C:A	acceptor_loss	1.0000
20:63414194:C:CC	acceptor_gain	1.0000
20:63415143:C:CT	acceptor_gain	1.0000
20:63415144:G:T	acceptor_gain	1.0000
20:63433899:GCCGA:G	acceptor_gain	1.0000
20:63433900:CCGA:C	acceptor_gain	1.0000
20:63433900:CCGAC:C	acceptor_gain	1.0000
20:63433901:CGA:C	acceptor_gain	1.0000
20:63433901:CGAC:C	acceptor_gain	1.0000
20:63433904:C:CC	acceptor_gain	1.0000
20:63439593:CTT:C	donor_loss	1.0000

AlphaMissense

5661 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63407344:A:G	L640P	1.000
20:63407353:A:G	L637P	1.000
20:63413459:A:G	L585P	1.000
20:63413459:A:T	L585Q	1.000
20:63413468:A:C	I582S	1.000
20:63413468:A:G	I582T	1.000
20:63413468:A:T	I582N	1.000
20:63413471:C:G	R581P	1.000
20:63413477:A:G	L579P	1.000
20:63413477:A:T	L579Q	1.000
20:63413479:C:A	M578I	1.000
20:63413479:C:G	M578I	1.000
20:63413479:C:T	M578I	1.000
20:63413480:A:C	M578R	1.000
20:63413480:A:G	M578T	1.000
20:63413480:A:T	M578K	1.000
20:63413486:A:G	L576P	1.000
20:63413488:G:C	H575Q	1.000
20:63413488:G:T	H575Q	1.000
20:63413489:T:C	H575R	1.000
20:63413490:G:C	H575D	1.000
20:63413492:C:A	G574V	1.000
20:63413492:C:T	G574D	1.000
20:63413493:C:A	G574C	1.000
20:63413493:C:G	G574R	1.000
20:63413495:G:T	A573D	1.000
20:63413499:A:G	S572P	1.000
20:63413501:T:C	Y571C	1.000
20:63413501:T:G	Y571S	1.000
20:63413502:A:C	Y571D	1.000

dbSNP variants (sampled 300 via entrez): RS1000026442 (20:63466537 C>T), RS1000091281 (20:63454782 G>A), RS1000099831 (20:63420378 C>G,T), RS1000209365 (20:63470713 T>C), RS1000224048 (20:63404712 C>G), RS1000226658 (20:63434482 C>A), RS1000268647 (20:63407941 C>T), RS1000314289 (20:63444078 GC>G), RS1000345453 (20:63443864 T>C), RS1000345827 (20:63428990 G>A,C), RS1000393622 (20:63462391 G>A), RS1000457259 (20:63449358 G>A), RS1000481094 (20:63453794 C>T), RS1000493005 (20:63465894 A>G), RS1000507939 (20:63433470 C>T)

Disease associations

OMIM: gene MIM:602235 | disease phenotypes: MIM:613720, MIM:121200, MIM:619681, MIM:300672, MIM:308350, MIM:121201, MIM:615024

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 7	Definitive	Autosomal dominant
seizures, benign familial neonatal, 1	Definitive	Autosomal dominant
seizures, benign familial neonatal, 2	Strong	Autosomal dominant
complex neurodevelopmental disorder	Strong	Autosomal dominant
neonatal-onset developmental and epileptic encephalopathy	Strong	Autosomal dominant
benign familial neonatal-infantile seizures	Supportive	Autosomal dominant
benign neonatal seizures	Supportive	Autosomal dominant
malignant migrating partial seizures of infancy	Supportive	Autosomal dominant
benign familial infantile epilepsy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (3)

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

Disease	Classification	Inheritance
neonatal-onset developmental and epileptic encephalopathy	Definitive	AD
neonatal encephalopathy with non-epileptic myoclonus	Definitive	AD
complex neurodevelopmental disorder	Definitive	AD

Mondo (21): early-infantile DEE (MONDO:0800491), developmental and epileptic encephalopathy, 7 (MONDO:0013387), developmental and epileptic encephalopathy (MONDO:0100620), seizures, benign familial neonatal, 1 (MONDO:0007365), intellectual disability (MONDO:0001071), dystonia, early-onset, and/or spastic paraplegia (MONDO:0859215), developmental and epileptic encephalopathy, 2 (MONDO:0010396), infantile spasms (MONDO:0018097), neurodevelopmental disorder (MONDO:0700092), developmental and epileptic encephalopathy, 1 (MONDO:0010632), benign neonatal seizures (MONDO:0016027), seizures, benign familial neonatal, 2 (MONDO:0007366), autosomal recessive congenital ichthyosis 10 (MONDO:0014011), complex neurodevelopmental disorder (MONDO:0100038), autism spectrum disorder (MONDO:0005258)

Orphanet (13): Early infantile developmental and epileptic encephalopathy (Orphanet:1934), KCNQ2-related developmental and epileptic encephalopathy (Orphanet:439218), Self-limited neonatal epilepsy (Orphanet:1949), West syndrome (Orphanet:3451), CDKL5-deficiency disorder (Orphanet:505652), Infantile epileptic spasms syndrome (Orphanet:697160), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Congenital ichthyosiform erythroderma (Orphanet:79394), Non-specific syndromic intellectual disability (Orphanet:528084), Neonatal-infantile onset epilepsy syndrome (Orphanet:693802), Early myoclonic encephalopathy (Orphanet:1935), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

94 total (30 of 94 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000505	Visual impairment
HP:0000826	Precocious puberty
HP:0000961	Cyanosis
HP:0000980	Pallor
HP:0001041	Facial erythema
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001268	Mental deterioration
HP:0001270	Motor delay
HP:0001273	Abnormal corpus callosum morphology
HP:0001276	Hypertonia
HP:0001285	Spastic tetraparesis
HP:0001332	Dystonia
HP:0001350	Slurred speech
HP:0001508	Failure to thrive
HP:0002018	Nausea
HP:0002020	Gastroesophageal reflux
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure
HP:0002072	Chorea
HP:0002079	Hypoplasia of the corpus callosum
HP:0002104	Apnea
HP:0002121	Generalized non-motor (absence) seizure
HP:0002131	Episodic ataxia
HP:0002133	Status epilepticus

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008103_74	Bipolar disorder	8.000000e-07
GCST008115_28	Bipolar I disorder	3.000000e-07
GCST008764_7	Perceived intensity of neohesperidin dihydrochalcone	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009963	bipolar I disorder

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C564064	CDKL5 deficiency disorder (supp.)
C567743	Epilepsy, Benign Neonatal, 1, And-Or Myokymia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2221348 (PROTEIN COMPLEX), CHEMBL2362996 (PROTEIN FAMILY), CHEMBL2363063 (PROTEIN FAMILY), CHEMBL2476 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 9,891 (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
CHEMBL255044	FLUPIRTINE	4	5,706
CHEMBL41355	EZOGABINE	4	3,996
CHEMBL266510	FLINDOKALNER	3	74
CHEMBL5095264	AZETUKALNER	3	115

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: vgic — Voltage-gated potassium channels (K_v)

Most potent curated ligand interactions (15 total), top 15:

Ligand	Action	Affinity	Parameter
ML252	Inhibitor	7.15	pIC50
ztz240	Activator	6.7	pEC50
ICA-27243	Activator	6.3	pEC50
QO-58	Activator	6.3	pEC50
ICA-069673	Activator	6.16	pEC50
XE991	Inhibitor	6.15	pIC50
L735821	Channel blocker	5.8	pIC50
zinc pyrithione	Activator	5.8	pEC50
retigabine	Activation	5.6	pEC50
(S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide	Activator	5.5	pEC50
linopirdine	Inhibitor	5.3	pIC50
flindokalner	Activator	5.0	pEC50
flupirtine	Activator	5.0	pEC50
tetraethylammonium	Channel blocker	3.9	pIC50
PIP2	Activator	3.7	pEC50

Binding affinities (BindingDB)

14 measured of 16 human assays (16 total across all organisms); most potent 14 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL598553	EC50	21 nM
CHEMBL599164	EC50	25 nM
CHEMBL598126	EC50	27 nM
CHEMBL604937	EC50	28 nM
CHEMBL599781	EC50	53 nM
CHEMBL596909	EC50	91 nM
CHEMBL591203	EC50	98 nM
1-[[2-(difluoromethoxy)-4-pyridinyl]methyl]-3-(2-fluorospiro[3.3]heptan-6-yl)urea	EC50	150 nM	US-20240316020: Novel Pyridine Compounds
CHEMBL603662	EC50	160 nM
CHEMBL599365	EC50	160 nM
CHEMBL603661	EC50	380 nM
CHEMBL597329	EC50	570 nM
CHEMBL603667	EC50	2080 nM
CHEMBL603874	EC50	2700 nM

ChEMBL bioactivities

308 potent at pChembl≥5 of 327 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.82	Ki	0.15	nM	CHEMBL5722941
9.74	IC50	0.18	nM	CHEMBL5722941
8.85	EC50	1.4	nM	CHEMBL6147947
8.25	EC50	5.623	nM	CHEMBL6148875
8.19	EC50	6.457	nM	CHEMBL6170048
8.10	EC50	8	nM	CHEMBL5783396
8.02	EC50	9.55	nM	CHEMBL6143552
8.01	EC50	9.8	nM	CHEMBL5412763
8.00	EC50	10	nM	CHEMBL2047506
7.96	EC50	10.96	nM	CHEMBL6151161
7.95	EC50	11.22	nM	CHEMBL6162279
7.92	EC50	12	nM	CHEMBL6151161
7.92	EC50	12.02	nM	CHEMBL6151161
7.87	EC50	13.49	nM	CHEMBL6143040
7.77	EC50	17	nM	CHEMBL6150442
7.77	EC50	16.98	nM	CHEMBL6150442
7.75	EC50	18	nM	CHEMBL4458793
7.73	EC50	18.62	nM	CHEMBL6150563
7.73	EC50	18.62	nM	CHEMBL6164400
7.70	EC50	20	nM	CHEMBL4250878
7.70	EC50	20	nM	CHEMBL4238783
7.70	EC50	20	nM	CHEMBL4278049
7.68	EC50	21	nM	CHEMBL598553
7.64	EC50	23	nM	CHEMBL6004216
7.64	EC50	23	nM	CHEMBL592297
7.62	EC50	24	nM	CHEMBL3621438
7.60	EC50	25	nM	CHEMBL599164
7.57	EC50	26.92	nM	CHEMBL6145412
7.57	EC50	27	nM	CHEMBL598126
7.55	EC50	28.18	nM	CHEMBL6150442
7.55	EC50	28	nM	CHEMBL604937
7.55	EC50	28	nM	CHEMBL599374
7.54	EC50	29	nM	CHEMBL589898
7.52	EC50	30	nM	CHEMBL2047511
7.52	EC50	30	nM	CHEMBL4250403
7.47	EC50	34	nM	CHEMBL4247074
7.43	EC50	37	nM	CHEMBL4093377
7.43	EC50	37	nM	CHEMBL4062193
7.42	EC50	38.02	nM	CHEMBL6144404
7.42	EC50	38.02	nM	CHEMBL6171400
7.40	EC50	40	nM	CHEMBL3621449
7.40	EC50	40	nM	CHEMBL4247002
7.40	EC50	40	nM	CHEMBL4276984
7.40	EC50	40	nM	CHEMBL1703636
7.36	EC50	44	nM	CHEMBL609624
7.36	EC50	44	nM	CHEMBL591302
7.34	EC50	45.71	nM	CHEMBL6141883
7.32	IC50	48	nM	CHEMBL343822
7.31	EC50	49	nM	CHEMBL5927703
7.31	EC50	49	nM	CHEMBL599376

PubChem BioAssay actives

254 with measured affinity, of 745 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[(1R,2aS,4S,5aS,8aS,10S,11aR,14aS,16S,17aS,19S,20aS,22S,23aS,25S,26aS,28S,29aS,31R,32aS,35aS,36R,38aS,39S,41aS,42S,44aS,45S,48R,50aS,51S,53aS,54S,56aS,57S,59aS,60S,63S,66S,69S,72S,75S,78S,87R,93S,96S,99S)-17a,20a,23a,53a,63-pentakis(4-aminobutyl)-31-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(2S)-5-carbamimidamido-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]pentanoyl]amino]pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-16,29a,72,78-tetrakis(2-amino-2-oxoethyl)-14a,26a-bis(3-amino-3-oxopropyl)-2a,38a,66-tribenzyl-28,50a,57-tris[(2S)-butan-2-yl]-4,5a,19,42,45,69-hexakis(3-carbamimidamidopropyl)-51,54-bis(2-carboxyethyl)-56a,99-bis(carboxymethyl)-36-[[(2S,3S)-1-(carboxymethylamino)-3-methyl-1-oxopentan-2-yl]carbamoyl]-39,60-bis[(1R)-1-hydroxyethyl]-75,93-bis(hydroxymethyl)-32a,35a,59a-tris[(4-hydroxyphenyl)methyl]-22-(1H-imidazol-4-ylmethyl)-96-(1H-indol-3-ylmethyl)-41a-methyl-25-(2-methylpropyl)-1a,3,4a,6,7a,9,10a,13a,15,16a,18,19a,21,22a,24,25a,27,28a,30,31a,34a,37a,38,40a,41,43a,44,47,49a,50,52a,53,55a,56,58a,59,61a,62,65,68,71,74,77,80,83,86,89,92,95,98-pentacontaoxo-33,34,63a,64a,67a,68a-hexathia-a,2,3a,5,6a,8,9a,12a,14,15a,17,18a,20,21a,23,24a,26,27a,29,30a,33a,36a,37,39a,40,42a,43,46,48a,49,51a,52,54a,55,57a,58,60a,61,64,67,70,73,76,79,82,85,88,91,94,97-pentacontazapentacyclo[85.74.4.448,111.010,14.0144,148]nonahexacontahectan-8a-yl]propanoic acid	2198828: Binding affinity to KV channel (unknown origin) assessed as inhibition constant	ki	0.0001	uM
N-[4-(2-bromo-6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide	2030288: Agonist activity at Kv7.2/Kv7.3 (unknown origin) expressed in human HEK293 cells by whole cell patch clamp assay	ec50	0.0098	uM
N-(6-chloro-3-pyridinyl)-4-phenoxybenzamide	669435: Agonist activity at KCNQ2/KCNQ3 expressed in CHO cells assessed as increase in KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ec50	0.0100	uM
cyclopropyl N-[2-amino-3-fluoro-4-[[4-(trifluoromethyl)phenyl]methylamino]phenyl]carbamate	1861512: Agonist activity at Kv7.2/3 (unknown origin) expressed in CHO cells co-expressing GFP	ec50	0.0180	uM
N-[(1R)-2-hydroxy-1-(3-methylsulfonylphenyl)ethyl]-5-(pentafluoro-lambda6-sulfanyl)-2-phenoxybenzamide	1414246: Activation of human Kv7.2/7.3 by patch clamp method	ec50	0.0200	uM
N-[4-(5,7-dihydro-4H-thieno[2,3-c]pyridin-6-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide	1398549: Channel opening activity at KCNQ2 (unknown origin) expressed in CHO cells after 10 mins by atomic absorption spectrophotometry-based Rb+ flow assay	ec50	0.0200	uM
N-[4-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide	1398549: Channel opening activity at KCNQ2 (unknown origin) expressed in CHO cells after 10 mins by atomic absorption spectrophotometry-based Rb+ flow assay	ec50	0.0200	uM
N-[(Z)-(5,6-difluoro-3-methyl-1,3-benzothiazol-2-ylidene)amino]adamantane-1-carboxamide	461899: Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	ec50	0.0210	uM
tert-butyl N-[(Z)-[3-methyl-6-(trifluoromethoxy)-1,3-benzothiazol-2-ylidene]amino]carbamate	461899: Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	ec50	0.0230	uM
N-(4,6-dimethoxy-2-thiomorpholin-4-ylpyrimidin-5-yl)-3,3-dimethylbutanamide	1249421: Activation of human Kv7.2/7.3 expressed in CHOK1 cells	ec50	0.0240	uM
N-[(Z)-[3-methyl-6-(trifluoromethoxy)-1,3-benzothiazol-2-ylidene]amino]adamantane-1-carboxamide	461899: Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	ec50	0.0250	uM
N-[(Z)-(3-methyl-1,3-benzothiazol-2-ylidene)amino]adamantane-1-carboxamide	461899: Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	ec50	0.0270	uM
N-[(Z)-(6-fluoro-3-methyl-1,3-benzothiazol-2-ylidene)amino]adamantane-1-carboxamide	461899: Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	ec50	0.0280	uM
N-[(Z)-[3-methyl-6-(trifluoromethoxy)-1,3-benzothiazol-2-ylidene]amino]cyclohexanecarboxamide	461899: Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	ec50	0.0280	uM
cyclopentyl N-[(Z)-[3-methyl-6-(trifluoromethoxy)-1,3-benzothiazol-2-ylidene]amino]carbamate	461899: Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	ec50	0.0290	uM
N-[2,6-dimethyl-4-(2-methyl-5,7-dihydro-4H-thieno[2,3-c]pyridin-6-yl)phenyl]-3,3-dimethylbutanamide	1398549: Channel opening activity at KCNQ2 (unknown origin) expressed in CHO cells after 10 mins by atomic absorption spectrophotometry-based Rb+ flow assay	ec50	0.0300	uM
N-(6-chloro-3-pyridinyl)-3-fluoro-4-phenoxybenzamide	669435: Agonist activity at KCNQ2/KCNQ3 expressed in CHO cells assessed as increase in KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ec50	0.0300	uM
N-[4-(3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide	1398549: Channel opening activity at KCNQ2 (unknown origin) expressed in CHO cells after 10 mins by atomic absorption spectrophotometry-based Rb+ flow assay	ec50	0.0340	uM
N-(3,4-difluorophenyl)-6-(trifluoromethoxy)-1H-pyrazolo[4,3-b]pyridin-3-amine	1454473: Activation of KCNQ2/3 (unknown origin)	ec50	0.0370	uM
N-(6-chloro-3-pyridinyl)-6-(trifluoromethyl)-1H-indazol-3-amine	1454473: Activation of KCNQ2/3 (unknown origin)	ec50	0.0370	uM
3-cyclopentyl-N-[4,6-dimethoxy-2-(4-methoxypiperidin-1-yl)pyrimidin-5-yl]propanamide	1249421: Activation of human Kv7.2/7.3 expressed in CHOK1 cells	ec50	0.0400	uM
N-[2,6-dimethyl-4-(7-methyl-2,3,4,5-tetrahydro-1-benzazepin-1-yl)phenyl]-3,3-dimethylbutanamide	1398549: Channel opening activity at KCNQ2 (unknown origin) expressed in CHO cells after 10 mins by atomic absorption spectrophotometry-based Rb+ flow assay	ec50	0.0400	uM
N-[(1S)-1-(3-methylsulfonylphenyl)ethyl]-2-phenoxy-5-(trifluoromethyl)benzamide	1414246: Activation of human Kv7.2/7.3 by patch clamp method	ec50	0.0400	uM
N-(2,4,6-trimethylphenyl)bicyclo[2.2.1]heptane-2-carboxamide	1414246: Activation of human Kv7.2/7.3 by patch clamp method	ec50	0.0400	uM
2-cyclopentyl-N-[(Z)-[3-methyl-6-(trifluoromethoxy)-1,3-benzothiazol-2-ylidene]amino]acetamide	461899: Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	ec50	0.0440	uM
4-fluoro-N-[(Z)-[3-methyl-6-(trifluoromethoxy)-1,3-benzothiazol-2-ylidene]amino]benzamide	461899: Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	ec50	0.0440	uM
10,10-bis[(2-fluoro-4-pyridinyl)methyl]anthracen-9-one	1611064: Inhibition of Kv7.2 in human HEK293 cells incubated for 1 hr by thallium flux assay	ic50	0.0480	uM
3,3-dimethyl-N-[(Z)-[3-methyl-6-(trifluoromethoxy)-1,3-benzothiazol-2-ylidene]amino]butanamide	461899: Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	ec50	0.0490	uM
N-[2-(4,4-difluoropiperidin-1-yl)-4,6-dimethoxypyrimidin-5-yl]-3,3-dimethylbutanamide	1249421: Activation of human Kv7.2/7.3 expressed in CHOK1 cells	ec50	0.0500	uM
trans-(1S,2S)-5,5-difluoro-N-[(1R)-2-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl]-2-phenylcyclohexane-1-carboxamide	1414246: Activation of human Kv7.2/7.3 by patch clamp method	ec50	0.0500	uM
ethyl N-[2-amino-3,5-difluoro-4-[[4-(trifluoromethyl)phenyl]methylamino]phenyl]carbamate	1861507: Agonist activity at Kv7.2 (unknown origin) assessed as shifting of voltage dependent activation to more negative potentials by SyncroPatch assay	ec50	0.0500	uM
3-cyclopentyl-N-[3-[4-(trifluoromethyl)phenyl]pyrazolo[1,5-a]pyrimidin-2-yl]propanamide	1557153: Agonist activity at human KCNQ2/3 expressed in HEK293 cells by FLIPR based thallium influx assay	ec50	0.0500	uM
N-[3-(4-fluoro-3-methylphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-2-yl]-3,3-dimethylbutanamide	1557153: Agonist activity at human KCNQ2/3 expressed in HEK293 cells by FLIPR based thallium influx assay	ec50	0.0500	uM
N-[(Z)-[3-methyl-5-(trifluoromethyl)-1,3-benzothiazol-2-ylidene]amino]adamantane-1-carboxamide	461899: Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	ec50	0.0530	uM
10,10-bis(pyridin-4-ylmethyl)anthracen-9-one	1611064: Inhibition of Kv7.2 in human HEK293 cells incubated for 1 hr by thallium flux assay	ic50	0.0550	uM
N-[2-amino-3-fluoro-4-[[4-(trifluoromethyl)phenyl]methylamino]phenyl]-3,3-dimethylbutanamide	1874639: Activation of Kv7.2/Kv7.3 channel (unknown origin) expressed in CHO cells assessed as maximum current density measured after 24 hrs by whole cell patch clamp based electrophysiological method	ec50	0.0600	uM
5-(2,6-dichloro-5-fluoro-3-pyridinyl)-3-phenyl-2-(trifluoromethyl)-1H-pyrazolo[1,5-a]pyrimidin-7-one	587711: Activation of KCNQ2/Q3 expressed in CHO cells by atomic absorption Rb’+ efflux assay	ec50	0.0600	uM
N-[4,6-dimethoxy-2-(1,4-oxazepan-4-yl)pyrimidin-5-yl]-3,3-dimethylbutanamide	1249421: Activation of human Kv7.2/7.3 expressed in CHOK1 cells	ec50	0.0620	uM
N-[(Z)-[3-methyl-6-(trifluoromethoxy)-1,3-benzothiazol-2-ylidene]amino]cyclopentanecarboxamide	461899: Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	ec50	0.0620	uM
N-(4,6-dimethoxy-2-piperidin-1-ylpyrimidin-5-yl)-3,3-dimethylbutanamide	1249421: Activation of human Kv7.2/7.3 expressed in CHOK1 cells	ec50	0.0640	uM
2-cyclopentyl-N-[3-(4-fluoro-3-methylphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-2-yl]acetamide	1557153: Agonist activity at human KCNQ2/3 expressed in HEK293 cells by FLIPR based thallium influx assay	ec50	0.0700	uM
3-cyclopentyl-N-[3-(4-fluoro-3-methylphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-2-yl]propanamide	1557153: Agonist activity at human KCNQ2/3 expressed in HEK293 cells by FLIPR based thallium influx assay	ec50	0.0700	uM
(2S)-2-phenyl-N-(2-pyrrolidin-1-ylphenyl)butanamide	697785: Antagonist activity at KCNQ2 expressed in CHO cells incubated for 3 mins by automated patch clamp assay	ic50	0.0700	uM
N-(6-chloro-3-pyridinyl)-3-fluoro-4-(4-fluorophenyl)sulfonylbenzamide	669435: Agonist activity at KCNQ2/KCNQ3 expressed in CHO cells assessed as increase in KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ec50	0.0700	uM
N-[(3-methylsulfonylphenyl)methyl]-5-(pentafluoro-lambda6-sulfanyl)-2-phenoxybenzamide	1414246: Activation of human Kv7.2/7.3 by patch clamp method	ec50	0.0800	uM
N-[(1R)-2-hydroxy-1-(3-methylsulfonylphenyl)ethyl]-2-phenoxy-5-(trifluoromethyl)benzamide	1414246: Activation of human Kv7.2/7.3 by patch clamp method	ec50	0.0800	uM
N-[1-[[4-(trifluoromethyl)phenyl]methyl]indol-5-yl]heptanamide	1604640: Activation of human Kv7.2 expressed in CHO cells assessed as increase in channel current amplitude by whole cell patch clamp electrophysiology assay	ec50	0.0800	uM
3-cyclopentyl-N-[3-(4-fluoro-3-methylphenyl)-6-methylpyrazolo[1,5-a]pyrimidin-2-yl]propanamide	1557153: Agonist activity at human KCNQ2/3 expressed in HEK293 cells by FLIPR based thallium influx assay	ec50	0.0800	uM
N-(6-chloro-3-pyridinyl)-3-fluoro-4-(4-fluorophenyl)sulfanylbenzamide	669435: Agonist activity at KCNQ2/KCNQ3 expressed in CHO cells assessed as increase in KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ec50	0.0800	uM
4-chloro-N-(6-chloro-3-pyridinyl)-3-fluorobenzamide	669435: Agonist activity at KCNQ2/KCNQ3 expressed in CHO cells assessed as increase in KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ec50	0.0800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
arsenite	affects binding, increases reaction, increases methylation	2
sodium arsenite	increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases methylation	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
cypermethrin	decreases expression	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
ezogabine	affects activity	1
10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone	decreases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
N-(1-(3-morpholin-4-ylphenyl)ethyl)-3-phenylacrylamide	affects binding, affects activity	1
bisphenol B	decreases expression	1
thifluzamide	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
MRK 003	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Benzimidazoles	increases activity, increases import, affects binding	1
Endosulfan	increases expression	1
Fluorouracil	affects reaction, decreases expression	1
Histamine	affects cotreatment, decreases activity, decreases reaction	1
Kainic Acid	increases response to substance	1
Methotrexate	decreases expression	1
Pentylenetetrazole	increases response to substance	1

ChEMBL screening assays

145 unique, capped per target: 136 binding, 7 functional, 1 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1070909	Binding	Activation of KCNQ2/KCNQ3 expressed in CHO cells by isotopic efflux assay	Novel KCNQ2/Q3 agonists as potential therapeutics for epilepsy and neuropathic pain. — J Med Chem
CHEMBL2050726	Functional	Agonist activity at KCNQ2/KCNQ3 expressed in CHO cells assessed as increase in KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	N-Pyridyl and Pyrimidine Benzamides as KCNQ2/Q3 Potassium Channel Openers for the Treatment of Epilepsy. — ACS Med Chem Lett
CHEMBL4385400	ADMET	Agonist activity at KCNQ2/KCNQ3 (unknown origin) expressed in CHOK1 cells assessed as increase in amplitude of outward current at 10 uM by whole cell patch clamp assay relative to control	Discovery of Novel Retigabine Derivatives as Potent KCNQ4 and KCNQ5 Channel Agonists with Improved Specificity. — ACS Med Chem Lett

Cellosaurus cell lines

12 cell lines: 7 induced pluripotent stem cell, 3 spontaneously immortalized cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0Y6	B’SYS CHO Kv7.2	Spontaneously immortalized cell line	Female
CVCL_C0Y7	B’SYS CHO Kv7.2/3	Spontaneously immortalized cell line	Female
CVCL_C6RT	NUIGi059-A	Induced pluripotent stem cell	Male
CVCL_C6RU	NUIGi059-B	Induced pluripotent stem cell	Male
CVCL_C6RV	NUIGi059-C	Induced pluripotent stem cell	Male
CVCL_C6S5	NUIGi063-A	Induced pluripotent stem cell	Female
CVCL_C6S6	NUIGi063-B	Induced pluripotent stem cell	Female
CVCL_C6S7	NUIGi063-C	Induced pluripotent stem cell	Female
CVCL_D1KA	PrecisION hKv7.2/Kv7.3-CHO	Spontaneously immortalized cell line	Female
CVCL_E9CY	SDCHi008-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
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
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01575639	PHASE3	COMPLETED	Prednisolone in Infantile Spasms- High Dose Versus Usual Dose
NCT01828437	PHASE3	COMPLETED	Addition of Pyridoxine to Prednisolone in Infantile Spasms
NCT02299115	PHASE3	WITHDRAWN	Prednisolone Versus Vigabatrin in the First-line Treatment of Infantile Spasms
NCT02953548	PHASE3	COMPLETED	Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms (GWPCARE7)
NCT02954887	PHASE3	COMPLETED	Phase 3 Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms: Open-label Extension Phase (GWPCARE7)
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00441896	PHASE2	COMPLETED	A Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms
NCT00442104	PHASE2	TERMINATED	Open-label Extension to Protocol 1042-0500
NCT02829827	PHASE2	TERMINATED	A Phase 2 Study of Radiprodil in Subjects With Drug-resistant Infantile Spasms (IS)
NCT03976076	PHASE2	TERMINATED	A Study of Orally Administered JBPOS0101 in Refractory Infantile Spasms Patients
NCT06819670	PHASE2	RECRUITING	A Study to Prevent Infantile Spasms Relapse
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT00006191	Not specified	COMPLETED	Effect of Levetiracetam on Brain Excitability
NCT02960347	Not specified	COMPLETED	Examining the Efficacy of tDCS in the Attenuation of Epileptic Paroxysmal Discharges and Clinical Seizures
NCT06938542	Not specified	ENROLLING_BY_INVITATION	Palliative Care Needs of Children With Rare Diseases and Their Families
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).