KCNH5

Summary

KCNH5 (potassium voltage-gated channel subfamily H member 5, HGNC:6254) is a protein-coding gene on chromosome 14q23.2, encoding Voltage-gated delayed rectifier potassium channel KCNH5 (Q8NCM2). Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel that mediates outward-rectifying potassium currents which, on depolarization, reaches a steady-state level and do not inactivate.

This gene encodes a member of voltage-gated potassium channels. Members of this family have diverse functions, including regulating neurotransmitter and hormone release, cardiac function, and cell volume. This protein is an outward-rectifying, noninactivating channel. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 27133 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neonatal/infantile epilepsy syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 884 total — 6 pathogenic, 6 likely-pathogenic (top 4% of genes corpus-wide)
• Regional missense constraint (gnomAD): 2 of 6 regions constrained (≈7% of expected missense variation)
• GTEx eGene: eQTL in 6 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 73
• Constraint (gnomAD): pLI 0.11 (intermediate), LOEUF 0.56 (moderately constrained)
• MANE Select transcript: NM_139318

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6254
Approved symbol	KCNH5
Name	potassium voltage-gated channel subfamily H member 5
Location	14q23.2
Locus type	gene with protein product
Status	Approved
Aliases	Kv10.2, H-EAG2, eag2, hEAG2
Ensembl gene	ENSG00000140015
Ensembl biotype	protein_coding
OMIM	605716
Entrez	27133

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

MANE Select: ENST00000322893

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 1

ENST00000322893, ENST00000394964, ENST00000394968, ENST00000420622, ENST00001137649

RefSeq mRNA: 2 — MANE Select: NM_139318 NM_139318, NM_172375

CCDS: CCDS45122, CCDS9756

Canonical transcript exons

ENST00000322893 — 11 exons

Exon	Start	End
ENSE00001172080	62779728	62779924
ENSE00001194217	62699464	62708455
ENSE00001304563	62950133	62950559
ENSE00001773437	62849653	62849852
ENSE00001781141	62802329	62802581
ENSE00001931443	63045114	63045458
ENSE00003681757	63016831	63016954
ENSE00003719681	62987072	62987187
ENSE00003721518	63001331	63001459
ENSE00003721941	63006366	63006472
ENSE00003741504	62980872	62981264

Expression profiles

Bgee: expression breadth broad, 83 present calls, max score 96.34.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3183 / max 15.0185, expressed in 136 samples.

Highest expression (Bgee): buccal mucosa cell, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis, oocyte, primordial germ cell in gonad.

Genetic regulation across tissues (GTEx eQTL / sQTL)

KCNH5 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

6 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	9.6e-15	+0.47	14:62708242:C:T
Brain Nucleus accumbens basal ganglia	eqtl	5.1e-04	-1.04	14:62802961:G:A
Pituitary	eqtl	1.7e-03	-0.27	14:63216735:A:C
Brain Frontal Cortex BA9	eqtl	8.7e-03	+0.14	14:62897217:C:T
Brain Cortex	eqtl	1.0e-02	+0.15	14:63166791:C:G
Brain Substantia nigra	eqtl	2.2e-02	-0.24	14:63102579:A:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
143588	0.2015	95
143587	0.1168	62

Top tissues by expression

showing 100 of 222 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.34	gold quality
secondary oocyte	CL:0000655	82.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.26	gold quality
oocyte	CL:0000023	74.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.83	gold quality
pigmented layer of retina	UBERON:0001782	71.06	gold quality
prefrontal cortex	UBERON:0000451	70.58	gold quality
lateral nuclear group of thalamus	UBERON:0002736	68.41	silver quality
Brodmann (1909) area 9	UBERON:0013540	67.51	gold quality
cortical plate	UBERON:0005343	67.19	gold quality
primary visual cortex	UBERON:0002436	67.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.70	gold quality
colonic epithelium	UBERON:0000397	66.60	gold quality
frontal cortex	UBERON:0001870	65.53	gold quality
neocortex	UBERON:0001950	64.35	gold quality
right frontal lobe	UBERON:0002810	61.54	gold quality
superior frontal gyrus	UBERON:0002661	61.42	gold quality
occipital lobe	UBERON:0002021	61.40	gold quality
cerebral cortex	UBERON:0000956	61.15	gold quality
Brodmann (1909) area 46	UBERON:0006483	60.41	gold quality
anterior cingulate cortex	UBERON:0009835	59.75	gold quality
Brodmann (1909) area 23	UBERON:0013554	59.24	silver quality
ventricular zone	UBERON:0003053	58.70	silver quality
parotid gland	UBERON:0001831	58.15	gold quality
postcentral gyrus	UBERON:0002581	57.80	silver quality
hypothalamus	UBERON:0001898	57.29	gold quality
corpus callosum	UBERON:0002336	56.76	gold quality
parietal lobe	UBERON:0001872	55.85	silver quality
middle temporal gyrus	UBERON:0002771	55.65	gold quality
pons	UBERON:0000988	55.16	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	54.36	gold quality
ganglionic eminence	UBERON:0004023	53.90	silver quality
forebrain	UBERON:0001890	53.36	gold quality
entorhinal cortex	UBERON:0002728	53.08	silver quality
temporal lobe	UBERON:0001871	52.03	gold quality
amygdala	UBERON:0001876	51.89	gold quality
brain	UBERON:0000955	50.51	gold quality
substantia nigra pars compacta	UBERON:0001965	49.46	gold quality
Ammon’s horn	UBERON:0001954	48.03	gold quality
tendon of biceps brachii	UBERON:0008188	47.67	gold quality
amniotic fluid	UBERON:0000173	46.18	gold quality
biceps brachii	UBERON:0001507	45.31	gold quality
substantia nigra pars reticulata	UBERON:0001966	44.91	gold quality
parietal pleura	UBERON:0002400	44.87	silver quality
subthalamic nucleus	UBERON:0001906	44.43	gold quality
sural nerve	UBERON:0015488	44.37	gold quality
upper leg skin	UBERON:0004262	44.35	silver quality
ventral tegmental area	UBERON:0002691	44.27	gold quality
placenta	UBERON:0001987	43.89	gold quality
deltoid	UBERON:0001476	43.80	gold quality
skin of hip	UBERON:0001554	43.47	silver quality
germinal epithelium of ovary	UBERON:0001304	43.42	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
midbrain	UBERON:0001891	43.22	gold quality
substantia nigra	UBERON:0002038	43.13	gold quality
medial globus pallidus	UBERON:0002477	43.08	gold quality
endometrium	UBERON:0001295	42.81	gold quality
skeletal muscle tissue	UBERON:0001134	42.37	gold quality
globus pallidus	UBERON:0001875	42.27	gold quality
pituitary gland	UBERON:0000007	41.93	gold quality
muscle tissue	UBERON:0002385	41.81	gold quality
cartilage tissue	UBERON:0002418	41.77	gold quality
vastus lateralis	UBERON:0001379	41.71	gold quality
quadriceps femoris	UBERON:0001377	41.66	gold quality
adrenal tissue	UBERON:0018303	41.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	41.44	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
dorsal root ganglion	UBERON:0000044	41.21	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
spinal cord	UBERON:0002240	40.97	gold quality
adenohypophysis	UBERON:0002196	40.91	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
adipose tissue of abdominal region	UBERON:0007808	40.19	gold quality
jejunum	UBERON:0002115	40.18	gold quality
peritoneum	UBERON:0002358	40.17	gold quality
omental fat pad	UBERON:0010414	40.17	gold quality
oviduct epithelium	UBERON:0004804	40.03	gold quality
nucleus accumbens	UBERON:0001882	40.01	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
trabecular bone tissue	UBERON:0002483	39.88	gold quality
bronchial epithelial cell	CL:0002328	39.84	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
bronchus	UBERON:0002185	39.81	gold quality
urethra	UBERON:0000057	39.80	gold quality
heart right ventricle	UBERON:0002080	39.79	gold quality
monocyte	CL:0000576	39.78	gold quality
pericardium	UBERON:0002407	39.77	gold quality
layer of synovial tissue	UBERON:0007616	39.77	gold quality
endothelial cell	CL:0000115	39.75	gold quality
synovial joint	UBERON:0002217	39.70	gold quality
nipple	UBERON:0002030	39.68	gold quality
decidua	UBERON:0002450	39.65	gold quality
penis	UBERON:0000989	39.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	62.42
E-ANND-3	yes	5.85

HPA expression

RNA tissue specificity: Tissue enhanced

40 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Olfactory bulb	tissue	56.9
Superior colliculi	tissue	31.8
Postcentral gyrus	tissue	29.0
Thalamus	tissue	26.6
Midbrain	tissue	25.8
Cerebral cortex	tissue	22.2
Somatosensory cortex	tissue	22.2
Pons	tissue	20.7
Temporal cortex	tissue	18.5
Occipital cortex	tissue	18.0
Hippocampal formation	tissue	17.0
Entorhinal cortex	tissue	17.0
Motor cortex	tissue	15.4
Septum	tissue	14.7
Hypothalamus	tissue	13.4
Retrosplenial and cingulate cortex	tissue	13.3
Prefrontal cortex	tissue	12.7
Medulla oblongata	tissue	12.6
Ventral forebrain	tissue	12.3
Insular cortex	tissue	10.9
Choroid plexus	tissue	10.5
Basal ganglia	tissue	9.6
Putamen	tissue	9.6
Spinal cord	tissue	9.5
Retrosplenial cortex	tissue	9.2
Periaqueductal gray	tissue	8.0
Frontal cortex	tissue	7.8
Amygdala	tissue	6.9
Cerebellum	tissue	5.0
Substantia nigra	tissue	5.0
Caudate putamen	tissue	4.7
Locus coeruleus	tissue	4.5
Retina	tissue	4.1
Hippocampus	tissue	2.5
Corpus callosum	tissue	2.1
Nucleus accumbens	tissue	1.7
Adrenal gland	tissue	1.0
Pituitary gland	tissue	0.3
Testis	tissue	0.3
Placenta	tissue	0.2

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Habenula (33.2), Ventral posteromedial thalamic nucleus (30.4), Pulvinar (28.8), Ventral posterolateral thalamic nucleus (27.6), Lateral geniculate body (27.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting KCNH5 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 70 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-452-5P	99.65	69.63	1762

Functional genomics

gnomAD constraint: pLI 0.106, LOEUF 0.555, missense Z 3.74 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000322893 splits into 6 regions with different missense tolerance; 2 are missense-constrained (≈7% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
14:62,707,511–62,779,741	362 / 394.4	0.92	no
14:62,779,742–62,779,924	57 / 76.0	0.75	no
14:62,802,329–62,802,469	20 / 57.9	0.35	yes (p 6.4e-07)
14:62,802,470–62,849,795	95 / 111.8	0.85	no
14:62,849,796–62,950,138	3 / 24.4	0.12	yes (p 1.5e-05)
14:62,950,139–63,045,186	370 / 561.3	0.66	no

Literature-anchored findings (GeneRIF, showing 14)

• molecular identification and characterisation (PMID:12135768)
• Methylation of KCNH5 was present in 80% of NSCLC tissues but only in 14% of noncancerous tissues. (PMID:18349282)
• data suggest that the ‘Per-Ant-Sim’ (PAS) and cyclic nucleotide binding (cNBD) domains at the N- and C-termini form interacting oligomers that have roles in channel function (PMID:19172261)
• Three-dimensional structure of human Kv10.2 ion channel studied by single particle electron microscopy and molecular modeling (PMID:22792721)
• This study performed whole exome sequencing demonistrated that the true de novo variants represent mutations in genes (KCNH5, CLCN4, and ARHGEF15) not previously associated with epilepsies in humans. (PMID:23647072)
• Our results demonstrate the critical role of the Arg327 residue in stabilizing the channel closed state and explicate for the first time the structural and functional change of a Kv10.2 channel mutation associated with neurological disease. (PMID:24133262)
• Study propose that hypomethylation of the placental-specific KCNH5 promoter is frequently associated with KCNH5 expression in melanoma cells. (PMID:24759919)
• The observed Ca(2+)-induced proteolytic cleavage of EAG2 channel may act as an adaptive response under physiological and/or pathological conditions. (PMID:25542181)
• EAG2 potassium channel has an evolutionarily conserved function for promoting brain tumor growth. (PMID:26258683)
• Chloride intracellular channel 1 cooperates with potassium channel EAG2 to promote medulloblastoma growth. (PMID:32097463)
• Regional heritability mapping identifies several novel loci (STAT4, ULK4, and KCNH5) for primary biliary cholangitis in the Japanese population. (PMID:33833419)
• A novel loss-of-function mutation of the voltage-gated potassium channel Kv10.2 involved in epilepsy and autism. (PMID:36068614)
• Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5. (PMID:36307226)
• Mechanism underlying delayed rectifying in human voltage-mediated activation Eag2 channel. (PMID:36928654)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnh5a	ENSDARG00000043220
danio_rerio	kcnh5b	ENSDARG00000069117
mus_musculus	Kcnh5	ENSMUSG00000034402
rattus_norvegicus	Kcnh5	ENSRNOG00000009542
drosophila_melanogaster	Elk	FBGN0011589
drosophila_melanogaster	Cngl	FBGN0263257
caenorhabditis_elegans		WBGENE00001171

Paralogs (17): KCNH2 (ENSG00000055118), CNGB1 (ENSG00000070729), KCNH4 (ENSG00000089558), HCN2 (ENSG00000099822), CNGA4 (ENSG00000132259), KCNH3 (ENSG00000135519), HCN4 (ENSG00000138622), KCNH1 (ENSG00000143473), HCN3 (ENSG00000143630), CNGA3 (ENSG00000144191), HCN1 (ENSG00000164588), CNGB3 (ENSG00000170289), KCNH6 (ENSG00000173826), CNGA2 (ENSG00000183862), KCNH8 (ENSG00000183960), KCNH7 (ENSG00000184611), CNGA1 (ENSG00000198515)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:3584508) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal startle reflex	1
increased thigmotaxis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryctolagus cuniculus	Q8WNY2	97.4%	Diamond
Bos taurus	O18965	96.9%	Diamond
Canis lupus familiaris	Q9TSZ3	96.2%	Diamond
Sus scrofa	Q9TUI4	96.0%	Diamond
Cavia porcellus	O08703	95.2%	Diamond
Listeria monocytogenes EGD-e	P58724	93.7%	Diamond
Gallus gallus	Q9PT84	61.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC00644	ncRNA	101954204
GPHB5	protein-coding	122876
RHOJ	protein-coding	57381

Protein

Protein identifiers

Voltage-gated delayed rectifier potassium channel KCNH5 — Q8NCM2 (reviewed: Q8NCM2)

Alternative names: Ether-a-go-go potassium channel 2, Potassium voltage-gated channel subfamily H member 5, Voltage-gated potassium channel subunit Kv10.2

All UniProt accessions (1): Q8NCM2

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel that mediates outward-rectifying potassium currents which, on depolarization, reaches a steady-state level and do not inactivate. The kinetic is characterized by a slow activation time course and a small voltage dependence of the activation time constants, therefore, starts to open at more negative voltages. The activation kinetics depend on the prepulse potential and external divalent cation concentration. The time course of activation is biphasic with a fast and a slowly activating current component. With negative prepulses, the current activation is delayed and slowed down several fold, whereas more positive prepulses speed up activation, therefore the activation rate depends on holding potential.

Subunit / interactions. Homotetramer. The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits. Heteromultimer with KCNH1/EAG.

Subcellular location. Membrane.

Tissue specificity. Detected in brain, skeletal muscle, heart, placenta, lung and liver, and at low levels in kidney.

Disease relevance. Developmental and epileptic encephalopathy 112 (DEE112) [MIM:620537] A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE112 is an autosomal dominant form characterized by onset in infancy, and a wide range of seizure types including focal and generalized seizures. Cognitive outcomes range from normal intellect to profound intellectual development impairment. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Contains a voltage sensor domain (VSD) formed from the S1-S4 transmembrane helices, a pore domain formed from the S5-pore loop-S6 domain and the C-terminal cyclic nucleotide binding homology domain (CNBHD). The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

Similarity. Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv10.2/KCNH5 sub-subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NCM2-1	1	yes
Q8NCM2-2	2, 2b
Q8NCM2-3	3

RefSeq proteins (2): NP_647479, NP_758963 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000014	PAS	Domain
IPR000595	cNMP-bd_dom	Domain
IPR000700	PAS-assoc_C	Domain
IPR001610	PAC	Repeat
IPR003938	K_chnl_volt-dep_EAG/ELK/ERG	Family
IPR003949	K_chnl_volt-dep_EAG	Family
IPR005821	Ion_trans_dom	Domain
IPR014710	PpnP-like_jellyroll	Homologous_superfamily
IPR018490	cNMP-bd_dom_sf	Homologous_superfamily
IPR035965	PAS-like_dom_sf	Homologous_superfamily
IPR050818	KCNH_animal-type	Family

Pfam: PF00027, PF00520, PF13426

Catalyzed reactions (Rhea)

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (110 total): helix 31, strand 23, turn 9, topological domain 8, sequence variant 8, transmembrane region 6, region of interest 5, splice variant 5, compositionally biased region 3, mutagenesis site 3, domain 2, chain 1, intramembrane region 1, short sequence motif 1, binding site 1, modified residue 1, glycosylation site 1, cross-link 1

Structure

Experimental structures (PDB)

6 structures by resolution:

PDB	Title	Method	Resolution (Å)
7YID	Human KCNH5 closed state 1	ELECTRON MICROSCOPY	3.4
7YIE	Human KCNH5-closed state 2	ELECTRON MICROSCOPY	3.4
7YIF	Human KCNH5 pre-open state 1	ELECTRON MICROSCOPY	3.5
7YIH	Human KCNH5 open state	ELECTRON MICROSCOPY	3.5
7YIG	Human KCNH5 pre-open state 2	ELECTRON MICROSCOPY	3.6
7YIJ	Human KCNH5 pore dilation but the non-conducting state	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCM2-F1	72.67	0.39

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Voltage-gated ion channels, Voltage-Gated Potassium Channels, Predicted membrane proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): centrosome; cytosol; nucleoplasm

Antibody reliability (HPA): IH uncertain · IF approved

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 (1)

Position	Role
550–667	a nucleoside 3’,5’-cyclic phosphate

Post-translational modifications (2)

Type	Positions
Phosphoserine	883
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	785

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	403

Mutagenesis-validated functional residues (3)

Position	Phenotype
337	left-shifts the half-activation membrane potential.
468	reduces the delayed rectifier potassium channel activity. has little effect on the voltage sensitivity.
472	almost loss of the delayed rectifier potassium channel activity. has little effect on the voltage sensitivity.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-1296072	Voltage gated Potassium channels	curated
R-HSA-112316	Neuronal System	—
R-HSA-1296071	Potassium Channels	—

MSigDB gene sets: 262 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, NKX25_02, REACTOME_POTASSIUM_CHANNELS, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOCC_CELL_SURFACE, ATGCAGT_MIR217, LHX3_01, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, MYOD_01, GATA6_01, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_MITOTIC_CELL_CYCLE, MYOD_Q6

GO Biological Process (7): potassium ion transport (GO:0006813), regulation of G2/M transition of mitotic cell cycle (GO:0010389), regulation of membrane potential (GO:0042391), potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (7): voltage-gated potassium channel activity (GO:0005249), delayed rectifier potassium channel activity (GO:0005251), calmodulin binding (GO:0005516), transmembrane transporter binding (GO:0044325), protein-containing complex binding (GO:0044877), monoatomic ion channel activity (GO:0005216), potassium channel activity (GO:0005267)

GO Cellular Component (5): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), cell surface (GO:0009986), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Potassium Channels	1
Neuronal System	1

GO top-level categories

27 GO namespaces:

Category	Terms
transport	2
protein binding	2
cellular anatomical structure	2
metal ion transport	1
G2/M transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G2/M phase transition	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
potassium channel activity	1
voltage-gated monoatomic cation channel activity	1
voltage-gated potassium channel activity	1
binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
transmembrane transporter complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
potassium ion transport	BP	direct assay
regulation of G2/M transition of mitotic cell cycle	BP	direct assay
cell surface	CC	direct assay
voltage-gated potassium channel complex	CC	direct assay
delayed rectifier potassium channel activity	MF	direct assay
voltage-gated potassium channel activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 646 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNH5	KCNQ3	O43525	484
KCNH5	KCNA3	P22001	462
KCNH5	KCNB2	Q92953	462
KCNH5	KCNQ2	O43526	453
KCNH5	KCNB1	Q14721	452
KCNH5	KCND1	Q9NSA2	448
KCNH5	KCND2	Q9NZV8	447
KCNH5	KCNMA1	Q12791	443
KCNH5	KCNA2	P16389	441
KCNH5	KCNT2	Q6UVM3	413
KCNH5	KCNC1	P48547	412
KCNH5	KCNT1	Q5JUK3	406
KCNH5	KCNQ5	Q9NR82	404
KCNH5	KCNQ1	P51787	397
KCNH5	KCNA10	Q16322	391

IntAct

Human interaction partners of KCNH5 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
HNRNPL	physical association	0.400	1

BioGRID (10 interactions; top human partners by supporting records): TUBA1B (Affinity Capture-MS; 2 records), CSK (Synthetic Lethality), HSPA8 (Affinity Capture-MS), KCNH4 (Negative Genetic), MBP (Affinity Capture-MS), PARP4 (Proximity Label-MS), RNF8 (Proximity Label-MS), TUBB (Affinity Capture-MS), TUBB4B (Affinity Capture-MS)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ KCNH5 homotetramer	1	KCNH5

Disease & clinical

Genetic variants

Variant evidence for KCNH5: 884 ClinVar records (12 pathogenic / likely pathogenic); 9 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	6
Uncertain significance	444
Likely benign	339
Benign	49

Top pathogenic / likely-pathogenic (12)

Showing all 12 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
100784	NM_139318.5(KCNH5):c.980G>A (p.Arg327His)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
1042182	NM_139318.5(KCNH5):c.998G>A (p.Arg333His)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
1488521	NM_139318.5(KCNH5):c.979C>T (p.Arg327Cys)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2713328	NM_139318.5(KCNH5):c.908A>G (p.Tyr303Cys)	Pathogenic	criteria provided, single submitter	1
2583163	NM_139318.5(KCNH5):c.1382C>A (p.Ala461Glu)	Likely pathogenic	criteria provided, single submitter	1
2835906	NM_139318.5(KCNH5):c.979C>A (p.Arg327Ser)	Likely pathogenic	criteria provided, single submitter	1
4041567	NM_139318.5(KCNH5):c.998G>T (p.Arg333Leu)	Likely pathogenic	criteria provided, single submitter	1
4278299	NM_139318.5(KCNH5):c.1679G>A (p.Arg560His)	Likely pathogenic	criteria provided, single submitter	1
4833037	NM_139318.5(KCNH5):c.388G>C (p.Asp130His)	Likely pathogenic	criteria provided, single submitter	1
2583108	NM_139318.5(KCNH5):c.2020-4A>G	Pathogenic	no assertion criteria provided	1
2583110	NM_139318.5(KCNH5):c.1402A>C (p.Thr468Pro)	Pathogenic	no assertion criteria provided	1
2583111	NM_139318.5(KCNH5):c.1412T>C (p.Phe471Ser)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore KCNH5’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 48 predictions of 1,472):

Position(s)	Effect	Δscore	Sites
14:62779726–62779727	donor_loss	1.0000	5
14:62849651–62849652	donor_loss	1.0000	4
14:62987070–62987071	donor_loss	1.0000	5
14:62987188–62987189	acceptor_gain	1.0000	2
14:63001329–63001330	donor_loss	1.0000	5
14:63001460–63001461	acceptor_loss	1.0000	6
14:63006364–63006365	donor_loss	1.0000	5
14:63006473–63006474	acceptor_loss	1.0000	6
14:63016829–63016830	donor_loss	1.0000	4
14:63016955–63016956	acceptor_loss	1.0000	6

AlphaMissense

3,712 missense substitutions predicted likely pathogenic (of 6,534 scored), across 730 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M59	9	0.976	0.999
M453	9	0.974	0.999
M532	9	0.946	0.999
D261	8	1.000	1.000
D296	8	1.000	1.000
N13	8	0.999	1.000
D218	8	0.999	1.000
D255	8	0.999	1.000
F258	8	0.999	1.000
F551	8	0.999	1.000
D251	8	0.998	0.999
D304	8	0.998	0.999
F464	8	0.998	1.000
D507	8	0.998	1.000
D535	8	0.998	1.000
D611	8	0.998	1.000
F266	8	0.997	1.000
H361	8	0.997	0.999
D531	8	0.997	0.999
D575	8	0.997	1.000

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:605716 | disease phenotypes: MIM:620537, MIM:618416

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
developmental and epileptic encephalopathy 112	Strong	Autosomal dominant	2

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
neonatal/infantile epilepsy syndrome	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
DDG2P	green
Early onset or syndromic epilepsy	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (3): early-infantile DEE (MONDO:0800491), developmental and epileptic encephalopathy 112 (MONDO:0957812), metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression (MONDO:0032736)

Orphanet (2): Early infantile developmental and epileptic encephalopathy (Orphanet:1934), Early myoclonic encephalopathy (Orphanet:1935)

HPO phenotypes

showing 60 of 73 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000158	Macroglossia
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001270	Motor delay
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001315	Diminished deep tendon reflex
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001508	Failure to thrive
HP:0001558	Decreased fetal movement
HP:0002020	Gastroesophageal reflux
HP:0002059	Cerebral atrophy
HP:0002063	Rigidity
HP:0002069	Bilateral tonic-clonic seizure
HP:0002121	Generalized non-motor (absence) seizure
HP:0002133	Status epilepticus
HP:0002188	Delayed CNS myelination
HP:0002317	Unsteady gait
HP:0002376	Developmental regression
HP:0002421	Poor head control
HP:0002509	Limb hypertonia
HP:0002521	Hypsarrhythmia
HP:0003584	Late onset
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0004305	Involuntary movements
HP:0004322	Short stature
HP:0006813	Focal hemiclonic seizure
HP:0007018	Attention deficit hyperactivity disorder
HP:0007099	Chiari type I malformation
HP:0007334	Bilateral tonic-clonic seizure with focal onset
HP:0007359	Focal-onset seizure
HP:0010844	EEG with multifocal slow activity
HP:0011153	Focal motor seizure
HP:0011167	Focal tonic seizure
HP:0011443	Abnormality of coordination
HP:0011463	Childhood onset

GWAS associations

9 associations:

Study	Trait	p-value
GCST002652_11	Cotinine glucuronidation	2e-9
GCST012490_514	Femur bone mineral density x serum urate levels interaction	4e-9
GCST005316_490	Intelligence (MTAG)	5e-8
GCST002301_4	Body mass index	5e-7
GCST001521_31	Subcutaneous adipose tissue	2e-6
GCST001850_4	Major depressive disorder	4e-6
GCST009391_1600	Metabolite levels	4e-6
GCST002347_2	Response to protease inhibitor treatment in hepatitis c (bilirubin toxicity)	6e-6
GCST006914_1	Sleep duration	9e-6

EFO canonical traits (from GWAS)

7 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004570	bilirubin measurement
EFO:0005657	response to protease inhibitor
EFO:0006508	cotinine glucuronidation measurement
EFO:0004337	intelligence
EFO:0008534	tryptophan measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2362996 (PROTEIN FAMILY)

PharmGKB: 1 entry (CPIC guideline: no)

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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
LY97241	Pore blocker	5.8	pIC50
quinidine	Pore blocker	3.8	pIC50

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 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

PubChem BioAssay actives

2 with measured affinity, of 34 total; 1 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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	4
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
afuresertib	decreases expression	1
methyleugenol	decreases expression	1
potassium perchlorate	increases expression	1
trichostatin A	decreases expression, increases expression	1
arsenite	decreases reaction, affects binding	1
sulforaphane	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
quinocetone	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Copper	affects cotreatment, decreases expression	1
Malathion	increases expression	1
Tretinoin	decreases expression	1

ChEMBL screening assays

21 unique, capped per target: 20 binding, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1787442	Binding	Inhibition of human recombinant Kv channel at 10 uM by radioligand binding assay	Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement. — *Bioorg Med Chem Lett*
CHEMBL5522525	Toxicity	Inhibition of human K+ channel by automated electrophysiology	Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure. — *J Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

25 trials:

NCT	Phase	Status	Title
NCT03347526	Phase 3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	Phase 3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	Phase 3	ACTIVE_NOT_RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	Phase 3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT07723976	Phase 3	NOT_YET_RECRUITING	A Study to Evaluate the Safety and Efficacy of CBD-OS in Participants With DEE
NCT04289467	Phase 2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	Phase 2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT04727970	Phase 1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	Phase 1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT03876444	Phase 2/3	UNKNOWN	Intravenous Methylprednisolone Versus Oral Prednisolone for Infantile Spasms
NCT05279118	Phase 2/3	UNKNOWN	Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome
NCT05364021	Phase 1/2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	Phase 1/2	TERMINATED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	Early Phase 1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT04302116	Not specified	RECRUITING	Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm
NCT05538936	Not specified	COMPLETED	The Effect of Spa and Massage on Babies on Colic Symptoms
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06266234	Not specified	RECRUITING	Characterization by Automated System on Infantile Spasmes
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07413211	Not specified	RECRUITING	Genetic Developmental and Epileptic Encephalopathy Natural History Study for Clinical Trial Readiness
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).
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