KCNH7

Summary

KCNH7 (potassium voltage-gated channel subfamily H member 7, HGNC:18863) is a protein-coding gene on chromosome 2q24.2, encoding Voltage-gated inwardly rectifying potassium channel KCNH7 (Q9NS40). Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel.

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily H. This member is a pore-forming (alpha) subunit. There are at least two alternatively spliced transcript variants derived from this gene and encoding distinct isoforms.

Source: NCBI Gene 90134 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epilepsy (Limited, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 110 total
• Druggable target: yes
• MANE Select transcript: NM_033272

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18863
Approved symbol	KCNH7
Name	potassium voltage-gated channel subfamily H member 7
Location	2q24.2
Locus type	gene with protein product
Status	Approved
Aliases	Kv11.3, HERG3, erg3
Ensembl gene	ENSG00000184611
Ensembl biotype	protein_coding
OMIM	608169
Entrez	90134

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000328032, ENST00000332142, ENST00000477019

RefSeq mRNA: 2 — MANE Select: NM_033272 NM_033272, NM_173162

CCDS: CCDS2219, CCDS2220

Canonical transcript exons

ENST00000332142 — 16 exons

Exon	Start	End
ENSE00001297884	162394389	162394485
ENSE00001298151	162446018	162446443
ENSE00001299106	162379853	162380021
ENSE00001299408	162423336	162423535
ENSE00001305842	162836537	162836767
ENSE00001307236	162371407	162372095
ENSE00001316282	162384688	162384939
ENSE00001316605	162435198	162435597
ENSE00001317374	162400189	162400441
ENSE00001320476	162396740	162396945
ENSE00001322934	162838443	162838767
ENSE00001324813	162536925	162537080
ENSE00001325992	162512654	162512674
ENSE00001330536	162373470	162373662
ENSE00003524600	162504443	162504657
ENSE00003636659	162517730	162518158

Expression profiles

Bgee: expression breadth broad, 90 present calls, max score 88.23.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8970 / max 88.8407, expressed in 171 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31568	0.3888	115
31567	0.2146	87
31566	0.1405	71
31570	0.1043	41
31569	0.0383	23
31563	0.0105	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.23	gold quality
pancreatic ductal cell	CL:0002079	78.82	gold quality
ventricular zone	UBERON:0003053	77.72	gold quality
ganglionic eminence	UBERON:0004023	76.87	gold quality
tibialis anterior	UBERON:0001385	74.00	gold quality
cortical plate	UBERON:0005343	70.78	gold quality
islet of Langerhans	UBERON:0000006	67.17	gold quality
prefrontal cortex	UBERON:0000451	64.61	gold quality
ileal mucosa	UBERON:0000331	63.92	gold quality
blood	UBERON:0000178	62.41	gold quality
corpus callosum	UBERON:0002336	61.45	gold quality
deltoid	UBERON:0001476	57.88	silver quality
epithelial cell of pancreas	CL:0000083	56.93	silver quality
frontal cortex	UBERON:0001870	55.73	gold quality
neocortex	UBERON:0001950	54.55	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
left testis	UBERON:0004533	53.34	gold quality
Brodmann (1909) area 46	UBERON:0006483	53.29	silver quality
buccal mucosa cell	CL:0002336	53.20	silver quality
upper leg skin	UBERON:0004262	53.10	gold quality
testis	UBERON:0000473	52.68	gold quality
right testis	UBERON:0004534	52.46	gold quality
spleen	UBERON:0002106	51.79	gold quality
adrenal tissue	UBERON:0018303	51.71	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	50.74	gold quality
leukocyte	CL:0000738	50.39	silver quality
myocardium	UBERON:0002349	50.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	59.77
E-ANND-3	yes	4.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

83 targeting KCNH7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3121-3P	99.82	71.96	3630

Literature-anchored findings (GeneRIF, showing 9)

• Transcripts for HERG1 were present in all adenomas and although transcripts for HERG2 and HERG3 were also detected, their expression level was more variable. (PMID:12634931)
• The recombinant wild-type ERG3 protein produced in HEK cells generates two prominent bands. When the entire CNBD of ERG3 protein was deleted, only an EndoH-sensitive band was generated, indicating that this band constitutes the immature species. (PMID:15961404)
• IFIH1 interferon induced helicase, GCA grancalcin or the potassium channel KCNH7 - are potential candidates implicated in the pathogenesis of multiple sclerosis. (PMID:18285833)
• IFIH1-GCA-KCNH7 locus is not associated with genetic susceptibility to multiple sclerosis in French patients (PMID:19156166)
• KCNH7 c.1181G>A had the highest enrichment among individuals with bipolar spectrum disorder (x2 5 7.3) and the strongest family-based association with bipolar 1 (P 5 0.021), bipolar spectrum (P 5 0.031) and any major affective disorder (P 5 0.016). (PMID:24986916)
• we have discovered that, the Kv11.3 (hERG3) a plasma-membrane potassium channel plays a critical role in the regulation of autophagy in a melanoma cell model (PMID:26942884)
• Low ERG3 expression is associated with epilepsy. (PMID:30016551)
• Discovery of a heme-binding domain in a neuronal voltage-gated potassium channel. (PMID:32723862)
• Potassium Ion Channel Protein (KCNH) Levels in Patients with Fibromyalgia Syndrome. (PMID:35818223)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnh7	ENSDARG00000062687
mus_musculus	Kcnh7	ENSMUSG00000059742
rattus_norvegicus	Kcnh7	ENSRNOG00000007528
drosophila_melanogaster	sei	FBGN0003353
drosophila_melanogaster	Elk	FBGN0011589
drosophila_melanogaster	CG6026	FBGN0038676
drosophila_melanogaster	CngA	FBGN0261612
drosophila_melanogaster	Cngl	FBGN0263257
drosophila_melanogaster	CngB	FBGN0266346
caenorhabditis_elegans		WBGENE00000487
caenorhabditis_elegans	tax-2	WBGENE00006525
caenorhabditis_elegans		WBGENE00006526
caenorhabditis_elegans		WBGENE00006830
caenorhabditis_elegans		WBGENE00022295

Paralogs (17): KCNH2 (ENSG00000055118), CNGB1 (ENSG00000070729), KCNH4 (ENSG00000089558), HCN2 (ENSG00000099822), CNGA4 (ENSG00000132259), KCNH3 (ENSG00000135519), HCN4 (ENSG00000138622), KCNH5 (ENSG00000140015), KCNH1 (ENSG00000143473), HCN3 (ENSG00000143630), CNGA3 (ENSG00000144191), HCN1 (ENSG00000164588), CNGB3 (ENSG00000170289), KCNH6 (ENSG00000173826), CNGA2 (ENSG00000183862), KCNH8 (ENSG00000183960), CNGA1 (ENSG00000198515)

Protein

Protein identifiers

Voltage-gated inwardly rectifying potassium channel KCNH7 — Q9NS40 (reviewed: Q9NS40)

Alternative names: Ether-a-go-go-related gene potassium channel 3, Potassium voltage-gated channel subfamily H member 7, Voltage-gated potassium channel subunit Kv11.3

All UniProt accessions (1): Q9NS40

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Exhibits faster activation and deactivation kinetics and slow inactivation at membrane potentials positive to 240 mV, resulting in the weakest inward rectification.

Subunit / interactions. The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate only within their subfamily.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in prolactin-secreting adenomas.

Activity regulation. Heme inhibits voltage-gated inwardly rectifying potassium channel activity.

Domain organisation. The S4-S5 linker acts as a signal integrator where it both couples voltage-sensor domain (VSD) movement to pore opening and closure, as well as providing a binding site for other domains that regulate activation and/or deactivation of the channel.

Similarity. Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv11.3/KCNH7 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NS40-1	1	yes
Q9NS40-2	2

RefSeq proteins (2): NP_150375, NP_775185 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000014	PAS	Domain
IPR000595	cNMP-bd_dom	Domain
IPR003938	K_chnl_volt-dep_EAG/ELK/ERG	Family
IPR003967	K_chnl_volt-dep_ERG	Family
IPR005821	Ion_trans_dom	Domain
IPR014710	RmlC-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), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (38 total): topological domain 8, transmembrane region 6, modified residue 5, sequence conflict 4, region of interest 3, splice variant 3, domain 2, chain 1, intramembrane region 1, coiled-coil region 1, short sequence motif 1, compositionally biased region 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6Y7Q	X-RAY DIFFRACTION	1.39

Predicted structure (AlphaFold)

No AlphaFold model available for Q9NS40 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Post-translational modifications (5): 174, 238, 319, 896, 899

Glycosylation sites (1): 600

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 119 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, BENPORATH_ES_WITH_H3K27ME3, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, AREB6_01, TGACCTY_ERR1_Q2, CACCAGC_MIR138, GGGTGGRR_PAX4_03, GOBP_MONOATOMIC_CATION_TRANSPORT, CEBP_Q2, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, chr2q24, CDPCR3HD_01, GOBP_TRANSMEMBRANE_TRANSPORT, TGGAAA_NFAT_Q4_01

GO Biological Process (6): potassium ion transport (GO:0006813), 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 (5): inward rectifier potassium channel activity (GO:0005242), heme binding (GO:0020037), monoatomic ion channel activity (GO:0005216), voltage-gated potassium channel activity (GO:0005249), potassium channel activity (GO:0005267)

GO Cellular Component (3): plasma membrane (GO:0005886), monoatomic ion channel complex (GO:0034702), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Potassium Channels	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
metal ion transport	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
voltage-gated potassium channel activity	1
ligand-gated monoatomic cation channel activity	1
tetrapyrrole binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
potassium channel activity	1
voltage-gated monoatomic cation channel activity	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
membrane	1
cell periphery	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1026 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNH7	GCA	P28676	887
KCNH7	IFIH1	Q9BYX4	681
KCNH7	PRL	P01236	588
KCNH7	SLC4A10	Q6U841	517
KCNH7	KCNG2	Q9UJ96	507
KCNH7	IGSF21	Q96ID5	505
KCNH7	CLVS1	Q8IUQ0	462
KCNH7	KCNJ13	O60928	453
KCNH7	KCNJ3	P48549	452
KCNH7	KCNV1	Q6PIU1	450
KCNH7	KCNQ5	Q9NR82	448
KCNH7	TBX15	Q96SF7	443
KCNH7	KCNK6	Q9Y257	440
KCNH7	KCNS2	Q9ULS6	432
KCNH7	LRMDA	Q9H2I8	431

IntAct

7 interactions, top by confidence:

A	B	Type	Score
KCNH7	GRB2	psi-mi:“MI:0915”(physical association)	0.400
KCNH7	LRSAM1	psi-mi:“MI:0915”(physical association)	0.400
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
KCNH2	KLHDC10	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): KCNH7 (Synthetic Lethality), KCNH7 (Affinity Capture-MS), KCNH7 (Affinity Capture-MS), LRSAM1 (Affinity Capture-MS), KCNH7 (Affinity Capture-MS), KCNH7 (Co-fractionation)

ESM2 similar proteins: A0A1D5PXA5, A0A1S4GYH6, A1Z7G7, B3MFV7, B3N8M1, B4GD14, B4HS00, B4J780, B4KMZ1, B4LNA8, B4P3A0, G5EFJ9, O01635, O35607, O54852, O73925, P22815, P30432, P34410, P40145, P40146, P48994, P51787, P57789, P79701, P91682, P97414, P97490, Q09274, Q10025, Q13873, Q19187, Q21974, Q24738, Q292N4, Q86GV3, Q95TU8, Q96L42, Q9EPK8, Q9ER47

Diamond homologs: A5K0N4, G5EFJ9, O08703, O08962, O18965, O35219, O54852, O54853, O89047, O95259, P29281, P59111, Q02280, Q12809, Q60603, Q63472, Q8I719, Q8NCM2, Q8WNY2, Q920E3, Q96L42, Q9EPI9, Q9ER47, Q9H252, Q9NS40, Q9PT84, Q9QWS8, Q9R1T9, Q9TSZ3, Q9TUI4, Q9ULD8, Q9UQ05, Q9WVJ0, W7JX98, A0A509AKL0, O64511, P93025, Q1M667, Q2NCA3, Q2QYY8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	10
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

4768 predictions. Top by Δscore:

Variant	Effect	Δscore
2:162373468:A:AC	donor_gain	1.0000
2:162373469:C:CT	donor_gain	1.0000
2:162373658:CAAGC:C	acceptor_gain	1.0000
2:162373659:AAGC:A	acceptor_gain	1.0000
2:162373660:AGCCT:A	acceptor_loss	1.0000
2:162373661:GC:G	acceptor_gain	1.0000
2:162373661:GCCTA:G	acceptor_loss	1.0000
2:162373662:CC:C	acceptor_gain	1.0000
2:162373662:CCTAC:C	acceptor_loss	1.0000
2:162373663:C:CC	acceptor_gain	1.0000
2:162373663:C:CG	acceptor_loss	1.0000
2:162379847:TTATA:T	donor_loss	1.0000
2:162379848:TATA:T	donor_loss	1.0000
2:162379849:ATAC:A	donor_gain	1.0000
2:162379850:TACC:T	donor_loss	1.0000
2:162379851:A:AG	donor_loss	1.0000
2:162379852:C:CT	donor_loss	1.0000
2:162379895:T:TA	donor_gain	1.0000
2:162380018:ATATC:A	acceptor_loss	1.0000
2:162380019:TAT:T	acceptor_gain	1.0000
2:162380019:TATCT:T	acceptor_loss	1.0000
2:162380020:ATC:A	acceptor_loss	1.0000
2:162380021:TCT:T	acceptor_loss	1.0000
2:162380022:C:CC	acceptor_gain	1.0000
2:162380022:CT:C	acceptor_loss	1.0000
2:162380023:T:A	acceptor_loss	1.0000
2:162394385:TTACC:T	donor_loss	1.0000
2:162394387:A:C	donor_loss	1.0000
2:162394388:C:CG	donor_loss	1.0000
2:162394485:CCTT:C	acceptor_gain	1.0000

AlphaMissense

7901 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:162396759:A:G	L865P	1.000
2:162396777:A:G	L859P	1.000
2:162396789:A:G	F855S	1.000
2:162396860:A:C	C831W	1.000
2:162396861:C:T	C831Y	1.000
2:162396870:A:G	L828P	1.000
2:162396873:G:T	A827D	1.000
2:162396927:C:A	G809V	1.000
2:162396927:C:T	G809E	1.000
2:162396928:C:G	G809R	1.000
2:162396928:C:T	G809R	1.000
2:162396930:A:G	F808S	1.000
2:162400191:A:G	L802P	1.000
2:162400194:A:T	I801N	1.000
2:162400198:C:G	A800P	1.000
2:162400233:C:A	G788V	1.000
2:162400233:C:T	G788D	1.000
2:162400234:C:G	G788R	1.000
2:162400245:A:G	F784S	1.000
2:162400251:A:G	L782P	1.000
2:162400392:A:G	L735P	1.000
2:162400416:A:G	L727S	1.000
2:162400427:G:C	F723L	1.000
2:162400427:G:T	F723L	1.000
2:162400428:A:G	F723S	1.000
2:162400429:A:G	F723L	1.000
2:162400437:A:G	L720P	1.000
2:162423352:C:T	G713D	1.000
2:162423368:A:G	W708R	1.000
2:162423368:A:T	W708R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000202 (2:162650745 G>A), RS1000000958 (2:162610384 T>C), RS1000001799 (2:162565267 C>T), RS1000003300 (2:162691570 G>A,C), RS1000006461 (2:162728178 T>G), RS1000007017 (2:162739773 T>C), RS1000009641 (2:162394902 C>T), RS1000009744 (2:162411727 T>C), RS1000012170 (2:162525955 G>A), RS1000013052 (2:162497028 C>A), RS1000038908 (2:162381505 C>T), RS1000039671 (2:162739538 C>T), RS1000045463 (2:162813480 A>G), RS1000048910 (2:162480804 C>T), RS1000050089 (2:162441595 T>C)

Disease associations

OMIM: gene MIM:608169 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
epilepsy	Limited	Autosomal dominant

Mondo (1): epilepsy (MONDO:0005027)

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001414_3	Phospholipid levels (plasma)	4.000000e-08
GCST002740_57	Inflammatory skin disease	4.000000e-11
GCST002861_1	Breast cancer (survival)	2.000000e-08
GCST003098_20	Diabetic kidney disease	1.000000e-06
GCST003264_1070	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST003268_17	Psoriasis vulgaris	5.000000e-13
GCST005196_210	Coronary artery disease	1.000000e-07
GCST005527_37	Psoriasis	3.000000e-08
GCST005527_5	Psoriasis	3.000000e-18
GCST006269_707	General cognitive ability	1.000000e-09
GCST008154_24	Trunk fat mass	4.000000e-06
GCST008157_69	Body fat mass	5.000000e-06
GCST009875_8	Type 1 diabetes	3.000000e-14
GCST010569_1	Polycystic ovary syndrome (metabolic subtype)	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0000714	survival time
EFO:0004713	FEV/FVC ratio
EFO:1001494	psoriasis vulgaris
EFO:0004337	intelligence

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2362996 (PROTEIN FAMILY)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17716942	KCNH7		0.00	0

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 (3 total), top 3:

Ligand	Action	Affinity	Parameter
ErgTx-1	Pore blocker	8.4	pKd
BeKm-1	Pore blocker	7.9	pKd
E4031	Channel blocker	6.7	pKd

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

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation, increases mutagenesis	3
Valproic Acid	affects cotreatment, increases expression	3
methyleugenol	decreases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
sodium arsenite	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	decreases expression	1
Doxorubicin	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Phenylmercuric Acetate	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Triclosan	decreases expression	1
Levonorgestrel	affects cotreatment, increases expression	1
Uranium Compounds	decreases expression	1
Okadaic Acid	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)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy