KCNH1

Summary

KCNH1 (potassium voltage-gated channel subfamily H member 1, HGNC:6250) is a protein-coding gene on chromosome 1q32.2, encoding Voltage-gated delayed rectifier potassium channel KCNH1 (O95259). 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.

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 of a voltage-gated non-inactivating delayed rectifier potassium channel. It is activated at the onset of myoblast differentiation. The gene is highly expressed in brain and in myoblasts. Overexpression of the gene may confer a growth advantage to cancer cells and favor tumor cell proliferation. Alternative splicing of this gene results in two transcript variants encoding distinct isoforms.

Source: NCBI Gene 3756 — RefSeq curated summary.

At a glance

• Gene–disease (curated): KCNH1 associated disorder (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 906 total — 14 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 129
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_172362

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6250
Approved symbol	KCNH1
Name	potassium voltage-gated channel subfamily H member 1
Location	1q32.2
Locus type	gene with protein product
Status	Approved
Aliases	Kv10.1, eag, h-eag, eag1, hEAG, K(V)10.1
Ensembl gene	ENSG00000143473
Ensembl biotype	protein_coding
OMIM	603305
Entrez	3756

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 11 protein_coding, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000271751, ENST00000367007, ENST00000624583, ENST00000638357, ENST00000638498, ENST00000638960, ENST00000638983, ENST00000639385, ENST00000639602, ENST00000639754, ENST00000639952, ENST00000640044, ENST00000640243, ENST00000640522, ENST00000640528, ENST00000640566, ENST00000640625, ENST00000640710, ENST00000640890, ENST00000865058

RefSeq mRNA: 2 — MANE Select: NM_172362 NM_002238, NM_172362

CCDS: CCDS1496, CCDS31015

Canonical transcript exons

ENST00000271751 — 11 exons

Exon	Start	End
ENSE00001010355	210919640	210920069
ENSE00001068333	211082780	211082898
ENSE00001068336	210775348	210775544
ENSE00001068338	211090562	211090690
ENSE00001167310	211018783	211019256
ENSE00001229254	211103496	211103602
ENSE00001229264	211107254	211107377
ENSE00001690855	210803967	210804166
ENSE00001758267	210797508	210797760
ENSE00003801336	211133867	211134148
ENSE00003809800	210678314	210684138

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 81.63.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3775 / max 147.6444, expressed in 414 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17338	1.0885	318
17339	1.0455	268
17336	0.1999	112
17337	0.0437	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 9	UBERON:0013540	81.63	gold quality
prefrontal cortex	UBERON:0000451	80.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.92	gold quality
right frontal lobe	UBERON:0002810	80.71	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.73	gold quality
cerebellar hemisphere	UBERON:0002245	77.63	gold quality
cerebellar cortex	UBERON:0002129	77.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.49	gold quality
anterior cingulate cortex	UBERON:0009835	76.73	gold quality
frontal cortex	UBERON:0001870	75.94	gold quality
neocortex	UBERON:0001950	75.21	gold quality
cerebellum	UBERON:0002037	75.13	gold quality
cerebral cortex	UBERON:0000956	72.34	gold quality
caudate nucleus	UBERON:0001873	72.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.16	gold quality
stromal cell of endometrium	CL:0002255	72.06	gold quality
putamen	UBERON:0001874	71.40	gold quality
endometrium epithelium	UBERON:0004811	70.78	gold quality
nucleus accumbens	UBERON:0001882	70.20	gold quality
islet of Langerhans	UBERON:0000006	69.47	gold quality
primary visual cortex	UBERON:0002436	69.11	gold quality
forebrain	UBERON:0001890	68.17	gold quality
brain	UBERON:0000955	67.96	gold quality
central nervous system	UBERON:0001017	67.78	gold quality
corpus callosum	UBERON:0002336	67.75	gold quality
amygdala	UBERON:0001876	67.69	gold quality
metanephric glomerulus	UBERON:0004736	66.83	gold quality
ganglionic eminence	UBERON:0004023	66.35	gold quality
Ammon’s horn	UBERON:0001954	65.74	gold quality
ventricular zone	UBERON:0003053	65.07	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	95.33
E-HCAD-25	yes	81.22
E-ANND-3	yes	5.19
E-MTAB-2983	no	11.36

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, TP53

miRNA regulators (miRDB)

167 targeting KCNH1, 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-4262	100.00	73.26	3931
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-22-3P	99.93	68.13	917

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• Regulation of an ERG K+ current by Src tyrosine kinase. (PMID:11834728)
• EAG channel activity in human tumors is shown for the first time. (PMID:15466192)
• Compounds like RPR260243 will be useful for studying the physiological role of HERG and may one day find use in treating cardiac disease. (PMID:15548764)
• identified three putative CaM-binding domains, two in the C-terminus (BD-C1: 674-683, BD-C2: 711-721) and one in the N-terminus (BD-N: 151-165) (PMID:16478480)
• It was shown that short interfering RNA sequences act specifically on EagI, reproducibly induce a significant decrease in the proliferation of tumor cell lines, and do not trigger any observable nonspecific responses. (PMID:16537547)
• High frequency of expression of Eag1 in primary tumours and the restriction of normal expression of the channel to the brain, suggests the application of this protein for diagnostic or therapeutic purposes. (PMID:17022811)
• analysis of KCNQ potassium channel mutations that cause cardiac arrhythmias in Drosophila, mimicing the effects of aging (PMID:17360457)
• Eag1 protein and mRNA are aberrantly expressed in colorectal cancer and occasionally expressed in colorectal adenoma. (PMID:17451210)
• IGF-1 regulates ether-a-go-go channel activity in breast neoplasms, via an Akt pathway to promote cell proliferation. (PMID:17520698)
• Eag1 is aberrantly expressed in gastric cancer tissues and cell lines and associated with cancer lymph node metastasis and stage and play an important role in the proliferation of gastric cancer cells. (PMID:17873312)
• Eag1 was aberrantly expressed in esophageal squamous cell carcinomas and correlated with poor prognosis after surgery. (PMID:18080766)
• Eag1 and Best1 improve intracellular Ca(2+) signaling and cell volume regulation. (PMID:18222922)
• The results indicate that Eag1 protein expression greatly overlaps with mRNA distribution in human. (PMID:18650019)
• Eag1 interferes with the cellular mechanism for maintaining oxygen homeostasis, increasing HIF-1 activity, and thereby VEGF secretion and tumor vascularization (PMID:18927085)
• 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)
• Calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. (PMID:19932096)
• hEag1 expression levels in acute myeloid leukemia as an independent predictive factor for reduced disease-free and overall survival. (PMID:20105281)
• Results suggest that regional differences in the relative abundance of ERG1 isoforms may represent a potential mechanism underlying the heterogeneity of both APD and APD restitution observed in mammalian hearts. (PMID:20126398)
• The BD-N and BD-C2 binding domains are sufficient for CaM binding to the native channel and BD-C1 is unable to bind CaM independently. (PMID:20523736)
• S100B is a potential alternative calcium sensor for hEAG1 potassium channels. (PMID:20708613)
• This study suggests that the SNPs within the kcnh1 genes we examined do not play a major role in schizophrenia in the Han Chinese population. (PMID:20933057)
• a role for Eag as a prognostic marker for survival in patients with ovarian cancer (PMID:21138547)
• This study is the first to demonstrate that K(+) channels such as hEag1 are directly involved in the IGF-1-induced up-regulation of cyclin D1 and E expression in MCF-7 cells. (PMID:21315112)
• Data suggest that to avoid the potential harmful side effect, hERG channel toxicity needs to be assessed in a timely and efficient fashion. (PMID:21320466)
• High EAG1 potassium channels is associated with epithelial-to-mesenchymal transition in lung cancer. (PMID:21508374)
• K(V)10.1 channels at the nuclear envelope might participate in the homeostasis of nuclear K(+), or indirectly interact with heterochromatin, both factors known to affect gene expression (PMID:21559285)
• We suggest Eag1 as a potential marker of cervical dysplasia and a risk indicator for developing cervical lesions in patients taking estrogens (PMID:21887469)
• These results demonstrate that hEAG1 channel activity is regulated by EGFR kinase at the tyrosine residues Tyr90, Try344, and Try485. (PMID:22061963)
• Overexpression of potassium channel ether a go-go is associated with osteosarcoma. (PMID:22248279)
• The functional state of KCNH1 channels is determined by the oxidative status of these linkers that provide an additional dimension of channel regulation. (PMID:22310694)
• KCNH1-encoded human hEAG1 potassium channel plays an important role in regulating the proliferation of induced pluripotent stem cells (PSC)-mesenchymal stem cells (MSCs) and bone marrow (BM)-MSCs. (PMID:22357737)
• hEAG1 expression is a biologically relevant feature that promotes cell proliferation and invasion, although independently of its ion-conducting function. (PMID:22466864)
• Human Eag1 may represent a target for the suppression of breast cancer cell migration, and thus prevention of metastasis development. (PMID:22495877)
• inhibition of either expression or activity of Eag1 leads to reduced proliferation of cancer cells, making Eag1 a potential anticancer target. Using Eag1 in cancer detection programs could help to reduce mortality from this disease (PMID:22778627)
• Silencing of Rabaptin-5 induces down-regulation of recycling of K(V)10.1 channel in transfected cells and reduction of K(V)10.1 current density in cells natively expressing K(V)10.1, indicating a role of Rabaptin-5 in channel trafficking. (PMID:22841712)
• Mutation Y464A in the S6 segment leads to EAG1 inactivation that can be prevented by additional mutations located in the S5 segment (F359A) or pore helix (L434A). (PMID:22930803)
• calcitriol antiproliferative effects by downregulating CYP24A1, upregulating vitamin D receptor (VDR) and targeting Eag1. (PMID:22984610)
• MiR-296-3p regulates cell growth and multi-drug resistance of human glioblastoma by targeting ether-a-go-go (EAG1). (PMID:22999387)
• Cortactin controls surface expression of the voltage-gated potassium channel K(V)10.1. (PMID:23144454)
• Eag1 K+ channel and ErbB were expressed in all human pituitary adenomas examined while ErbB2 expression was more variable. (PMID:23413122)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnh1b	ENSDARG00000023236
danio_rerio	kcnh1a	ENSDARG00000024167
mus_musculus	Kcnh1	ENSMUSG00000058248
rattus_norvegicus	Kcnh1	ENSRNOG00000003841
drosophila_melanogaster	eag	FBGN0000535
caenorhabditis_elegans		WBGENE00000487
caenorhabditis_elegans		WBGENE00022295

Paralogs (17): KCNH2 (ENSG00000055118), CNGB1 (ENSG00000070729), KCNH4 (ENSG00000089558), HCN2 (ENSG00000099822), CNGA4 (ENSG00000132259), KCNH3 (ENSG00000135519), HCN4 (ENSG00000138622), KCNH5 (ENSG00000140015), HCN3 (ENSG00000143630), CNGA3 (ENSG00000144191), HCN1 (ENSG00000164588), CNGB3 (ENSG00000170289), KCNH6 (ENSG00000173826), CNGA2 (ENSG00000183862), KCNH8 (ENSG00000183960), KCNH7 (ENSG00000184611), CNGA1 (ENSG00000198515)

Protein

Protein identifiers

Voltage-gated delayed rectifier potassium channel KCNH1 — O95259 (reviewed: O95259)

Alternative names: Ether-a-go-go potassium channel 1, Potassium voltage-gated channel subfamily H member 1, Voltage-gated potassium channel subunit Kv10.1

All UniProt accessions (11): O95259, A0A0S1TJ81, A0A1W2PNI2, A0A1W2PP68, A0A1W2PPA2, A0A1W2PRD8, A0A1W2PRG6, A0A1W2PRV9, A0A1W2PRZ5, A0A1W2PS62, A0A1X7SBS6

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 activation kinetics depend on the prepulse potential and external divalent cation concentration. With negative prepulses, the current activation is delayed and slowed down several fold, whereas more positive prepulses speed up activation. The time course of activation is biphasic with a fast and a slowly activating current component. Activates at more positive membrane potentials and exhibit a steeper activation curve. Channel properties are modulated by subunit assembly. Mediates IK(NI) current in myoblasts. Involved in the regulation of cell proliferation and differentiation, in particular adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (MSCs).

Subunit / interactions. Homomultimer. The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits. Heteromultimer with KCNH5/EAG2. Interacts with ALG10B. Interacts with RABEP1. Interacts (via C-terminus) with CTTN. Interacts (via C-terminal cytoplasmic region) with Ca(2+)-bound calmodulin. Interacts with the spider kappa-theraphotoxin-Aa1a and mu/kappa-theraphotoxin-Ap1a.

Subcellular location. Cell membrane. Nucleus inner membrane. Cell projection. Dendrite. Axon. Presynaptic cell membrane. Perikaryon. Postsynaptic density membrane. Early endosome membrane.

Tissue specificity. Highly expressed in brain and in myoblasts at the onset of fusion, but not in other tissues. Detected in HeLa (cervical carcinoma), SH-SY5Y (neuroblastoma) and MCF-7 (epithelial tumor) cells, but not in normal epithelial cells.

Post-translational modifications. Channel activity is regulated via tyrosine phosphorylation/dephosphorylation by SRC and PTPN6.

Disease relevance. Temple-Baraitser syndrome (TMBTS) [MIM:611816] A developmental disorder characterized by intellectual disability, epilepsy, hypoplasia or aplasia of the thumb and great toe nails, and broadening and/or elongation of the thumbs and halluces, which have a tubular aspect. Some patients show facial dysmorphism. The disease is caused by variants affecting the gene represented in this entry. Zimmermann-Laband syndrome 1 (ZLS1) [MIM:135500] A form of Zimmermann-Laband syndrome, a rare developmental disorder characterized by facial dysmorphism with bulbous nose and thick floppy ears, gingival enlargement, hypoplasia or aplasia of terminal phalanges and nails, hypertrichosis, joint hyperextensibility, and hepatosplenomegaly. Some patients manifest intellectual disability with or without epilepsy. ZLS1 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Channel activity is inhibited by interaction with Ca(2+)-bound calmodulin. Interaction of a single pore-forming alpha subunit with a calmodulin chain is sufficient to promote channel closure. Channel activity is not regulated by cyclic nucleotides. Channel activity is inhibited by binding intracellular phosphatidylinositol-3,5-bisphosphate and phosphatidylinositol-4,5-bisphosphate (PIP2), but is not inhibited by phosphatidylinositol 4-phosphate. Inhibited by the spider kappa-theraphotoxin-Aa1a and mu/kappa-theraphotoxin-Ap1a.

Domain organisation. The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Conformational changes of voltage-sensor are driven by an electric field generated by a potassium gradient across the membrane. The C-terminal region interacts with the cyclic nucleotide-binding domain and contributes to regulate channel gating. The PAS and PAC domain interact with the cyclic nucleotide-binding domain and contribute to the regulation of channel gating. Calmodulin binding clamps together the PAS and PAC domain with the cyclic nucleotide-binding domain from a neighboring subunit and causes a conformation change that leads to channel closure. The cyclic nucleotide-binding domain lacks residues that are essential for nucleotide-binding and cannot bind cyclic nucleotides. Instead, residues from the C-terminal domain (the so-called intrinsic ligand) bind in the cavity that would be expected to bind cyclic nucleotides. Interaction with the C-terminal region hinders interaction with CALM and reduces the affinity for CALM. The PAS and the cyclic nucleotide-binding domain (CNBHD) interact with the transmembrane voltage sensors (VS) that modulate voltage-dependent gating and provide evidence that VS movement destabilizes these interactions to promote channel opening.

Similarity. Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv10.1/KCNH1 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O95259-1	2, hEAGB	yes
O95259-2	1, hEAG

RefSeq proteins (2): NP_002229, NP_758872* (*=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	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 (55 total): sequence variant 9, topological domain 8, transmembrane region 6, region of interest 6, strand 5, helix 4, modified residue 3, mutagenesis site 3, domain 2, compositionally biased region 2, glycosylation site 2, chain 1, intramembrane region 1, short sequence motif 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5J7E	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95259-F1	73.78	0.41

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 (3): 974, 978, 981

Glycosylation sites (2): 415, 433

Mutagenesis-validated functional residues (3):

Position	Phenotype
699–701	shifts the voltage-dependence of channel gating and decreases the rate of channel opening.
737	abolishes inhibition of channel activity by elevated cytoplasmic ca(2+).
740	abolishes inhibition of channel activity by elevated cytoplasmic ca(2+).

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: 460 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, BENPORATH_ES_WITH_H3K27ME3, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, MORF_EPHA7, MORF_RAB3A, GOBP_REGULATION_OF_CYTOSOLIC_CALCIUM_ION_CONCENTRATION, GOBP_CELLULAR_RESPONSE_TO_CALCIUM_ION, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_MYOTUBE_DIFFERENTIATION, GOCC_NEURON_PROJECTION

GO Biological Process (9): potassium ion transport (GO:0006813), myoblast fusion (GO:0007520), regulation of cell population proliferation (GO:0042127), regulation of membrane potential (GO:0042391), cellular response to calcium ion (GO:0071277), potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (8): delayed rectifier potassium channel activity (GO:0005251), calmodulin binding (GO:0005516), phosphatidylinositol bisphosphate binding (GO:1902936), monoatomic ion channel activity (GO:0005216), voltage-gated potassium channel activity (GO:0005249), potassium channel activity (GO:0005267), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (16): nuclear inner membrane (GO:0005637), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), axon (GO:0030424), dendrite (GO:0030425), early endosome membrane (GO:0031901), presynaptic membrane (GO:0042734), perikaryon (GO:0043204), postsynaptic density membrane (GO:0098839), nucleus (GO:0005634), endosome (GO:0005768), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702), cell projection (GO:0042995), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

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
cellular anatomical structure	3
transport	2
binding	2
neuron projection	2
synaptic membrane	2
metal ion transport	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
cell population proliferation	1
regulation of cellular process	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
response to calcium ion	1
cellular response to metal ion	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
protein binding	1
anion 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
organelle inner membrane	1
nuclear membrane	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
dendritic tree	1
early endosome	1
endosome membrane	1
presynapse	1
neuronal cell body	1
postsynaptic density	1

Protein interactions and networks

STRING

1066 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNH1	LPGAT1	Q92604	833
KCNH1	PPP2R5A	Q15172	781
KCNH1	CALM1	P02593	701
KCNH1	CALML3	P27482	658
KCNH1	KCNMA1	Q12791	658
KCNH1	CALML5	Q9NZT1	658
KCNH1	CALML6	Q8TD86	652
KCNH1	CALML4	Q96GE6	652
KCNH1	KCNB1	Q14721	594
KCNH1	KCNA2	P16389	584
KCNH1	KCNA3	P22001	584
KCNH1	LAMB3	Q13751	583
KCNH1	SCN5A	Q14524	579
KCNH1	ORAI1	Q96D31	559
KCNH1	KCNA4	P22459	522

IntAct

22 interactions, top by confidence:

A	B	Type	Score
CALM1	KCNH1	psi-mi:“MI:0407”(direct interaction)	0.720
KCNH1	CALM1	psi-mi:“MI:0407”(direct interaction)	0.720
KCNH1	CALM1	psi-mi:“MI:0915”(physical association)	0.720
KCNH1	SDCBP	psi-mi:“MI:0915”(physical association)	0.560
KCNH1	FASTKD5	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	KCNH1	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	KCNH1	psi-mi:“MI:0915”(physical association)	0.560
FASTKD5	KCNH1	psi-mi:“MI:0915”(physical association)	0.560
KCNH1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
KCNH1	S100B	psi-mi:“MI:0915”(physical association)	0.400
Rabep1	KCNH1	psi-mi:“MI:0915”(physical association)	0.370
KCNH1	Kcnh1	psi-mi:“MI:0915”(physical association)	0.370
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
RABEP1	KCNH1	psi-mi:“MI:0403”(colocalization)	0.270
RAB11A	KCNH1	psi-mi:“MI:0403”(colocalization)	0.270
KCNH1	RAB7A	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (21): SDCBP (Two-hybrid), WDYHV1 (Two-hybrid), FASTKD5 (Two-hybrid), KCNH1 (Affinity Capture-MS), KCNH1 (Protein-RNA), KCNH1 (Two-hybrid), KCNH1 (Two-hybrid), KCNH1 (Two-hybrid), KCNH1 (Affinity Capture-Western), KCNH1 (Affinity Capture-MS), KCNH1 (Affinity Capture-Western), MKRN1 (Affinity Capture-Western), KCNH1 (Reconstituted Complex), KCNH1 (Affinity Capture-MS), KCNH1 (Affinity Capture-Western)

ESM2 similar proteins: A0A0M3R8G1, A0A0M4FLW6, A9YWR6, B8ALI0, D3GE74, D4AYW0, H6WS93, H6WS94, O81016, O95259, P29973, P45844, P50530, P93025, Q00194, Q00195, Q03720, Q16281, Q28279, Q2PCF1, Q2QV81, Q5W274, Q5Z9S8, Q60603, Q62398, Q62927, Q63472, Q64343, Q7PC84, Q7PC86, Q7PC87, Q84K47, Q8GU83, Q8GU92, Q8H8V7, Q8RWI9, Q8RXN0, Q90805, Q93YS4, Q9C8J8

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

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	9
Uncertain significance	391
Likely benign	346
Benign	68

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
1375576	NM_172362.3(KCNH1):c.1379G>A (p.Ser460Asn)	Pathogenic
1451849	NM_172362.3(KCNH1):c.1790T>C (p.Phe597Ser)	Pathogenic
162520	NM_172362.3(KCNH1):c.1480A>G (p.Ile494Val)	Pathogenic
162521	NM_172362.3(KCNH1):c.1546C>T (p.Leu516Phe)	Pathogenic
162522	NM_172362.3(KCNH1):c.1508A>G (p.Gln503Arg)	Pathogenic
162523	NM_172362.3(KCNH1):c.651G>C (p.Lys217Asn)	Pathogenic
183415	NM_172362.3(KCNH1):c.1123G>A (p.Gly375Arg)	Pathogenic
183416	NM_172362.3(KCNH1):c.1135C>G (p.Leu379Val)	Pathogenic
183417	NM_172362.3(KCNH1):c.1147G>C (p.Val383Leu)	Pathogenic
183419	NM_172362.3(KCNH1):c.1055C>A (p.Ser352Tyr)	Pathogenic
2499611	NM_172362.3(KCNH1):c.1123G>C (p.Gly375Arg)	Pathogenic
2709304	NM_172362.3(KCNH1):c.1060A>G (p.Lys354Glu)	Pathogenic
3340366	NM_172362.3(KCNH1):c.1474G>A (p.Ala492Thr)	Pathogenic
449572	NM_172362.3(KCNH1):c.1465C>T (p.Leu489Phe)	Pathogenic
1034355	NM_172362.3(KCNH1):c.1559G>A (p.Arg520Gln)	Likely pathogenic
1690786	NM_172362.3(KCNH1):c.1481T>C (p.Ile494Thr)	Likely pathogenic
2505231	NM_172362.3(KCNH1):c.210G>A (p.Met70Ile)	Likely pathogenic
2584506	NM_172362.3(KCNH1):c.1678C>T (p.Pro560Ser)	Likely pathogenic
420958	NM_172362.3(KCNH1):c.1062A>C (p.Lys354Asn)	Likely pathogenic
4530651	NM_172362.3(KCNH1):c.1070G>T (p.Arg357Leu)	Likely pathogenic
560720	NM_172362.3(KCNH1):c.596A>G (p.Lys199Arg)	Likely pathogenic
633559	NM_172362.3(KCNH1):c.881C>T (p.Thr294Met)	Likely pathogenic
807914	NM_172362.3(KCNH1):c.1478C>A (p.Thr493Asn)	Likely pathogenic

SpliceAI

3782 predictions. Top by Δscore:

Variant	Effect	Δscore
1:210684134:ACAAT:A	acceptor_gain	1.0000
1:210684135:CAAT:C	acceptor_gain	1.0000
1:210684135:CAATC:C	acceptor_gain	1.0000
1:210684136:AAT:A	acceptor_gain	1.0000
1:210684137:AT:A	acceptor_gain	1.0000
1:210684137:ATC:A	acceptor_loss	1.0000
1:210684139:C:CC	acceptor_gain	1.0000
1:210684140:T:A	acceptor_loss	1.0000
1:210775342:GCTCA:G	donor_loss	1.0000
1:210775343:CTCAC:C	donor_loss	1.0000
1:210775344:TCA:T	donor_loss	1.0000
1:210775345:CAC:C	donor_loss	1.0000
1:210775346:A:AC	donor_gain	1.0000
1:210775346:AC:A	donor_gain	1.0000
1:210775347:C:CC	donor_gain	1.0000
1:210775347:C:CG	donor_loss	1.0000
1:210775347:CC:C	donor_gain	1.0000
1:210775347:CCCT:C	donor_gain	1.0000
1:210775353:T:TA	donor_gain	1.0000
1:210775542:TTCC:T	acceptor_loss	1.0000
1:210775543:TCCTA:T	acceptor_loss	1.0000
1:210775545:CT:C	acceptor_loss	1.0000
1:210775546:T:C	acceptor_loss	1.0000
1:210781389:C:A	donor_gain	1.0000
1:210797503:CCTA:C	donor_loss	1.0000
1:210797504:CTA:C	donor_loss	1.0000
1:210797505:TACCT:T	donor_loss	1.0000
1:210797507:C:CG	donor_loss	1.0000
1:210797520:C:CT	donor_gain	1.0000
1:210797521:C:CT	donor_gain	1.0000

AlphaMissense

6554 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:210684020:A:G	F744S	1.000
1:210684029:A:G	F741S	1.000
1:210684032:A:G	L740P	1.000
1:210684041:A:T	V737D	1.000
1:210684046:G:C	H735Q	1.000
1:210684046:G:T	H735Q	1.000
1:210684047:T:C	H735R	1.000
1:210684130:G:C	F707L	1.000
1:210684130:G:T	F707L	1.000
1:210684131:A:G	F707S	1.000
1:210684132:A:G	F707L	1.000
1:210775358:A:C	L701W	1.000
1:210775358:A:G	L701S	1.000
1:210775376:A:G	L695P	1.000
1:210775387:G:C	F691L	1.000
1:210775387:G:T	F691L	1.000
1:210775388:A:G	F691S	1.000
1:210775389:A:G	F691L	1.000
1:210775399:G:C	F687L	1.000
1:210775399:G:T	F687L	1.000
1:210775400:A:C	F687C	1.000
1:210775400:A:G	F687S	1.000
1:210775401:A:G	F687L	1.000
1:210775411:G:C	F683L	1.000
1:210775411:G:T	F683L	1.000
1:210775412:A:G	F683S	1.000
1:210775413:A:G	F683L	1.000
1:210775418:A:G	L681P	1.000
1:210775430:A:G	L677P	1.000
1:210775445:A:T	I672N	1.000

dbSNP variants (sampled 300 via entrez): RS1000004045 (1:211081641 T>TA), RS1000008195 (1:211125400 T>C), RS1000016310 (1:211122450 A>C), RS1000018206 (1:210921950 C>T), RS1000052501 (1:210792791 CT>C), RS1000057316 (1:211000142 A>G,T), RS1000059416 (1:210723501 A>C), RS1000063012 (1:210963617 A>G), RS1000068418 (1:210895561 T>C), RS1000073117 (1:211077598 C>G), RS1000081900 (1:210823637 G>A), RS1000089656 (1:210846249 C>A), RS1000092515 (1:211036361 G>A), RS1000103573 (1:210837311 A>G), RS1000107873 (1:210850185 C>G,T)

Disease associations

OMIM: gene MIM:603305 | disease phenotypes: MIM:611816, MIM:135500

GenCC curated gene-disease

Disease	Classification	Inheritance
Temple-Baraitser syndrome	Strong	Autosomal dominant
KCNH1 associated disorder	Strong	Autosomal dominant
Zimmermann-Laband syndrome 1	Moderate	Autosomal dominant
Zimmermann-Laband syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
KCNH1 associated disorder	Definitive	AD

Mondo (7): Temple-Baraitser syndrome (MONDO:0012735), Zimmermann-Laband syndrome 1 (MONDO:0024526), KCNH1 associated disorder (MONDO:0100485), epilepsy (MONDO:0005027), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), Zimmermann-Laband syndrome (MONDO:0000200)

Orphanet (3): Temple-Baraitser syndrome (Orphanet:420561), Zimmermann-Laband syndrome (Orphanet:3473), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

129 total (30 of 129 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000040	Long penis
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000169	Gingival fibromatosis
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000194	Open mouth
HP:0000212	Gingival overgrowth
HP:0000218	High palate
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000272	Malar flattening
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000294	Low anterior hairline
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000400	Macrotia

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001853_1	Circulating vasoactive peptide levels	2.000000e-06
GCST002930_14	Cobalt levels	7.000000e-06
GCST003101_1	Bone mineral density (spine) and age at menarche	2.000000e-06
GCST003587_3	Cancer	1.000000e-07
GCST003611_2	Bone mineral density (total hip)	2.000000e-07
GCST003612_2	Bone mineral density (femoral neck)	2.000000e-07
GCST006988_68	Blond vs. brown/black hair color	7.000000e-09
GCST010056_2	Cholesterol	9.000000e-06
GCST012488_31	L1-L4 bone mineral density x serum urate levels interaction	1.000000e-07
GCST90002383_346	Hematocrit	8.000000e-11
GCST90002384_23	Hemoglobin	5.000000e-10

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0005196	vasoactive peptide measurement
EFO:0004703	age at menarche
EFO:0007701	spine bone mineral density
EFO:1001515	ovarian endometrioid carcinoma
EFO:1001516	ovarian serous carcinoma
EFO:0007702	hip bone mineral density
EFO:0007785	femoral neck bone mineral density
EFO:0003924	hair color
EFO:0007806	total cholesterol change measurement
EFO:0004531	urate measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

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
C567516	Temple-Baraitser Syndrome (supp.)
C536725	Zimmerman Laband syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2362996 (PROTEIN FAMILY), CHEMBL3841 (SINGLE PROTEIN)

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 (12 total), top 12:

Ligand	Action	Affinity	Parameter
LY97241	Channel blocker	8.3	pIC50
terfenadine	Channel blocker	7.8	pIC50
dofetilide	Channel blocker	7.5	pIC50
calmodulin	Channel blocker	7.2	pIC50
astemizole	Channel blocker	6.7	pIC50
clofilium	Channel blocker	6.6	pIC50
E4031	Channel blocker	6.4	pIC50
haloperidol	Channel blocker	6.2	pIC50
MK-499	Channel blocker	6.0	pIC50
ICA-105574	Inhibition	5.9	pIC50
quinidine	Channel blocker	5.8	pIC50
imipramine	Channel blocker	5.7	pIC50

ChEMBL bioactivities

7 potent at pChembl≥5 of 8 total, top 7 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
6.31	IC50	490	nM	CHEMBL3261075
5.75	IC50	1780	nM	CHEMBL4521954
5.43	IC50	3720	nM	CHEMBL4557890
5.38	IC50	4170	nM	CHEMBL4525199
5.14	IC50	7240	nM	CHEMBL4441612

PubChem BioAssay actives

7 with measured affinity, of 57 total; 6 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-[3-[(3R)-1-amino-3-methyl-4H-pyrrolo[1,2-a]pyrazin-3-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	1511280: Inhibition of human ERG	ic50	0.4900	uM
N-[3-[(6R)-4-amino-6-methyl-7H-pyrazolo[1,5-a]pyrazin-6-yl]phenyl]-5-cyanopyridine-2-carboxamide	1511280: Inhibition of human ERG	ic50	1.7800	uM
N-[3-[(6R)-8-amino-6-methyl-5H-imidazo[1,5-a]pyrazin-6-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	1511280: Inhibition of human ERG	ic50	3.7200	uM
N-[3-[(6R)-8-amino-6-methyl-5H-imidazo[1,2-a]pyrazin-6-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	1511280: Inhibition of human ERG	ic50	4.1700	uM
N-[3-[(6R)-4-amino-6-methyl-7H-triazolo[1,5-a]pyrazin-6-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	1511280: Inhibition of human ERG	ic50	7.2400	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Astemizole	affects binding, decreases activity, decreases reaction, increases activity	7
E 4031	decreases activity, affects binding	2
FR900359	decreases phosphorylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
desmethylastemizole	decreases activity	1
CGP 52608	affects binding, increases reaction	1
procyanidin B1	affects binding, decreases activity	1
jinfukang	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression	1
Wortmannin	decreases reaction, increases activity	1
Zoledronic Acid	decreases expression	1
Fulvestrant	affects cotreatment, increases expression, decreases reaction, decreases expression	1
Barium	decreases activity	1
Benperidol	affects binding, decreases activity	1
Benzamides	affects binding, decreases activity	1
Benzo(a)pyrene	affects methylation	1
Butyrophenones	affects binding, decreases activity	1
Cisplatin	decreases expression, affects cotreatment	1
Dibenzoxazepines	affects binding, decreases activity	1
Estradiol	affects cotreatment, increases expression, decreases reaction	1
Imipramine	affects binding, decreases activity	1
Piperidines	affects binding, decreases activity	1
Quinidine	decreases reaction, increases activity	1
Sulpiride	affects binding, decreases activity	1
Tamoxifen	affects cotreatment, increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

24 unique, capped per target: 23 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

Cellosaurus cell lines

3 cell lines: 1 induced pluripotent stem cell, 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4ZF	ZJUCHi003-A	Induced pluripotent stem cell	Female
CVCL_D7T2	Ubigene A-549 KCNH1 KO	Cancer cell line	Male
CVCL_E5JF	HEK293 Kv10.1	Transformed cell line	Female

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
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