KCNE1

Summary

KCNE1 (potassium voltage-gated channel subfamily E regulatory subunit 1, HGNC:6240) is a protein-coding gene on chromosome 21q22.12, encoding Potassium voltage-gated channel subfamily E member 1 (P15382). Ancillary protein that functions as a regulatory subunit of the voltage-gated potassium (Kv) channel complex composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunits.

The product of this gene belongs to the potassium channel KCNE family. Potassium ion channels are essential to many cellular functions and show a high degree of diversity, varying in their electrophysiologic and pharmacologic properties. This gene encodes a transmembrane protein known to associate with the product of the KVLQT1 gene to form the delayed rectifier potassium channel. Mutation in this gene are associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long-QT syndrome. Alternatively spliced transcript variants encoding the same protein have been identified.

Source: NCBI Gene 3753 — RefSeq curated summary.

At a glance

• Gene–disease (curated): long QT syndrome 5 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 98
• Clinical variants (ClinVar): 1,273 total — 13 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 37
• Druggable target: yes — 14 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000219

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6240
Approved symbol	KCNE1
Name	potassium voltage-gated channel subfamily E regulatory subunit 1
Location	21q22.12
Locus type	gene with protein product
Status	Approved
Aliases	minK, IsK, JLNS2, LQT5
Ensembl gene	ENSG00000180509
Ensembl biotype	protein_coding
OMIM	176261
Entrez	3753

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000337385, ENST00000399284, ENST00000399286, ENST00000399289, ENST00000416357, ENST00000432085, ENST00000489175, ENST00000611936, ENST00000621601, ENST00000683028, ENST00000683564, ENST00000684073, ENST00000684327, ENST00000684616, ENST00000878208, ENST00000878209, ENST00000878210, ENST00000878211, ENST00000878212, ENST00000942358, ENST00000942359

RefSeq mRNA: 8 — MANE Select: NM_000219 NM_000219, NM_001127668, NM_001127669, NM_001127670, NM_001270402, NM_001270403, NM_001270404, NM_001270405

CCDS: CCDS13636

Canonical transcript exons

ENST00000399286 — 4 exons

Exon	Start	End
ENSE00001340746	34458654	34458764
ENSE00001340749	34511101	34511315
ENSE00001340756	34512027	34512210
ENSE00001954035	34446690	34449684

Expression profiles

Bgee: expression breadth ubiquitous, 121 present calls, max score 83.80.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7010 / max 89.1706, expressed in 263 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190279	1.1149	215
190280	0.3617	135
190278	0.1462	81
190277	0.0636	22
209302	0.0143	3
190276	0.0003	0

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	83.80	gold quality
monocyte	CL:0000576	81.38	gold quality
leukocyte	CL:0000738	80.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.57	gold quality
granulocyte	CL:0000094	76.93	gold quality
spleen	UBERON:0002106	72.23	gold quality
right lung	UBERON:0002167	71.26	gold quality
upper lobe of left lung	UBERON:0008952	71.12	gold quality
apex of heart	UBERON:0002098	70.90	gold quality
bone marrow cell	CL:0002092	70.69	gold quality
fallopian tube	UBERON:0003889	70.39	gold quality
heart left ventricle	UBERON:0002084	70.29	gold quality
bone marrow	UBERON:0002371	70.14	gold quality
right uterine tube	UBERON:0001302	70.02	gold quality
right lobe of liver	UBERON:0001114	69.26	gold quality
liver	UBERON:0002107	68.58	gold quality
lung	UBERON:0002048	68.38	gold quality
vermiform appendix	UBERON:0001154	68.17	gold quality
heart	UBERON:0000948	68.09	gold quality
right atrium auricular region	UBERON:0006631	67.65	gold quality
cortical plate	UBERON:0005343	65.69	gold quality
omental fat pad	UBERON:0010414	63.05	gold quality
adult mammalian kidney	UBERON:0000082	62.88	gold quality
adipose tissue	UBERON:0001013	62.11	gold quality
subcutaneous adipose tissue	UBERON:0002190	61.39	gold quality
left uterine tube	UBERON:0001303	61.07	gold quality
mucosa of stomach	UBERON:0001199	60.67	gold quality
right adrenal gland cortex	UBERON:0035827	59.88	gold quality
right adrenal gland	UBERON:0001233	59.62	gold quality
left adrenal gland	UBERON:0001234	59.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NKX2-5, SP1, TFAP2A, THRA

miRNA regulators (miRDB)

88 targeting KCNE1, 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-6873-3P	100.00	71.42	2626
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055

Literature-anchored findings (GeneRIF, showing 40)

• binds sarcomeric protein T-cap (telethonin) (PMID:11697903)
• regulation by PKA-dependent phosphorylation requires a macromolecular complex that includes PKA, PP1, and the targeting protein yotiao (PMID:11799244)
• We report the association between the minK 38G allele and clinical atrial fibrillation. (PMID:12228786)
• All three members of the SGK family of kinases SGK1-3 and protein kinase B stimulate the slowly activating K(+) channel KCNE1/KCNQ1. The kinases may thus participate in the regulation of KCNE1-dependent transport and excitability. (PMID:12634932)
• Two MinK subunits are necessary, sufficient, and the norm in I(Ks) voltage-gated potassium channels. (PMID:14527430)
• ER quality control prevents minK-L51H/KvLQT1 complexes from trafficking to the plasma membrane, resulting in decreased I(Ks). (PMID:14761891)
• Expression of KCNQ1 and KCNE1 associated with early stages of spermatogenesis and with presence of undifferentiated healthy or neoplastic germ cells. KCNQ1/KCNE1 may be involved in K+ transport, probably during germ-cell development. (PMID:15389592)
• A a variant upstream of the KCNE1 gene (rs727957, +1.2 ms/allele, P=0.0051)is associated with QT interval length. (PMID:15746444)
• This suggests that genetic determinants located in KCNQ1, KCNE1, KCNH2 and SCN5A influence QTc length in healthy individuals and may represent risk factors for arrhythmias or cardiac sudden death in patients with cardiovascular diseases. (PMID:16132053)
• Potassium channel gene variants are associated with inherited long QT syndromes (PMID:16266404)
• interaction of MiRP2-72 with KCNQ1-338; and MinK-59,58 with KCNQ1-339, 340 (PMID:16308347)
• The result indicates that 112G/A SNP in the KCNE1 gene and 198T/C SNP in the KCNE3 gene could determine an increased susceptibility to develop MD. (PMID:16374062)
• None of the SNPs of KCNE1 were associated with atrial fibrillation phenotype. (PMID:16563243)
• did not find any mutations in aldosterone-secreting adenomas (PMID:16610241)
• These results suggest that KCNE2 can functionally couple to KCNQ1 even in the presence of KCNE1. (PMID:16631607)
• Polymorphisms within the KCNE1 gene are associated with susceptibility Noise-induced hearing loss. (PMID:16823764)
• no association between atrial fibrillation and single nucleotide polymorphisms (PMID:17016049)
• The errant KCNE1 trafficking observed in human embryonic kidney cells may be due, in part, to the presence of endogenous voltage-gated potassium channels in these cells. (PMID:17065152)
• G38S polymorphism in the MinK gene seems to be associated with incidence of lone AF in the population; GG genotype may relate to increased risk of AF in the study; G38S polymorphism in the MinK gene could be used as a genetic marker of risk of lone AF. (PMID:17165161)
• We demonstrated that 9.5% of cases diagnosed as SIDS carry functionally significant genetic variants in LQTS genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CAV3). (PMID:17210839)
• External pH can modify current amplitude and biophysical properties of KCNQ1. KCNE subunits work as molecular switches by modulating the pH sensitivity of human KCNQ1. (PMID:17310097)
• KCNE1 mutations may be associated with mild LQTS phenotypes, and KCNE1 gene screening is of clinical importance for asymptomatic and mild LQTS patients. (PMID:17341399)
• In chronic heart failure (CHF), the relative abundance of KCNE1 compared to KCNQ1 genes might contribute to the prolongation of QT interval through reducing the net outward current during the plateau of the action potential. (PMID:17384445)
• biophysical analysis of MinK in IK channels shows an alpha-helical transmembrane span traversing the channel corpus (PMID:17545244)
• postrepolarization refractoriness to I(Ks) (coassembly of KCNQ1 and KCNE1 )can promote wavebreak formation and fibrillatory conduction during pacing and sustained reentry and may have important implications in tachyarrhythmias (PMID:17626898)
• analysis of data from 186 Jervell and Lange-Nielsen syndrome patients; most mutations (90.5%) are on the KCNQ1 gene; mutations on the KCNE1 gene are associated with a more benign course (PMID:17646758)
• KCNE1’s secondary structure includes several alpha-helices and demonstrate that its distal C-terminus is disordered. (PMID:17892302)
• Results suggest that during biogenesis of channels HERG is more likely to assemble with KCNE1 than KCNE2 due to distinctly different trafficking rates and retention in the cell rather than differences in relative affinity. (PMID:17895974)
• The components of the cardiac slow rectifier channel are discussed. (PMID:17980676)
• KCNE peptides differently modulate the voltage sensor in KCNQ1 K(+) channels. (PMID:18079560)
• KCNE1 is probably the major K(+)-channel involved in regulatory volume decrease in human spermatozoa, and channel activity is regulated beyond the extent of protein expression. (PMID:18157847)
• KCNE4 directly associates with KCNQ1, and can co-associate together with KCNE1 in the same KCNQ1 complex to form a ’triple subunit’ complex (KCNE1-KCNQ1-KCNE4). (PMID:18279388)
• KCNE1 lodges at the inter-VSD S4-S1 interface between two adjacent subunits, a strategic location to exert its striking action on Kv7.1 gating functions (PMID:18398469)
• W248F KCNQ1 plus KCNE1 channels reconstitute hardly measurable I(Ks) currents in Jervell and Lange Nielsen syndrome (PMID:18441444)
• introducing 40-43Cys showed that Cys145 of the KCNQ1 can form disulfide bonds with 40C and 41C, but not E1 42C or 43C (coexpression in COS-7 cells and oocytes) (PMID:18504315)
• Data show that transmembrane domain of KCNE1 is a curved alpha-helix and is flanked by intra- and extracellular domains that forms an interface with an intersubunit cleft in KCNQ1 that is associated with most known gain-of-function disease mutations. (PMID:18611041)
• The effect of 3 ion channel gene single nucleotide polymorphisms (SNPs), rs1805127, rs727957 KCNE1, and rs1805124 SCN5A, on T-wave alternans during a clinical exercise test, was examined. (PMID:18674739)
• Modeling of the adrenergic response of the human IKs current (hKCNQ1/hKCNE1) stably expressed in HEK-293 cells. (PMID:18757482)
• In post-MI patients two exonic polymorphisms, H558R in SCN5A and S38G in KCNE1 were detected. H558R was associated with an increase in QT dispersion at minimum and maximum heart rate and QT interval prolongation before premature ventricular beats (PMID:18803136)
• Depolarization of embryonic cells by misexpression of KCNE1 induced melanocytes to overproliferate, spread out, and become highly invasive of blood vessels, liver, gut, and neural tube, leading to a deeply hyperpigmented phenotype (PMID:18931301)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kcne1	ENSMUSG00000039639
rattus_norvegicus	Kcne1	ENSRNOG00000001984

Paralogs (1): KCNE2 (ENSG00000159197)

Protein

Protein identifiers

Potassium voltage-gated channel subfamily E member 1 — P15382 (reviewed: P15382)

Alternative names: Delayed rectifier potassium channel subunit IsK, IKs producing slow voltage-gated potassium channel subunit beta Mink, Minimal potassium channel

All UniProt accessions (2): C7S316, P15382

UniProt curated annotations — full annotation on UniProt →

Function. Ancillary protein that functions as a regulatory subunit of the voltage-gated potassium (Kv) channel complex composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunits. KCNE1 beta subunit modulates the gating kinetics and enhances stability of the channel complex. Alters the gating of the delayed rectifier Kv channel containing KCNB1 alpha subunit. Associates with KCNQ1/KVLQT1 alpha subunit to form the slowly activating delayed rectifier cardiac potassium (IKs) channel responsible for ventricular muscle action potential repolarization. The outward current reaches its steady state only after 50 seconds. Assembly with KCNH2/HERG alpha subunit Kv channel may regulate the rapidly activating component of the delayed rectifying potassium current (IKr) in heart.

Subunit / interactions. Interacts with KCNB1. Interacts with KCNC2. Associates with KCNH2/HERG. Interacts with KNCQ1; targets the complex KNCQ1-KCNE1 to the membrane raft. The complex KNCQ1-KNCE1 interacts with the scolopendra toxin SSD609.

Subcellular location. Cell membrane. Apical cell membrane. Membrane raft.

Tissue specificity. Expressed in lung, kidney, testis, ovaries, small intestine, peripheral blood leukocytes. Expressed in the heart. Not detected in pancreas, spleen, prostate and colon. Restrictively localized in the apical membrane portion of epithelial cells.

Post-translational modifications. Phosphorylation inhibits the potassium current. N-glycosylation at Asn-26 occurs post-translationally, and requires prior cotranslational glycosylation at Asn-5.

Disease relevance. Jervell and Lange-Nielsen syndrome 2 (JLNS2) [MIM:612347] An autosomal recessive disorder characterized by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death. The disease is caused by variants affecting the gene represented in this entry. Long QT syndrome 5 (LQT5) [MIM:613695] A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the potassium channel KCNE family.

RefSeq proteins (8): NP_000210, NP_001121140, NP_001121141, NP_001121142, NP_001257331, NP_001257332, NP_001257333, NP_001257334 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000369	K_chnl_KCNE	Family
IPR005424	KCNE1	Family

Pfam: PF02060

UniProt features (53 total): sequence variant 27, mutagenesis site 9, helix 5, glycosylation site 3, turn 2, chain 1, transmembrane region 1, topological domain 1, region of interest 1, site 1, modified residue 1, strand 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9VEC	ELECTRON MICROSCOPY	2.7
9U7F	ELECTRON MICROSCOPY	2.9
9UC8	ELECTRON MICROSCOPY	3.36
9VEI	ELECTRON MICROSCOPY	3.9
2K21	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15382-F1	70.91	0.14

Functional residue map

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

Catalytic / active sites (1): 19 (interacts with the scolopendra toxin ssd609)

Post-translational modifications (1): 102

Glycosylation sites (3): 5, 7, 26

Mutagenesis-validated functional residues (9):

Position	Phenotype
5	no measurable effect on assembly with kcnq1 or cell surface expression of the kcne1/kcnq1 channel complex, and loss of g
6	no measurable effect on assembly with kcnq1 or cell surface expression of the kcne1/kcnq1 channel complex. loss of glyco
7	50% reduction of cell surface expression of the kcne1/kcnq1 channel complex, and loss of glycosylation at n-5 and t-7; w
15	no change in inhibition of the complex kcnq1-kcne1 by the scolopendra toxin ssd609.
19	loss inhibition of the complex kcnq1-kcne1 by the scolopendra toxin ssd609.
28	no measurable effect on assembly with kcnq1 or cell surface expression of the kcne1/kcnq1 channel complex, and loss of g
32	increase in inhibition of the complex kcnq1-kcne1 by the scolopendra toxin ssd609.
69	lowers current 2-fold and leads to faster deactivation of kcnq1/kcne1 channel.
109–129	totally suppressed interaction with kcnq1 c-terminus.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5576890	Phase 3 - rapid repolarisation
R-HSA-5576893	Phase 2 - plateau phase
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction

MSigDB gene sets: 296 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_VESICLE_ORGANIZATION, GOBP_PROTEIN_TARGETING, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_PROTEIN_TARGETING_TO_MEMBRANE

GO Biological Process (26): epithelial cell maturation (GO:0002070), sensory perception of sound (GO:0007605), vestibular nucleus development (GO:0021750), secretory granule organization (GO:0033363), regulation of membrane potential (GO:0042391), regulation of potassium ion transport (GO:0043266), regulation of ventricular cardiac muscle cell membrane repolarization (GO:0060307), cellular response to cAMP (GO:0071320), potassium ion transmembrane transport (GO:0071805), cardiac muscle cell action potential involved in contraction (GO:0086002), cardiac muscle cell contraction (GO:0086003), ventricular cardiac muscle cell action potential (GO:0086005), membrane repolarization (GO:0086009), membrane repolarization during action potential (GO:0086011), membrane repolarization during cardiac muscle cell action potential (GO:0086013), regulation of heart rate by cardiac conduction (GO:0086091), negative regulation of protein targeting to membrane (GO:0090315), potassium ion export across plasma membrane (GO:0097623), membrane repolarization during ventricular cardiac muscle cell action potential (GO:0098915), regulation of potassium ion transmembrane transport (GO:1901379), positive regulation of potassium ion transmembrane transport (GO:1901381), negative regulation of delayed rectifier potassium channel activity (GO:1902260), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220), heart contraction (GO:0060047)

GO Molecular Function (9): delayed rectifier potassium channel activity (GO:0005251), potassium channel regulator activity (GO:0015459), telethonin binding (GO:0031433), transmembrane transporter binding (GO:0044325), voltage-gated potassium channel activity (GO:0005249), potassium channel activity (GO:0005267), protein binding (GO:0005515), voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization (GO:0086008), voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization (GO:1902282)

GO Cellular Component (9): lysosome (GO:0005764), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), cell surface (GO:0009986), apical plasma membrane (GO:0016324), Z disc (GO:0030018), membrane raft (GO:0045121), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cardiac conduction	2
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
potassium ion transport	2
ventricular cardiac muscle cell membrane repolarization	2
cardiac muscle cell action potential	2
potassium ion transmembrane transport	2
membrane repolarization during cardiac muscle cell action potential	2
voltage-gated potassium channel activity	2
potassium channel activity	2
epithelial cell development	1
cell maturation	1
sensory perception of mechanical stimulus	1
pons development	1
medulla oblongata development	1
neural nucleus development	1
endomembrane system organization	1
vesicle organization	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
regulation of metal ion transport	1
regulation of cardiac muscle cell membrane repolarization	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
monoatomic cation transmembrane transport	1
cardiac muscle cell contraction	1
cardiac muscle contraction	1
actin-mediated cell contraction	1
cardiac muscle cell action potential involved in contraction	1
regulation of membrane potential	1
action potential	1
membrane repolarization	1
membrane repolarization during action potential	1
cardiac muscle cell membrane repolarization	1
regulation of heart rate	1
cardiac conduction	1
protein targeting to membrane	1
negative regulation of cellular process	1
regulation of protein targeting to membrane	1
negative regulation of establishment of protein localization	1
export across plasma membrane	1

Protein interactions and networks

STRING

970 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNE1	KCNQ1	P51787	999
KCNE1	KCNH2	Q12809	985
KCNE1	SCN5A	Q14524	977
KCNE1	KCNE3	Q9Y6H6	970
KCNE1	AKAP9	Q99996	969
KCNE1	KCNE4	Q8WWG9	914
KCNE1	KCNE5	Q9UJ90	904
KCNE1	KCNJ2	P48049	891
KCNE1	KCNQ4	P56696	880
KCNE1	KCNQ3	O43525	867
KCNE1	SCN4B	Q8IWT1	856
KCNE1	KCNQ2	O43526	849
KCNE1	CACNA1C	Q13936	803
KCNE1	SNTA1	Q13424	797
KCNE1	KCNJ5	P48544	796

IntAct

11 interactions, top by confidence:

A	B	Type	Score
KCNE1	KCNQ1	psi-mi:“MI:2364”(proximity)	0.580
KCNQ1	KCNE1	psi-mi:“MI:2364”(proximity)	0.580
KCNE1	KCNQ1	psi-mi:“MI:0915”(physical association)	0.580
KCNE1	KCNQ1	psi-mi:“MI:0407”(direct interaction)	0.580
KCNE1	Tcap	psi-mi:“MI:0915”(physical association)	0.510
Tcap	KCNE1	psi-mi:“MI:0915”(physical association)	0.510
CALM1	KCNE1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNE1	Kcnq1	psi-mi:“MI:0915”(physical association)	0.400
KCNE1	GPR89A	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): TPM3 (Two-hybrid), UBASH3A (Two-hybrid), KCNE1 (Affinity Capture-Western), KCNE1 (Reconstituted Complex), GPR89A (Affinity Capture-MS), TM9SF3 (Affinity Capture-MS), MTFP1 (Affinity Capture-MS), INTS5 (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), PIK3CB (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS), INTS7 (Affinity Capture-MS), SFXN3 (Affinity Capture-MS), SLC4A7 (Affinity Capture-MS), SLC7A3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GU71, A6QPI4, B2RV13, D4A6L0, E1BBQ2, F1LQY6, G3UW36, O08856, P15382, P53801, P55199, P56182, Q08CB3, Q0VF94, Q148E1, Q17RQ9, Q2KJ58, Q32Q90, Q4R5F9, Q4V8A6, Q4VA36, Q5I0I4, Q5NVI6, Q5R8Q2, Q5T6X4, Q5T848, Q5XII8, Q68EN5, Q6P767, Q8C419, Q8CHT6, Q8R143, Q8R1T1, Q8TBN0, Q8VDV3, Q8WUX9, Q90YH8, Q91WM6, Q91ZP9, Q96IL0

Diamond homologs: P15382, P15383, P23299, P63160, P63161, Q28705, Q5R8Q2, Q60409, Q9BDR0, Q9D808, Q9TUH9, Q9WTW3, Q9XSP1, Q9Y6J6, Q8WWG9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKCA	“down-regulates activity”	KCNE1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1273 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	6
Uncertain significance	179
Likely benign	77
Benign	37

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1065921	NM_000219.6(KCNE1):c.1A>T (p.Met1Leu)	Pathogenic
132654	NM_000219.6(KCNE1):c.154G>A (p.Gly52Arg)	Pathogenic
13476	NM_000219.6(KCNE1):c.20C>T (p.Thr7Ile)	Pathogenic
1415503	NM_000219.6(KCNE1):c.230del (p.Pro77fs)	Pathogenic
1431647	NC_000021.8:g.(?35821543)(35821932_?)del	Pathogenic
3601178	NM_000219.6(KCNE1):c.122del (p.Lys41fs)	Pathogenic
430060	NM_000219.6(KCNE1):c.12dup (p.Asn5Ter)	Pathogenic
4724223	NM_000219.6(KCNE1):c.76_92del (p.Asn26fs)	Pathogenic
527017	NM_000219.6(KCNE1):c.202_205del (p.Ser68fs)	Pathogenic
547162	NM_000219.6(KCNE1):c.138C>A (p.Tyr46Ter)	Pathogenic
547163	NM_000219.6(KCNE1):c.50G>A (p.Trp17Ter)	Pathogenic
547164	NM_000219.6(KCNE1):c.51G>A (p.Trp17Ter)	Pathogenic
812588	NM_000219.6(KCNE1):c.94dup (p.Arg32fs)	Pathogenic
132655	NM_000219.6(KCNE1):c.155G>C (p.Gly52Ala)	Likely pathogenic
132663	NM_000219.6(KCNE1):c.209A>T (p.Lys70Met)	Likely pathogenic
132675	NM_000219.6(KCNE1):c.259T>C (p.Trp87Arg)	Likely pathogenic
265208	NM_000219.6(KCNE1):c.262C>T (p.Gln88Ter)	Likely pathogenic
418270	NM_000219.6(KCNE1):c.217C>T (p.His73Tyr)	Likely pathogenic
620398	NM_000219.6(KCNE1):c.268A>T (p.Lys90Ter)	Likely pathogenic

SpliceAI

395 predictions. Top by Δscore:

Variant	Effect	Δscore
21:34449686:T:C	acceptor_gain	0.9900
21:34459523:ACTT:A	donor_loss	0.9900
21:34459525:TTA:T	donor_loss	0.9900
21:34459526:TA:T	donor_loss	0.9900
21:34459527:A:AC	donor_gain	0.9900
21:34459527:AC:A	donor_gain	0.9900
21:34459527:ACC:A	donor_gain	0.9900
21:34459528:C:CA	donor_loss	0.9900
21:34459528:C:CC	donor_gain	0.9900
21:34459528:CC:C	donor_gain	0.9900
21:34459528:CCC:C	donor_gain	0.9900
21:34459528:CCCG:C	donor_gain	0.9900
21:34459528:CCCGG:C	donor_gain	0.9900
21:34449680:CACCT:C	acceptor_gain	0.9800
21:34449682:CCTCT:C	acceptor_gain	0.9700
21:34449683:CT:C	acceptor_gain	0.9700
21:34449685:C:CC	acceptor_gain	0.9500
21:34449686:T:TC	acceptor_gain	0.9500
21:34458737:C:CC	acceptor_gain	0.9200
21:34449681:ACCT:A	acceptor_gain	0.9100
21:34449684:TC:T	acceptor_loss	0.9000
21:34449685:C:CA	acceptor_loss	0.9000
21:34449685:CTTAA:C	acceptor_loss	0.9000
21:34449686:T:A	acceptor_loss	0.9000
21:34459523:A:C	donor_gain	0.9000
21:34449559:T:TA	acceptor_gain	0.8600
21:34449678:CACAC:C	acceptor_gain	0.7900
21:34449700:C:CT	acceptor_loss	0.7300
21:34449692:GAAAA:G	acceptor_loss	0.7200
21:34449693:AAAAA:A	acceptor_loss	0.7200

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000017224 (21:34501561 A>G), RS1000048215 (21:34501307 G>C), RS1000049657 (21:34450712 G>T), RS1000076799 (21:34448605 G>A), RS1000176079 (21:34490508 A>G), RS1000254836 (21:34502541 T>A,C), RS1000272823 (21:34507203 A>G), RS1000397657 (21:34513044 C>T), RS1000430276 (21:34513305 T>C), RS1000448021 (21:34455726 C>T), RS1000545032 (21:34496577 A>C), RS1000731192 (21:34447484 G>A), RS1000875127 (21:34508504 G>A), RS1001082700 (21:34508025 G>A), RS1001280749 (21:34512554 A>T)

Disease associations

OMIM: gene MIM:176261 | disease phenotypes: MIM:612347, MIM:613695, MIM:192500, MIM:220400, MIM:613693

GenCC curated gene-disease

Disease	Classification	Inheritance
long QT syndrome 5	Definitive	Autosomal dominant
Jervell and Lange-Nielsen syndrome 2	Strong	Autosomal recessive
Jervell and Lange-Nielsen syndrome	Supportive	Autosomal recessive
atrial fibrillation	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
long QT syndrome 5	Limited	AD

Mondo (16): long QT syndrome (MONDO:0002442), Jervell and Lange-Nielsen syndrome 2 (MONDO:0012871), long QT syndrome 5 (MONDO:0013372), familial long QT syndrome (MONDO:0019171), noise induced hearing loss (MONDO:0013098), Jervell and Lange-Nielsen syndrome (MONDO:0002441), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587), Jervell and Lange-Nielsen syndrome 1 (MONDO:0024540), cardiomyopathy (MONDO:0004994), long QT syndrome 6 (MONDO:0013370), cardiac rhythm disease (MONDO:0007263), dilated cardiomyopathy (MONDO:0005021), hypertrophic cardiomyopathy (MONDO:0005045), sensorineural hearing loss disorder (MONDO:0020678), atrial fibrillation (MONDO:0004981)

Orphanet (8): Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768), Jervell and Lange-Nielsen syndrome (Orphanet:90647), Inherited arrhythmogenic cardiomyopathy (Orphanet:247), Rare cardiomyopathy (Orphanet:167848), Dilated cardiomyopathy (Orphanet:217604), Rare hypertrophic cardiomyopathy (Orphanet:217569), Rare genetic deafness (Orphanet:96210)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0001197	Abnormality of prenatal development or birth
HP:0001250	Seizure
HP:0001279	Syncope
HP:0001645	Sudden cardiac death
HP:0001657	Prolonged QT interval
HP:0001658	Myocardial infarction
HP:0001663	Ventricular fibrillation
HP:0001664	Torsade de pointes
HP:0001688	Sinus bradycardia
HP:0001727	Thromboembolic stroke
HP:0001891	Iron deficiency anemia
HP:0001907	Thromboembolism
HP:0001962	Palpitations
HP:0002094	Dyspnea
HP:0002321	Vertigo
HP:0002900	Hypokalemia
HP:0003546	Exercise intolerance
HP:0003577	Congenital onset
HP:0004308	Ventricular arrhythmia
HP:0005110	Atrial fibrillation
HP:0005135	Abnormal T-wave
HP:0005184	Prolonged QTc interval
HP:0006682	Premature ventricular contraction
HP:0007185	Loss of consciousness
HP:0008527	Congenital sensorineural hearing impairment
HP:0008619	Bilateral sensorineural hearing impairment
HP:0011476	Profound sensorineural hearing impairment

GWAS associations

98 associations (top):

Study	Trait	p-value
GCST000561_7	Electrocardiographic traits	2.000000e-12
GCST002500_39	QT interval	2.000000e-18
GCST005171_55	QT interval	1.000000e-17
GCST007009_8	Hippocampal volume	2.000000e-07
GCST007218_8	QT interval	3.000000e-15
GCST008043_21	QT interval	1.000000e-21
GCST008043_5	QT interval	4.000000e-20
GCST010107_22	L-selectin levels	8.000000e-06
GCST010651_5	Long QT syndrome	5.000000e-07
GCST010796_3826	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-08
GCST010796_3827	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_3828	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_3829	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_3830	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_3831	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_3832	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4076	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-18
GCST010796_4077	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-18
GCST010796_4078	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-18
GCST010796_4079	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-16
GCST010796_4080	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-15
GCST010796_4081	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-14
GCST010796_4082	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-14
GCST010796_4083	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-12
GCST010796_4084	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-10
GCST010796_4085	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-09
GCST010796_4086	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4153	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-30
GCST010796_4154	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-08
GCST010796_4155	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0005035	hippocampal volume
EFO:0008202	L-Selectin measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D001281	Atrial Fibrillation	C14.280.067.198; C23.550.073.198
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D006317	Hearing Loss, Noise-Induced	C09.218.458.341.887.460; C10.597.751.418.341.887.460; C23.888.592.763.393.341.887.460
D029593	Jervell-Lange Nielsen Syndrome	C14.280.067.565.440; C14.280.123.625.440; C16.131.240.400.715.440
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
C567343	Jervell And Lange-Nielsen Syndrome 2 (supp.)
C566766	Long Qt Syndrome 5 (supp.)
C566333	Long Qt Syndrome 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2221347 (PROTEIN COMPLEX), CHEMBL4872 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

14 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 295,815 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1111	AMBRISENTAN	4	7,009
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL1189679	PALONOSETRON	4	9,399
CHEMBL1323	DARUNAVIR	4	15,382
CHEMBL1346	DARIFENACIN	4	8,259
CHEMBL1382	TOLTERODINE	4	13,460
CHEMBL1734	SOLIFENACIN	4	296
CHEMBL1908360	EVEROLIMUS	4	73,430
CHEMBL254316	RALTEGRAVIR	4	12,743
CHEMBL256907	MARAVIROC	4	5
CHEMBL270190	ALVIMOPAN	4	1,781
CHEMBL434394	NEBIVOLOL	4	9,645
CHEMBL535	SUNITINIB	4	79,020
CHEMBL584	NELFINAVIR	4	36,859

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1805128	Toxicity	3	amiodarone;Antibiotics;antipsychotics;diuretics;quinidine;sotalol
rs1805128	Toxicity	3	qt-prolonging drugs	Acquired Long QT Syndrome (aLQTS)

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs727957	KCNE1		0.00	0
rs1805128	KCNE1	3	3.25	2	amiodarone;Antibiotics;antipsychotics;diuretics;quinidine;sotalol;qt-prolonging drugs
rs1805127	KCNE1		0.00	0
rs4817668	KCNE1		0.00	0

ChEMBL bioactivities

30 potent at pChembl≥5 of 66 total, top 29 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.05	IC50	9	nM	CHEMBL42205
7.30	IC50	50	nM	CHEMBL124454
6.92	IC50	120	nM	CHEMBL298475
6.70	IC50	200	nM	CHEMBL124308
6.62	IC50	240	nM	CHEMBL340910
6.60	IC50	250	nM	CHEMBL125307
6.40	IC50	400	nM	CHEMBL127885
6.36	IC50	440	nM	CHEMBL340236
6.16	IC50	700	nM	CHEMBL340025
6.10	IC50	790	nM	CHEMBL4065169
6.05	IC50	900	nM	CHEMBL124810
5.96	IC50	1100	nM	CHEMBL338171
5.92	IC50	1200	nM	CHEMBL127435
5.89	IC50	1300	nM	CHEMBL2047511
5.85	IC50	1400	nM	CHEMBL2152523
5.72	IC50	1900	nM	CHEMBL2047506
5.70	IC50	2000	nM	CHEMBL42205
5.66	IC50	2200	nM	CHEMBL124812
5.54	IC50	2900	nM	CHEMBL2046674
5.51	IC50	3100	nM	CHEMBL125259
5.47	IC50	3400	nM	CHEMBL2046681
5.47	IC50	3400	nM	CHEMBL2046683
5.30	IC50	5000	nM	CHEMBL44297
5.30	IC50	5000	nM	CHEMBL434045
5.24	IC50	5800	nM	CHEMBL2046673
5.24	IC50	5800	nM	CHEMBL2047516
5.16	IC50	6900	nM	CHEMBL338273
5.09	IC50	8120	nM	CHEMBL2164048
5.00	IC50	1e+04	nM	DULOXETINE

PubChem BioAssay actives

30 with measured affinity, of 209 total; 28 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
2-(2-fluorophenyl)-2-(4-fluorophenyl)-2-phenylacetamide	74322: Selectivity for gardos channel; (Gardos channel vs 2000 nM for the cardiac IKs channel).)	ic50	0.0090	uM
N-[(3R,4S)-3-hydroxy-2,2-dimethyl-6-phenylmethoxy-3,4-dihydrochromen-4-yl]-N-methylethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	0.0500	uM
N-[(3R,4S)-3-hydroxy-2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-3,4-dihydrochromen-4-yl]-N-methylmethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	0.1200	uM
N-(3-hydroxy-2,2-dimethyl-6-phenylmethoxy-3,4-dihydrochromen-4-yl)-N-methylmethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	0.2000	uM
N-[3-hydroxy-2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-3,4-dihydrochromen-4-yl]-N-methylmethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	0.2400	uM
N-(6-butoxy-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)-N-methylmethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	0.2500	uM
N-[(3S,4R)-3-hydroxy-2,2-dimethyl-6-phenylmethoxy-3,4-dihydrochromen-4-yl]-N-methylethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	0.4000	uM
N-[(3S,4R)-3-hydroxy-2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-3,4-dihydrochromen-4-yl]-N-methylmethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	0.4400	uM
N-[(3R,4S)-6-fluoro-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-N-methylethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	0.7000	uM
N-[6-[(1S)-1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]-2-pyridinyl]methanesulfonamide	1437178: Inhibition of human KCNQ1/KCNE1 expressed in HEK293 cells assessed as reduction in slowly activating delayed rectifier cardiac potassium current by patch clamp electrophysiology method	ic50	0.7900	uM
N-(3-hydroxy-2,2-dimethyl-6-propoxy-3,4-dihydrochromen-4-yl)-N-methylmethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	0.9000	uM
N-(6-chloro-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)-N-methylmethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	1.1000	uM
N-(6-fluoro-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)-N-methylethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	1.2000	uM
N-(6-chloro-3-pyridinyl)-3-fluoro-4-phenoxybenzamide	669436: Antagonist activity at KCNQ1/MINK expressed in CHO cells assessed as inhibition of KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ic50	1.3000	uM
1-[(1R,2R)-1,2-diphenyl-2-piperidin-1-ylethyl]piperidine	1594150: Inhibition of IKs (unknown origin)	ic50	1.4000	uM
N-(6-chloro-3-pyridinyl)-4-phenoxybenzamide	669436: Antagonist activity at KCNQ1/MINK expressed in CHO cells assessed as inhibition of KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ic50	1.9000	uM
N-[(3S,4R)-6-fluoro-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-N-methylethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	2.2000	uM
N-(6-chloro-3-pyridinyl)-4-(trifluoromethyl)benzamide	669436: Antagonist activity at KCNQ1/MINK expressed in CHO cells assessed as inhibition of KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ic50	2.9000	uM
N-(3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)-N-methylethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	3.1000	uM
N-(6-chloro-3-pyridinyl)-3-fluoro-4-(trifluoromethyl)benzamide	669436: Antagonist activity at KCNQ1/MINK expressed in CHO cells assessed as inhibition of KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ic50	3.4000	uM
N-(6-chloro-3-pyridinyl)-4-fluoro-3-(trifluoromethyl)benzamide	669436: Antagonist activity at KCNQ1/MINK expressed in CHO cells assessed as inhibition of KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ic50	3.4000	uM
N-[(3R,4S)-6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-N-methylethanesulfonamide	161294: Inhibition of human IKs-channel expressed in Xenopus oocytes,(Experiment 1)	ic50	5.0000	uM
N-[(3S,4R)-6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-N-methylethanesulfonamide	161295: Inhibition of human IKs-channel expressed in Xenopus oocytes,(Experiment 2)	ic50	5.0000	uM
N-(6-chloro-3-pyridinyl)-3-fluoro-4-propan-2-ylsulfanylbenzamide	669436: Antagonist activity at KCNQ1/MINK expressed in CHO cells assessed as inhibition of KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ic50	5.8000	uM
N-(6-chloro-3-pyridinyl)-3-(trifluoromethyl)benzamide	669436: Antagonist activity at KCNQ1/MINK expressed in CHO cells assessed as inhibition of KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ic50	5.8000	uM
N-(6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)-N-methylethanesulfonamide	161293: Inhibition of human IKs-channel expressed in Xenopus oocytes	ic50	6.9000	uM
(2S)-2-phenyl-N-(2-pyrrolidin-1-ylphenyl)butanamide	697781: Antagonist activity at KCNQ1/E1 expressed in CHO cells incubated for 3 mins by automated patch clamp assay	ic50	8.1200	uM
Duloxetine	1207368: Inhibition of slow delayed inward rectifying potassium current (Iks) in Chinese Hamster Ovary (CHO) cells expressing hKvLQT1/hminK measured using IonWorks Quattro automated patch clamp platform	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	4
sodium arsenite	decreases expression	2
Smoke	increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
barium chloride	affects binding, decreases activity	1
ginsenoside Re	increases expression	1
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	affects binding, decreases reaction, increases activity	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane	affects binding, decreases activity	1
HMR 1556	affects binding, decreases activity	1
ginsenoside Rb1	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
N-(1-(3-morpholin-4-ylphenyl)ethyl)-3-phenylacrylamide	decreases activity, increases reaction	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
Ropivacaine	affects binding, decreases activity	1
Air Pollutants	increases abundance, increases expression	1
Barium	affects binding, decreases activity	1
Benzo(a)pyrene	increases methylation	1
Bupivacaine	decreases reaction, increases response to substance, affects binding, decreases activity	1
Diethylhexyl Phthalate	increases expression	1
Fonofos	increases methylation	1
Isoproterenol	decreases reaction, affects binding, increases activity	1
Mepivacaine	affects binding, decreases activity	1
Parathion	increases methylation	1
Pentobarbital	decreases activity	1
Potassium	affects binding, affects transport	1

ChEMBL screening assays

117 unique, capped per target: 63 functional, 47 binding, 6 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2050727	Functional	Antagonist activity at KCNQ1/MINK expressed in CHO cells assessed as inhibition of KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	N-Pyridyl and Pyrimidine Benzamides as KCNQ2/Q3 Potassium Channel Openers for the Treatment of Epilepsy. — ACS Med Chem Lett
CHEMBL2090504	Binding	Activity at IKs channel	Use of small-molecule crystal structures to address solubility in a novel series of G protein coupled receptor 119 agonists: optimization of a lead and in vivo evaluation. — J Med Chem
CHEMBL4004501	ADMET	Inhibition of human KCNQ1/KCNE1 expressed in HEK293 cells assessed as reduction in slowly activating delayed rectifier cardiac potassium current by patch clamp electrophysiology method	Discovery of MK-1832, a Kv1.5 inhibitor with improved selectivity and pharmacokinetics. — Bioorg Med Chem Lett

Cellosaurus cell lines

10 cell lines: 6 induced pluripotent stem cell, 2 spontaneously immortalized cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0Y8	B’SYS CHO KvLQT1/minK	Spontaneously immortalized cell line	Female
CVCL_C0YK	B’SYS HEK 293 KvLQT1/minK	Transformed cell line	Female
CVCL_E5JP	HEK293 Kv7.1 + KCNE1	Transformed cell line	Female
CVCL_LC64	PrecisION hKCNQ1/hminK-CHO	Spontaneously immortalized cell line	Female
CVCL_VF17	UFRJi001-A	Induced pluripotent stem cell	Male
CVCL_VF18	UFRJi002-A	Induced pluripotent stem cell	Female
CVCL_VF19	UFRJi003-A	Induced pluripotent stem cell	Female
CVCL_YM80	XACHi007-A	Induced pluripotent stem cell	Male
CVCL_YM81	XACHi008-A	Induced pluripotent stem cell	Male
CVCL_YM82	XACHi009-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00032591	PHASE4	COMPLETED	The Home INR Study
NCT00127712	PHASE4	COMPLETED	Prevention of Atrial Fibrillation Following Noncardiac Thoracic Surgery
NCT00157781	PHASE4	COMPLETED	LEAF - Low Energy In Atrial Fibrillation
NCT00170313	PHASE4	TERMINATED	CORE: Study to Evaluate the Conducted AF-Response-Algorithm in Patients Suffering From Heart Failure and Atrial Fibrillation
NCT00189319	PHASE4	COMPLETED	To Evaluate the Impact of Oral Flecainide on Quality of Life in Patients With Paroxysmal Atrial Fibrillation
NCT00196144	PHASE4	COMPLETED	FFS - Far Field Sensing Test Study in Cardiac Dual Chamber Pacemakers
NCT00196157	PHASE4	UNKNOWN	Line Versus Spot Ablation in Persistent Atrial Fibrillation
NCT00196183	PHASE4	COMPLETED	Trigger- vs. Substrate-Ablation for Paroxysmal Atrial Fibrillation
NCT00196209	PHASE4	UNKNOWN	Cardioversion vs. Catheter Ablation for Persistent Atrial Fibrillation
NCT00227344	PHASE4	TERMINATED	CACAF2 Study: Catheter Ablation for Cure of Atrial Fibrillation
NCT00232219	PHASE4	COMPLETED	Use of Fish Oils to Reduce Recurrence of Atrial Fibrillation Following DC Cardioversion
NCT00232232	PHASE4	COMPLETED	Use of Fish Oils to Prevent Atrial Mechanical Stunning and Atrial Remodeling Due to Atrial Arrhythmia
NCT00232245	PHASE4	COMPLETED	Use of Fish Oils to Reduce the Frequency and Duration of Episodes of Atrial Fibrillation in Patients With Paroxysmal Atrial Fibrillation.
NCT00239226	PHASE4	COMPLETED	Electrophysiologically Guided PAcing Site Selection Study
NCT00247780	PHASE4	COMPLETED	Cavotricuspid Isthmusblock and Circumferential Pulmonary Vein Isolation in Patients With Atrial Fibrillation
NCT00256152	PHASE4	COMPLETED	Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial
NCT00262119	PHASE4	COMPLETED	MINERVA: MINimizE Right Ventricular Pacing to Prevent Atrial Fibrillation and Heart Failure
NCT00287209	PHASE4	COMPLETED	Reduction of Atrial Fibrillation Study in Patients Undergoing Coronary Artery Bypass Grafting. (RASCABG 1 Study)
NCT00289042	PHASE4	COMPLETED	Assessment of Cardioversion Using Transesophageal Echocardiography II (ACUTE II)
NCT00313443	PHASE4	COMPLETED	Concentrations of Amiodarone in Fat Tissue During Chronic Treatment
NCT00340314	PHASE4	COMPLETED	A Trial of Circumferential Pulmonary Vein Ablation (CPVA) Versus Antiarrhythmic Drug Therapy in for Paroxysmal Atrial Fibrillation (AF)
NCT00343499	PHASE4	TERMINATED	The Use of DIOVAN to Reduce Post-Cardioversion Recurrence of Atrial Fibrillation Trial (the DRAFT Trial)
NCT00408473	PHASE4	TERMINATED	Comparative Study of Flecainide CR and Placebo in the Early Treatment of Atrial Fibrillation.
NCT00420017	PHASE4	COMPLETED	Prevention of Atrial Fibrillation Following Esophagectomy
NCT00438113	PHASE4	COMPLETED	Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF
NCT00446966	PHASE4	COMPLETED	Fish Oil for Reduction of Atrial Fibrillation After Cardiac Surgery
NCT00449410	PHASE4	COMPLETED	Silent Cerebrovascular Lesion and Cognitive Decline Prevention by Cholesterol Lowering in Elderly AF Patients
NCT00466973	PHASE4	WITHDRAWN	Atrial Fibrillation Ablation Device Comparison Study
NCT00511173	PHASE4	COMPLETED	Comparison of Warfarin Dosing Using Decision Model Versus Pharmacogenetic Algorithm
NCT00512915	PHASE4	COMPLETED	Avoid FFS - Use of the Atrial Pacemaker Lead 1699 With Very Short Tip Ring Spacing to Avoid Far Field Sensing
NCT00552084	PHASE4	COMPLETED	Evaluating the Effectiveness of Fish Oil Supplements at Reducing the Recurrence of Atrial Fibrillation
NCT00559988	PHASE4	TERMINATED	Combined Use of BIOTRONIK Home Monitoring and Predefined Anticoagulation to Reduce Stroke Risk
NCT00579098	PHASE4	COMPLETED	The Use of Statins Following a Left Atrial Catheter Ablation Procedure to Prevent Atrial Fibrillation
NCT00586287	PHASE4	COMPLETED	Study to Find Out the Appropriate Initial Dose of the Anticoagulant Drug Phenprocoumon
NCT00597077	PHASE4	COMPLETED	Atrial Fibrillation and Congestive Heart Failure Trial
NCT00603317	PHASE4	COMPLETED	Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
NCT00605748	PHASE4	UNKNOWN	Pulmonary Vein (PV) -Isolation: Arrhythmogenic Vein(s) Versus All Veins
NCT00643188	PHASE4	COMPLETED	Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF
NCT00678340	PHASE4	COMPLETED	Randomized Trial of Two Ablation Catheters in Paroxysmal Atrial Fibrillation
NCT00680927	PHASE4	COMPLETED	Reveal® XT Performance Trial (XPECT)