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Kv11.1

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Target id: 572

Nomenclature: Kv11.1

Family: Voltage-gated potassium channels (Kv)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 1159 7q36.1 KCNH2 potassium voltage-gated channel subfamily H member 2
Mouse 6 1 1162 5 10.94 cM Kcnh2 potassium voltage-gated channel, subfamily H (eag-related), member 2
Rat 6 1 1163 4q11 Kcnh2 potassium voltage-gated channel subfamily H member 2
Previous and Unofficial Names Click here for help
eag-related protein 1 | erg1 | ERG-1 | ether-a-go-go-related gene potassium channel 1 | ether-à-go-go-related gene | HERG | potassium channel, voltage gated eag related subfamily H, member 2 | potassium voltage-gated channel | potassium voltage-gated channel, subfamily H (eag-related), member 2
Database Links Click here for help
Alphafold Q12809 (Hs), O35219 (Mm), O08962 (Rn)
CATH/Gene3D 2.60.120.10
ChEMBL Target CHEMBL240 (Hs)
DrugBank Target Q12809 (Hs)
Ensembl Gene ENSG00000055118 (Hs), ENSMUSG00000038319 (Mm), ENSRNOG00000009872 (Rn)
Entrez Gene 3757 (Hs), 16511 (Mm), 117018 (Rn)
Human Protein Atlas ENSG00000055118 (Hs)
KEGG Gene hsa:3757 (Hs), mmu:16511 (Mm), rno:117018 (Rn)
OMIM 152427 (Hs)
Orphanet ORPHA122777 (Hs)
Pharos Q12809 (Hs)
RefSeq Nucleotide NM_172057 (Hs), NM_172056 (Hs), NM_000238 (Hs), NM_013569 (Mm), NM_053949 (Rn)
RefSeq Protein NP_742054 (Hs), NP_742053 (Hs), NP_000229 (Hs), NP_038597 (Mm), NP_446401 (Rn)
UniProtKB Q12809 (Hs), O35219 (Mm), O08962 (Rn)
Wikipedia KCNH2 (Hs)
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Kv11.3 77
Kv11.2 77
Auxiliary Subunits
Name References
KCNE1, minK 18,43,78
KCNE2, miRP1 1,26
Other Associated Proteins
Name References
GM130 56
KCR1 39,46
FKBP38 73
Hjd-2 73
Hop 73
Bag-2 73
Hsc 70 17
Hsp90 17
caveolin-3 28
Associated Protein Comments
Controversy regarding MiRP1 interaction [76]
Functional Characteristics Click here for help
cardiac IKR
Ion Selectivity and Conductance Click here for help
Species:  Human
Macroscopic current rectification:  IKr
References:  31,60,62-63,66,72
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  - - HEK 293 cells. Human
Inactivation  -90.0 - 66
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -35.0 – -15.0 100.0 60,63,72 Xenopus laevis oocyte Human
Inactivation  - 4.0 – 20.0 31,62
Comments  τ activation at 20mV, τ inactivation at 40mV

Under voltage clamp, longer pulses drive V0.5 to more negative potentials. Removing the amino terminus causes negative shift that is no longer sensitive to pulse duration [63,72].

C-type inactivation mediates the strong rectifying properties characteristic of Kv11.1 / hERG channels [62,66].

The amino terminus slows deactivation and promotes C-type inactivation [75]. See [74] for detailed kinetic analysis of all hERG gating transitions, and see [59] for summary.

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
A-935142 Small molecule or natural product Hs - - - 2x10-5 - 67
⤷ Conc range: 2x10-5 M [67]
PD-118057 Small molecule or natural product Hs - - - 1x10-5 - 83
⤷ Conc range: 1x10-5 M [83]
RPR260243 Small molecule or natural product Hs - - - 3x10-6 - 35
⤷ Conc range: 3x10-6 M [35]
PD-307243 Small molecule or natural product Hs - - - 2x10-6 - 25
⤷ Conc range: 2x10-6 M [25]
rottlerin Small molecule or natural product Click here for species-specific activity table Hs Activation 6.5 pEC50 - - 80
⤷ pEC50 6.5 [80]
ginsenoside Rg3 Small molecule or natural product Hs Activation 6.4 pEC50 - - 10
⤷ pEC50 6.4 [10]
ICA-105574 Small molecule or natural product Click here for species-specific activity table Hs Activation 6.3 pEC50 - - 21
⤷ pEC50 6.3 [21]
NS1643 Small molecule or natural product Click here for species-specific activity table Hs Activation 5.0 pEC50 - - 9,29
⤷ pEC50 5.0 [9,29]
VU0405601 Small molecule or natural product Hs Activation 4.9 – 5.0 pEC50 - - 50
⤷ pEC50 4.9 – 5.0 [50]
KB-130015 Small molecule or natural product Hs Activation 4.9 pEC50 - - 22
⤷ pEC50 4.9 [22]
NS3623 Small molecule or natural product Hs Activation 4.1 pEC50 - - 30
⤷ pEC50 4.1 [30]
Activator Comments
NS1643: Slows inactivation and thus gives appearance of activating, does not directly affect activation [9,29]
Mallotoxin: speeds activation and slows deactivation [80].
RPR260243 is an activator of Kv11.1, and has been demonstrated to inhibit channel closure, which leads to a persistent HERG channel current upon repolarisation [35].

For a review of hERG activators see [58].
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
PF-04885614 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.7 pIC50 - - 6
⤷ pIC50 5.7 (IC50 1.8x10-6 M) [6]
Description: Inhibition of hERG measured in a fluorescence polarisation assay, using hERG expressed in HEK-293S cells.
nemiralisib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.5 pIC50 - - 14
⤷ pIC50 5.5 (IC50 3.162x10-6 M) [14]
zorifertinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 4.9 pIC50 - - 81
⤷ pIC50 4.9 (IC50 1.33x10-5 M) [81]
Description: Channel inhibition measured in a conventional manual whole-cell patch clamp study.
Gating inhibitors Click here for help
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
APETx-1 Peptide Hs - 7.4 pKd - - 82
⤷ pKd 7.4 [82]
APETx-1 Peptide Hs Inhibition 7.5 pIC50 - - 13
⤷ pIC50 7.5 [13]
Gating Inhibitor Comments
APETx-1 is a sea anemone toxin which inhibits by binding to the S3b region of the voltage sensor [82].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
ErgTx-1 Peptide Click here for species-specific activity table Hs - 8.3 pKd - -70.0 53
⤷ pKd 8.3 [53]
Holding voltage: -70.0 mV
BeKm-1 Peptide Hs - 8.2 pKd - - 38
⤷ pKd 8.2 [38]
ErgTx-1 Peptide Click here for species-specific activity table Rn - 8.2 pKd - -70.0 53
⤷ pKd 8.2 [53]
Holding voltage: -70.0 mV
γ-KTx1.7 Peptide Click here for species-specific activity table Hs - 7.9 pKd - - 54
⤷ pKd 7.9 [54]
BeKm-1 Peptide Click here for species-specific activity table Rn - 7.7 pKd - -70.0 53
⤷ pKd 7.7 [53]
Holding voltage: -70.0 mV
E4031 Small molecule or natural product Click here for species-specific activity table Rn - 7.0 pKd - - 64
⤷ pKd 7.0 [64]
dofetilide Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.2 pKi - - 65
⤷ pKi 8.2 (Ki 6.4x10-9 M) [65]
astemizole Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - 9.0 pIC50 - - 85
⤷ pIC50 9.0 (IC50 1x10-9 M) [85]
E4031 Small molecule or natural product Click here for species-specific activity table Hs - 8.1 pIC50 - - 84
⤷ pIC50 8.1 (IC50 7.7x10-9 M) [84]
ibutilide Small molecule or natural product Approved drug Primary target of this compound Hs - 7.6 – 8.0 pIC50 - - 36,49
⤷ pIC50 7.6 – 8.0 (IC50 2.51x10-8 – 1x10-8 M) [36,49]
cisapride Small molecule or natural product Approved drug Click here for species-specific activity table Hs - 7.4 pIC50 - - 52
⤷ pIC50 7.4 (IC50 4.45x10-8 M) [52]
halofantrine Small molecule or natural product Approved drug Guide to Malaria Pharmacology Ligand Hs Inhibition 7.4 pIC50 - - 47
⤷ pIC50 7.4 (IC50 4x10-8 M) [47]
terfenadine Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs - 7.3 pIC50 - - 52
⤷ pIC50 7.3 (IC50 5.6x10-8 M) [52]
AZD3778 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 4.8 pIC50 - - 7
⤷ pIC50 4.8 (IC50 1.58x10-5 M) [7]
MK-7145 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 4.7 pIC50 - - 69
⤷ pIC50 4.7 (IC50 2.2x10-5 M) [69]
Description: In a hERG electrophysiology assay.
riluzole Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.3 pIC50 - - 61
⤷ pIC50 4.3 (IC50 5x10-5 M) [61]
Description: Inhibition of currents via human Kv11.1 (hERG) channels expressed in HEK293 cells in whole-cell patch-clamp experiments.
disopyramide Small molecule or natural product Approved drug Hs Inhibition 4.0 pIC50 - - 36
⤷ pIC50 4.0 (IC50 9.12x10-5 M) [36]
View species-specific channel blocker tables
Channel Blocker Comments
E-4031, dofetilide, terfenadine, and many other compounds, see [70] for review.
Drugs cross the cell membrane and enter hERG channels through open intracellular gate, where they may become trapped when channels close. Binding sites involve F656 and Y652 in the channel vestibule [41,44-45]. There remains controversy as to whether inhibition arises from a simple pore block mechanism or more complex processes also involving inactivation.
See [16,23] for studies involving Kv10 / EAG that provide intriguing insights into the role of inactivation in Kv11.1 / hERG drug binding.

BeKm-1 is also a scorpion toxin which binds to the outer mouth of the pore [38]. ERG Toxin-1 / CnERG1 is a low nM binding scorpion toxin which inhibits by binding to outer mouth of the pore [32,48].

Compounds have been identified that increase Kv11.1 function by enhancing ER export and may be useful as therapeutic agents in treating inherited or acquired LQTS [51].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LUF7244 Small molecule or natural product Hs Negative 5.4 pIC50 79
⤷ pIC50 5.4 (IC50 3.9x10-6 M) [79]
Description: Measuring LUF7244-induced reduction in [3H]dofetilide binding to the hKv11.1 channel in vitro.
Tissue Distribution Click here for help
CNS - widely expressed, developing spinal cord
Species:  Rat
Technique:  In situ hybridisation
References:  19,27,57,64
Tissue Distribution Comments
Detected in the heart of all mammalian species studied to date, using electrophysiology, biochemistry and Northern blot. Also cancer cells of many types [4], and gut, pancreatic beta cells and many others.
Physiological Functions Click here for help
hERG in smooth muscle contractility
Species:  Human
Tissue:  Jejenum
References:  15
Role in pancreatic beta cell secretion
Species:  Human
Tissue:  Pancreatic islet cells
References:  55
hERG channels regulate excitability in developing neurons
Species:  Mouse
Tissue:  Neural crest, spinal cord neurons
References:  5,19-20
In the human heart, Kv11.1 / hERG 1a and 1b subunits mediate the repolarizing cardiac current IKr. IKr peaks during late repolarization as a result of rebound from inactivation and slow deactivation. Loss of hERG function by mutations of the hERG gene (KCNH2) or by block by drugs intended largely for other therapeutic targets causes long QT syndrome (LQTS), which can lead to catastrophic arrhythmias and sudden death.
Species:  Human
Tissue:  Heart
References:  60,71,84
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0002128 abnormal blood circulation PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0001544 abnormal cardiovascular system physiology PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0000428 abnormal craniofacial morphology PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0000267 abnormal heart development PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0000266 abnormal heart morphology PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0000269 abnormal looping morphogenesis PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0004145 abnormal muscle electrophysiology PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0006126 abnormal outflow tract development PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0001698 decreased embryo size PMID: 18948620 
Kcnh2tm1Hjd Kcnh2tm1Hjd/Kcnh2tm1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0005333 decreased heart rate PMID: 12612061 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0006207 embryonic lethality during organogenesis PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0001636 irregular heartbeat PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0005312 pericardial effusion PMID: 18948620 
Kcnh2tm1.1Hjd Kcnh2tm1.1Hjd/Kcnh2tm1.1Hjd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1341722  MP:0006341 small first branchial arch PMID: 18948620 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Long QT syndrome 2; LQT2
Synonyms: Long QT syndrome [Disease Ontology: DOID:2843]
Romano-Ward syndrome [Orphanet: ORPHA101016]
Disease Ontology: DOID:2843
OMIM: 613688
Orphanet: ORPHA101016
Role:  Mutations in hERG (KCNH2) can reduce IKr function and lead to reduced repolarization, prolonged ventricular action potentials and Torsades de Pointes arrhythmia.
Most mutations cause an accumulation of hERG subunits in the endoplasmic reticulum. Others cause functional defects or nonsense-mediated mRNA decay. Most drugs causing LQTS target IKr/hERG channels.
Therapeutic use:  hERG stable cell lines are used for counterscreening drugs in development as a safety test to prevent acquired LQTS
References:  2,12,24,60,70-71
Disease:  Schizophrenia
Disease Ontology: DOID:5419
OMIM: 181500
Orphanet: ORPHA3140
Role:  SNPs within intron 2 of KCNH2 are associated with schizophrenia, lower intelligence quotient scores and cognitive processing speed. Additionally, postmortem examination of hippocampi from individuals with these SNPs revealed increased mRNA levels of a brain isoform of KCNH2 (KCNH2-3.1). This isoform lacks a domain that is required for slow channel deactivation and overexpression of KCNH2-3.1 in primary cortical neurons induces a high frequency, nonadapting firing pattern.
References:  3,33
Disease:  Short QT syndrome-1; SQT1
Synonyms: Familial short QT syndrome [Orphanet: ORPHA51083]
OMIM: 609620
Orphanet: ORPHA51083
References:  8,68
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human N588K 1764C>G/A Two different point mutations at nucleotide 1764, a C->G transversion, and a C->A transversion, both cause an amino acid change from asparagine to lysine at position 588. 8
Missense Human T618I 1853C>T 68
Clinically-Relevant Mutations and Pathophysiology Comments
There are more than 200 mutations known for the KCNH2 gene.
Gene Expression and Pathophysiology Click here for help
hERG subunits are aberrantly expressed (either over or mis-expressed) in many tumour types
Tissue or cell type:  Human primary cancers, tumour cell lines
Pathophysiology:  Putatively; Control of cell proliferation, regulation of tumour cell invasiveness (involving integrin family), control of tumour cell neoangiogensis (involving angiogenic factors).
Species:  Human
Technique:  -
References:  4
Application of NS1643 (hERG agonist) inhibits proliferation of breast cancer cells by activating a senescence program
Tissue or cell type:  Breast cancer cells
Pathophysiology:  Decreased proliferation is accompanied by arrest of the cell cycle in G0/G1 phase
Species:  None
Technique: 
References:  40
CpG methylation of KCNH2 is inversely correlated with tumour gene expression in clear-cell ovarian tumours
Tissue or cell type:  Clear-cell ovarian tumours
Pathophysiology: 
Species:  Human
Technique: 
References:  11
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  hERG USO
Amino acids:  888
Nucleotide accession:  NM_172056
Protein accession:  NP_742053
References:  39
Type:  Splice variant
Species:  Human
Description:  hERG 1b variant; also referred to as isoform c. These subunits reduce rectification by increasing the rate of recovery from inactivation, thus yielding larger amplitude currents during ventricular action potential. Leads to somewhat reduced E-4031 sensitivity.
Amino acids:  819
Nucleotide accession:  NM_172057
Protein accession:  NP_742054
References:  34,37,41-42
Type:  Splice variant
Species:  Human
Description:  Isoform a
Amino acids:  1159
Nucleotide accession:  NM_000238
Protein accession:  NP_000229
Type:  Splice variant
Species:  Human
Description:  KCNH2-3.1
Amino acids:  1063
References:  33
Biologically Significant Variant Comments
These are alternative transcripts rather than splice variants.

References

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1. Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA. (1999) MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell, 97 (2): 175-87. [PMID:10219239]

2. Anderson CL, Delisle BP, Anson BD, Kilby JA, Will ML, Tester DJ, Gong Q, Zhou Z, Ackerman MJ, January CT. (2006) Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism. Circulation, 113 (3): 365-73. [PMID:16432067]

3. Apud JA, Zhang F, Decot H, Bigos KL, Weinberger DR. (2012) Genetic variation in KCNH2 associated with expression in the brain of a unique hERG isoform modulates treatment response in patients with schizophrenia. Am J Psychiatry, 169 (7): 725-34. [PMID:22706279]

4. Arcangeli A. (2005) Expression and role of hERG channels in cancer cells. Novartis Found Symp, 266: 225-32; discussion 232-4. [PMID:16050271]

5. Arcangeli A, Rosati B, Cherubini A, Crociani O, Fontana L, Ziller C, Wanke E, Olivotto M. (1997) HERG- and IRK-like inward rectifier currents are sequentially expressed during neuronal development of neural crest cells and their derivatives. Eur J Neurosci, 9 (12): 2596-604. [PMID:9517465]

6. Bagal SK, Kemp MI, Bungay PJ, Hay TL, Murata Y, Payne CE, Stevens EB, Brown A, Blakemore DC, Corbett MS et al.. (2016) Discovery and optimisation of potent and highly subtype selective Nav1.8 inhibitors with reduced cardiovascular liabilities. Med. Chem. Commun, 7: 1925-1931. DOI: 10.1039/C6MD00281A

7. Bahl A, Barton P, Bowers K, Brough S, Evans R, Luckhurst CA, Mochel T, Perry MW, Rigby A, Riley RJ et al.. (2012) The discovery of CCR3/H1 dual antagonists with reduced hERG risk. Bioorg Med Chem Lett, 22 (21): 6688-93. [PMID:23031591]

8. Brugada R, Hong K, Dumaine R, Cordeiro J, Gaita F, Borggrefe M, Menendez TM, Brugada J, Pollevick GD, Wolpert C et al.. (2004) Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation, 109 (1): 30-5. [PMID:14676148]

9. Casis O, Olesen SP, Sanguinetti MC. (2006) Mechanism of action of a novel human ether-a-go-go-related gene channel activator. Mol Pharmacol, 69 (2): 658-65. [PMID:16284303]

10. Choi SH, Shin TJ, Hwang SH, Lee BH, Kang J, Kim HJ, Jo SH, Choe H, Nah SY. (2011) Ginsenoside Rg(3) decelerates hERG K(+) channel deactivation through Ser631 residue interaction. Eur J Pharmacol, 663 (1-3): 59-67. [PMID:21586280]

11. Cicek MS, Koestler DC, Fridley BL, Kalli KR, Armasu SM, Larson MC, Wang C, Winham SJ, Vierkant RA, Rider DN et al.. (2013) Epigenome-wide ovarian cancer analysis identifies a methylation profile differentiating clear-cell histology with epigenetic silencing of the HERG K+ channel. Hum Mol Genet, 22 (15): 3038-47. [PMID:23571109]

12. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. (1995) A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell, 80 (5): 795-803. [PMID:7889573]

13. Diochot S, Loret E, Bruhn T, Béress L, Lazdunski M. (2003) APETx1, a new toxin from the sea anemone Anthopleura elegantissima, blocks voltage-gated human ether-a-go-go-related gene potassium channels. Mol Pharmacol, 64 (1): 59-69. [PMID:12815161]

14. Down K, Amour A, Baldwin IR, Cooper AW, Deakin AM, Felton LM, Guntrip SB, Hardy C, Harrison ZA, Jones KL et al.. (2015) Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease. J Med Chem, 58 (18): 7381-99. [PMID:26301626]

15. Farrelly AM, Ro S, Callaghan BP, Khoyi MA, Fleming N, Horowitz B, Sanders KM, Keef KD. (2003) Expression and function of KCNH2 (HERG) in the human jejunum. Am J Physiol Gastrointest Liver Physiol, 284 (6): G883-95. [PMID:12736144]

16. Ficker E, Dennis AT, Wang L, Brown AM. (2003) Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERG. Circ Res, 92 (12): e87-100. [PMID:12775586]

17. Ficker E, Jarolimek W, Kiehn J, Baumann A, Brown AM. (1998) Molecular determinants of dofetilide block of HERG K+ channels. Circ Res, 82 (3): 386-95. [PMID:9486667]

18. Finley MR, Li Y, Hua F, Lillich J, Mitchell KE, Ganta S, Gilmour RF, Freeman LC. (2002) Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart. Am J Physiol Heart Circ Physiol, 283 (1): H126-38. [PMID:12063283]

19. Furlan F, Guasti L, Avossa D, Becchetti A, Cilia E, Ballerini L, Arcangeli A. (2005) Interneurons transiently express the ERG K+ channels during development of mouse spinal networks in vitro. Neuroscience, 135 (4): 1179-92. [PMID:16165280]

20. Furlan F, Taccola G, Grandolfo M, Guasti L, Arcangeli A, Nistri A, Ballerini L. (2007) ERG conductance expression modulates the excitability of ventral horn GABAergic interneurons that control rhythmic oscillations in the developing mouse spinal cord. J Neurosci, 27 (4): 919-28. [PMID:17251434]

21. Gerlach AC, Stoehr SJ, Castle NA. (2010) Pharmacological removal of human ether-à-go-go-related gene potassium channel inactivation by 3-nitro-N-(4-phenoxyphenyl) benzamide (ICA-105574). Mol Pharmacol, 77 (1): 58-68. [PMID:19805508]

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