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Validated All-in-One™ qPCR Primer for KCNH2(NM_000238.3) Search again
Product ID:
HQP009998
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
ERG-1, ERG1, H-ERG, HERG, HERG1, Kv11.1, LQT2, SQT1
Gene Description:
potassium voltage-gated channel subfamily H member 2
Target Gene Accession:
NM_000238.3(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
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| A | B |
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Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
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Summary
This gene encodes a voltage-activated potassium channel belonging to the eag family. It shares sequence similarity with the Drosophila ether-a-go-go (eag) gene. Mutations in this gene can cause long QT syndrome type 2 (LQT2). Transcript variants encoding distinct isoforms have been identified. [provided by RefSeq].
Gene References into function
- the trafficking-deficient pore mutation HERG G601S was rescued by a series of HERG channel blockers that increased cell surface expression. Rescue by these pharmacological chaperones varied directly with their blocking potency.
- Patients with mutations in the pore region of the HERG gene are at markedly increased risk for arrhythmia-related cardiac events compared with patients with nonpore mutations
- Mapping the binding site of a human ether-a-go-go-related gene-specific peptide toxin (ErgTx) to the channel's outer vestibule
- a key function of the C-terminal 104 amino acids is to mask the RGR ER retention signal, which becomes exposed when mutations truncate the HERG C terminus.
- The common K897T polymorphism of the HERG channel is associated with the maximal duration and transmural dispersion of ventricular repolarization in middle-aged females.
- identification of the residues that are important for the binding specificity to the scorpion toxin BeKm-1
- positioning of S6 aromatic residues relative to the central cavity of the channel, not inactivation per se determines drug block of HERG or eag channels
- the cytoplasmic C terminus of HERG participates in the tethering or possibly targeting of HERG-containing vesicles within the Golgi via its interaction with GM130
- determination of relation of a PAS domain mutation in HERG to a trafficking deficiency at body temperature, apart from effects on channel deactivation
- Description of a HERG isoform found in human and rabbit colon that has a functional role in smooth muscle
- cell cycle dependent expression of isoforms in tumor cells
- Three KCNH2 mutations, L413P, E444D and L559H were identified in long QT syndrome in China.
- We conclude that normal HERG function in HEK293 cells requires basal activity of PKB. Our data represent the first evidence that PKB phosphorylation regulates K(+) channels
- Different proximal amino-terminal domain sequences contribute to set HERG gating characteristics and its regulation by TRH
- sustains a cardiac-type action potential in neuroblastoma S cells
- The strong effects of Cs+ on inactivation but not on activation highlight the importance of ion and channel interactions during the onset of inactivation in the HERG channel.
- Transcripts for HERG1 were present in all adenomas and although transcripts for HERG2 and HERG3 were also detected, their expression level was more variable.
- Voltage-dependent profile of human ether-a-go-go-related gene channel block is influenced by a single residue in the S6 transmembrane domain.
- gene expression; KCNH2 channels play a fundamental role in the control of motility patterns in human jejunum through their ability to modulate the electrical behavior of smooth muscle cells
- procainamide inhibits the HERG K(+) channel by a primarily 'open' or 'activated' channel state blocking mechanism and that avidity of drug-binding is decreased by extensive I(HERG) inactivation
- defective trafficking as a common mechanism for abnormal channel function resulting from mutations of critical COOH-terminal residues, including the long QT syndrome mutant HERGN861I
- the amphipathic helix in the S5P linker interacts with the pore region of the channel in a voltage-dependent manner
- erythromycin and clarithromycin significantly inhibit the HERG potassium current at clinically relevant concentrations
- In 2 of 3 families with hereditary short-QT syndrome and a high incidence of ventricular arrhythmias and sudden cardiac death,we identified 2 different missense mutations in the cardiac IKr channel HERG (KCNH2).
- HERG C-terminus mutations may have a role in with long QT syndrome
- herg1 gene and HERG1 protein were expressed in a high percentage of primary human colorectal cancers, with the highest incidence occurring in metastatic cancers
- that the TNF-alpha/TNFR1 system impairs HERG/I(Kr) function mainly by stimulating reactive oxygen species, particularly superoxide anion, but not by altering HERG expression
- Four single nucleotide polymorphisms were identified in sudden infant death syndrome: K897T, P967L, R1047L, and Q1068R.
- The KCNH2 A561T mutant channel revealed a post-translational defect that resulted in absence of the voltage-dependent delayed rectifier potassium current.
- WT channels K525 stabilizes the closed state, R531 stabilizes the open state and R534 participates in interactions that stabilize pre-open closed states.
- HERG channels are selectively involved in proliferation of distinct uterine cancer cells.
- The NMR structure of gamma-KTx1.1 & critical residues for its binding to hERG channel were studied, showing a novel interaction between scorpion gamma-KTx & hERG channel, in which the toxin acts as a turret blocker over the channel's outer vestibule.
- Physiological role for PIP2 regulation of the rapidly activating delayed rectifier K+ current during autonomic stimulation and localize a site of interaction to the COOH-terminal tail of the HERG K+ channel.
- native ventricular IKr channels are heteromers containing two alpha subunit types, ERG1a and -1b
- T1945+6C is a disease-causing mutation. It alters KCNH2 splicing and cosegregates with the LQT2 phenotype.
- Here we describe the mechanism by which both drugs block human Eag1 (hEag1) channels.
- currents are modulated by alpha(1A)-adrenoceptors via protein kinases A and C
- analysis of HERG channel function by dynamic action potential clamp technique
- 1047L in leads KCNH2 to a functional impairment of the KCNH2 channel, which may contribute to the higher incidence of Torsades de Pointes in 1047L carriers when challenged with a channel blocker.
- results define regions on the S4 domain voltage sensor that contribute differentially to hERG activation and inactivation gating
- Frameshift mutation at the C-terminus region with additional 147 amino acids evoked a loss of function of the HERG channel.
- A novel nonpore missense mutation K28E in the Per-Arnt-Sim domain of the KCNH2 channel is associated with a malignant Long-QT Syndrome phenotype.
- 2 SNPs in the KCNH2 gene, the previously described K897T variant (rs1805123, -1.9 ms/allele, P=0.0006) & a gene variant that tags a different haplotype in the same block (rs3815459, +1.7 ms/allele, P=0.0004)are associated with QT interval length.
- degradation of LQT2 mutant channels is mediated by the cytosolic proteasome in a process that involves mannose trimming, polyubiquitination, and deglycosylation of mutant channels
- The blockade of HERG cardiac K+ current by antifungal drug micronazole was studied.
- KCNH2 gene channels are physically linked to {beta}1 integrins and modulate adhesion-dependent signaling.
- A genetic basis has been identified linking the disease to mutations in KCNH2 in the familial forms of the disease.
- The Loss of function caused by C-terminal truncation, which includes all or part of the CNBD in human ether-a-go-go-related gene potassium channel(HERG), has been related to abnormal channel trafficking.
- It is the first splice mutation of HERG reported in Chinese LQTS families.
- findings underscore the importance of the S5-P linker in HERG channel function
- 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.
- data indicate that the HERG S4 domain is loosely packed within the rest of the voltage sensor domain and is likely to be lipid exposed.
- I593R mutation in HERG activates the unfolded protein response pathway.
- A novel nonpore missense mutation K28E in the Per-Arnt-Sim domain of the KCNH2 channel is associated with a malignant Long-QT Syndrome phenotype.
- The results demonstrate that the surface expression of HERG is strictly regulated, and that ceramide modifies HERG currents and targets the protein for lysosomal degradation.
- In 2 of 3 families with hereditary short-QT syndrome and a high incidence of ventricular arrhythmias and sudden cardiac death,we identified 2 different missense mutations in the cardiac IKr channel HERG (KCNH2).
- We identified the first large gene rearrangement consisting of a tandem duplication of 3.7 kb in KCNH2 responsible for LQTS in a Dutch family
- Results suggest that chronic exposure to certain drugs and their effects on Kir2.1 and ERG potassium channels may be an important aspect of acquired QT prolongation.
- dominant trafficking deficient mechanism, class 2, for the loss of Kv11.1 channel function in LQT2 mutation
- 897T variant of HERG significantly more common among patients with aldosteronoma
- Binding site is not identical for all drugs that preferentially block hERG in the open state.
- The rubidium efflux assay provides a higher-throughput means to identify potent hERG channel blocking agents, but lacks the sensitivity.
- the S4-S5 linker directly couples voltage sensor movement to the activation gate in the human ether-a'-go-go-related gene (hERG) K+ channel
- The results are consistent with predictions based on the distribution of these charged residues, and confirm that there is functional coupling between D456 and K525 and between D411 and K538.
- Charged residues on the alpha-helix of the pore helix (S5P linker) contribute significantly to the differences in inactivation characteristics of the ether-a-go-go (EAG) family channels.
- Results suggest that the Kv11.1 sequence and secondary structure of mRNA in the G/C rich region leads to template switching producing a cDNA product with a 171 bp deletion.
- Na+ permeation and blockade of hERG channels provide novel ways to extend our understanding of the hERG gating mechanisms.
- patients who reportedly are genotype negative may benefit from re-examination of those regions susceptible to allelic dropout due to primer-disrupting SNPs, particularly exon 4 in KCNH2.
- Long QT syndrome patients with mutations on the HERG gene have greater QT interval prolongation than patients with mutations of the KCNQ1 gene.
- Data here reported, support the hypothesis that hERG1 expression marks an early step of the progression of normality to cancer in the human esophagus through a metaplastic and dysplastic stage.
- These results suggest that the dynamic association of 14-3-3 proteins to both beta(1)AR and Kv11.1 channels is involved in the adrenergic modulation of this critical regulator of cardiac repolarization and refractoriness.
- Upon co-expression with 14-3-3epsilon, mutant HERG channels still bound 14-3-3epsilon but did not respond with a hyperpolarizing shift in voltage dependence as seen in wild-type channels.
- The effect of potassium on drug block of the hERG potassium channel stably expressed in human embryonic kidney (HEK-293) cells using whole-cell voltage-clamp techniques is reported.
- In summary, thioridazine is one of the most potent hERG K(+) channel blockers amongst antipsychotics, exhibiting characteristics of a preferential open/activated channel blocker and binding at a high affinity site in the hERG channel pore.
- the proliferative effect of arachidonic acid is in part mediated by activation of hEAG channels
- missense mutation (G604S) in the S5/pore region of human ether-a-go-go-related potassium channel (HERG) causes long QT syndrome in a Chinese family with a high incidence of sudden unexpected death
- 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).
- N-terminal interactions mediate hERG 1a/1b subunit assembly, a process whose perturbation may represent a new mechanism for disease.
- Based on these analyses, we propose a working model for the open conformation of the outer vestibule of the hERG channel, in which the S5-P linkers interact with the pore loops to influence ion flux through the pore.
- The role of HERG in the regulation of SP1, NF-kappaB and Nkx3.1 metabolism in neoplastic cells is reported.
- Calcium and/or diacylglycerol sensitive isotypes of PKC modulate hERG currents through a mechanism that involves direct phosphorylation of sites on the amino terminus of hERG to inhibit channel function.
- Overexpression of hERG1 channels mediate the FLT-1-dependent cell migration and invasion, and hence confer a greater malignancy in acute myeloid leukemia
- Production of structural models of the channel pore domain, into each of which has been placed a potassium channel blocker.
- Brompheniramine inhibited the HERG potassium channel through the residue Y652 and F656 and these residues may be an obligatory determinant in inhibition of HERG current for brompheniramine.
- A HERG mutation c.1039 C>T (p.Pro347Ser or P347S) was found responsible for symptomatic congenital LQTS in a Dutch family, displaying heterogeneity of clinical symptoms.
- The Ala490Pro mutation of the human ether-a-go-go-related gene is a rare, novel mutation that was inherited in this family, leading to Romano-Ward syndrome with complete penetrance.
- FKBP38 is a co-chaperone of HERG and contributes via the Hsc70/Hsp90 chaperone system to the trafficking of wild type and mutant HERG potassium channels
- The hERG R1014X mutation led to a reduced level of mutant mRNA compared with the wild-type allele. Degradation of hERG mutant mRNA by nonsense-mediated mRNA decay is an important mechanism in LQT2 patients with nonsense or frameshift mutations.
- The functional consequences of methionine oxidation of hERG channels stably expressed in a human embryonic kidney cell line (HEK 293) and native hERG channels in a human neuroblastoma cell line (SH-SY5Y) were studied.
- define a putative binding site for RPR260243 and confirm the importance of an interaction between the S4-S5 linker and the S6 domain in electromechanical coupling of voltage-gated K(+) channels
- Two common genetic variants of KCNH2 protein are associated with continuous QT interval duration in a community sample.
- ceramide-induced I(HERG) impairment may contribute to QT prolongation in prolonged myocardial ischemia, heart failure and diabetic cardiomyopathy
- The kinetics of the HERG1 current in K562 cells resembled the rapid component of the native cardiac delayed rectifier current, known to be conducted by heterotetrameric HERG1 channels.
- Findings indicate that the hERG inner helix glycine residues are required for the tight packing of the channel helices and that the flexibility afforded by glycine or proline residues is not universally required for activation gating.
- The K897T polymorphism of the KCNH2 gene may not be a major genetic determinant for the cardiac T-wave alternans (TWA), but the influence of the CC genotype on QT interval deserves further research among women.
- 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.
- HERG protein is involved in carcinogenesis of gastric cancer and is a potential therapeutic target of gastric cancer.
- result suggested that the herg played an important role in regulating the growth and proliferation of SH-SY5Y cells
- PD-307243 causes instantaneous current through HERG.
- hERG 1a promotes 1b trafficking by overcoming the RXR-mediated retention
- Functional expression in CHO-K1 stable cell line improved with lowering temperature of the culturing environment
- The differential sensitivity of hERG1 and rERG3 channels to the agonist effect of RPR could be accounted for by a single S5 residue (Thr556 in hERG1, Ile558 in rERG3).
- Inhibition of HERG currents may contribute to the arrhythmogenic side effects of protriptyline.
- mRNA levels of all HERG1 and KCNQ1 isoforms were asymmetrically distributed within the heart, being more abundant in the right atria and ventricles relative to the left atria and ventricles
- hERG1 activation involves a cooperative conformational change involving the entire voltage sensing module, while inactivation may involve a more limited interaction between R531 and D456, D460 and D509.
- A systematic candidate gene-based analysis of KCNH2 (HERG)found a genetic association including positive replication between the K897-allele and higher incidence of Atrial Fibrilation.
- Results demonstrate that 2398+1G>C activates a cryptic site and generates a full-length hERG protein with an insertion of 18 amino acids, which leads to a trafficking defect of the mutant channel.
- Results describe the production of histamine H3 receptor antagonists with minimal ERG potassium channel affinity.
- Droperidol potently inhibits transfected HERG channels and this is the probable mechanism for prolongation of the QT interval.
- The researchers found evidence of the near functional knockout of HERG in the homozygous HERG Q1070X condition in this family, which destroys the functional ion channel and leads to fetal arrhythmia and recurrent intrauterine fetal loss.
- Results suggest that G604S mutation causes loss of function in hERG through a dominant-negative effect on WT-hERG channel function, and further accentuates this suppression by forming heteromultimeric functional channels with WT-hERG subunits.
- Ang II produces an inhibitory effect on I(Kr)/hERG currents via AT(1) receptors linked to the PKC pathway in ventricular myocytes.
- hERG1b is likely to play a role in the formation of the native I (Kr) current
- The weak increase in HERG current density in WT-mutant coassembled channels contributes to the development of QTc prolongation and arrhythmias at febrile temperatures. Fever is a potential trigger of life-threatening arrhythmias in LQT type-2 patients.
- The silencing of USO-containing hERG1 isoforms induces a higher I(hERG1) density in tumors, an effect that apparently regulates neurite outgrowth in neuroblastoma cells and apoptosis in leukemia cells.
- These results demonstrate that hypoxia enhances the production of ROS in the mitochondria, resulting in down-regulation of hERG translation and decreased hERG-mediated K+ conductance.
- arrhythmia-associated mutations in HERG and KCNQ1 were preferentially found at evolutionarily conserved sites and unevenly distributed among functionally conserved domains
- The electrophysiological, glycosylation, trafficking and assembly properties of three novel KCNH2 mutations identified in Taiwanese patients with LQTS (p.N633D, p.R744fs, and p.P923fs)were studied.
- Report cardiac KCNH2 gene mutations in sudden infant death syndrome.
- stimulation of AR45 receptors by androgens up-regulates HERG K+ channel abundance and activity mainly through stabilizing HERG protein in an ERK1/2 dependent mechanism, and suggest a mechanism to explain the sex difference in the long QT syndrome
- Regulation of hERG channels by protein tyrosine kinases modifies the channel activity and thus likely alters electrophysiological properties including action potential duration and cell excitability in human heart and neurons.
- C-linker/CNBD region of HERG hangs centrally below the transmembrane core, with the initial portion of the amino terminus around its top and side surfaces directed towards the gating machinery
- C-terminal mutations localized in proximity to each other may exhibit strongly different and poorly correlated clinical and cellular phenotypes.
- The physiological implication of HERG-FHL2 interaction showed a significant increase in the HERG current amplitude and a faster deactivation of the tail current in human embryonic kidney 293 cells co-expressing HERG and FHL2.
- Rerport mutational analysis of block and facilitation of HERG current by a class III anti-arrhythmic agent, nifekalant.
- Kv11.1 (ERG1) K+ channels localize in cholesterol and sphingolipid enriched membranes and are modulated by membrane cholesterol.
- The researchers found an association between gene deletions and duplications in the KCNH2 gene and the risk of long QT syndrome.
- mutations specifically disrupting hERG 1b function are expected to reduce cardiac I Kr and enhance drug sensitivity, and represent a potential mechanism underlying inherited or acquired LQTS.
- the hERG1 polymorphism at codon 897, which is read as a Thr instead of a Lys, creates a phosphorylation site for the Akt protein kinase on the Kv11.1 channel protein
- the rare T allele of SNP K897T has a protective effect against QTc prolongation
- We identified a novel hERG/F627L mutation that results in LQTS
- Data indicate that HERG channels interact with caveolin-1 and are negatively regulated by this interaction.
- Mice bearing the human LQT2 Asn629Asp human ERG mutation develop cardiac defects including altered looping architecture, poorly developed bulbus cordis, and distorted aortic sac and branchial arches.
- The novel mutation found in this study is a frameshift/deletion at aa 915 in the C-terminal region of hERG that removes a putative assembly domain of the channel protein and is associated with arrythmias and syncope
- Report molecular determinants of hERG channel block by terfenadine and cisapride.
- Report effects of common antitussive drugs on the hERG potassium channel current.
- Ventricular arrhythmias induced by papaverine could result from blockage of the HERG channel at the cardiac myocytes.
- gene mutation in a Chinese family with congenital long QT syndrome (LQTS)
- The disease-causing gene was mapped to chromosome 7 in the KCNH2 gene; sequencing showed a missense mutatation, A614V, in exon 9.
- An Alanine at position 653 in hERG1 is required for normal voltage dependence of channel gating and a charged residue in this position prevents channel closure.
- The present study describes a profound biophysical characterization of HERG-N588K revealing both loss-of-function and gain-of-function properties of the mutant.