KCNH2 (hERG): The Cardiac Potassium Channel Gene in Long QT Syndrome and Drug-Induced Arrhythmia
A comprehensive biomedical resource on KCNH2 genetics, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | KCNH2 |
|---|---|
| Full Name | Potassium voltage-gated channel subfamily H member 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q36.1 |
| NCBI Gene ID | 3757 ncbi.nlm.nih.gov/gene/3757 |
| Ensembl ID | ENSG00000055118 |
| UniProt ID | Q12809 |
| OMIM ID | 152427 |
| HGNC ID | 6251 |
| Aliases | hERG, HERG, Kv11.1, LQT2, SQT1, ERG1 |
Description
KCNH2 encodes the alpha subunit of the voltage-gated potassium channel Kv11.1, also known as hERG (human Ether-à-go-go-Related Gene). This channel mediates the rapidly activating delayed rectifier potassium current (IKr) in cardiac myocytes, which is critical for phase 3 repolarization of the cardiac action potential. Mutations in KCNH2 cause Long QT syndrome type 2 (LQT2), a disorder predisposing to ventricular arrhythmias and sudden death. Additionally, KCNH2 is a major target for drug-induced QT prolongation, as many medications block the hERG channel.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Long QT syndrome 2 (LQT2) | Loss-of-function mutations reduce IKr current, prolonging cardiac repolarization and increasing risk of torsades de pointes. | ClinVar, OMIM |
| Short QT syndrome 1 (SQT1) | Gain-of-function mutations increase IKr, shortening the QT interval and predisposing to atrial fibrillation and sudden death. | OMIM, ClinVar |
| Drug-induced QT prolongation | Pharmacological blockade of hERG by various drugs (e.g., antiarrhythmics, antipsychotics) mimics loss-of-function, leading to acquired LQTS. | NCBI Gene, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | High (nTPM ~ 80) | Predominant expression in cardiac tissue |
| Brain | Moderate (nTPM ~ 20) | Expression in neuronal tissues |
| Skeletal muscle | Low (nTPM ~ 5) | Minimal expression |
| Liver | Low (nTPM ~ 3) | Low expression |
| Kidney | Low (nTPM ~ 2) | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPSC-derived) | High | Relevant for functional studies |
| HEK293 | Low (endogenous) | Often used for heterologous expression |
| SH-SY5Y (neuroblastoma) | Moderate | Neuronal expression model |
| HeLa | Low | Minimal endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Ala561Thr (A561T) | Missense | Rare | Loss-of-function; associated with LQT2 |
| p.Gly628Ser (G628S) | Missense | Rare | Dominant-negative effect; severe LQT2 |
| p.Asn588Lys (N588K) | Missense | Rare | Gain-of-function; associated with SQT1 |
| c.1930delC (frameshift) | Deletion | Rare | Loss-of-function; LQT2 |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish IKr current, leading to prolonged action potential duration and LQT2.
Gain of Function (GOF)
Mutations that increase IKr current, shortening action potential duration and causing SQT1.
Dominant Negative (DN)
Mutant subunits co-assemble with wild-type subunits, impairing channel function in a dominant manner, often seen in LQT2.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated potassium channel activity | • delayed rectifier potassium channel activity |
| • protein homodimerization activity | • plasma membrane |
| • integral component of plasma membrane | • regulation of heart contraction |
| • cardiac muscle cell action potential |
Pathways
• Cardiac muscle contraction (KEGG hsa04260)
• Adrenergic signaling in cardiomyocytes (KEGG hsa04261)
• Cholinergic synapse (KEGG hsa04725)
• Ion channel transport (Reactome: R-HSA-5576891)
Protein Summary
The KCNH2 protein (Kv11.1) is a 1159-amino acid voltage-gated potassium channel subunit. It forms tetramers to create functional channels that conduct the rapidly activating delayed rectifier potassium current (IKr). The channel has six transmembrane domains (S1-S6), with the S4 segment serving as the voltage sensor and the S5-P-S6 region forming the selectivity filter. The N- and C-termini are cytoplasmic and contain domains important for channel trafficking and assembly. Mutations affecting these domains can disrupt channel function and cause cardiac arrhythmias.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNH2 Knockout HEK293 Cell Line | EDJ-KQ5041 | Human | 3757 | Details Get a Quote |
| KCNH2 Knockout A-549 Cell Line | EDJ-KQ27943 | Human | 3757 | Details Get a Quote |
| KCNH2 Knockout HCT 116 Cell Line | EDJ-KQ27944 | Human | 3757 | Details Get a Quote |
| KCNH2 Knockout HeLa Cell Line | EDJ-KQ53709 | Human | 3757 | Details Get a Quote |
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