KCNQ1 (Potassium Voltage-Gated Channel Subfamily Q Member 1)
A critical ion channel gene implicated in cardiac arrhythmias, deafness, and cancer susceptibility.
Gene Information Card
| Symbol | KCNQ1 |
|---|---|
| Full Name | Potassium voltage-gated channel subfamily Q member 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.5-p15.4 |
| NCBI Gene ID | 3784 ncbi.nlm.nih.gov/gene/3784 |
| Ensembl ID | ENSG00000053918 |
| UniProt ID | P51787 |
| OMIM ID | 607542 |
| HGNC ID | 6294 |
| Aliases | ATFB1, ATFB3, CLCN1, JLNS1, KCNA8, KCNA9, KVLQT1, LQT1, RWS |
Description
KCNQ1 encodes the pore-forming alpha subunit of a voltage-gated potassium channel that is critical for cardiac repolarization, epithelial ion transport, and auditory function. The channel typically forms heterotetramers with KCNE accessory subunits. Mutations in KCNQ1 are associated with inherited cardiac arrhythmias, including long QT syndrome and short QT syndrome, as well as Jervell and Lange-Nielsen syndrome (deafness with arrhythmia). Altered KCNQ1 expression has also been implicated in certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Long QT syndrome 1 (LQT1) | Loss-of-function mutations reduce cardiac IKs current, prolonging action potential duration and increasing risk of arrhythmia. | ClinVar, OMIM |
| Jervell and Lange-Nielsen syndrome (JLNS) | Homozygous or compound heterozygous loss-of-function mutations cause severe LQT and sensorineural deafness due to defective endolymph production. | OMIM, ClinVar |
| Short QT syndrome 2 (SQT2) | Gain-of-function mutations increase IKs current, shortening action potential duration and predisposing to atrial fibrillation and sudden death. | OMIM, ClinVar |
| Atrial fibrillation (familial) | Both gain- and loss-of-function mutations have been reported, leading to altered atrial refractoriness. | OMIM, ClinVar |
| Type 2 diabetes (susceptibility) | Common variants in KCNQ1 are associated with impaired insulin secretion, though the mechanism is not fully defined. | NCBI, OMIM |
| Colorectal cancer (prognosis) | KCNQ1 expression is often downregulated; loss of expression correlates with poor prognosis, possibly via effects on cell proliferation. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | High (approx. 100 nTPM) | Strong expression in cardiac muscle, especially ventricles. |
| Kidney | Moderate (approx. 30 nTPM) | Expressed in renal tubular epithelial cells. |
| Pancreas | Moderate (approx. 20 nTPM) | Expressed in pancreatic beta cells. |
| Lung | Low (approx. 5 nTPM) | Low expression in lung tissue. |
| Liver | Low (approx. 3 nTPM) | Minimal expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | Not determined | Often used for heterologous expression studies. |
| HL-1 (cardiac myocyte) | Not determined | Endogenous expression; used for cardiac electrophysiology. |
| Caco-2 (colorectal) | Moderate | Expression correlates with differentiation. |
| MCF7 (breast cancer) | Low | Reduced expression compared to normal breast tissue. |
| A549 (lung cancer) | Low | Low expression; not a major site. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg518Ter (R518X) | Nonsense | Rare (founder mutation in some populations) | Truncated protein; loss of function; causes LQT1. |
| p.Ala341Val (A341V) | Missense | Common in LQT1 cohorts | Dominant-negative effect; reduces IKs current. |
| p.Gly314Ser (G314S) | Missense | Rare | Loss of function; associated with JLNS when homozygous. |
| p.Val307Leu (V307L) | Missense | Rare | Gain of function; associated with SQT2. |
| p.Arg231His (R231H) | Missense | Rare | Loss of function; associated with atrial fibrillation. |
Mutation functional classification
Loss of Function (LOF)
Most LQT1 mutations are loss-of-function, reducing IKs current amplitude or altering channel gating.
Gain of Function (GOF)
SQT2 mutations increase IKs current, shortening action potential duration.
Dominant Negative (DN)
Many LQT1 mutations exert dominant-negative effects, interfering with wild-type subunits in heterotetramers.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated potassium channel activity | • delayed rectifier potassium channel activity |
| • protein homodimerization activity | • protein heterodimerization activity |
| • plasma membrane | • integral component of plasma membrane |
| • regulation of heart contraction | • potassium ion transmembrane transport |
| • cellular response to hypoxia | • auditory receptor cell differentiation |
Pathways
• Cardiac muscle contraction (KEGG hsa04260)
• Adrenergic signaling in cardiomyocytes (KEGG hsa04261)
• Cholinergic synapse (KEGG hsa04725)
• Ion channel transport (Reactome R-HSA-983712)
• Voltage gated potassium channels (Reactome R-HSA-1296072)
Protein Summary
The KCNQ1 protein (also known as KvLQT1) is a 676-amino acid voltage-gated potassium channel subunit. It contains six transmembrane domains (S1-S6) with a pore loop between S5 and S6. The functional channel is a tetramer, typically composed of four KCNQ1 subunits, and associates with KCNE1 (minK) to form the slow delayed rectifier potassium current (IKs) in cardiac myocytes. This current is crucial for phase 3 repolarization of the cardiac action potential. In the inner ear, KCNQ1/KCNE1 channels are essential for potassium secretion into the endolymph. Mutations affecting the protein's structure or function lead to channelopathies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNQ1 Knockout HEK293 Cell Line | EDJ-KQ2359 | Human | 3784 | Details Get a Quote |
| KCNQ1 Knockout HCT 116 Cell Line | EDJ-KQ22798 | Human | 3784 | Details Get a Quote |
| KCNQ1 Knockout HeLa Cell Line | EDJ-KQ22799 | Human | 3784 | Details Get a Quote |
| KCNQ1 Knockout A-549 Cell Line | EDJ-KQ62202 | Human | 3784 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
