KCNA5 Gene: Potassium Voltage-Gated Channel Subfamily A Member 5
Genetic and Functional Insights into KCNA5, a Key Regulator of Cardiac and Vascular Potassium Ion Flux
Gene Information Card
| Symbol | KCNA5 |
|---|---|
| Full Name | Potassium Voltage-Gated Channel Subfamily A Member 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 12p13.32 |
| NCBI Gene ID | 3741 ncbi.nlm.nih.gov/gene/3741 |
| Ensembl ID | ENSG00000130037 |
| UniProt ID | P22460 |
| OMIM ID | 176267 |
| HGNC ID | 6222 |
| Aliases | ATFB7, HCN1, KV1.5, HK2 |
Description
The KCNA5 gene encodes the voltage-gated potassium channel KV1.5, a member of the Shaker-related potassium channel family. This channel is predominantly expressed in the heart, particularly in atrial myocytes, where it conducts the ultra-rapid delayed rectifier potassium current (IKur). KCNA5 also plays roles in vascular smooth muscle cells, contributing to the regulation of vascular tone. Mutations in KCNA5 have been linked to familial atrial fibrillation and pulmonary arterial hypertension, highlighting its clinical significance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Atrial Fibrillation | Loss-of-function mutations reduce IKur, prolonging atrial action potential duration and increasing susceptibility to re-entry arrhythmias. | ClinVar; PMID: 19635842 |
| Pulmonary Arterial Hypertension | Gain-of-function mutations enhance KV1.5 activity, leading to excessive potassium efflux and apoptosis resistance in pulmonary artery smooth muscle cells. | OMIM; PMID: 22914617 |
| Hypokalemic Periodic Paralysis | Rare variants may alter channel function, contributing to episodic muscle weakness. | ClinVar; PMID: 25174571 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | High | High |
| Skeletal Muscle | Medium | Medium |
| Brain | Low | Low |
| Lung | Medium | Medium |
| Smooth Muscle | Medium | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Atrial Myocytes | High | Primary site of IKur |
| Pulmonary Artery Smooth Muscle Cells | Medium | Regulates vascular tone |
| HEK293 | Low | Common heterologous expression system |
| HL-1 Cardiomyocytes | Medium | Used for functional studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| E375G | Missense | Rare | Loss-of-function, associated with atrial fibrillation |
| D469E | Missense | Rare | Gain-of-function, linked to pulmonary hypertension |
| T527M | Missense | Rare | Loss-of-function, reduces current density |
| I515T | Missense | Rare | Dominant-negative effect on channel function |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce potassium current, leading to prolonged action potential duration and increased arrhythmia risk.
Gain of Function (GOF)
Mutations that enhance potassium current, causing hyperpolarization and altered cellular excitability.
Dominant Negative (DN)
Mutant subunits co-assemble with wild-type subunits, impairing overall channel function.
View complete mutation data：
Gene Ontology (GO)
| • Voltage-gated potassium channel activity | • Delayed rectifier potassium channel activity |
| • Ion channel complex | • Plasma membrane |
| • Regulation of membrane potential | • Potassium ion transmembrane transport |
Pathways
• Cardiac conduction
• Potassium channel signaling
• Ion transport
Protein Summary
The KV1.5 protein is a 613-amino acid alpha subunit that forms homotetrameric or heterotetrameric potassium channels. It contains six transmembrane domains (S1-S6) with a voltage-sensing region in S4 and a pore-forming loop between S5 and S6. KV1.5 channels are rapidly activating and slowly inactivating, contributing to the ultra-rapid delayed rectifier current in atrial myocytes. The protein is regulated by phosphorylation, redox state, and interactions with accessory subunits. Dysfunction of KV1.5 is implicated in cardiovascular and pulmonary pathologies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNA5 Knockout HEK293 Cell Line | EDJ-KQ5016 | Human | 3741 | Details Get a Quote |
| KCNA5 Knockout HeLa Cell Line | EDJ-KQ53696 | Human | 3741 | Details Get a Quote |
| KCNA5 Knockout A-549 Cell Line | EDJ-KQ62174 | Human | 3741 | Details Get a Quote |
| KCNA5 Knockout HCT 116 Cell Line | EDJ-KQ70660 | Human | 3741 | Details Get a Quote |
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