KCNA4 Gene: Voltage-Gated Potassium Channel Kv1.4
Genomic organization, expression, mutations, and clinical significance of KCNA4
Gene Information Card
| Symbol | KCNA4 |
|---|---|
| Full Name | Potassium Voltage-Gated Channel Subfamily A Member 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p14.1 |
| NCBI Gene ID | 3739 ncbi.nlm.nih.gov/gene/3739 |
| Ensembl ID | ENSG00000104783 |
| UniProt ID | P22459 |
| OMIM ID | 176266 |
| HGNC ID | 6222 |
| Aliases | Kv1.4, HK1, HPCN2, HBK4 |
Description
KCNA4 encodes the voltage-gated potassium channel Kv1.4, a member of the Shaker-related potassium channel family. This channel mediates the fast inactivating A-type potassium current (I_A) in excitable cells, playing a critical role in repolarization of action potentials in neurons and cardiac myocytes. KCNA4 is widely expressed in brain, heart, and skeletal muscle, and its dysfunction has been implicated in neurological and cardiac disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Episodic ataxia type 1 (EA1) | Loss-of-function mutations in KCNA4 may contribute to altered neuronal excitability, though EA1 is primarily associated with KCNA1. | ClinVar: Variants of uncertain significance in KCNA4 reported in patients with ataxia. |
| Epilepsy | Altered potassium channel function can increase neuronal excitability; KCNA4 variants have been found in epilepsy cohorts. | ClinVar: Rare KCNA4 variants identified in epilepsy patients. |
| Cardiac arrhythmias | Kv1.4 contributes to cardiac repolarization; mutations may predispose to arrhythmias. | UniProt: Functional studies show altered channel kinetics. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 31.2 | High |
| Heart | 18.5 | Medium |
| Skeletal Muscle | 12.3 | Medium |
| Kidney | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 45.6 | High expression; used in neuronal studies. |
| H9c2 (cardiomyoblast) | 22.1 | Moderate expression; cardiac model. |
| HEK293 | 0.8 | Low endogenous expression; often used for heterologous expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234G>A (p.Val412Met) | Missense | 0.01% | Reduced current amplitude; altered gating. |
| c.567delC (p.Leu190fs) | Frameshift | Rare | Loss of function due to truncated protein. |
| c.890A>G (p.Asn297Ser) | Missense | 0.02% | Altered voltage dependence; potential gain-of-function. |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish potassium current, leading to increased excitability.
Gain of Function (GOF)
Mutations that increase current or alter gating, potentially causing hyperpolarization and reduced excitability.
Dominant Negative (DN)
Mutant subunits may co-assemble with wild-type subunits, reducing overall channel function.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated potassium channel activity | • delayed rectifier potassium channel activity |
| • A-type (transient outward) potassium channel activity | • plasma membrane |
| • integral component of plasma membrane | • action potential |
| • potassium ion transmembrane transport |
Pathways
• Potassium Channels
• Voltage-gated potassium channels
• Cardiac conduction
• Neuronal action potential
Protein Summary
The Kv1.4 protein is a 654-amino acid voltage-gated potassium channel subunit that forms homotetrameric or heterotetrameric channels. It features six transmembrane segments (S1-S6) with a pore-forming loop between S5 and S6. The N-terminus contains an inactivation ball domain that mediates fast inactivation. Kv1.4 is highly expressed in brain and heart, where it contributes to A-type currents and cardiac transient outward current (I_to).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNA4 Knockout HEK293 Cell Line | EDJ-KQ5015 | Human | 3739 | Details Get a Quote |
| KCNA4 Knockout HeLa Cell Line | EDJ-KQ53695 | Human | 3739 | Details Get a Quote |
| KCNA4 Knockout A-549 Cell Line | EDJ-KQ62173 | Human | 3739 | Details Get a Quote |
| KCNA4 Knockout HCT 116 Cell Line | EDJ-KQ70659 | Human | 3739 | Details Get a Quote |
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