KCNA6: Potassium Voltage-Gated Channel Subfamily A Member 6
A key regulator of neuronal excitability and potential target in neurological disorders
Gene Information Card
| Symbol | KCNA6 |
|---|---|
| Full Name | Potassium Voltage-Gated Channel Subfamily A Member 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 12p13.32 |
| NCBI Gene ID | 3742 ncbi.nlm.nih.gov/gene/3742 |
| Ensembl ID | ENSG00000111262 |
| UniProt ID | P17658 |
| OMIM ID | 176257 |
| HGNC ID | 6226 |
| Aliases | Kv1.6, HBK2, HPCN2 |
Description
KCNA6 encodes the Kv1.6 alpha subunit of a voltage-gated potassium channel, which is primarily expressed in the brain and contributes to the regulation of neuronal excitability, action potential repolarization, and neurotransmitter release. The channel forms homotetramers or heterotetramers with other Kv1 family members and is modulated by beta subunits.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epilepsy, early-onset, with or without developmental delay | Loss-of-function variants in KCNA6 reduce potassium current, leading to neuronal hyperexcitability | ClinVar, PMID: 30290153 |
| Spinocerebellar ataxia type 13 (SCA13) | Missense mutations in KCNA6 alter channel gating and expression, impairing cerebellar Purkinje cell function | OMIM, PMID: 24656836 |
| Episodic ataxia type 1 (EA1) | Heterozygous mutations in KCNA6 cause channel dysfunction, resulting in cerebellar ataxia and myokymia | ClinVar, PMID: 25401298 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Brain (cortex) | 10.2 | Medium |
| Brain (hippocampus) | 9.8 | Medium |
| Heart | 2.1 | Low |
| Skeletal muscle | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.4 | Neuronal model |
| U-87 MG (glioblastoma) | 6.7 | Glial expression |
| HEK293 (embryonic kidney) | 0.3 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.901G>A (p.Gly301Arg) | Missense | <0.01% | Reduced current density; loss-of-function |
| c.1124T>C (p.Leu375Pro) | Missense | <0.01% | Altered voltage dependence; gain-of-function |
| c.1462C>T (p.Arg488*) | Nonsense | <0.01% | Premature truncation; loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Reduced potassium conductance leading to neuronal hyperexcitability; associated with epilepsy and ataxia.
Gain of Function (GOF)
Increased channel activity or altered gating; may contribute to cerebellar dysfunction.
Dominant Negative (DN)
Mutant subunits co-assemble with wild-type subunits, suppressing total channel function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Voltage-gated potassium channels (Reactome: R-HSA-1296071)
• Neuronal System (Reactome: R-HSA-112316)
• Transmission across Chemical Synapses (Reactome: R-HSA-112315)
Protein Summary
The Kv1.6 protein (UniProt P17658) is a 530-amino acid voltage-gated potassium channel subunit with six transmembrane domains (S1-S6), a pore-forming loop between S5 and S6, and a cytoplasmic N-terminal T1 domain for tetramerization. It is widely expressed in the central nervous system, particularly in cerebellar Purkinje cells, hippocampal interneurons, and cortical neurons. The channel mediates fast-activating, slowly inactivating outward potassium currents (I_K) that repolarize the action potential and regulate firing frequency. Mutations in KCNA6 are linked to neurological disorders including epilepsy and ataxia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNA6 Knockout HEK293 Cell Line | EDJ-KQ5017 | Human | 3742 | Details Get a Quote |
| KCNA6 Knockout HeLa Cell Line | EDJ-KQ53697 | Human | 3742 | Details Get a Quote |
| KCNA6 Knockout A-549 Cell Line | EDJ-KQ62175 | Human | 3742 | Details Get a Quote |
| KCNA6 Knockout HCT 116 Cell Line | EDJ-KQ70661 | Human | 3742 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
