KCNA2: Potassium Voltage-Gated Channel Subfamily A Member 2
A critical gene encoding a voltage-gated potassium channel involved in neuronal excitability and linked to epileptic encephalopathies.
Gene Information Card
| Symbol | KCNA2 |
|---|---|
| Full Name | Potassium Voltage-Gated Channel Subfamily A Member 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p13.3 |
| NCBI Gene ID | 3737 ncbi.nlm.nih.gov/gene/3737 |
| Ensembl ID | ENSG00000177301 |
| UniProt ID | P16389 |
| OMIM ID | 176262 |
| HGNC ID | 6222 |
| Aliases | HK4, KV1.2, RBK2, HUKIV, MGC138244 |
Description
KCNA2 encodes the voltage-gated potassium channel subunit KV1.2, which forms homotetrameric or heterotetrameric channels that mediate delayed rectifier potassium currents. These channels are critical for repolarization of action potentials, particularly in neurons. Mutations in KCNA2 are associated with a spectrum of neurological disorders, including developmental and epileptic encephalopathies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Developmental and Epileptic Encephalopathy 32 (DEE32) | Loss-of-function or gain-of-function mutations disrupt channel gating or expression, leading to altered neuronal excitability and seizures. | ClinVar, OMIM |
| Episodic Ataxia Type 1 (EA1) | Dominant-negative mutations reduce potassium current, impairing cerebellar Purkinje cell repolarization and causing motor incoordination. | OMIM, ClinVar |
| Autism Spectrum Disorder (ASD) | Rare missense variants may alter channel kinetics, contributing to synaptic dysfunction and neurodevelopmental phenotypes. | ClinVar, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Cerebral Cortex | 15.2 | High |
| Cerebellum | 10.8 | High |
| Heart | 3.4 | Medium |
| Skeletal Muscle | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.7 | Neuronal model, high expression |
| U-87 MG (glioblastoma) | 6.1 | Glial cell line, moderate expression |
| HEK293 (embryonic kidney) | 2.3 | Low endogenous expression, used for heterologous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.890C>T (p.Thr297Ile) | Missense | Rare | Gain-of-function; increased potassium current, linked to DEE32 |
| c.1129G>A (p.Glu377Lys) | Missense | Rare | Loss-of-function; reduced channel expression, associated with EA1 |
| c.1219C>T (p.Arg407Trp) | Missense | Rare | Dominant-negative; suppresses wild-type channel function, causes severe epilepsy |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce potassium current, often by impairing channel trafficking or gating, leading to hyperexcitability and epilepsy (e.g., p.Glu377Lys).
Gain of Function (GOF)
Mutations that increase potassium current, causing accelerated repolarization and neuronal hypoexcitability, also linked to epilepsy (e.g., p.Thr297Ile).
Dominant Negative (DN)
Mutations that produce non-functional subunits that co-assemble with wild-type subunits, reducing overall channel activity (e.g., p.Arg407Trp).
View complete mutation data：
Gene Ontology (GO)
Pathways
• Voltage-gated potassium channels (Reactome: R-HSA-1296071)
• Transmission across Chemical Synapses (Reactome: R-HSA-112315)
• Neuronal System (Reactome: R-HSA-112316)
Protein Summary
The KV1.2 protein (UniProt P16389) is a 499-amino acid voltage-gated potassium channel subunit with six transmembrane segments (S1-S6). It forms functional channels as a homotetramer or heterotetramer with other KV1 family members. KV1.2 is highly expressed in the brain, where it regulates neuronal firing frequency and neurotransmitter release. Post-translational modifications include N-glycosylation and phosphorylation, which modulate channel activity and trafficking.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNA2 Knockout HEK293 Cell Line | EDJ-KQ5014 | Human | 3737 | Details Get a Quote |
| KCNA2 Knockout HeLa Cell Line | EDJ-KQ53693 | Human | 3737 | Details Get a Quote |
| KCNA2 Knockout A-549 Cell Line | EDJ-KQ62171 | Human | 3737 | Details Get a Quote |
| KCNA2 Knockout HCT 116 Cell Line | EDJ-KQ70657 | Human | 3737 | Details Get a Quote |
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