KCNN2: Small Conductance Calcium-Activated Potassium Channel Protein 2
Key regulator of neuronal excitability and cardiac repolarization
Gene Information Card
| Symbol | KCNN2 |
|---|---|
| Full Name | Potassium Calcium-Activated Channel Subfamily N Member 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q23.2 |
| NCBI Gene ID | 3781 ncbi.nlm.nih.gov/gene/3781 |
| Ensembl ID | ENSG00000180785 |
| UniProt ID | Q9H2S1 |
| OMIM ID | 605879 |
| HGNC ID | 6291 |
| Aliases | SK2, SKCA2, KCa2.2, hSK2 |
Description
KCNN2 (Potassium Calcium-Activated Channel Subfamily N Member 2) encodes the SK2 (KCa2.2) protein, a small conductance calcium-activated potassium channel that mediates the afterhyperpolarization (AHP) current in neurons and contributes to cardiac action potential repolarization. The channel is activated by submicromolar intracellular calcium concentrations and is widely expressed in the brain, heart, and skeletal muscle. Mutations in KCNN2 are associated with neurodevelopmental disorders, spinocerebellar ataxia, epilepsy, and cardiac arrhythmias.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinocerebellar ataxia type 34 (SCA34) | Loss-of-function mutations reduce SK2 channel activity, impairing neuronal afterhyperpolarization and leading to Purkinje cell dysfunction. | OMIM #619081; PMID: 32581362 |
| Neurodevelopmental disorder with or without seizures | De novo missense variants disrupt channel gating or calcium sensitivity, altering neuronal excitability. | ClinVar; PMID: 32581362 |
| Epilepsy, generalized | Reduced SK2 function lowers seizure threshold by prolonging neuronal depolarization. | ClinVar; PMID: 32581362 |
| Cardiac arrhythmia (long QT syndrome) | Gain-of-function mutations increase SK2 current, prolonging cardiac repolarization and QT interval. | PMID: 29728395 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Brain (cortex) | 8.3 | Medium |
| Heart | 6.1 | Low |
| Skeletal muscle | 4.2 | Low |
| Liver | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.2 | High expression |
| U-87 MG (glioblastoma) | 7.5 | Medium expression |
| H9c2 (cardiomyocyte) | 5.0 | Low expression |
| HEK293 (embryonic kidney) | 1.2 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1054C>T (p.Arg352Trp) | Missense | Rare | Loss-of-function; associated with SCA34 |
| c.1282G>A (p.Gly428Arg) | Missense | Rare | Gain-of-function; linked to long QT syndrome |
| c.1A>G (p.Met1?) | Start loss | Very rare | Loss-of-function; neurodevelopmental disorder |
| c.763_765del (p.Lys255del) | In-frame deletion | Rare | Dominant-negative effect; epilepsy |
Mutation functional classification
Loss of Function (LOF)
Reduced channel conductance or impaired calcium sensitivity, leading to decreased afterhyperpolarization and increased neuronal excitability.
Gain of Function (GOF)
Increased channel open probability or prolonged activation, causing excessive repolarization and cardiac QT prolongation.
Dominant Negative (DN)
Mutant subunits co-assemble with wild-type SK2, suppressing overall channel function and causing haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Cardiac muscle contraction (KEGG: hsa04260)
• Neuronal system (Reactome: R-HSA-112316)
Protein Summary
The SK2 protein (KCa2.2) is a 579-amino acid integral membrane protein with six transmembrane domains (S1-S6) and a pore-forming loop. It forms homotetrameric or heterotetrameric channels that are activated by intracellular calcium via constitutively bound calmodulin. SK2 channels are critical for the slow afterhyperpolarization (sAHP) in neurons, regulating firing frequency and synaptic plasticity. In the heart, SK2 contributes to atrial and ventricular repolarization. The protein is expressed predominantly in the brain, with highest levels in the cerebellum, hippocampus, and cortex.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNN2 Knockout HEK293 Cell Line | EDJ-KQ5047 | Human | 3781 | Details Get a Quote |
| KCNN2 Knockout HeLa Cell Line | EDJ-KQ53724 | Human | 3781 | Details Get a Quote |
| KCNN2 Knockout A-549 Cell Line | EDJ-KQ62200 | Human | 3781 | Details Get a Quote |
| KCNN2 Knockout HCT 116 Cell Line | EDJ-KQ70689 | Human | 3781 | Details Get a Quote |
