KCNN3
Potassium Calcium-Activated Channel Subfamily N Member 3
Gene Information Card
| Symbol | KCNN3 |
|---|---|
| Full Name | Potassium Calcium-Activated Channel Subfamily N Member 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 3782 ncbi.nlm.nih.gov/gene/3782 |
| Ensembl ID | ENSG00000143603 |
| UniProt ID | Q9UGI1 |
| OMIM ID | 602983 |
| HGNC ID | 6292 |
| Aliases | SK3, SKCA3, KCa2.3 |
Description
KCNN3 encodes a member of the small-conductance calcium-activated potassium channel (SK) family. The protein, SK3, forms homotetrameric channels that are activated by intracellular calcium via calmodulin binding. SK3 channels regulate neuronal excitability, muscle contraction, and cell proliferation. The gene is located on chromosome 1q21.3 and is associated with several neurological and psychiatric disorders, as well as cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Altered KCNN3 expression may affect dopaminergic signaling and neuronal firing patterns. | OMIM 602983; PMID: 11566899 |
| Bipolar Disorder | Polymorphisms in KCNN3 have been linked to mood regulation and lithium response. | OMIM 602983; PMID: 12402272 |
| Breast Cancer | SK3 overexpression promotes cell migration and metastasis via calcium signaling. | COSMIC; PMID: 26980724 |
| Atrial Fibrillation | Gain-of-function variants in KCNN3 increase atrial repolarization and arrhythmia risk. | ClinVar; PMID: 23571586 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Skeletal Muscle | 6.7 | Low |
| Kidney | 4.2 | Not detected |
| Liver | 1.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression |
| MCF7 (breast cancer) | 9.8 | Moderate expression |
| HEK293 (embryonic kidney) | 3.4 | Low expression |
| HepG2 (liver cancer) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1262G>A (p.Arg421His) | Missense | 0.01% | Reduced calcium sensitivity |
| c.2155C>T (p.Arg719Trp) | Missense | 0.005% | Gain-of-function; associated with atrial fibrillation |
| c.1057_1059del (p.Lys353del) | In-frame deletion | <0.001% | Loss of function; altered channel gating |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce channel activity or expression, e.g., p.Lys353del, impairing neuronal repolarization.
Gain of Function (GOF)
Mutations that increase channel open probability or calcium sensitivity, e.g., p.Arg719Trp, linked to atrial fibrillation.
Dominant Negative (DN)
Not well documented for KCNN3; most mutations are recessive or haploinsufficient.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• cAMP signaling pathway (KEGG: hsa04024)
• Cholinergic synapse (KEGG: hsa04725)
• Dopaminergic synapse (KEGG: hsa04728)
Protein Summary
The SK3 protein (UniProt Q9UGI1) is a 736-amino acid transmembrane protein with six membrane-spanning domains and a calmodulin-binding domain in the C-terminus. It forms homotetrameric channels that conduct potassium ions upon calcium binding to calmodulin. SK3 is predominantly expressed in the brain, heart, and skeletal muscle, where it modulates afterhyperpolarization and action potential firing. Dysregulation of SK3 is implicated in neurological disorders and cancer metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNN3 Knockout HEK293 Cell Line | EDJ-KQ5048 | Human | 3782 | Details Get a Quote |
| KCNN3 Knockout HeLa Cell Line | EDJ-KQ53725 | Human | 3782 | Details Get a Quote |
| KCNN3 Knockout A-549 Cell Line | EDJ-KQ62201 | Human | 3782 | Details Get a Quote |
| KCNN3 Knockout HCT 116 Cell Line | EDJ-KQ70690 | Human | 3782 | Details Get a Quote |
