KCNK2
Potassium Two Pore Domain Channel Subfamily K Member 2
Gene Information Card
| Symbol | KCNK2 |
|---|---|
| Full Name | Potassium Two Pore Domain Channel Subfamily K Member 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q41 |
| NCBI Gene ID | 3776 ncbi.nlm.nih.gov/gene/3776 |
| Ensembl ID | ENSG00000082482 |
| UniProt ID | O95069 |
| OMIM ID | 603219 |
| HGNC ID | 6278 |
| Aliases | TREK1, TREK-1, K2p2.1, TPKC1 |
Description
KCNK2 encodes TREK-1, a member of the two-pore domain (K2P) potassium channel family. TREK-1 is a mechanosensitive, thermosensitive, and pH-sensitive channel that contributes to background potassium conductance, regulating neuronal excitability, cardiac function, and pain perception. It is widely expressed in the central nervous system, heart, and other tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Major Depressive Disorder | Reduced TREK-1 activity is linked to altered neuronal excitability and antidepressant response; knockout mice show antidepressant-like behavior. | PMID: 15294142, ClinVar |
| Bipolar Disorder | Genetic variants in KCNK2 have been associated with bipolar disorder in genome-wide studies. | PMID: 21926972 |
| Migraine | TREK-1 modulates cortical spreading depression and trigeminal pain pathways. | PMID: 20096330 |
| Epilepsy | Loss-of-function mutations in KCNK2 may contribute to seizure susceptibility. | PMID: 23354118 |
| Cardiac Arrhythmia | TREK-1 contributes to cardiac repolarization; altered expression may predispose to arrhythmias. | PMID: 16908766 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Heart | 8.3 | Medium |
| Lung | 4.1 | Low |
| Kidney | 3.8 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.2 | Neuroblastoma cell line |
| HEK293 | 2.1 | Low endogenous expression |
| H9c2 | 7.8 | Rat cardiomyoblast |
| U87MG | 9.5 | Glioblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.754G>A (p.Gly252Ser) | Missense | <0.01% | Reduced channel activity in vitro |
| c.1012C>T (p.Arg338Trp) | Missense | <0.01% | Altered pH sensitivity |
| c.1285G>A (p.Gly429Arg) | Missense | <0.01% | Loss of mechanosensitivity |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Gly252Ser reduce potassium conductance, leading to increased neuronal excitability.
Gain of Function (GOF)
Not well documented; some variants may enhance channel opening under specific conditions.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported in KCNK2.
View complete mutation data：
Gene Ontology (GO)
| • inward rectifier potassium channel activity (GO:0005242) | • potassium channel activity (GO:0005267) |
| • mechanosensitive ion channel activity (GO:0008381) | • outward rectifier potassium channel activity (GO:0015271) |
| • potassium ion transport (GO:0006813) | • protein homooligomerization (GO:0051260) |
| • plasma membrane (GO:0005886) |
Pathways
• REACT:14797 – Potassium Channels
• WP:WP285 – Ion Channels and their Functional Role in Vascular Endothelium
• WP:WP475 – Neurotransmitter Release Cycle
Protein Summary
TREK-1 (UniProt O95069) is a 426-amino acid protein with four transmembrane segments and two pore domains. It forms homodimers and functions as a background potassium channel. The channel is activated by membrane stretch, intracellular acidosis, heat, and certain lipids (e.g., arachidonic acid). It is inhibited by G-protein-coupled receptor signaling and volatile anesthetics. TREK-1 plays key roles in neuroprotection, pain modulation, and mood regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNK2 Knockout HEK293 Cell Line | EDJ-KQ3681 | Human | 3776 | Details Get a Quote |
| KCNK2 Knockout HeLa Cell Line | EDJ-KQ25670 | Human | 3776 | Details Get a Quote |
| KCNK2 Knockout A-549 Cell Line | EDJ-KQ62197 | Human | 3776 | Details Get a Quote |
| KCNK2 Knockout HCT 116 Cell Line | EDJ-KQ70684 | Human | 3776 | Details Get a Quote |
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