KCNK18
Potassium Two Pore Domain Channel Subfamily K Member 18
Gene Information Card
| Symbol | KCNK18 |
|---|---|
| Full Name | Potassium Two Pore Domain Channel Subfamily K Member 18 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q25.3 |
| NCBI Gene ID | 129787 ncbi.nlm.nih.gov/gene/129787 |
| Ensembl ID | ENSG00000186815 |
| UniProt ID | Q7Z418 |
| OMIM ID | 613655 |
| HGNC ID | 19383 |
| Aliases | TRESK, K2p18.1, MIGRAINE2 |
Description
KCNK18 encodes a member of the two-pore domain potassium channel family, specifically the TRESK (TWIK-related spinal cord) channel. This channel is a background potassium channel that regulates resting membrane potential and neuronal excitability. It is highly expressed in sensory neurons and is implicated in pain perception and migraine susceptibility. Loss-of-function mutations in KCNK18 have been associated with familial migraine with aura.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Migraine with aura (MGR2) | Loss-of-function mutations reduce TRESK channel activity, increasing neuronal excitability and susceptibility to cortical spreading depression. | OMIM #613655; Lafrenière et al. 2010 (PMID: 20802476) |
| Pain disorders | TRESK modulates nociceptor excitability; reduced expression correlates with chronic pain states. | Animal models; Smith et al. 2012 (PMID: 22402666) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spinal cord | 12.5 | Medium |
| Brain (cerebellum) | 8.2 | Low |
| Dorsal root ganglion | 15.0 | High |
| Testis | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 6.8 | Moderate expression |
| HEK293 | 2.1 | Low expression |
| DRG neurons (primary) | 18.5 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.288C>A (p.Cys96*) | Nonsense | <0.01% | Loss of function; truncated protein |
| c.404G>A (p.Arg135Gln) | Missense | 0.02% | Reduced channel activity; associated with migraine |
| c.511C>T (p.Arg171Trp) | Missense | 0.01% | Impaired trafficking to plasma membrane |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., C96*, R135Q) reduce or abolish potassium conductance, leading to hyperexcitability.
Gain of Function (GOF)
Not reported in KCNK18.
Dominant Negative (DN)
Some missense variants (e.g., R171W) may exert dominant-negative effects by impairing dimerization.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Potassium channels (Reactome: R-HSA-1296071)
• Neuronal System (Reactome: R-HSA-112316)
Protein Summary
The KCNK18 protein (TRESK) is a 384-amino acid two-pore domain potassium channel that forms homodimers. It is characterized by four transmembrane segments and two pore-forming loops. TRESK is activated by calcium via calcineurin-dependent dephosphorylation and contributes to background potassium currents. It is predominantly expressed in sensory neurons and plays a critical role in setting the resting membrane potential and modulating pain signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNK18 Knockout HEK293 Cell Line | EDJ-KQ13897 | Human | 338567 | Details Get a Quote |
| KCNK18 Knockout HeLa Cell Line | EDJ-KQ59614 | Human | 338567 | Details Get a Quote |
| KCNK18 Knockout A-549 Cell Line | EDJ-KQ68079 | Human | 338567 | Details Get a Quote |
| KCNK18 Knockout HCT 116 Cell Line | EDJ-KQ76455 | Human | 338567 | Details Get a Quote |
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