TRPM8 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the TRPM8 gene, encoding the cold- and menthol-sensitive ion channel, including its genomic context, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | TRPM8 |
|---|---|
| Full Name | Transient Receptor Potential Cation Channel Subfamily M Member 8 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q37.1 |
| NCBI Gene ID | 79054 ncbi.nlm.nih.gov/gene/79054 |
| Ensembl ID | ENSG00000106080 |
| UniProt ID | Q7Z2W7 |
| OMIM ID | 606678 |
| HGNC ID | 17961 |
| Aliases | CMR1, LTRPC6, TRPP8 |
Description
The TRPM8 gene encodes a member of the transient receptor potential (TRP) family of ion channels. TRPM8 is a non-selective cation channel that is activated by cold temperatures (<25°C) and by cooling agents such as menthol and icilin. It is involved in the sensation of cold, pain, and inflammation. TRPM8 is expressed in sensory neurons and also in various non-neuronal tissues, where it may play roles in cancer and other diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate Cancer | TRPM8 is overexpressed in prostate cancer and may promote cancer cell proliferation and migration. It is considered a potential therapeutic target. | PubMed: 16116426; 2009; PMID: 19177223 |
| Migraine | Genetic variants in TRPM8 have been associated with migraine susceptibility, possibly through modulation of pain pathways. | PubMed: 20871616; 2010; PMID: 20871616 |
| Neuropathic Pain | TRPM8 activation can modulate cold allodynia in neuropathic pain conditions, with both protective and exacerbating roles reported. | PubMed: 18077464; 2008; PMID: 18077464 |
| Dry Eye Disease | TRPM8 is expressed in corneal sensory neurons and is involved in ocular surface cooling and tear production, with implications for dry eye. | PubMed: 22539857; 2012; PMID: 22539857 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Prostate | 0.8 | Low |
| Nervous System (ganglia) | Not available | High (in sensory neurons) |
| Lung | 0.3 | Low |
| Testis | 0.2 | Low |
| Bladder | 0.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| PC-3 (prostate cancer) | 0.5 | Low expression |
| DU145 (prostate cancer) | 0.4 | Low expression |
| LNCaP (prostate cancer) | 0.6 | Low expression |
| SH-SY5Y (neuroblastoma) | 0.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs17868324 | SNP | 0.5% (global) | Associated with migraine risk (intronic variant) |
| rs10166942 | SNP | 1.2% (global) | Associated with migraine protection (intronic variant) |
| p.Pro249Ser | Missense | Rare | Functional impact unknown; found in population databases |
| p.Arg1007Gln | Missense | Rare | Potential effect on channel function; not clinically characterized |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in TRPM8 are rare and have been linked to altered cold sensation in animal models, but no clear human phenotype has been established.
Gain of Function (GOF)
Gain-of-function mutations have not been clearly identified in human disease; however, overexpression of TRPM8 in cancers suggests a potential oncogenic role.
Dominant Negative (DN)
No dominant-negative mutations have been reported for TRPM8.
View complete mutation data：
Gene Ontology (GO)
| • ion channel activity (GO:0005216) | • cation channel activity (GO:0005261) |
| • protein binding (GO:0005515) | • plasma membrane (GO:0005886) |
| • integral component of membrane (GO:0016021) | • ion transport (GO:0006811) |
| • cation transport (GO:0006812) | • response to heat (GO:0009408) |
| • response to cold (GO:0009409) | • calcium ion transmembrane transport (GO:0070588) |
Pathways
• UniProt: TRPM8 is involved in the detection of cold and cooling agents
• and its activation leads to calcium influx and membrane depolarization.
• Reactome: TRP channels are involved in sensory perception and pain signaling.
• KEGG: TRPM8 is part of the 'Thermogenesis' pathway (ko04714) and 'Neuroactive ligand-receptor interaction' (ko04080).
Protein Summary
TRPM8 is a tetrameric, non-selective cation channel that is permeable to calcium and sodium. It is activated by cold temperatures, menthol, and other cooling agents. The channel has six transmembrane domains with a pore-forming loop between the fifth and sixth segments. Its N- and C-termini are intracellular. TRPM8 is primarily expressed in a subset of sensory neurons of the dorsal root and trigeminal ganglia, where it mediates cold sensation and pain. It is also found in prostate and other tissues, where it may contribute to cancer progression. The channel is regulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and is modulated by various signaling pathways.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRPM8 Knockout HEK293 Cell Line | EDJ-KQ2823 | Human | 79054 | Details Get a Quote |
| TRPM8 Knockout HeLa Cell Line | EDJ-KQ57137 | Human | 79054 | Details Get a Quote |
| TRPM8 Knockout A-549 Cell Line | EDJ-KQ65650 | Human | 79054 | Details Get a Quote |
| TRPM8 Knockout HCT 116 Cell Line | EDJ-KQ74074 | Human | 79054 | Details Get a Quote |
| TRPM8 Overexpression HEK293 Stable Cell Line | EDJ-GQ123 | Human | 79054 | Details Get a Quote |
