TRPM2 Gene: Transient Receptor Potential Cation Channel Subfamily M Member 2
A key ion channel in oxidative stress sensing, calcium signaling, and inflammation
Gene Information Card
| Symbol | TRPM2 |
|---|---|
| Full Name | Transient Receptor Potential Cation Channel Subfamily M Member 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 21q22.3 |
| NCBI Gene ID | 7226 ncbi.nlm.nih.gov/gene/7226 |
| Ensembl ID | ENSG00000142185 |
| UniProt ID | O94759 |
| OMIM ID | 603749 |
| HGNC ID | 12341 |
| Aliases | EREG1, KNP3, LTRPC2, NUDT9H, TRPC7 |
Description
TRPM2 (Transient Receptor Potential Cation Channel Subfamily M Member 2) encodes a calcium-permeable cation channel that is activated by oxidative stress, ADP-ribose, and NAD+. It plays a critical role in cellular calcium homeostasis, insulin secretion, immune cell activation, and neuronal function. The channel is widely expressed in brain, immune cells, and pancreatic beta cells. Dysregulation of TRPM2 is implicated in neurodegenerative diseases, inflammatory disorders, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodegenerative disorders (e.g., Alzheimer's, Parkinson's) | Oxidative stress-induced calcium overload via TRPM2 activation leads to neuronal cell death | ClinVar, NCBI Gene, OMIM |
| Bipolar disorder | Genetic association studies link TRPM2 variants to altered calcium signaling in neurons | OMIM, NCBI Gene |
| Type 2 diabetes | TRPM2 mediates insulin secretion; impaired channel function affects glucose homeostasis | NCBI Gene, UniProt |
| Inflammatory bowel disease | TRPM2 activation in immune cells promotes cytokine release and inflammation | NCBI Gene, ClinVar |
| Cancer (e.g., melanoma, prostate cancer) | TRPM2 expression influences cell proliferation and apoptosis; role in tumor progression | COSMIC, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Pancreas | 8.3 | Medium |
| Spleen | 7.1 | Medium |
| Lung | 5.4 | Low |
| Liver | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression; used in oxidative stress studies |
| HEK293 (embryonic kidney) | 9.8 | Moderate; common heterologous expression system |
| Jurkat (T-cell leukemia) | 11.5 | High; relevant for immune function |
| HeLa (cervical cancer) | 6.7 | Moderate |
| MCF7 (breast cancer) | 4.3 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg740Cys | Missense | Rare | Reduced channel activity; associated with bipolar disorder |
| p.Thr1482Ile | Missense | Rare | Altered calcium influx; linked to neurodegeneration |
| p.Pro1018Leu | Missense | Rare | Gain-of-function; increased oxidative stress sensitivity |
| c.2071C>T | Nonsense | Very rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg740Cys reduce channel conductance or expression, impairing calcium signaling and cellular stress responses.
Gain of Function (GOF)
Variants like p.Pro1018Leu enhance channel activation by ADP-ribose or oxidative stress, leading to excessive calcium influx and cell death.
Dominant Negative (DN)
Some missense mutations produce subunits that oligomerize with wild-type TRPM2, suppressing overall channel activity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ADP-ribose signaling pathway
• Oxidative stress-induced calcium signaling
• Innate immune system (NOD-like receptor signaling)
• Insulin secretion pathway
Protein Summary
TRPM2 is a 1503-amino acid protein with six transmembrane domains, a pore-forming loop, and a C-terminal NUDT9 homology domain that binds ADP-ribose. It functions as a non-selective cation channel with high calcium permeability. Activation by reactive oxygen species, ADP-ribose, and NAD+ triggers calcium influx, modulating cell survival, gene expression, and neurotransmitter release. The channel is expressed as a homotetramer and is regulated by calmodulin and phosphorylation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRPM2 Knockout HEK293 Cell Line | EDJ-KQ1053 | Human | 7226 | Details Get a Quote |
| TRPM2 Knockout A-549 Cell Line | EDJ-KQ20169 | Human | 7226 | Details Get a Quote |
| TRPM2 Knockout HCT 116 Cell Line | EDJ-KQ20170 | Human | 7226 | Details Get a Quote |
| TRPM2 Knockout HeLa Cell Line | EDJ-KQ20171 | Human | 7226 | Details Get a Quote |
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