TRPM2

Chr 21

transient receptor potential cation channel subfamily M member 2

Also known as: EREG1, KNP3, LTRPC2, LTrpC-2, NUDT9H, NUDT9L1, TRPC7

NCBI Gene: 7226ENSG00000142185UniProt: O94759

The protein encoded by this gene forms a tetrameric cation channel that is permeable to calcium, sodium, and potassium and is regulated by free intracellular ADP-ribose. The encoded protein is activated by oxidative stress and confers susceptibility to cell death. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. Additional transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2016]

Research Assistant →
3
Active trials
110
Pubs (1 yr)
79
P/LP submissions
0%
P/LP missense
1.11
LOEUF
GOF
Mechanism· predicted
Clinical Summary— TRPM2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
74 unique Pathogenic / Likely Pathogenic· 222 VUS of 420 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — TRPM2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.11LOEUF
pLI 0.000
Z-score 0.72
OE 0.91 (0.75–1.11)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.33Z-score
OE missense 1.03 (0.98–1.09)
988 obs / 958.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.91 (0.75–1.11)
0≤0.351.4
Missense OE1.03 (0.98–1.09)
0≤0.61.4
Synonymous OE1.20
0≤1.21.6
LoF obs/exp: 70 / 76.8Missense obs/exp: 988 / 958.8Syn Z: -3.29
DN
0.6065th %ile
GOF
0.6834th %ile
LOF
0.3454th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

420 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic70
Likely Pathogenic4
VUS222
Likely Benign34
Benign52
Conflicting1
70
Pathogenic
4
Likely Pathogenic
222
VUS
34
Likely Benign
52
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
70
0
70
Likely Pathogenic
0
0
4
0
4
VUS
0
205
17
0
222
Likely Benign
0
21
5
8
34
Benign
0
9
34
9
52
Conflicting
—1
Total023513017383

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRPM2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Synergistic disruption of the blood-brain barrier in tree shrews by Methamphetamine and HIV-1 Tat via TRPM2-Mediated astrocyte inflammation.
Teng HX et al.·Brain Behav Immun
2026
Pathophysiological significance of the TRPM2 ion channel as a potential target in cancer, neurological disorders, and ischemia/reperfusion injury.
Sultana S et al.·Pharmacol Res
2026
Selenium Nanoparticles Protect Retinal Pigment Epithelial Cells Against Experimental Age-Related Macular Degeneration-Induced Mitochondrial Oxidative Toxicity and Apoptosis Through the Modulation of the TRPM2 Channel.
Argun M et al.·J Biochem Mol Toxicol
2026
TRPM2 Channel Involvement in the Hesperidin-Mediated Potentiation of Cisplatin's Antitumor Action in Laryngeal Carcinoma Cells.
Çınar R et al.·Int J Mol Sci
2026Open Access
Protective role of zingerone against high glucose-Induced retinal pigment epithelial cell damage through modulation of the TRPM2 channel pathway.
Çiğ E et al.·Mol Biol Rep
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients