TRPM2

Summary

TRPM2 (transient receptor potential cation channel subfamily M member 2, HGNC:12339) is a protein-coding gene on chromosome 21q22.3, encoding Transient receptor potential cation channel subfamily M member 2 (O94759). Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels.

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.

Source: NCBI Gene 7226 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 483 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003307

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12339
Approved symbol	TRPM2
Name	transient receptor potential cation channel subfamily M member 2
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KNP3, LTRPC2, NUDT9L1, NUDT9H, EREG1
Ensembl gene	ENSG00000142185
Ensembl biotype	protein_coding
OMIM	603749
Entrez	7226

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000300481, ENST00000300482, ENST00000397928, ENST00000397932, ENST00000431901, ENST00000490982, ENST00000498430, ENST00000903457

RefSeq mRNA: 5 — MANE Select: NM_003307 NM_001320350, NM_001320351, NM_001320352, NM_001433516, NM_003307

CCDS: CCDS13710, CCDS82681

Canonical transcript exons

ENST00000397928 — 32 exons

Exon	Start	End
ENSE00001050770	44366754	44366934
ENSE00001136239	44369177	44369343
ENSE00001136423	44364114	44364282
ENSE00001211363	44354648	44354736
ENSE00001530923	44353621	44353865
ENSE00003465034	44400259	44400371
ENSE00003484543	44395414	44395551
ENSE00003488936	44435131	44435217
ENSE00003499642	44437062	44437167
ENSE00003500029	44390904	44391025
ENSE00003509381	44378997	44379197
ENSE00003510537	44423645	44423732
ENSE00003518763	44382718	44382820
ENSE00003529143	44405905	44406037
ENSE00003534191	44418423	44418555
ENSE00003538028	44439067	44439168
ENSE00003546538	44440789	44440905
ENSE00003546941	44426660	44426736
ENSE00003547493	44424852	44424939
ENSE00003562029	44405142	44405260
ENSE00003563694	44375833	44376013
ENSE00003575443	44391272	44391625
ENSE00003580935	44425670	44425827
ENSE00003597184	44399296	44399441
ENSE00003599280	44397747	44397876
ENSE00003604228	44406594	44406765
ENSE00003621257	44413891	44414074
ENSE00003626924	44417927	44418108
ENSE00003630131	44427010	44427111
ENSE00003636376	44401681	44401897
ENSE00003691176	44377712	44377773
ENSE00003749845	44441692	44442644

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 89.60.

FANTOM5 (CAGE): breadth broad, TPM avg 9.0269 / max 1145.3604, expressed in 673 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189470	5.3413	438
189469	1.4536	335
189467	0.8060	136
189483	0.4226	120
189471	0.2771	119
189480	0.2528	32
189478	0.1298	46
189472	0.0979	25
189482	0.0563	32
189479	0.0370	25

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	89.60	gold quality
caudate nucleus	UBERON:0001873	88.42	gold quality
nucleus accumbens	UBERON:0001882	88.02	gold quality
monocyte	CL:0000576	87.78	gold quality
putamen	UBERON:0001874	87.40	gold quality
mononuclear cell	CL:0000842	87.35	gold quality
leukocyte	CL:0000738	86.85	gold quality
cingulate cortex	UBERON:0003027	86.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.48	gold quality
anterior cingulate cortex	UBERON:0009835	86.47	gold quality
granulocyte	CL:0000094	86.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.01	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.07	gold quality
cerebellar hemisphere	UBERON:0002245	84.98	gold quality
cerebellar cortex	UBERON:0002129	84.90	gold quality
prefrontal cortex	UBERON:0000451	84.29	gold quality
spleen	UBERON:0002106	83.62	gold quality
frontal cortex	UBERON:0001870	83.04	gold quality
cerebellum	UBERON:0002037	82.92	gold quality
neocortex	UBERON:0001950	82.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.51	gold quality
telencephalon	UBERON:0001893	82.33	gold quality
hypothalamus	UBERON:0001898	82.14	gold quality
cerebral cortex	UBERON:0000956	81.58	gold quality
amygdala	UBERON:0001876	81.17	gold quality
forebrain	UBERON:0001890	81.13	gold quality
brain	UBERON:0000955	80.58	gold quality
central nervous system	UBERON:0001017	80.54	gold quality
blood	UBERON:0000178	80.02	gold quality
spinal cord	UBERON:0002240	79.83	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

35 targeting TRPM2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-558	97.50	67.16	977

Literature-anchored findings (GeneRIF, showing 40)

• LTRPC2 represents an important intrinsic mechanism that mediates Ca2+ and Na+ overload in response to disturbance of redox state in cell death (PMID:11804595)
• channel acitvation is dependent on criticial intracellular Ca2+ (PMID:12529379)
• evidence of role in neutrophil granulocytes by forming an entry pathway for Na(+) and Ca(2+), which is regulated by ADP-ribose and the redox state (PMID:12564954)
• TRPM2-S is an important physiologic isoform of TRPM2 and modulates channel activity and induction of cell death by oxidative stress through TRPM2-L. (PMID:12594222)
• oxidative and nitrosative stress induces TRPM2 activation in which mitochondria are induced to produce free ADP-ribose and release it to the cytosol, where its subsequent accumulation induces TRPM2 gating (PMID:15561722)
• The SSF-TRPM2 protein still maintained H2(O2)-induced Ca2+ influx activity. In addition, we found that the major transcripts in human and mouse start from a novel 5’ non-coding exon; we could not detect any striatum short transcript in mouse brain. (PMID:15708008)
• TRPM2 is a coincidence detector for adenosine diphosphatae ribose and cyclic adp ribose signaling. (PMID:15808509)
• LTRPC2 protein is a likely component of the calcium release activated nonselective cation channel in lymphocytes (PMID:16075382)
• Findings suggest genetic variants of the TRPM2 gene increase risk for BD and support the notion that TRPM2 may be involved in the pathophysiology of bipolar disorder. (PMID:16252251)
• Data show that one mechanism through which oxidative stress or TNF-alpha mediates cell death is activation of TRPM2, resulting in increased internal calcium, followed by caspase activation and PARP cleavage. (PMID:16306129)
• gene silencing of TRPM2 abolished the adenosine diphosphoribose - and ConA-mediated inward current. (PMID:16316998)
• data demonstrate the requirement for CaM in TRPM2 activation; they suggest that Ca(2+) entering through TRPM2 enhances interaction of CaM with TRPM2 at the IQ-like motif in the N terminus, providing crucial positive feedback for channel activation (PMID:16461353)
• a SIR2 reaction metabolite modulates TRPM2 ion channel (PMID:16565078)
• Cyclic ADP-ribose and NAADP strongly activate natively expressed TRPM2 chanels in Jurkat T cells. (PMID:16585058)
• TRPM2 is a potential molecular target for cADPR, which regulates Ca(2+) entry into pancreatic beta-cells at body temperature depending on the production of cADPR-related molecules, thereby regulating insulin secretion. (PMID:16601673)
• ADP-ribose and Ca2+ in concert behave as a messenger system for agonist-induced influx of Ca2+ through TRPM2 in granulocytes (PMID:16719842)
• Screening of bipolar affective disorder patients for mutations in TRPM2 led to identification of three novel and four known transitions, indicating TRPM2 as a candidate gene of bipolar affective disorder. (PMID:16733555)
• detailed expression profile of TRPM2 mRNA within the central nervous system (PMID:16777714)
• These results taken together suggest that the cysteine residues in the pore region are obligatory for TRPM2 channel function. (PMID:16822940)
• examined role of a coiled-coil domain in the intracellular C terminus of TRPM2 subunit in subunit interaction and channel assembly (PMID:17060318)
• in light of the wide-spread expression and growing list of cellular functions of TRPM2, useful therapeutic applications are expected for future drugs that block TRPM2 channels or inhibit their activation–{REVIEW} (PMID:17217061)
• Tyrosine phosphorylation of TRPM2 by PTPL1 controls activation/function. (PMID:17251321)
• the transmembrane segment S6 has a role in determining cation versus anion selectivity of TRPM2 and TRPM8 (PMID:17604279)
• TRPM2 agonist-binding ADPRase domain and the ion gate in the transmembrane region are separately located in the molecule. (PMID:17940282)
• TRPM2 mediates H2O2-induced increase in endothelial permeability through the activation of Ca2+ entry via TRPM2. (PMID:18048770)
• TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. (PMID:18542050)
• The regulation of TRPM2 activation in human neutrophils, is characterized. (PMID:18572241)
• during conditions of oxidative stress in lymphocytes, TRPM2 acts as a downstream effector of the PARP/poly(ADP-ribose) glycohydrolase pathway through PARP-dependent formation of ADP-ribose. (PMID:18599483)
• that Glu-960, Gln-981, Asp-987, and Glu-1022 residues are engaged in determining divalent cationic permeation properties of the TRPM2 channel. (PMID:18687688)
• Study describes the computational identification of a melanoma-enriched antisense transcript, TRPM2-AS, mapped within the locus of TRPM2, an ion channel capable of mediating susceptibility to cell death (PMID:18957938)
• A variant of the transient receptor potential melastatin 2 (TRPM2) gene may confer susceptibility to parkinsonism-dementia and amyotrophic lateral sclerosis. (PMID:19004782)
• This study supports a role for TRPM2 in the pathogenesis of bipolar disorder and the G allele of rs1556314 at exon 11 of TRPM2 in BD-I but not bipolar disorder type II (BD-II). (PMID:19133961)
• functional TRPM2 channels mediate H(2)O(2)-induced Ca(2+) entry in beta-cells, a process potently inhibited by N-(p-amylcinnamoyl)anthranilic acid (PMID:19382906)
• Data show that TRPM2 and ADPR represent multimodal signaling elements regulating Ca2+ mobilization in beta cells through membrane depolarization, Ca2+ influx, and release of Ca2+ from intracellular stores. (PMID:19454650)
• These results collectively suggest the requirement for the N-terminal CC domain for protein expression and function, but not subunit interaction, of the TRPM2 channel. (PMID:19652898)
• Its activation by oxidative stress leads to chemokine production in macrophage, which causes chronic inflammation. (review) (PMID:19749482)
• [REVIEW] TRPM1 and TRPM2, are localized in intracellular compartments and are involved in melanin synthesis and oxidative stress-induced cell death (PMID:19887679)
• TRPM2 is essential for prostate cancer cell proliferation and may be a potential target for the selective treatment of prostate cancer. (PMID:20029400)
• Data demonstrate that TRPM2 is required for the LPS-induced production of IL-6, IL-8, IL-10, and TNF-alpha. (PMID:20107186)
• The calcium-permeable non-selective cation channel TRPM2 is modulated by cellular acidification. (PMID:20194125)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	trpm2	ENSDARG00000101641
mus_musculus	Trpm2	ENSMUSG00000009292
rattus_norvegicus	Trpm2	ENSRNOG00000001216
caenorhabditis_elegans		WBGENE00004149
caenorhabditis_elegans		WBGENE00020972
caenorhabditis_elegans		WBGENE00021404
caenorhabditis_elegans		WBGENE00021408

Paralogs (7): TRPM5 (ENSG00000070985), TRPM3 (ENSG00000083067), TRPM7 (ENSG00000092439), TRPM6 (ENSG00000119121), TRPM4 (ENSG00000130529), TRPM1 (ENSG00000134160), TRPM8 (ENSG00000144481)

Protein

Protein identifiers

Transient receptor potential cation channel subfamily M member 2 — O94759 (reviewed: O94759)

Alternative names: Estrogen-responsive element-associated gene 1 protein, Long transient receptor potential channel 2, Transient receptor potential channel 7, Transient receptor potential melastatin 2

All UniProt accessions (3): O94759, C9JZQ8, E9PGK7

UniProt curated annotations — full annotation on UniProt →

Function. Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels. Functions as a ligand-gated ion channel, gated by intracellular adenosine diphosphate ribose (ADP-ribose), Ca(2+), warm temperature, and oxidative stress. The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2’-phosphate. Binding of ADP-ribose to the cytoplasmic Nudix domain causes a conformation change; the channel is primed but still requires Ca(2+) binding to trigger channel opening. Extracellular Ca(2+) passes through the channel and increases channel activity. Contributes to Ca(2+) release from intracellular stores in response to ADP-ribose. Plays a role in numerous processes that involve signaling via intracellular Ca(2+) levels. Besides, mediates the release of lysosomal Zn(2+) stores in response to reactive oxygen species, leading to increased cytosolic Zn(2+) levels. Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis. Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca(2+) levels. Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection. Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca(2+) levels. Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its role in increasing cytoplasmic Ca(2+) and Zn(2+) levels. Confers susceptibility to cell death following oxidative stress. Lacks cation channel activity. Does not mediate cation transport in response to oxidative stress or ADP-ribose. Lacks cation channel activity and negatively regulates the channel activity of isoform 1. Negatively regulates susceptibility to cell death in reposponse to oxidative stress.

Subunit / interactions. Homotetramer. Isoform 1 can interact with isoform 3. This interaction decreases Ca(2+) influx through isoform 1 and suppresses susceptibility to oxidative stress-induced cell death.

Subcellular location. Cell membrane. Perikaryon. Cell projection. Cytoplasmic vesicle. Lysosome Cell membrane Cell membrane Cell membrane.

Tissue specificity. Highly expressed in brain and peripheral blood cells, such as neutrophils. Also detected in bone marrow, spleen, heart, liver and lung. Isoform 2 is found in neutrophil granulocytes.

Post-translational modifications. Phosphorylation of TRPM2 at Thr-740 by protein kinase C (PKC) counteracts the effect of cytosolic Ca(2+) and elevates the temperature threshold.

Activity regulation. Activated by intracellular ADP-ribose, beta-NAD (NAD(+)) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species. Ca(2+) and PI(4,5)P2 are required for channel opening by ADP-ribose. Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius). Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius). Activated by moderate heat (35 to 40 degrees Celsius). Inactivated by exposure to extracellular pH between 4.0 and 6.5; irreversibly inactivated when open channels are exposed to extracellular pH between 4.0 and 6.5, while pre-exposure of closed channels to extracellular pH 5.5 gives rise to currents that rapidly inactivate, but protects against irreversible inactivation. Inactivated by intracellular ATP. Activated by arachidonic acid. Inhibited by 2-aminoethyl diphenylborinate (2-APB).

Domain organisation. Contains two binding sites for ADP-ribose, one in the N-terminal part of the channel and the other in the C-terminal nudix hydrolase domain. Both sites seem to have a role in channel opening, but the interaction of ADP-ribose with the N-terminal site is absolutely required for channel activation.

Similarity. Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM2 sub-subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
O94759-1	1, TRPM2-L	yes
O94759-2	2
O94759-3	3, TRPM2-S

RefSeq proteins (4): NP_001307279, NP_001307280, NP_001420445, NP_003298* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000086	NUDIX_hydrolase_dom	Domain
IPR005821	Ion_trans_dom	Domain
IPR015797	NUDIX_hydrolase-like_dom_sf	Homologous_superfamily
IPR041491	TRPM_SLOG	Domain
IPR050927	TRPM	Family
IPR057366	TRPM-like	Domain

Pfam: PF00520, PF18139, PF25508, PF25969

Catalyzed reactions (Rhea), 2 shown:

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (226 total): helix 59, strand 51, mutagenesis site 32, turn 25, binding site 15, sequence variant 13, topological domain 10, transmembrane region 6, intramembrane region 3, splice variant 3, region of interest 2, short sequence motif 2, chain 1, domain 1, modified residue 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
8E6U	ELECTRON MICROSCOPY	3.2
6PUO	ELECTRON MICROSCOPY	3.3
8E6V	ELECTRON MICROSCOPY	3.3
8E6Q	ELECTRON MICROSCOPY	3.4
6MIX	ELECTRON MICROSCOPY	3.6
7VQ2	ELECTRON MICROSCOPY	3.68
6PUS	ELECTRON MICROSCOPY	3.7
6PUU	ELECTRON MICROSCOPY	3.7
8E6T	ELECTRON MICROSCOPY	3.7
7VQ1	ELECTRON MICROSCOPY	3.76
6PUR	ELECTRON MICROSCOPY	4.4
8E6S	ELECTRON MICROSCOPY	4.6
8E6R	ELECTRON MICROSCOPY	5.6
6MIZ	ELECTRON MICROSCOPY	6.1
6MJ2	ELECTRON MICROSCOPY	6.36

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94759-F1	78.51	0.21

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (15): 174; 179; 302; 333; 336; 843; 846; 869; 1073; 1381; 1382; 1431 …

Post-translational modifications (1): 740

Disulfide bonds (1): 996–1008

Mutagenesis-validated functional residues (32):

Position	Phenotype
215	abolishes lowering of temperature threshold for activation in response to reactive oxygen species. abolishes channel act
295	abolishes channel activation in response to adp-ribose/ca(2+).
302	no significant effect on channel activity; when associated with a-358. abolishes channel activation in response to adp-r
358	no significant effect on channel activity; when associated with a-302.
918	decreases in sensitivity to pip2.
952	strongly reduces channel activity at ph 7.3. increased residual channel activity after exposure to ph 5.5.
958	no effect on channel activity.
961	mildly decreases channel activity.
962	abolishes channel activity.
968	abolishes channel activity.
973	no effect on channel activity.
980	decreases permeability of ca(2+) over na(+).
981	increases the permeability of ca(2+) over na(+).
982	alters the reversal potential. increases the permeability of ca(2+) over na(+).
982	no change in the reversal potential. no change in the ion selectivity to ca(2+) over na(+).
984–985	prevents fast inactivation of the channel.
984	no change in the reversal potential. no change in the ion selectivity to ca(2+) over na(+).
985	no change in the reversal potential. no change in the ion selectivity to ca(2+) over na(+).
995	moderately decreases channel activity.
1002	strongly increased residual channel activity after exposure to ph 5.5.
1005	decreases channel activity.
1007	nearly abolishes channel activity.
1077	decreases in sensitivity to pip2.
1228–1503	loss of channel activity.
1397	only slight effect on activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3295583	TRP channels
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 87 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_TRANSITION_METAL_ION_TRANSPORT, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GGGTGGRR_PAX4_03, GOBP_MONOATOMIC_CATION_TRANSPORT, REACTOME_EFFECTS_OF_PIP2_HYDROLYSIS, GOBP_REGULATION_OF_CYTOSOLIC_CALCIUM_ION_CONCENTRATION, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_FERTILIZATION, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_NUCLEAR_ENVELOPE, chr5q31, GOBP_HOMEOSTATIC_PROCESS

GO Biological Process (26): temperature homeostasis (GO:0001659), dendritic cell chemotaxis (GO:0002407), calcium ion transport (GO:0006816), response to heat (GO:0009408), response to purine-containing compound (GO:0014074), regulation of actin cytoskeleton organization (GO:0032956), response to hydroperoxide (GO:0033194), release of sequestered calcium ion into cytosol (GO:0051209), protein homotetramerization (GO:0051289), regulation of filopodium assembly (GO:0051489), cellular response to hydrogen peroxide (GO:0070301), calcium ion transmembrane transport (GO:0070588), cellular response to calcium ion (GO:0071277), cellular response to temperature stimulus (GO:0071502), zinc ion transmembrane transport (GO:0071577), dendritic cell differentiation (GO:0097028), calcium ion transmembrane import into cytosol (GO:0097553), calcium ion import across plasma membrane (GO:0098703), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), manganese ion transport (GO:0006828), calcium-mediated signaling (GO:0019722), monoatomic ion transmembrane transport (GO:0034220), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085), manganese ion transmembrane transport (GO:0071421)

GO Molecular Function (11): monoatomic cation channel activity (GO:0005261), calcium channel activity (GO:0005262), sodium channel activity (GO:0005272), manganese ion transmembrane transporter activity (GO:0005384), calcium ion binding (GO:0005509), intracellularly gated calcium channel activity (GO:0015278), mono-ADP-D-ribose binding (GO:0072571), ligand-gated calcium channel activity (GO:0099604), monoatomic ion channel activity (GO:0005216), metal ion binding (GO:0046872), metal ion transmembrane transporter activity (GO:0046873)

GO Cellular Component (11): lysosome (GO:0005764), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), cytoplasmic vesicle membrane (GO:0030659), specific granule membrane (GO:0035579), cell projection (GO:0042995), perikaryon (GO:0043204), tertiary granule membrane (GO:0070821), ficolin-1-rich granule membrane (GO:0101003), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Stimuli-sensing channels	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion transport	3
secretory granule membrane	3
cellular anatomical structure	3
response to temperature stimulus	2
calcium ion transmembrane import into cytosol	2
monoatomic cation transmembrane transport	2
monoatomic cation transmembrane transporter activity	2
monoatomic cation channel activity	2
tertiary granule	2
multicellular organismal-level homeostasis	1
leukocyte chemotaxis	1
dendritic cell migration	1
response to stress	1
response to nitrogen compound	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
response to oxidative stress	1
response to oxygen-containing compound	1
intercellular transport	1
protein homooligomerization	1
protein tetramerization	1
filopodium assembly	1
regulation of plasma membrane bounded cell projection assembly	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
calcium ion transport	1
response to calcium ion	1
cellular response to metal ion	1
zinc ion transport	1
mononuclear cell differentiation	1
calcium ion transmembrane transport	1
calcium ion import	1
inorganic cation import across plasma membrane	1
calcium ion import into cytosol	1
transport	1
monoatomic ion channel activity	1
calcium ion transmembrane transporter activity	1
sodium ion transmembrane transporter activity	1
transition metal ion transmembrane transporter activity	1

Protein interactions and networks

STRING

656 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPM2	TRPV1	Q8NER1	782
TRPM2	STIM1	Q13586	729
TRPM2	ORAI1	Q96D31	701
TRPM2	STIM2	Q9P246	671
TRPM2	PARG	Q86W56	669
TRPM2	ORAI3	Q9BRQ5	665
TRPM2	ORAI2	Q96SN7	663
TRPM2	TRPC6	Q9Y210	656
TRPM2	RNF24	Q9Y225	650
TRPM2	TRPV2	Q9Y5S1	640
TRPM2	ANK1	P16157	626
TRPM2	PKD2L2	Q9NZM6	612
TRPM2	TRPA1	O75762	610
TRPM2	ANK3	Q12955	610
TRPM2	ANK2	Q01484	610

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TRPM2	TRPM2	psi-mi:“MI:0407”(direct interaction)	0.360
PPP1R12A	TRPM2	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): TRPM2 (Affinity Capture-RNA), TRPM2 (Affinity Capture-MS), EFHC1 (Affinity Capture-Western), TRPM2 (Reconstituted Complex), TRPM2 (Affinity Capture-Western), TRIM21 (Affinity Capture-Western), TRPM2 (Affinity Capture-MS), TRPM2 (Affinity Capture-MS), EPPK1 (Cross-Linking-MS (XL-MS)), TRPM2 (Cross-Linking-MS (XL-MS)), TRPM2 (Co-fractionation), TRPM2 (Co-fractionation), TRPM2 (Co-fractionation), TRPM2 (Co-fractionation), TRPM2 (Affinity Capture-RNA)

ESM2 similar proteins: A0A5B9, A6NDV4, A6QLK4, B1AWJ5, E9PTA2, O75051, O94759, P01850, P01851, P01852, P01857, P01859, P01860, P01861, P01869, P01870, P01906, P01909, P03987, P06333, P0DSE2, P0DTU4, P11364, P15151, P15981, P20759, P20762, P32506, P54900, Q1WIM1, Q1WIM3, Q3TMX7, Q6P767, Q6ZRP7, Q7TQ33, Q812F8, Q8N126, Q8NFZ8, Q8R143, Q8R464

Diamond homologs: A0A0R4IMY7, A7T1N0, A8DYE2, E9PTA2, J9SQF3, O94759, Q2TV84, Q2WEA5, Q5XIG0, Q7TN37, Q7Z2W7, Q7Z4N2, Q8BVU5, Q8R455, Q8R4D5, Q8TD43, Q91YD4, Q9BW91, Q9ESQ5, Q9HCF6, Q9JJH7, Q9NZQ8, S5UH55, Q09297, Q8CIR4, Q923J1, Q925B3, Q96QT4, Q9BX84, Q93971

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKCA	“up-regulates activity”	TRPM2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

483 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	349
Likely benign	37
Benign	47

Top pathogenic / likely-pathogenic (0)

SpliceAI

9846 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44350274:AGGTA:A	donor_loss	1.0000
21:44354646:A:AG	acceptor_gain	1.0000
21:44354647:G:GG	acceptor_gain	1.0000
21:44364110:GCA:G	acceptor_loss	1.0000
21:44364111:CAG:C	acceptor_loss	1.0000
21:44366094:G:T	donor_gain	1.0000
21:44366095:A:T	donor_gain	1.0000
21:44366749:C:A	acceptor_gain	1.0000
21:44366751:CAG:C	acceptor_loss	1.0000
21:44366752:A:AG	acceptor_gain	1.0000
21:44366752:A:C	acceptor_loss	1.0000
21:44366752:AGTAC:A	acceptor_gain	1.0000
21:44366753:G:GT	acceptor_gain	1.0000
21:44366753:GT:G	acceptor_gain	1.0000
21:44366753:GTAC:G	acceptor_gain	1.0000
21:44366753:GTACG:G	acceptor_gain	1.0000
21:44366931:ACAG:A	donor_loss	1.0000
21:44366932:CAG:C	donor_loss	1.0000
21:44366933:AG:A	donor_loss	1.0000
21:44366936:T:A	donor_loss	1.0000
21:44376005:A:T	donor_gain	1.0000
21:44376011:G:GT	donor_gain	1.0000
21:44377709:TAG:T	acceptor_loss	1.0000
21:44377710:AGG:A	acceptor_loss	1.0000
21:44377711:G:T	acceptor_loss	1.0000
21:44377711:GGT:G	acceptor_gain	1.0000
21:44377770:GCAC:G	donor_gain	1.0000
21:44377773:CG:C	donor_loss	1.0000
21:44377774:G:GG	donor_gain	1.0000
21:44377775:T:A	donor_loss	1.0000

AlphaMissense

9917 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:44414056:T:C	L1043P	0.999
21:44369182:T:A	W204R	0.998
21:44369182:T:C	W204R	0.998
21:44414054:C:A	N1042K	0.998
21:44414054:C:G	N1042K	0.998
21:44417967:T:A	W1063R	0.998
21:44417967:T:C	W1063R	0.998
21:44406037:G:A	M930I	0.997
21:44406037:G:C	M930I	0.997
21:44406037:G:T	M930I	0.997
21:44406633:T:A	W944R	0.997
21:44406633:T:C	W944R	0.997
21:44406663:G:C	A954P	0.997
21:44417934:T:C	F1052L	0.997
21:44417936:C:A	F1052L	0.997
21:44417936:C:G	F1052L	0.997
21:44417969:G:C	W1063C	0.997
21:44417969:G:T	W1063C	0.997
21:44390969:T:A	W462R	0.996
21:44390969:T:C	W462R	0.996
21:44390988:C:A	A468D	0.996
21:44395501:T:A	W628R	0.996
21:44395501:T:C	W628R	0.996
21:44406738:T:C	F979L	0.996
21:44406740:C:A	F979L	0.996
21:44406740:C:G	F979L	0.996
21:44413914:T:A	C996S	0.996
21:44413915:G:C	C996S	0.996
21:44417980:G:C	R1067P	0.996
21:44390976:G:C	R464P	0.995

dbSNP variants (sampled 300 via entrez): RS1000000320 (21:44435234 C>T), RS1000028365 (21:44362057 G>A,T), RS1000082273 (21:44434317 G>A), RS1000133480 (21:44428058 C>G), RS1000176336 (21:44415956 G>A), RS1000224832 (21:44381804 G>A), RS1000263579 (21:44413656 C>T), RS1000278629 (21:44381624 G>A), RS1000285585 (21:44380102 C>T), RS1000331617 (21:44418953 C>T), RS1000334874 (21:44377384 G>A), RS1000378641 (21:44413456 T>C), RS1000421945 (21:44428235 T>A), RS1000448634 (21:44409517 C>T), RS1000475714 (21:44363498 C>T)

Disease associations

OMIM: gene MIM:603749 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003672_11	Docetaxel-induced peripheral neuropathy in metastatic castrate-resistant prostate cancer	9.000000e-06
GCST007559_10	Sleep duration (short sleep)	8.000000e-10
GCST009267_16	Dental caries (decayed, missing and filled teeth)	4.000000e-06
GCST009531_11	Body fat percentage	4.000000e-08
GCST010206_3	Anorectal malformation	6.000000e-17
GCST010991_49	Parkinson’s disease	9.000000e-08
GCST012438_1	Interleukin-6 levels in non-alcoholic fatty liver disease x mastiha supplementation interaction	8.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007800	body fat percentage
EFO:0004810	interleukin-6 measurement
EFO:0600067	mastiha supplement exposure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1250402 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 281,251 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL55643	COPPER	4
CHEMBL752	ADENOSINE PHOSPHATE	4	165,316
CHEMBL808	ECONAZOLE	4	24,813
CHEMBL23588	FLUFENAMIC ACID	2	34,797

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Transient Receptor Potential channels (TRP)

Most potent curated ligand interactions (8 total), top 8:

Ligand	Action	Affinity	Parameter
tatM2NX	Antagonist	6.4	pIC50
2-APB	Antagonist	6.1	pIC50
Zn2+	Channel blocker	6.0	pIC50
ACAA	Antagonist	5.8	pIC50
cADPR	Agonist	5.0	pEC50
ADP ribose	Agonist	4.4	pEC50
OAADPR	Activation	4.0	pKd
NAADP	Agonist	3.1	pEC50

ChEMBL bioactivities

39 potent at pChembl≥5 of 53 total, top 32 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.89	IC50	13	nM	CHEMBL4878260
7.60	IC50	25	nM	CHEMBL4161122
6.68	IC50	210	nM	SCALARADIAL
6.50	IC50	320	nM	CHEMBL173443
6.40	IC50	398	nM	CHEMBL4863360
6.39	IC50	410	nM	CHEMBL4864346
6.33	IC50	467	nM	CHEMBL4856222
6.22	IC50	600	nM	CHEMBL127336
6.10	IC50	788	nM	CHEMBL4863549
6.08	IC50	830	nM	CHEMBL4849043
6.01	IC50	987	nM	CHEMBL4856093
6.00	IC50	1000	nM	CHEMBL169233
5.92	IC50	1200	nM	CHEMBL169233
5.77	IC50	1700	nM	CHEMBL173443
5.64	IC50	2290	nM	CHEMBL6151257
5.59	IC50	2560	nM	CHEMBL176974
5.58	IC50	2600	nM	COPPER
5.55	IC50	2800	nM	CHEMBL6174866
5.54	IC50	2890	nM	CHEMBL6148339
5.52	IC50	3000	nM	CHEMBL3110206
5.52	IC50	3000	nM	ECONAZOLE
5.52	IC50	3000	nM	CLOTRIMAZOLE
5.51	IC50	3080	nM	CHEMBL6174567
5.48	IC50	3280	nM	CHEMBL6164834
5.43	IC50	3700	nM	CHEMBL4176916
5.40	IC50	4000	nM	CHEMBL4159037
5.35	IC50	4500	nM	CHEMBL173443
5.34	IC50	4600	nM	CHEMBL4174768
5.30	IC50	5000	nM	CHEMBL169233
5.29	IC50	5100	nM	CHEMBL4167784
5.21	IC50	6200	nM	CHEMBL4872096
5.09	IC50	8100	nM	CHEMBL4873412

PubChem BioAssay actives

35 with measured affinity, of 365 total; 22 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
ethyl 2-[3-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4H-cyclohepta[d]pyrazol-1-yl]acetate	1775860: Inhibition of human TRPM2 expressed in HEK293T cells assessed as blocked of ADPR-activated current by whole cell patch clamp electrophysiology	ic50	0.0130	uM
2-(dimethylamino)-N-(6-oxo-5H-phenanthridin-2-yl)acetamide;hydrate;hydrochloride	1503196: Inhibition of human FLAG-tagged TRPM2 expressed in HEK293 cells assessed as reduction in H2O2-induced intracellular calcium flux pretreated for 30 secs followed by H2O2 addition measured for 120 secs by Fluo4-AM dye based fluorescence assay	ic50	0.0250	uM
[(4aS,4bR,6S,6aS,7R,10aS,10bR,12aS)-7,8-diformyl-1,1,4a,6a,10b-pentamethyl-2,3,4,4b,5,6,7,10,10a,11,12,12a-dodecahydrochrysen-6-yl] acetate	1503188: Inhibition of human FLAG-tagged TRPM2 expressed in HEK293 cells assessed as reduction in ADPR-induced intracellular calcium flux after 30 to 60 mins by whole cell patch clamp electrophysiology method	ic50	0.2100	uM
2-[[(E)-3-(4-pentylphenyl)prop-2-enoyl]amino]benzoic acid	1359285: Inhibition of human TRPM2 expressed in HEK293 cells assessed as reduction in ADPR-induced channel currents treated extracellularly after 60 secs by whole cell patch clamp electrophysiology method	ic50	0.3200	uM
2-[[(E)-3-[4-(3-nitrophenyl)phenyl]prop-2-enoyl]amino]benzoic acid	1775860: Inhibition of human TRPM2 expressed in HEK293T cells assessed as blocked of ADPR-activated current by whole cell patch clamp electrophysiology	ic50	0.3980	uM
5-bromo-2-[[(E)-3-(4-phenylphenyl)prop-2-enoyl]amino]benzoic acid	1775860: Inhibition of human TRPM2 expressed in HEK293T cells assessed as blocked of ADPR-activated current by whole cell patch clamp electrophysiology	ic50	0.4100	uM
4-methyl-2-[[(E)-3-(4-pentylphenyl)prop-2-enoyl]amino]benzoic acid	1775860: Inhibition of human TRPM2 expressed in HEK293T cells assessed as blocked of ADPR-activated current by whole cell patch clamp electrophysiology	ic50	0.4670	uM
5-(4-piperidin-1-ylbutoxy)-3,4-dihydro-2H-isoquinolin-1-one	1503196: Inhibition of human FLAG-tagged TRPM2 expressed in HEK293 cells assessed as reduction in H2O2-induced intracellular calcium flux pretreated for 30 secs followed by H2O2 addition measured for 120 secs by Fluo4-AM dye based fluorescence assay	ic50	0.6000	uM
2-[[(E)-3-[4-[3-(trifluoromethyl)phenyl]phenyl]prop-2-enoyl]amino]benzoic acid	1775860: Inhibition of human TRPM2 expressed in HEK293T cells assessed as blocked of ADPR-activated current by whole cell patch clamp electrophysiology	ic50	0.7880	uM
2-[[(E)-3-[4-(3-fluorophenyl)phenyl]prop-2-enoyl]amino]benzoic acid	1775860: Inhibition of human TRPM2 expressed in HEK293T cells assessed as blocked of ADPR-activated current by whole cell patch clamp electrophysiology	ic50	0.8300	uM
5-methyl-2-[[(E)-3-(4-pentylphenyl)prop-2-enoyl]amino]benzoic acid	1775860: Inhibition of human TRPM2 expressed in HEK293T cells assessed as blocked of ADPR-activated current by whole cell patch clamp electrophysiology	ic50	0.9870	uM
2-diphenylboranyloxyethanamine	1065919: Inhibition of human TRPM2 expressed in HEK293 cells	ic50	1.0000	uM
2-[[(E)-3-(4-phenylphenyl)prop-2-enoyl]amino]benzoic acid	1775860: Inhibition of human TRPM2 expressed in HEK293T cells assessed as blocked of ADPR-activated current by whole cell patch clamp electrophysiology	ic50	2.5600	uM
Clotrimazole	1065914: Inhibition of TRPM2 (unknown origin)	ic50	3.0000	uM
Econazole	1065914: Inhibition of TRPM2 (unknown origin)	ic50	3.0000	uM
[[(2R,3S,5R)-5-(6-amino-8-phenylpurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R)-3,4,5-trihydroxyoxolan-2-yl]methyl hydrogen phosphate	1065917: Antagonist activity at human TRPM2 expressed in HEK293 cells assessed as inhibition of ADPR-induced maximum outward potassium current at +15 mV by whole-cell patch-clamp electrophysiology	ic50	3.0000	uM
6-bromo-8-methyl-2-(5-naphthalen-1-yl-1H-pyrazol-4-yl)-2,3-dihydro-1H-quinazolin-4-one	1359285: Inhibition of human TRPM2 expressed in HEK293 cells assessed as reduction in ADPR-induced channel currents treated extracellularly after 60 secs by whole cell patch clamp electrophysiology method	ic50	3.7000	uM
6-chloro-8-methyl-2-(5-naphthalen-1-yl-1H-pyrazol-4-yl)-2,3-dihydro-1H-quinazolin-4-one	1359285: Inhibition of human TRPM2 expressed in HEK293 cells assessed as reduction in ADPR-induced channel currents treated extracellularly after 60 secs by whole cell patch clamp electrophysiology method	ic50	4.0000	uM
6-bromo-8-methyl-2-(5-phenyl-1H-pyrazol-4-yl)-2,3-dihydro-1H-quinazolin-4-one	1359285: Inhibition of human TRPM2 expressed in HEK293 cells assessed as reduction in ADPR-induced channel currents treated extracellularly after 60 secs by whole cell patch clamp electrophysiology method	ic50	4.6000	uM
6-chloro-8-methyl-2-(5-phenyl-1H-pyrazol-4-yl)-2,3-dihydro-1H-quinazolin-4-one	1359285: Inhibition of human TRPM2 expressed in HEK293 cells assessed as reduction in ADPR-induced channel currents treated extracellularly after 60 secs by whole cell patch clamp electrophysiology method	ic50	5.1000	uM
[4-[2-(diethylamino)ethyl]-2-methylimidazo[1,2-a]benzimidazol-1-yl]-(4-phenylphenyl)methanone	1784468: Inhibition of human TRPM2 expressed in HEK293T cells cotransfected with GFP assessed as reduction in ADPR-induced current by whole cell patch-clamp method	ic50	6.2000	uM
1-benzofuran-2-yl-[4-[2-(diethylamino)ethyl]-2-methylimidazo[1,2-a]benzimidazol-1-yl]methanone	1784468: Inhibition of human TRPM2 expressed in HEK293T cells cotransfected with GFP assessed as reduction in ADPR-induced current by whole cell patch-clamp method	ic50	8.1000	uM

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
4-amylcinnamoylanthranilic acid	decreases reaction, increases activity, increases reaction, decreases activity	3
Adenosine Diphosphate Ribose	decreases reaction, increases activity, increases reaction	3
Hydrogen Peroxide	increases activity, increases response to substance	3
2-aminoethoxydiphenyl borate	decreases reaction, increases activity, decreases activity	2
Calcium	decreases activity, decreases reaction, increases abundance, affects reaction, increases transport	2
aristolochic acid I	increases expression	1
diphenoquinone	decreases activity	1
ethyl-p-hydroxybenzoate	increases expression	1
lead nitrate	decreases reaction, increases activity	1
zinc chromate	decreases expression, increases abundance	1
ferrous chloride	decreases reaction, increases activity	1
chromium hexavalent ion	decreases expression, increases abundance	1
pinostrobin	increases expression	1
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	decreases activity	1
abrine	increases expression	1
Decitabine	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases reaction, increases activity, increases reaction	1
Clotrimazole	decreases activity, decreases reaction, increases abundance	1
Econazole	decreases activity, decreases reaction, increases abundance	1
Lithium	decreases reaction, increases expression	1
Mercuric Chloride	decreases reaction, increases activity	1
Miconazole	decreases reaction, increases activity	1
Monensin	decreases reaction, increases expression, decreases expression	1
Mustard Gas	affects response to substance, decreases activity, decreases reaction, increases abundance, affects reaction	1
Ozone	increases abundance, affects expression	1
Valproic Acid	increases methylation	1
Eicosapentaenoic Acid	increases reaction, decreases reaction, increases activity	1

ChEMBL screening assays

59 unique, capped per target: 58 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1252890	Binding	Induction of TRPM2 S-nitrosylation in HEK cells assessed as increase in Ca2+ level from extracellular space at 30 uM	Nitric oxide activates TRP channels by cysteine S-nitrosylation. — Nat Chem Biol
CHEMBL3734573	Functional	Inhibition of TRPM2 (unknown origin) expressed in HEK293 cells assessed as effect on agonist-induced Ca2+ changes	Agents and methods for treating ischemic and other diseases

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1LC	Abcam Jurkat TRPM2 KO	Cancer cell line	Male
CVCL_D1R5	Abcam K-562 TRPM2 KO	Cancer cell line	Female
CVCL_D2MS	Abcam Raji TRPM2 KO	Cancer cell line	Male
CVCL_E2MP	HAP1 TRPM2 (-) 1	Cancer cell line	Male
CVCL_E2MQ	HAP1 TRPM2 (-) 2	Cancer cell line	Male
CVCL_E2MR	HAP1 TRPM2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.