TISIDB

Summary
Symbol	TRPM2
Name	transient receptor potential cation channel, subfamily M, member 2
Aliases	KNP3; LTRPC2; NUDT9L1; NUDT9H; EREG1; LTrpC-2; estrogen-responsive element-associated gene 1 protein; long t ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cell membrane Multi-pass membrane protein Perikaryon Cell projection Cytoplasmic vesicle Lysosome Note=Detected at the cell membrane and in intracellular vesicles in cortical neurons. Detected on neuronal cell bodies and neurites (By similarity). Detected on the cell membrane in polymorphonuclear neutrophils. Detected on cytoplasmic vesicles and lysosomes in immature bone marrow dendritic cells (By similarity). ; SUBCELLULAR LOCATION: Isoform 1: Cell membrane Multi-pass membrane protein ; SUBCELLULAR LOCATION: Isoform 2: Cell membrane Multi-pass membrane protein ; SUBCELLULAR LOCATION: Isoform 3: Cell membrane Multi-pass membrane protein
Domain	PF00520 Ion transport protein
Function	Isoform 1: Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels (PubMed:11960981, PubMed:12594222, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:20660597, PubMed:27383051, PubMed:27068538). Extracellular calcium passes through the channel and increases channel activity by binding to the cytoplasmic domain and stabilizing the channel in an open conformation (PubMed:19171771). Also contributes to Ca(2+) release from intracellular stores in response to ADP-ribose (PubMed:19454650). Plays a role in numerous processes that involve signaling via intracellular Ca(2+) levels (Probable). Besides, mediates the release of lysosomal Zn(2+) stores in response to reactive oxygen species, leading to increased cytosolic Zn(2+) levels (PubMed:25562606, PubMed:27068538). Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Activated by intracellular ADP-ribose, beta-NAD (NAD(+)) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:11960981, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:27383051, PubMed:27068538). The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate (PubMed:20650899, PubMed:25918360). Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius) (PubMed:22493272). 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 (By similarity). 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 (By similarity). 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 (PubMed:27068538). Confers susceptibility to cell death following oxidative stress (PubMed:12594222, PubMed:25562606). ; FUNCTION: Isoform 2: Lacks cation channel activity. Does not mediate cation transport in response to oxidative stress or ADP-ribose. ; FUNCTION: Isoform 3: Lacks cation channel activity and negatively regulates the channel activity of isoform 1. Negatively regulates susceptibility to cell death in reposponse to oxidative stress.

> Gene Ontology [ TOP ]
Biological Process	GO:0002790 peptide secretion GO:0002791 regulation of peptide secretion GO:0002793 positive regulation of peptide secretion GO:0006814 sodium ion transport GO:0006816 calcium ion transport GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0006979 response to oxidative stress GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0009306 protein secretion GO:0009914 hormone transport GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0010817 regulation of hormone levels GO:0014074 response to purine-containing compound GO:0015672 monovalent inorganic cation transport GO:0015833 peptide transport GO:0023061 signal release GO:0030072 peptide hormone secretion GO:0030073 insulin secretion GO:0032024 positive regulation of insulin secretion GO:0034599 cellular response to oxidative stress GO:0035725 sodium ion transmembrane transport GO:0036473 cell death in response to oxidative stress GO:0036475 neuron death in response to oxidative stress GO:0042698 ovulation cycle GO:0042886 amide transport GO:0044849 estrous cycle GO:0046879 hormone secretion GO:0046883 regulation of hormone secretion GO:0046887 positive regulation of hormone secretion GO:0048511 rhythmic process GO:0050708 regulation of protein secretion GO:0050714 positive regulation of protein secretion GO:0050796 regulation of insulin secretion GO:0051047 positive regulation of secretion GO:0051222 positive regulation of protein transport GO:0051480 regulation of cytosolic calcium ion concentration GO:0051592 response to calcium ion GO:0055074 calcium ion homeostasis GO:0060401 cytosolic calcium ion transport GO:0060402 calcium ion transport into cytosol GO:0070509 calcium ion import GO:0070588 calcium ion transmembrane transport GO:0070838 divalent metal ion transport GO:0070997 neuron death GO:0071241 cellular response to inorganic substance GO:0071248 cellular response to metal ion GO:0071277 cellular response to calcium ion GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0072511 divalent inorganic cation transport GO:0090087 regulation of peptide transport GO:0090276 regulation of peptide hormone secretion GO:0090277 positive regulation of peptide hormone secretion GO:0097553 calcium ion transmembrane import into cytosol GO:0098657 import into cell GO:0098659 inorganic cation import into cell GO:0098703 calcium ion import across plasma membrane GO:0098739 import across plasma membrane GO:0099587 inorganic ion import into cell GO:1900407 regulation of cellular response to oxidative stress GO:1900409 positive regulation of cellular response to oxidative stress GO:1901214 regulation of neuron death GO:1901216 positive regulation of neuron death GO:1902656 calcium ion import into cytosol GO:1902882 regulation of response to oxidative stress GO:1902884 positive regulation of response to oxidative stress GO:1903201 regulation of oxidative stress-induced cell death GO:1903203 regulation of oxidative stress-induced neuron death GO:1903209 positive regulation of oxidative stress-induced cell death GO:1903223 positive regulation of oxidative stress-induced neuron death GO:1903532 positive regulation of secretion by cell GO:1904951 positive regulation of establishment of protein localization GO:1990035 calcium ion import into cell
Molecular Function	GO:0005216 ion channel activity GO:0005261 cation channel activity GO:0005262 calcium channel activity GO:0005272 sodium channel activity GO:0015077 monovalent inorganic cation transmembrane transporter activity GO:0015081 sodium ion transmembrane transporter activity GO:0015085 calcium ion transmembrane transporter activity GO:0015267 channel activity GO:0015276 ligand-gated ion channel activity GO:0022803 passive transmembrane transporter activity GO:0022834 ligand-gated channel activity GO:0022836 gated channel activity GO:0022838 substrate-specific channel activity GO:0046873 metal ion transmembrane transporter activity GO:0047631 ADP-ribose diphosphatase activity GO:0072509 divalent inorganic cation transmembrane transporter activity GO:0099604 ligand-gated calcium channel activity
Cellular Component	GO:0043025 neuronal cell body GO:0044297 cell body

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04621 NOD-like receptor signaling pathway hsa04921 Oxytocin signaling pathway
Reactome	R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-983712: Ion channel transport R-HSA-6798695: Neutrophil degranulation R-HSA-2672351: Stimuli-sensing channels R-HSA-3295583: TRP channels R-HSA-382551: Transmembrane transport of small molecules

Summary
Symbol	TRPM2
Name	transient receptor potential cation channel, subfamily M, member 2
Aliases	KNP3; LTRPC2; NUDT9L1; NUDT9H; EREG1; LTrpC-2; estrogen-responsive element-associated gene 1 protein; long t ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TRPM2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	TRPM2
Name	transient receptor potential cation channel, subfamily M, member 2
Aliases	KNP3; LTRPC2; NUDT9L1; NUDT9H; EREG1; LTrpC-2; estrogen-responsive element-associated gene 1 protein; long t ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

[ TOP ]

Statistical results of TRPM2 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	TRPM2
Name	transient receptor potential cation channel, subfamily M, member 2
Aliases	KNP3; LTRPC2; NUDT9L1; NUDT9H; EREG1; LTrpC-2; estrogen-responsive element-associated gene 1 protein; long t ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the expression difference of TRPM2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.109	0.782
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.368	0.716
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.449	0.617
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.159	0.657
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.099	0.961
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.492	0.856
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.075	0.845
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.01	0.992
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.14	0.909
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.194	0.263
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.382	0.374
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.061	0.622

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TRPM2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	21.4	5.9	15.5	0.304
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	30	0	30	0.528
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	8.2	-4.5	0.671
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	10.2	-6.5	0.425
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	35.3	-30.5	0.0313
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	16.7	-4.2	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	45.5	-45.5	0.0109
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	0	22.2	0.12
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	TRPM2
Name	transient receptor potential cation channel, subfamily M, member 2
Aliases	KNP3; LTRPC2; NUDT9L1; NUDT9H; EREG1; LTrpC-2; estrogen-responsive element-associated gene 1 protein; long t ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TRPM2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	TRPM2
Name	transient receptor potential cation channel, subfamily M, member 2
Aliases	KNP3; LTRPC2; NUDT9L1; NUDT9H; EREG1; LTrpC-2; estrogen-responsive element-associated gene 1 protein; long t ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TRPM2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TRPM2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TRPM2
Name	transient receptor potential cation channel, subfamily M, member 2
Aliases	KNP3; LTRPC2; NUDT9L1; NUDT9H; EREG1; LTrpC-2; estrogen-responsive element-associated gene 1 protein; long t ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TRPM2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	TRPM2
Name	transient receptor potential cation channel, subfamily M, member 2
Aliases	KNP3; LTRPC2; NUDT9L1; NUDT9H; EREG1; LTrpC-2; estrogen-responsive element-associated gene 1 protein; long t ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TRPM2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TRPM2
Name	transient receptor potential cation channel, subfamily M, member 2
Aliases	KNP3; LTRPC2; NUDT9L1; NUDT9H; EREG1; LTrpC-2; estrogen-responsive element-associated gene 1 protein; long t ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TRPM2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TRPM2
Name	transient receptor potential cation channel, subfamily M, member 2
Aliases	KNP3; LTRPC2; NUDT9L1; NUDT9H; EREG1; LTrpC-2; estrogen-responsive element-associated gene 1 protein; long t ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TRPM2 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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