TISIDB

Summary
Symbol	TRPM8
Name	transient receptor potential cation channel, subfamily M, member 8
Aliases	LTRPC6; TRPP8; LTrpC-6; long transient receptor potential channel 6; short form of the TRPM8 cationic channe ......
Chromosomal Location	2q37
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. Membrane raft. Endoplasmic reticulum membrane. Note=Localizes to membrane rafts but is also located in the cell membrane outside of these regions where channel response to cold is enhanced compared to membrane rafts (By similarity). Located in the endoplasmic reticulum in prostate cancer cells.
Domain	PF00520 Ion transport protein
Function	Receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. Activated by icilin, eucalyptol, menthol, cold and modulation of intracellular pH. Involved in menthol sensation. Permeable for monovalent cations sodium, potassium, and cesium and divalent cation calcium. Temperature sensing is tightly linked to voltage-dependent gating. Activated upon depolarization, changes in temperature resulting in graded shifts of its voltage-dependent activation curves. The chemical agonist menthol functions as a gating modifier, shifting activation curves towards physiological membrane potentials. Temperature sensitivity arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing. In prostate cancer cells, shows strong inward rectification and high calcium selectivity in contrast to its behavior in normal cells which is characterized by outward rectification and poor cationic selectivity. Plays a role in prostate cancer cell migration (PubMed:25559186). Isoform 2 and isoform 3 negatively regulate menthol- and cold-induced channel activity by stabilizing the closed state of the channel.

> Gene Ontology [ TOP ]
Biological Process	GO:0006816 calcium ion transport GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0009266 response to temperature stimulus GO:0009409 response to cold GO:0009581 detection of external stimulus GO:0009582 detection of abiotic stimulus GO:0016048 detection of temperature stimulus GO:0050951 sensory perception of temperature stimulus GO:0050955 thermoception GO:0051259 protein oligomerization GO:0051260 protein homooligomerization GO:0051262 protein tetramerization GO:0051289 protein homotetramerization GO:0055074 calcium ion homeostasis GO:0070206 protein trimerization GO:0070207 protein homotrimerization GO:0070588 calcium ion transmembrane transport GO:0070838 divalent metal ion transport GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0072511 divalent inorganic cation transport
Molecular Function	GO:0005216 ion channel activity GO:0005261 cation channel activity GO:0005262 calcium channel activity GO:0015085 calcium ion transmembrane transporter activity GO:0015267 channel activity GO:0022803 passive transmembrane transporter activity GO:0022838 substrate-specific channel activity GO:0046873 metal ion transmembrane transporter activity GO:0072509 divalent inorganic cation transmembrane transporter activity
Cellular Component	GO:0009897 external side of plasma membrane GO:0045121 membrane raft GO:0098552 side of membrane GO:0098589 membrane region GO:0098857 membrane microdomain

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04750 Inflammatory mediator regulation of TRP channels
Reactome	R-HSA-983712: Ion channel transport R-HSA-2672351: Stimuli-sensing channels R-HSA-3295583: TRP channels R-HSA-382551: Transmembrane transport of small molecules

Summary
Symbol	TRPM8
Name	transient receptor potential cation channel, subfamily M, member 8
Aliases	LTRPC6; TRPP8; LTrpC-6; long transient receptor potential channel 6; short form of the TRPM8 cationic channe ......
Chromosomal Location	2q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TRPM8 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	TRPM8
Name	transient receptor potential cation channel, subfamily M, member 8
Aliases	LTRPC6; TRPP8; LTrpC-6; long transient receptor potential channel 6; short form of the TRPM8 cationic channe ......
Chromosomal Location	2q37
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 TRPM8 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	TRPM8
Name	transient receptor potential cation channel, subfamily M, member 8
Aliases	LTRPC6; TRPP8; LTrpC-6; long transient receptor potential channel 6; short form of the TRPM8 cationic channe ......
Chromosomal Location	2q37
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 TRPM8 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	-0.565	0.417
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.714	0.554
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.439	0.639
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.28	0.65
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.695	0.586
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.233	0.861
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.148	0.203
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.322	0.805
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	3.025	0.0209
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.651	0.601
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	-0.315	0.844
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.172	0.536

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of TRPM8 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	7.1	5.9	1.2	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	33.3	-23.3	0.423
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	18.5	2.7	15.8	0.0147
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	18.5	1.7	16.8	0.0108
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	11.8	-2.3	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	18.2	-10.5	0.576
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	7.9	0	7.9	0.26
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
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	TRPM8
Name	transient receptor potential cation channel, subfamily M, member 8
Aliases	LTRPC6; TRPP8; LTrpC-6; long transient receptor potential channel 6; short form of the TRPM8 cationic channe ......
Chromosomal Location	2q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TRPM8. 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	TRPM8
Name	transient receptor potential cation channel, subfamily M, member 8
Aliases	LTRPC6; TRPP8; LTrpC-6; long transient receptor potential channel 6; short form of the TRPM8 cationic channe ......
Chromosomal Location	2q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TRPM8. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TRPM8. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TRPM8
Name	transient receptor potential cation channel, subfamily M, member 8
Aliases	LTRPC6; TRPP8; LTrpC-6; long transient receptor potential channel 6; short form of the TRPM8 cationic channe ......
Chromosomal Location	2q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TRPM8. 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	TRPM8
Name	transient receptor potential cation channel, subfamily M, member 8
Aliases	LTRPC6; TRPP8; LTrpC-6; long transient receptor potential channel 6; short form of the TRPM8 cationic channe ......
Chromosomal Location	2q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TRPM8 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TRPM8
Name	transient receptor potential cation channel, subfamily M, member 8
Aliases	LTRPC6; TRPP8; LTrpC-6; long transient receptor potential channel 6; short form of the TRPM8 cationic channe ......
Chromosomal Location	2q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TRPM8 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TRPM8
Name	transient receptor potential cation channel, subfamily M, member 8
Aliases	LTRPC6; TRPP8; LTrpC-6; long transient receptor potential channel 6; short form of the TRPM8 cationic channe ......
Chromosomal Location	2q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TRPM8 collected from DrugBank database.

> Drugs from DrugBank database

[ TOP ]

Details on drugs targeting TRPM8.

ID	Name	Drug Type	Targets	#Targets
DB00825	Menthol	Small Molecule	OPRK1, TRPA1, TRPM8, TRPV3	4
DB09061	Cannabidiol	Small Molecule	CACNA1G, CACNA1H, CACNA1I, CHRNA7, CNR1, CNR2, GLRA1, GLRA1, GLRA3 ......	25

Browse TRPM8