TISIDB

Summary
Symbol	GRM4
Name	glutamate receptor, metabotropic 4
Aliases	GPRC1D; mGlu4; MGLUR4; Metabotropic glutamate receptor 4
Chromosomal Location	6p21.3
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
Domain	PF00003 7 transmembrane sweet-taste receptor of 3 GCPR PF01094 Receptor family ligand binding region PF07562 Nine Cysteines Domain of family 3 GPCR
Function	G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity.

> Gene Ontology [ TOP ]
Biological Process	GO:0000187 activation of MAPK activity GO:0001505 regulation of neurotransmitter levels GO:0006836 neurotransmitter transport GO:0007187 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger GO:0007188 adenylate cyclase-modulating G-protein coupled receptor signaling pathway GO:0007193 adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway GO:0007196 adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway GO:0007215 glutamate receptor signaling pathway GO:0007216 G-protein coupled glutamate receptor signaling pathway GO:0007269 neurotransmitter secretion GO:0007270 neuron-neuron synaptic transmission GO:0023061 signal release GO:0032147 activation of protein kinase activity GO:0033674 positive regulation of kinase activity GO:0035249 synaptic transmission, glutamatergic GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0043523 regulation of neuron apoptotic process GO:0045860 positive regulation of protein kinase activity GO:0050804 modulation of synaptic transmission GO:0051402 neuron apoptotic process GO:0051966 regulation of synaptic transmission, glutamatergic GO:0070997 neuron death GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0099531 presynaptic process involved in chemical synaptic transmission GO:0099643 signal release from synapse GO:1901214 regulation of neuron death
Molecular Function	GO:0001640 adenylate cyclase inhibiting G-protein coupled glutamate receptor activity GO:0001642 group III metabotropic glutamate receptor activity GO:0008066 glutamate receptor activity GO:0098988 G-protein coupled glutamate receptor activity
Cellular Component	GO:0042734 presynaptic membrane GO:0097060 synaptic membrane GO:0098793 presynapse

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04080 Neuroactive ligand-receptor interaction hsa04724 Glutamatergic synapse hsa04742 Taste transduction
Reactome	R-HSA-420499: Class C/3 (Metabotropic glutamate/pheromone receptors) R-HSA-418594: G alpha (i) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

Summary
Symbol	GRM4
Name	glutamate receptor, metabotropic 4
Aliases	GPRC1D; mGlu4; MGLUR4; Metabotropic glutamate receptor 4
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between GRM4 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	GRM4
Name	glutamate receptor, metabotropic 4
Aliases	GPRC1D; mGlu4; MGLUR4; Metabotropic glutamate receptor 4
Chromosomal Location	6p21.3
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

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Statistical results of GRM4 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	Sensitive to T cell-mediated killing
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	GRM4
Name	glutamate receptor, metabotropic 4
Aliases	GPRC1D; mGlu4; MGLUR4; Metabotropic glutamate receptor 4
Chromosomal Location	6p21.3
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

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Points in the above scatter plot represent the expression difference of GRM4 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	1
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0	1
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0	1
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.147	0.788
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.497	0.651
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.302	0.801
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0	1
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0	1
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.065	0.876
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	-0.065	0.918
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.032	0.915

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of GRM4 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	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
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	0	1.4	-1.4	1
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	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
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	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	6.2	16	0.53
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	11.1	8.9	1
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	13.2	0	13.2	0.0705
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	18.2	0	18.2	0.274
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	GRM4
Name	glutamate receptor, metabotropic 4
Aliases	GPRC1D; mGlu4; MGLUR4; Metabotropic glutamate receptor 4
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GRM4. 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	GRM4
Name	glutamate receptor, metabotropic 4
Aliases	GPRC1D; mGlu4; MGLUR4; Metabotropic glutamate receptor 4
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GRM4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GRM4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	GRM4
Name	glutamate receptor, metabotropic 4
Aliases	GPRC1D; mGlu4; MGLUR4; Metabotropic glutamate receptor 4
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GRM4. 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	GRM4
Name	glutamate receptor, metabotropic 4
Aliases	GPRC1D; mGlu4; MGLUR4; Metabotropic glutamate receptor 4
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of GRM4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	GRM4
Name	glutamate receptor, metabotropic 4
Aliases	GPRC1D; mGlu4; MGLUR4; Metabotropic glutamate receptor 4
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between GRM4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	GRM4
Name	glutamate receptor, metabotropic 4
Aliases	GPRC1D; mGlu4; MGLUR4; Metabotropic glutamate receptor 4
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting GRM4 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting GRM4.

ID	Name	Drug Type	Targets	#Targets
DB00142	Glutamic Acid	Small Molecule	AADAT, AASS, ABAT, ALDH18A1, ASNS, BCAT1, BCAT2, CCBL2, CPQ, DNPEP ......	69

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