TISIDB

Summary
Symbol	HRH3
Name	histamine receptor H3
Aliases	GPCR97; HH3R; H3R; Histamine H3 receptor
Chromosomal Location	20q13.33
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	PF00001 7 transmembrane receptor (rhodopsin family)
Function	The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization.

> Gene Ontology [ TOP ]
Biological Process	GO:0001505 regulation of neurotransmitter levels GO:0001820 serotonin secretion GO:0006820 anion transport GO:0006835 dicarboxylic acid transport GO:0006836 neurotransmitter transport GO:0006837 serotonin 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:0007197 adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway GO:0007207 phospholipase C-activating G-protein coupled acetylcholine receptor signaling pathway GO:0007213 G-protein coupled acetylcholine receptor signaling pathway GO:0007269 neurotransmitter secretion GO:0007271 synaptic transmission, cholinergic GO:0014047 glutamate secretion GO:0014048 regulation of glutamate secretion GO:0014050 negative regulation of glutamate secretion GO:0014061 regulation of norepinephrine secretion GO:0014062 regulation of serotonin secretion GO:0014063 negative regulation of serotonin secretion GO:0015711 organic anion transport GO:0015837 amine transport GO:0015844 monoamine transport GO:0015850 organic hydroxy compound transport GO:0015874 norepinephrine transport GO:0023061 signal release GO:0043271 negative regulation of ion transport GO:0044070 regulation of anion transport GO:0046942 carboxylic acid transport GO:0048243 norepinephrine secretion GO:0050432 catecholamine secretion GO:0050433 regulation of catecholamine secretion GO:0050890 cognition GO:0051048 negative regulation of secretion GO:0051051 negative regulation of transport GO:0051937 catecholamine transport GO:0051952 regulation of amine transport GO:0060359 response to ammonium ion GO:0071242 cellular response to ammonium ion GO:0095500 acetylcholine receptor signaling pathway GO:0099531 presynaptic process involved in chemical synaptic transmission GO:0099643 signal release from synapse GO:1903531 negative regulation of secretion by cell GO:1903792 negative regulation of anion transport GO:1903831 signal transduction involved in cellular response to ammonium ion GO:1905144 response to acetylcholine GO:1905145 cellular response to acetylcholine
Molecular Function	GO:0004969 histamine receptor activity GO:0008227 G-protein coupled amine receptor activity GO:0015464 acetylcholine receptor activity GO:0016907 G-protein coupled acetylcholine receptor activity GO:0030594 neurotransmitter receptor activity GO:0099528 G-protein coupled neurotransmitter receptor activity
Cellular Component	GO:0098793 presynapse

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04080 Neuroactive ligand-receptor interaction
Reactome	R-HSA-375280: Amine ligand-binding receptors R-HSA-373076: Class A/1 (Rhodopsin-like receptors) R-HSA-418594: G alpha (i) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-390650: Histamine receptors R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

Summary
Symbol	HRH3
Name	histamine receptor H3
Aliases	GPCR97; HH3R; H3R; Histamine H3 receptor
Chromosomal Location	20q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HRH3 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	HRH3
Name	histamine receptor H3
Aliases	GPCR97; HH3R; H3R; Histamine H3 receptor
Chromosomal Location	20q13.33
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 HRH3 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	HRH3
Name	histamine receptor H3
Aliases	GPCR97; HH3R; H3R; Histamine H3 receptor
Chromosomal Location	20q13.33
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 HRH3 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	-0.217	0.426
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.618	0.322
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.069	0.876
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.03	0.972
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.603	0.625
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.689	0.622
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	1
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	1
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.877	0.0156

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of HRH3 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	25	25	0.222
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	HRH3
Name	histamine receptor H3
Aliases	GPCR97; HH3R; H3R; Histamine H3 receptor
Chromosomal Location	20q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HRH3. 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	HRH3
Name	histamine receptor H3
Aliases	GPCR97; HH3R; H3R; Histamine H3 receptor
Chromosomal Location	20q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HRH3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HRH3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HRH3
Name	histamine receptor H3
Aliases	GPCR97; HH3R; H3R; Histamine H3 receptor
Chromosomal Location	20q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HRH3. 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	HRH3
Name	histamine receptor H3
Aliases	GPCR97; HH3R; H3R; Histamine H3 receptor
Chromosomal Location	20q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HRH3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HRH3
Name	histamine receptor H3
Aliases	GPCR97; HH3R; H3R; Histamine H3 receptor
Chromosomal Location	20q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HRH3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HRH3
Name	histamine receptor H3
Aliases	GPCR97; HH3R; H3R; Histamine H3 receptor
Chromosomal Location	20q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HRH3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting HRH3.

ID	Name	Drug Type	Targets	#Targets
DB00370	Mirtazapine	Small Molecule	ADRA1A, ADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2C, ADRB1, ADRB2, DRD1 ......	23
DB05080	OBE101	Small Molecule	HRH1, HRH3	2
DB05381	Histamine	Small Molecule	HRH1, HRH2, HRH3, HRH4, SLC18A2	5
DB06698	Betahistine	Small Molecule	HRH1, HRH3	2
DB11642	Pitolisant	Small Molecule	HRH3, KCNH2	2

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