TISIDB

Summary
Symbol	AHR
Name	aryl hydrocarbon receptor
Aliases	bHLHe76; AH-receptor; ah receptor; aromatic hydrocarbon receptor; class E basic helix-loop-helix protein 76
Chromosomal Location	7p15
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	Cytoplasm. Nucleus. Note=Initially cytoplasmic; upon binding with ligand and interaction with a HSP90, it translocates to the nucleus.
Domain	PF00010 Helix-loop-helix DNA-binding domain PF00989 PAS fold PF08447 PAS fold
Function	Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.

> Gene Ontology [ TOP ]
Biological Process	GO:0002694 regulation of leukocyte activation GO:0006805 xenobiotic metabolic process GO:0007623 circadian rhythm GO:0009410 response to xenobiotic stimulus GO:0009636 response to toxic substance GO:0030522 intracellular receptor signaling pathway GO:0030888 regulation of B cell proliferation GO:0032922 circadian regulation of gene expression GO:0032943 mononuclear cell proliferation GO:0032944 regulation of mononuclear cell proliferation GO:0042100 B cell proliferation GO:0042113 B cell activation GO:0046651 lymphocyte proliferation GO:0048511 rhythmic process GO:0050670 regulation of lymphocyte proliferation GO:0050864 regulation of B cell activation GO:0050865 regulation of cell activation GO:0051249 regulation of lymphocyte activation GO:0070661 leukocyte proliferation GO:0070663 regulation of leukocyte proliferation GO:0071466 cellular response to xenobiotic stimulus
Molecular Function	GO:0004874 aryl hydrocarbon receptor activity GO:0004879 RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding GO:0008134 transcription factor binding GO:0031072 heat shock protein binding GO:0035326 enhancer binding GO:0046982 protein heterodimerization activity GO:0051879 Hsp90 protein binding GO:0070888 E-box binding GO:0098531 transcription factor activity, direct ligand regulated sequence-specific DNA binding
Cellular Component	GO:0005667 transcription factor complex GO:0034751 aryl hydrocarbon receptor complex GO:0034752 cytosolic aryl hydrocarbon receptor complex GO:0034753 nuclear aryl hydrocarbon receptor complex GO:0043235 receptor complex GO:0044445 cytosolic part

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-8937144: Aryl hydrocarbon receptor signalling R-HSA-211859: Biological oxidations R-HSA-211897: Cytochrome P450 - arranged by substrate type R-HSA-211976: Endogenous sterols R-HSA-535734: Fatty acid, triacylglycerol, and ketone body metabolism R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins R-HSA-1989781: PPARA activates gene expression R-HSA-211945: Phase 1 - Functionalization of compounds R-HSA-400206: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) R-HSA-211981: Xenobiotics

> KEGG and Reactome Pathway

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KEGG

Reactome

R-HSA-8937144: Aryl hydrocarbon receptor signalling
R-HSA-211859: Biological oxidations
R-HSA-211897: Cytochrome P450 - arranged by substrate type
R-HSA-211976: Endogenous sterols
R-HSA-535734: Fatty acid, triacylglycerol, and ketone body metabolism
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-1989781: PPARA activates gene expression
R-HSA-211945: Phase 1 - Functionalization of compounds
R-HSA-400206: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-211981: Xenobiotics

Summary
Symbol	AHR
Name	aryl hydrocarbon receptor
Aliases	bHLHe76; AH-receptor; ah receptor; aromatic hydrocarbon receptor; class E basic helix-loop-helix protein 76
Chromosomal Location	7p15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between AHR 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

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Literatures describing the relation between AHR and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23144293	Brain neoplasm	Inhibit immunity	Further, it was also recently shown that TDO-2-dependent production of KYN by brain tumors might be a novel mechanism for suppressing antitumor immunity and supporting tumor growth through the activation of the Aryl hydrocarbon receptor (AhR). This newly identified TDO-2-KYN-AhR signaling pathway opens up exciting future research opportunities and may represent a novel therapeutic target in cancer therapy.

Summary
Symbol	AHR
Name	aryl hydrocarbon receptor
Aliases	bHLHe76; AH-receptor; ah receptor; aromatic hydrocarbon receptor; class E basic helix-loop-helix protein 76
Chromosomal Location	7p15
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 AHR 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	AHR
Name	aryl hydrocarbon receptor
Aliases	bHLHe76; AH-receptor; ah receptor; aromatic hydrocarbon receptor; class E basic helix-loop-helix protein 76
Chromosomal Location	7p15
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 AHR 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	0.016	0.974
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.476	0.822
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.387	0.783
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.095	0.856
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.737	0.775
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.138	0.713
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.246	0.634
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.061	0.976
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.633	0.771
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.65	0.509
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	1.094	0.503
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.125	0.293

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of AHR 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	3.7	2.7	1	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	3.7	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	19	0	19	0.113
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	25	0	25	0.473
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	0	15.4	0.482
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	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	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
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	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	0	9.1	0.458
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	20	0	20	0.294

Summary
Symbol	AHR
Name	aryl hydrocarbon receptor
Aliases	bHLHe76; AH-receptor; ah receptor; aromatic hydrocarbon receptor; class E basic helix-loop-helix protein 76
Chromosomal Location	7p15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of AHR. 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	AHR
Name	aryl hydrocarbon receptor
Aliases	bHLHe76; AH-receptor; ah receptor; aromatic hydrocarbon receptor; class E basic helix-loop-helix protein 76
Chromosomal Location	7p15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of AHR. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by AHR. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	AHR
Name	aryl hydrocarbon receptor
Aliases	bHLHe76; AH-receptor; ah receptor; aromatic hydrocarbon receptor; class E basic helix-loop-helix protein 76
Chromosomal Location	7p15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of AHR. 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	AHR
Name	aryl hydrocarbon receptor
Aliases	bHLHe76; AH-receptor; ah receptor; aromatic hydrocarbon receptor; class E basic helix-loop-helix protein 76
Chromosomal Location	7p15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of AHR expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	AHR
Name	aryl hydrocarbon receptor
Aliases	bHLHe76; AH-receptor; ah receptor; aromatic hydrocarbon receptor; class E basic helix-loop-helix protein 76
Chromosomal Location	7p15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between AHR and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	AHR
Name	aryl hydrocarbon receptor
Aliases	bHLHe76; AH-receptor; ah receptor; aromatic hydrocarbon receptor; class E basic helix-loop-helix protein 76
Chromosomal Location	7p15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting AHR collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting AHR.

ID	Name	Drug Type	Targets	#Targets
DB00338	Omeprazole	Small Molecule	AHR, ATP4A	2
DB00379	Mexiletine	Small Molecule	AHR, SCN5A	2
DB00393	Nimodipine	Small Molecule	AHR, CACNA1C, CACNA1D, CACNA1F, CACNA1S, CACNB1, CACNB2, CACNB3, C ......	10
DB00499	Flutamide	Small Molecule	AHR, AR, NR1I2	3
DB01076	Atorvastatin	Small Molecule	AHR, DPP4, HMGCR	3
DB01097	Leflunomide	Small Molecule	AHR, DHODH, PTK2B	3
DB01404	Ginseng	Small Molecule	AHR, IL6, PTGS2	3
DB02052	Indirubin-3'-Monoxime	Small Molecule	AHR, CDK1, CDK2, CDK5, CDK5R1, GSK3B	6
DB02709	Resveratrol	Small Molecule	AHR, AKT1, ALOX15, ALOX5, APP, CBR1, CLEC14A, CSNK2A1, ESR1, ITGA5 ......	25
DB04216	Quercetin	Small Molecule	ACTB, AHR, ATP5A1, ATP5B, ATP5C1, CBR1, CEBPB, CSNK2A1, CSNK2B, CY ......	27
DB06732	beta-Naphthoflavone	Small Molecule	AHR, CYP1B1, ESR1, ESRRA, NR2F1	5
DB07715	Emodin	Small Molecule	AHR, CSNK2A1	2
DB08624	BENZOTHIAZOLE	Small Molecule	AHR, F2	2
DB08995	Diosmin	Small Molecule	AHR	1
DB11577	Indigotindisulfonic Acid	Small Molecule	AHR	1
DB11937	Kynurenic Acid	Small Molecule	AHR, GPR35	2
DB12116	Epigallocatechin Gallate	Small Molecule	AHR, DHFRL1, DNMT1	3
DB12328	Cantharidin	Small Molecule	AHR	1
DB12379	Indirubin	Small Molecule	AHR, CYP1A1	2

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