TISIDB

Summary
Symbol	CYP19A1
Name	cytochrome P450, family 19, subfamily A, polypeptide 1
Aliases	ARO; P-450AROM; CPV1; ARO1; CYAR; aromatase; CYP19; cytochrome P450, subfamily XIX (aromatization of androge ......
Chromosomal Location	15q21
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	Membrane; Peripheral membrane protein.
Domain	PF00067 Cytochrome P450
Function	Catalyzes the formation of aromatic C18 estrogens from C19 androgens.

> Gene Ontology [ TOP ]
Biological Process	GO:0001655 urogenital system development GO:0002544 chronic inflammatory response GO:0002676 regulation of chronic inflammatory response GO:0002677 negative regulation of chronic inflammatory response GO:0002683 negative regulation of immune system process GO:0002685 regulation of leukocyte migration GO:0002686 negative regulation of leukocyte migration GO:0002688 regulation of leukocyte chemotaxis GO:0002689 negative regulation of leukocyte chemotaxis GO:0006694 steroid biosynthetic process GO:0006703 estrogen biosynthetic process GO:0008202 steroid metabolic process GO:0008209 androgen metabolic process GO:0008210 estrogen metabolic process GO:0010758 regulation of macrophage chemotaxis GO:0010760 negative regulation of macrophage chemotaxis GO:0010817 regulation of hormone levels GO:0016125 sterol metabolic process GO:0030336 negative regulation of cell migration GO:0030595 leukocyte chemotaxis GO:0030850 prostate gland development GO:0031348 negative regulation of defense response GO:0032102 negative regulation of response to external stimulus GO:0034754 cellular hormone metabolic process GO:0035265 organ growth GO:0040013 negative regulation of locomotion GO:0042445 hormone metabolic process GO:0042446 hormone biosynthetic process GO:0048246 macrophage chemotaxis GO:0048608 reproductive structure development GO:0048732 gland development GO:0050727 regulation of inflammatory response GO:0050728 negative regulation of inflammatory response GO:0050900 leukocyte migration GO:0050920 regulation of chemotaxis GO:0050922 negative regulation of chemotaxis GO:0051271 negative regulation of cellular component movement GO:0060326 cell chemotaxis GO:0060736 prostate gland growth GO:0061458 reproductive system development GO:0097529 myeloid leukocyte migration GO:1901615 organic hydroxy compound metabolic process GO:2000146 negative regulation of cell motility
Molecular Function	GO:0004497 monooxygenase activity GO:0005506 iron ion binding GO:0008395 steroid hydroxylase activity GO:0009055 electron carrier activity GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016712 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen GO:0019825 oxygen binding GO:0020037 heme binding GO:0046906 tetrapyrrole binding GO:0070330 aromatase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04913 Ovarian steroidogenesis hsa00140 Steroid hormone biosynthesis hsa01100 Metabolic pathways
Reactome	R-HSA-211859: Biological oxidations R-HSA-211897: Cytochrome P450 - arranged by substrate type R-HSA-211976: Endogenous sterols R-HSA-193144: Estrogen biosynthesis R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins R-HSA-196071: Metabolism of steroid hormones R-HSA-211945: Phase 1 - Functionalization of compounds R-HSA-209943: Steroid hormones

Summary
Symbol	CYP19A1
Name	cytochrome P450, family 19, subfamily A, polypeptide 1
Aliases	ARO; P-450AROM; CPV1; ARO1; CYAR; aromatase; CYP19; cytochrome P450, subfamily XIX (aromatization of androge ......
Chromosomal Location	15q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CYP19A1 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 CYP19A1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
19188178	Breast Carcinoma	Inhibit immunity (T cell function)	This study suggests that aromatase inhibitors may have an indirect antitumor mechanism of action through reducing Tregs in breast tumors and may be of use in estrogen receptor-alpha-negative tumors in combination with immunotherapy approaches.

Summary
Symbol	CYP19A1
Name	cytochrome P450, family 19, subfamily A, polypeptide 1
Aliases	ARO; P-450AROM; CPV1; ARO1; CYAR; aromatase; CYP19; cytochrome P450, subfamily XIX (aromatization of androge ......
Chromosomal Location	15q21
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 CYP19A1 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	CYP19A1
Name	cytochrome P450, family 19, subfamily A, polypeptide 1
Aliases	ARO; P-450AROM; CPV1; ARO1; CYAR; aromatase; CYP19; cytochrome P450, subfamily XIX (aromatization of androge ......
Chromosomal Location	15q21
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 CYP19A1 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	-0.673	0.189
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.035	0.209
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.423	0.548
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.022	0.973
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.205	0.868
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.301	0.823
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.691	0.323
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.595	0.556
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.802	0.452
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.795	0.256
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	1.984	0.0236
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.583	0.0852

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CYP19A1 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	4.1	-0.4	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	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	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	0	0	0	1
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	7.9	0	7.9	0.26
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	12.5	0	12.5	0.485
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	CYP19A1
Name	cytochrome P450, family 19, subfamily A, polypeptide 1
Aliases	ARO; P-450AROM; CPV1; ARO1; CYAR; aromatase; CYP19; cytochrome P450, subfamily XIX (aromatization of androge ......
Chromosomal Location	15q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CYP19A1. 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	CYP19A1
Name	cytochrome P450, family 19, subfamily A, polypeptide 1
Aliases	ARO; P-450AROM; CPV1; ARO1; CYAR; aromatase; CYP19; cytochrome P450, subfamily XIX (aromatization of androge ......
Chromosomal Location	15q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CYP19A1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CYP19A1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CYP19A1
Name	cytochrome P450, family 19, subfamily A, polypeptide 1
Aliases	ARO; P-450AROM; CPV1; ARO1; CYAR; aromatase; CYP19; cytochrome P450, subfamily XIX (aromatization of androge ......
Chromosomal Location	15q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CYP19A1. 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	CYP19A1
Name	cytochrome P450, family 19, subfamily A, polypeptide 1
Aliases	ARO; P-450AROM; CPV1; ARO1; CYAR; aromatase; CYP19; cytochrome P450, subfamily XIX (aromatization of androge ......
Chromosomal Location	15q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CYP19A1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CYP19A1
Name	cytochrome P450, family 19, subfamily A, polypeptide 1
Aliases	ARO; P-450AROM; CPV1; ARO1; CYAR; aromatase; CYP19; cytochrome P450, subfamily XIX (aromatization of androge ......
Chromosomal Location	15q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CYP19A1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CYP19A1
Name	cytochrome P450, family 19, subfamily A, polypeptide 1
Aliases	ARO; P-450AROM; CPV1; ARO1; CYAR; aromatase; CYP19; cytochrome P450, subfamily XIX (aromatization of androge ......
Chromosomal Location	15q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CYP19A1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CYP19A1.

ID	Name	Drug Type	Targets	#Targets
DB00184	Nicotine	Small Molecule	CHAT, CHRNA10, CHRNA2, CHRNA3, CHRNA4, CHRNA5, CHRNA6, CHRNA7, CHR ......	13
DB00357	Aminoglutethimide	Small Molecule	CYP11A1, CYP19A1	2
DB00655	Estrone	Small Molecule	AR, CYP19A1, ESR1, ESR2, SHBG	5
DB00894	Testolactone	Small Molecule	CYP19A1	1
DB00990	Exemestane	Small Molecule	CYP19A1	1
DB01006	Letrozole	Small Molecule	CYP19A1	1
DB01026	Ketoconazole	Small Molecule	AR, CYP19A1, CYP21A2, KCNH2, NR1I2, NR1I3	6
DB01217	Anastrozole	Small Molecule	CYP19A1	1
DB02342	2-Methoxyestradiol	Small Molecule	COMT, CYP19A1, CYP1A1, CYP1B1, HIF1A	5
DB03467	Naringenin	Small Molecule	AKR1C1, CYP19A1, CYP1B1, ESR1, ESR2, KANSL3, SHBG	7
DB04539	Glyphosate	Small Molecule	CYP19A1	1
DB05749	MPI-674	Small Molecule	CYP19A1	1

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