TISIDB

Summary
Symbol	FSHR
Name	follicle stimulating hormone receptor
Aliases	FSHRO; LGR1; ODG1; FSHR1O; FSH receptor; follitropin receptor; FSH-R; Follicle-stimulating hormone receptor
Chromosomal Location	2p21-p16
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) PF12369 Gonadotropin hormone receptor transmembrane region PF13306 Leucine rich repeats (6 copies) PF01462 Leucine rich repeat N-terminal domain
Function	Receptor for follicle-stimulating hormone or follitropin (PubMed:11847099, PubMed:24058690). The activity of this receptor is mediated by G proteins which activate adenylate cyclase (PubMed:11847099). Induces cAMP production through the activation of PI3K-AKT and SRC-ERK1/2 signaling pathways (PubMed:24058690).

> Gene Ontology [ TOP ]
Biological Process	GO:0001541 ovarian follicle development GO:0001545 primary ovarian follicle growth GO:0002521 leukocyte differentiation GO:0002573 myeloid leukocyte differentiation GO:0002761 regulation of myeloid leukocyte differentiation GO:0006140 regulation of nucleotide metabolic process GO:0006164 purine nucleotide biosynthetic process GO:0006171 cAMP biosynthetic process 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:0007189 adenylate cyclase-activating G-protein coupled receptor signaling pathway GO:0007190 activation of adenylate cyclase activity GO:0007283 spermatogenesis GO:0007292 female gamete generation GO:0007548 sex differentiation GO:0008406 gonad development GO:0008584 male gonad development GO:0008585 female gonad development GO:0009150 purine ribonucleotide metabolic process GO:0009152 purine ribonucleotide biosynthetic process GO:0009165 nucleotide biosynthetic process GO:0009187 cyclic nucleotide metabolic process GO:0009190 cyclic nucleotide biosynthetic process GO:0009260 ribonucleotide biosynthetic process GO:0009755 hormone-mediated signaling pathway GO:0010737 protein kinase A signaling GO:0010738 regulation of protein kinase A signaling GO:0014065 phosphatidylinositol 3-kinase signaling GO:0014066 regulation of phosphatidylinositol 3-kinase signaling GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling GO:0022602 ovulation cycle process GO:0030099 myeloid cell differentiation GO:0030316 osteoclast differentiation GO:0030799 regulation of cyclic nucleotide metabolic process GO:0030801 positive regulation of cyclic nucleotide metabolic process GO:0030802 regulation of cyclic nucleotide biosynthetic process GO:0030804 positive regulation of cyclic nucleotide biosynthetic process GO:0030808 regulation of nucleotide biosynthetic process GO:0030810 positive regulation of nucleotide biosynthetic process GO:0030814 regulation of cAMP metabolic process GO:0030816 positive regulation of cAMP metabolic process GO:0030817 regulation of cAMP biosynthetic process GO:0030819 positive regulation of cAMP biosynthetic process GO:0031279 regulation of cyclase activity GO:0031281 positive regulation of cyclase activity GO:0042698 ovulation cycle GO:0042699 follicle-stimulating hormone signaling pathway GO:0043410 positive regulation of MAPK cascade GO:0045137 development of primary sexual characteristics GO:0045637 regulation of myeloid cell differentiation GO:0045670 regulation of osteoclast differentiation GO:0045761 regulation of adenylate cyclase activity GO:0045762 positive regulation of adenylate cyclase activity GO:0045981 positive regulation of nucleotide metabolic process GO:0046058 cAMP metabolic process GO:0046390 ribose phosphate biosynthetic process GO:0046545 development of primary female sexual characteristics GO:0046546 development of primary male sexual characteristics GO:0046660 female sex differentiation GO:0046661 male sex differentiation GO:0048015 phosphatidylinositol-mediated signaling GO:0048017 inositol lipid-mediated signaling GO:0048232 male gamete generation GO:0048511 rhythmic process GO:0048608 reproductive structure development GO:0051339 regulation of lyase activity GO:0051349 positive regulation of lyase activity GO:0052652 cyclic purine nucleotide metabolic process GO:0061458 reproductive system development GO:0070371 ERK1 and ERK2 cascade GO:0070372 regulation of ERK1 and ERK2 cascade GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0072522 purine-containing compound biosynthetic process GO:1900371 regulation of purine nucleotide biosynthetic process GO:1900373 positive regulation of purine nucleotide biosynthetic process GO:1900542 regulation of purine nucleotide metabolic process GO:1900544 positive regulation of purine nucleotide metabolic process GO:1901293 nucleoside phosphate biosynthetic process GO:1902105 regulation of leukocyte differentiation GO:1903706 regulation of hemopoiesis
Molecular Function	GO:0001653 peptide receptor activity GO:0004963 follicle-stimulating hormone receptor activity GO:0008528 G-protein coupled peptide receptor activity GO:0016500 protein-hormone receptor activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04024 cAMP signaling pathway hsa04080 Neuroactive ligand-receptor interaction hsa04913 Ovarian steroidogenesis
Reactome	R-HSA-373076: Class A/1 (Rhodopsin-like receptors) R-HSA-418555: G alpha (s) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-375281: Hormone ligand-binding receptors R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

Summary
Symbol	FSHR
Name	follicle stimulating hormone receptor
Aliases	FSHRO; LGR1; ODG1; FSHR1O; FSH receptor; follitropin receptor; FSH-R; Follicle-stimulating hormone receptor
Chromosomal Location	2p21-p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between FSHR 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 FSHR and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26112923	Ovarian Carcinoma	Inhibit immunity (T cell function)	Receptor ligand-based anti-FSHR immunoreceptors were constructed that contained small binding fragments from the ligand for FSHR, FSH, fused to T-cell transmembrane and T-cell signaling domains. Human T cells transduced to express anti-FSHR immunoreceptors were specifically immunoreactive against FSHR-expressing human and mouse ovarian cancer cell lines in an MHC-nonrestricted manner and mediated effective lysis of FHSR-expressing tumor cells, but not FSHR-deficient targets, in vitro.
27435394	Ovarian Carcinoma	Promote immunity (T cell function); essential for immunotherapy	FSHR is expressed in gynecologic malignancies of different histologic types but not in nonovarian healthy tissues. T cells redirected against FSHR+ tumor cells with full-length FSH represent a promising therapeutic alternative against a broad range of ovarian malignancies, with negligible toxicity even in the presence of cognate targets in tumor-free ovaries.

Summary
Symbol	FSHR
Name	follicle stimulating hormone receptor
Aliases	FSHRO; LGR1; ODG1; FSHR1O; FSH receptor; follitropin receptor; FSH-R; Follicle-stimulating hormone receptor
Chromosomal Location	2p21-p16
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 FSHR 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	FSHR
Name	follicle stimulating hormone receptor
Aliases	FSHRO; LGR1; ODG1; FSHR1O; FSH receptor; follitropin receptor; FSH-R; Follicle-stimulating hormone receptor
Chromosomal Location	2p21-p16
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 FSHR 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	-0.858	0.265
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.016	0.461
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.677	0.617
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	-0.298	0.144

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of FSHR 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	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	11.1	12.5	-1.4	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	22.2	-22.2	0.505
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	5.3	0	5.3	0.507
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	0	0	0	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	FSHR
Name	follicle stimulating hormone receptor
Aliases	FSHRO; LGR1; ODG1; FSHR1O; FSH receptor; follitropin receptor; FSH-R; Follicle-stimulating hormone receptor
Chromosomal Location	2p21-p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FSHR. 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	FSHR
Name	follicle stimulating hormone receptor
Aliases	FSHRO; LGR1; ODG1; FSHR1O; FSH receptor; follitropin receptor; FSH-R; Follicle-stimulating hormone receptor
Chromosomal Location	2p21-p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FSHR. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FSHR. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	FSHR
Name	follicle stimulating hormone receptor
Aliases	FSHRO; LGR1; ODG1; FSHR1O; FSH receptor; follitropin receptor; FSH-R; Follicle-stimulating hormone receptor
Chromosomal Location	2p21-p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FSHR. 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	FSHR
Name	follicle stimulating hormone receptor
Aliases	FSHRO; LGR1; ODG1; FSHR1O; FSH receptor; follitropin receptor; FSH-R; Follicle-stimulating hormone receptor
Chromosomal Location	2p21-p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of FSHR expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	FSHR
Name	follicle stimulating hormone receptor
Aliases	FSHRO; LGR1; ODG1; FSHR1O; FSH receptor; follitropin receptor; FSH-R; Follicle-stimulating hormone receptor
Chromosomal Location	2p21-p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between FSHR and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	FSHR
Name	follicle stimulating hormone receptor
Aliases	FSHRO; LGR1; ODG1; FSHR1O; FSH receptor; follitropin receptor; FSH-R; Follicle-stimulating hormone receptor
Chromosomal Location	2p21-p16
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting FSHR collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting FSHR.

ID	Name	Drug Type	Targets	#Targets
DB00032	Menotropins	Biotech	FSHR, LHCGR	2
DB00066	Follitropin	Biotech	FSHR	1
DB00094	Urofollitropin	Biotech	FSHR	1
DB00097	Choriogonadotropin alfa	Biotech	FSHR, LHCGR	2
DB04786	Suramin	Small Molecule	F2, FSHR, P2RY2, PLA2G2A, RYR1, SIRT5	6

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