TISIDB

Summary
Symbol	FOXL2
Name	forkhead box L2
Aliases	BPES1; BPES; PFRK; PINTO; POF3; forkhead transcription factor FOXL2; Forkhead box protein L2
Chromosomal Location	3q23
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	Nucleus
Domain	PF00250 Forkhead domain
Function	Transcriptional regulator. Critical factor essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination. Prevents trans-differentiation of ovary to testis through transcriptional repression of the Sertoli cell-promoting gene SOX9 (By similarity). Has apoptotic activity in ovarian cells. Suppresses ESR1-mediated transcription of PTGS2/COX2 stimulated by tamoxifen (By similarity). Is a regulator of CYP19 expression (By similarity). Participates in SMAD3-dependent transcription of FST via the intronic SMAD-binding element (By similarity). Is a transcriptional repressor of STAR. Activates SIRT1 transcription under cellular stress conditions. Activates transcription of OSR2.

> Gene Ontology [ TOP ]
Biological Process	GO:0000737 DNA catabolic process, endonucleolytic GO:0001541 ovarian follicle development GO:0001555 oocyte growth GO:0001654 eye development GO:0002074 extraocular skeletal muscle development GO:0006308 DNA catabolic process GO:0006309 apoptotic DNA fragmentation GO:0006921 cellular component disassembly involved in execution phase of apoptosis GO:0007281 germ cell development GO:0007292 female gamete generation GO:0007338 single fertilization GO:0007423 sensory organ development GO:0007517 muscle organ development GO:0007519 skeletal muscle tissue development GO:0007530 sex determination GO:0007548 sex differentiation GO:0008406 gonad development GO:0008585 female gonad development GO:0009566 fertilization GO:0009914 hormone transport GO:0009994 oocyte differentiation GO:0010817 regulation of hormone levels GO:0010950 positive regulation of endopeptidase activity GO:0010952 positive regulation of peptidase activity GO:0014706 striated muscle tissue development GO:0016049 cell growth GO:0018993 somatic sex determination GO:0019101 female somatic sex determination GO:0019439 aromatic compound catabolic process GO:0022412 cellular process involved in reproduction in multicellular organism GO:0022601 menstrual cycle phase GO:0022602 ovulation cycle process GO:0023061 signal release GO:0030237 female sex determination GO:0030262 apoptotic nuclear changes GO:0032274 gonadotropin secretion GO:0032275 luteinizing hormone secretion GO:0032276 regulation of gonadotropin secretion GO:0032278 positive regulation of gonadotropin secretion GO:0033684 regulation of luteinizing hormone secretion GO:0033686 positive regulation of luteinizing hormone secretion GO:0034655 nucleobase-containing compound catabolic process GO:0042698 ovulation cycle GO:0042703 menstruation GO:0043010 camera-type eye development GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0044057 regulation of system process GO:0044060 regulation of endocrine process GO:0044270 cellular nitrogen compound catabolic process GO:0044848 biological phase GO:0045137 development of primary sexual characteristics GO:0045862 positive regulation of proteolysis GO:0046545 development of primary female sexual characteristics GO:0046660 female sex differentiation GO:0046700 heterocycle catabolic process GO:0046879 hormone secretion GO:0046880 regulation of follicle-stimulating hormone secretion GO:0046881 positive regulation of follicle-stimulating hormone secretion GO:0046883 regulation of hormone secretion GO:0046884 follicle-stimulating hormone secretion GO:0046887 positive regulation of hormone secretion GO:0048048 embryonic eye morphogenesis GO:0048477 oogenesis GO:0048511 rhythmic process GO:0048562 embryonic organ morphogenesis GO:0048568 embryonic organ development GO:0048588 developmental cell growth GO:0048592 eye morphogenesis GO:0048599 oocyte development GO:0048608 reproductive structure development GO:0050886 endocrine process GO:0051047 positive regulation of secretion GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0060014 granulosa cell differentiation GO:0060065 uterus development GO:0060537 muscle tissue development GO:0060538 skeletal muscle organ development GO:0060986 endocrine hormone secretion GO:0061458 reproductive system development GO:0090305 nucleic acid phosphodiester bond hydrolysis GO:0090596 sensory organ morphogenesis GO:0097194 execution phase of apoptosis GO:1901361 organic cyclic compound catabolic process GO:1903532 positive regulation of secretion by cell GO:2000116 regulation of cysteine-type endopeptidase activity GO:2001056 positive regulation of cysteine-type endopeptidase activity
Molecular Function	GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0000987 core promoter proximal region sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001159 core promoter proximal region DNA binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0030331 estrogen receptor binding GO:0031624 ubiquitin conjugating enzyme binding GO:0035257 nuclear hormone receptor binding GO:0035258 steroid hormone receptor binding GO:0043028 cysteine-type endopeptidase regulator activity involved in apoptotic process GO:0044390 ubiquitin-like protein conjugating enzyme binding GO:0051427 hormone receptor binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	FOXL2
Name	forkhead box L2
Aliases	BPES1; BPES; PFRK; PINTO; POF3; forkhead transcription factor FOXL2; Forkhead box protein L2
Chromosomal Location	3q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between FOXL2 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	FOXL2
Name	forkhead box L2
Aliases	BPES1; BPES; PFRK; PINTO; POF3; forkhead transcription factor FOXL2; Forkhead box protein L2
Chromosomal Location	3q23
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

[ TOP ]

Statistical results of FOXL2 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	FOXL2
Name	forkhead box L2
Aliases	BPES1; BPES; PFRK; PINTO; POF3; forkhead transcription factor FOXL2; Forkhead box protein L2
Chromosomal Location	3q23
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

[ TOP ]

Points in the above scatter plot represent the expression difference of FOXL2 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	-0.635	0.0402
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.121	0.0566
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.29	0.517
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.56	0.536
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.056	0.478
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.074	0.964
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.18	0.823
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-1.081	0.487
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.787	0.636
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	-0.038	0.909

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of FOXL2 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	10	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
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	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	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	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	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	FOXL2
Name	forkhead box L2
Aliases	BPES1; BPES; PFRK; PINTO; POF3; forkhead transcription factor FOXL2; Forkhead box protein L2
Chromosomal Location	3q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FOXL2. 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	FOXL2
Name	forkhead box L2
Aliases	BPES1; BPES; PFRK; PINTO; POF3; forkhead transcription factor FOXL2; Forkhead box protein L2
Chromosomal Location	3q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FOXL2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FOXL2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	FOXL2
Name	forkhead box L2
Aliases	BPES1; BPES; PFRK; PINTO; POF3; forkhead transcription factor FOXL2; Forkhead box protein L2
Chromosomal Location	3q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FOXL2. 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	FOXL2
Name	forkhead box L2
Aliases	BPES1; BPES; PFRK; PINTO; POF3; forkhead transcription factor FOXL2; Forkhead box protein L2
Chromosomal Location	3q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of FOXL2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	FOXL2
Name	forkhead box L2
Aliases	BPES1; BPES; PFRK; PINTO; POF3; forkhead transcription factor FOXL2; Forkhead box protein L2
Chromosomal Location	3q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between FOXL2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	FOXL2
Name	forkhead box L2
Aliases	BPES1; BPES; PFRK; PINTO; POF3; forkhead transcription factor FOXL2; Forkhead box protein L2
Chromosomal Location	3q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting FOXL2 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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