TISIDB

Summary
Symbol	FLCN
Name	folliculin
Aliases	MGC17998; MGC23445; FLCL; BHD skin lesion fibrofolliculoma protein; birt-Hogg-Dube syndrome protein
Chromosomal Location	17p11.2
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=Mainly localized in the nucleus. Colocalizes with FNIP1 and FNIP2 in the cytoplasm.
Domain	PF11704 Vesicle coat protein involved in Golgi to plasma membrane transport PF16692 Folliculin C-terminal domain
Function	May be a tumor suppressor. May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. May regulate phosphorylation of RPS6KB1.

> Gene Ontology [ TOP ]
Biological Process	GO:0000002 mitochondrial genome maintenance GO:0000910 cytokinesis GO:0001558 regulation of cell growth GO:0001655 urogenital system development GO:0001701 in utero embryonic development GO:0001822 kidney development GO:0001933 negative regulation of protein phosphorylation GO:0002244 hematopoietic progenitor cell differentiation GO:0002320 lymphoid progenitor cell differentiation GO:0002328 pro-B cell differentiation GO:0006091 generation of precursor metabolites and energy GO:0006140 regulation of nucleotide metabolic process GO:0006164 purine nucleotide biosynthetic process GO:0006473 protein acetylation GO:0006475 internal protein amino acid acetylation GO:0006754 ATP biosynthetic process GO:0006914 autophagy GO:0007043 cell-cell junction assembly GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007179 transforming growth factor beta receptor signaling pathway GO:0007265 Ras protein signal transduction GO:0007266 Rho protein signal transduction GO:0009116 nucleoside metabolic process GO:0009118 regulation of nucleoside metabolic process GO:0009119 ribonucleoside metabolic process GO:0009123 nucleoside monophosphate metabolic process GO:0009124 nucleoside monophosphate biosynthetic process GO:0009126 purine nucleoside monophosphate metabolic process GO:0009127 purine nucleoside monophosphate biosynthetic process GO:0009141 nucleoside triphosphate metabolic process GO:0009142 nucleoside triphosphate biosynthetic process GO:0009144 purine nucleoside triphosphate metabolic process GO:0009145 purine nucleoside triphosphate biosynthetic process GO:0009150 purine ribonucleotide metabolic process GO:0009152 purine ribonucleotide biosynthetic process GO:0009156 ribonucleoside monophosphate biosynthetic process GO:0009161 ribonucleoside monophosphate metabolic process GO:0009163 nucleoside biosynthetic process GO:0009165 nucleotide biosynthetic process GO:0009167 purine ribonucleoside monophosphate metabolic process GO:0009168 purine ribonucleoside monophosphate biosynthetic process GO:0009199 ribonucleoside triphosphate metabolic process GO:0009201 ribonucleoside triphosphate biosynthetic process GO:0009205 purine ribonucleoside triphosphate metabolic process GO:0009206 purine ribonucleoside triphosphate biosynthetic process GO:0009260 ribonucleotide biosynthetic process GO:0010506 regulation of autophagy GO:0010508 positive regulation of autophagy GO:0010639 negative regulation of organelle organization GO:0010821 regulation of mitochondrion organization GO:0010823 negative regulation of mitochondrion organization GO:0015980 energy derivation by oxidation of organic compounds GO:0016049 cell growth GO:0016570 histone modification GO:0016573 histone acetylation GO:0017015 regulation of transforming growth factor beta receptor signaling pathway GO:0018205 peptidyl-lysine modification GO:0018393 internal peptidyl-lysine acetylation GO:0018394 peptidyl-lysine acetylation GO:0030308 negative regulation of cell growth GO:0030336 negative regulation of cell migration GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway GO:0030808 regulation of nucleotide biosynthetic process GO:0030809 negative regulation of nucleotide biosynthetic process GO:0031056 regulation of histone modification GO:0031929 TOR signaling GO:0032006 regulation of TOR signaling GO:0032007 negative regulation of TOR signaling GO:0032008 positive regulation of TOR signaling GO:0032042 mitochondrial DNA metabolic process GO:0032465 regulation of cytokinesis GO:0032844 regulation of homeostatic process GO:0032845 negative regulation of homeostatic process GO:0034329 cell junction assembly GO:0034330 cell junction organization GO:0034504 protein localization to nucleus GO:0035023 regulation of Rho protein signal transduction GO:0035024 negative regulation of Rho protein signal transduction GO:0035065 regulation of histone acetylation GO:0040013 negative regulation of locomotion GO:0042278 purine nucleoside metabolic process GO:0042326 negative regulation of phosphorylation GO:0042451 purine nucleoside biosynthetic process GO:0042455 ribonucleoside biosynthetic process GO:0043409 negative regulation of MAPK cascade GO:0043457 regulation of cellular respiration GO:0043467 regulation of generation of precursor metabolites and energy GO:0043491 protein kinase B signaling GO:0043543 protein acylation GO:0043687 post-translational protein modification GO:0045216 cell-cell junction organization GO:0045333 cellular respiration GO:0045785 positive regulation of cell adhesion GO:0045926 negative regulation of growth GO:0045978 negative regulation of nucleoside metabolic process GO:0045980 negative regulation of nucleotide metabolic process GO:0046034 ATP metabolic process GO:0046128 purine ribonucleoside metabolic process GO:0046129 purine ribonucleoside biosynthetic process GO:0046390 ribose phosphate biosynthetic process GO:0046578 regulation of Ras protein signal transduction GO:0046580 negative regulation of Ras protein signal transduction GO:0048871 multicellular organismal homeostasis GO:0051052 regulation of DNA metabolic process GO:0051053 negative regulation of DNA metabolic process GO:0051056 regulation of small GTPase mediated signal transduction GO:0051058 negative regulation of small GTPase mediated signal transduction GO:0051271 negative regulation of cellular component movement GO:0051302 regulation of cell division GO:0051896 regulation of protein kinase B signaling GO:0051898 negative regulation of protein kinase B signaling GO:0060537 muscle tissue development GO:0070371 ERK1 and ERK2 cascade GO:0070372 regulation of ERK1 and ERK2 cascade GO:0070373 negative regulation of ERK1 and ERK2 cascade GO:0071559 response to transforming growth factor beta GO:0071560 cellular response to transforming growth factor beta stimulus GO:0072001 renal system development GO:0072111 cell proliferation involved in kidney development GO:0072522 purine-containing compound biosynthetic process GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway GO:0090100 positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway GO:0090183 regulation of kidney development GO:0090185 negative regulation of kidney development GO:0090287 regulation of cellular response to growth factor stimulus GO:0097009 energy homeostasis GO:0097193 intrinsic apoptotic signaling pathway GO:1900180 regulation of protein localization to nucleus GO:1900181 negative regulation of protein localization to nucleus GO:1900371 regulation of purine nucleotide biosynthetic process GO:1900372 negative regulation of purine nucleotide biosynthetic process GO:1900542 regulation of purine nucleotide metabolic process GO:1900543 negative regulation of purine nucleotide metabolic process GO:1901293 nucleoside phosphate biosynthetic process GO:1901532 regulation of hematopoietic progenitor cell differentiation GO:1901657 glycosyl compound metabolic process GO:1901659 glycosyl compound biosynthetic process GO:1901722 regulation of cell proliferation involved in kidney development GO:1901723 negative regulation of cell proliferation involved in kidney development GO:1901856 negative regulation of cellular respiration GO:1901858 regulation of mitochondrial DNA metabolic process GO:1901859 negative regulation of mitochondrial DNA metabolic process GO:1901861 regulation of muscle tissue development GO:1901862 negative regulation of muscle tissue development GO:1901873 regulation of post-translational protein modification GO:1901874 negative regulation of post-translational protein modification GO:1901983 regulation of protein acetylation GO:1902275 regulation of chromatin organization GO:1902532 negative regulation of intracellular signal transduction GO:1903578 regulation of ATP metabolic process GO:1903579 negative regulation of ATP metabolic process GO:1903706 regulation of hemopoiesis GO:1903828 negative regulation of cellular protein localization GO:1903844 regulation of cellular response to transforming growth factor beta stimulus GO:1903846 positive regulation of cellular response to transforming growth factor beta stimulus GO:2000146 negative regulation of cell motility GO:2000505 regulation of energy homeostasis GO:2000506 negative regulation of energy homeostasis GO:2000756 regulation of peptidyl-lysine acetylation GO:2000973 regulation of pro-B cell differentiation GO:2001169 regulation of ATP biosynthetic process GO:2001170 negative regulation of ATP biosynthetic process GO:2001233 regulation of apoptotic signaling pathway GO:2001235 positive regulation of apoptotic signaling pathway GO:2001242 regulation of intrinsic apoptotic signaling pathway GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
Molecular Function	GO:0005085 guanyl-nucleotide exchange factor activity
Cellular Component	GO:0005929 cilium GO:0030496 midbody GO:0044291 cell-cell contact zone GO:0072372 primary cilium

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04150 mTOR signaling pathway
Reactome	-

Summary
Symbol	FLCN
Name	folliculin
Aliases	MGC17998; MGC23445; FLCL; BHD skin lesion fibrofolliculoma protein; birt-Hogg-Dube syndrome protein
Chromosomal Location	17p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between FLCN 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	FLCN
Name	folliculin
Aliases	MGC17998; MGC23445; FLCL; BHD skin lesion fibrofolliculoma protein; birt-Hogg-Dube syndrome protein
Chromosomal Location	17p11.2
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 FLCN 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	Second most enriched score: 0.52	Sensitive to T cell-mediated killing
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	FLCN
Name	folliculin
Aliases	MGC17998; MGC23445; FLCL; BHD skin lesion fibrofolliculoma protein; birt-Hogg-Dube syndrome protein
Chromosomal Location	17p11.2
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 FLCN 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	-0.059	0.751
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.238	0.887
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.072	0.953
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.072	0.843
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.272	0.902
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.182	0.949
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.194	0.546
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.216	0.876
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.669	0.668
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.117	0.927
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	0.612	0.725
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.053	0.481

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of FLCN 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	0	0	1
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	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	3.7	0.27
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	3.7	0.314
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	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	7.7	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	FLCN
Name	folliculin
Aliases	MGC17998; MGC23445; FLCL; BHD skin lesion fibrofolliculoma protein; birt-Hogg-Dube syndrome protein
Chromosomal Location	17p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FLCN. 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	FLCN
Name	folliculin
Aliases	MGC17998; MGC23445; FLCL; BHD skin lesion fibrofolliculoma protein; birt-Hogg-Dube syndrome protein
Chromosomal Location	17p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FLCN. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FLCN. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	FLCN
Name	folliculin
Aliases	MGC17998; MGC23445; FLCL; BHD skin lesion fibrofolliculoma protein; birt-Hogg-Dube syndrome protein
Chromosomal Location	17p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FLCN. 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	FLCN
Name	folliculin
Aliases	MGC17998; MGC23445; FLCL; BHD skin lesion fibrofolliculoma protein; birt-Hogg-Dube syndrome protein
Chromosomal Location	17p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of FLCN expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	FLCN
Name	folliculin
Aliases	MGC17998; MGC23445; FLCL; BHD skin lesion fibrofolliculoma protein; birt-Hogg-Dube syndrome protein
Chromosomal Location	17p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between FLCN and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	FLCN
Name	folliculin
Aliases	MGC17998; MGC23445; FLCL; BHD skin lesion fibrofolliculoma protein; birt-Hogg-Dube syndrome protein
Chromosomal Location	17p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting FLCN collected from DrugBank database.

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

Browse FLCN