FLCN

Summary

FLCN (folliculin, HGNC:27310) is a protein-coding gene on chromosome 17p11.2, encoding Folliculin (Q8NFG4). Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis. In precision oncology, FLCN c.1285dupC confers sensitivity to Everolimus in Renal Cell Carcinoma (CIViC Level C). It is haploinsufficient (ClinGen: sufficient evidence).

This gene is located within the Smith-Magenis syndrome region on chromosome 17. Mutations in this gene are associated with Birt-Hogg-Dube syndrome, which is characterized by fibrofolliculomas, renal tumors, lung cysts, and pneumothorax. Alternative splicing of this gene results in two transcript variants encoding different isoforms.

Source: NCBI Gene 201163 — RefSeq curated summary.

At a glance

• Gene–disease (curated): obsolete Birt-Hogg-Dube syndrome (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 2,943 total — 354 pathogenic, 57 likely-pathogenic
• Phenotypes (HPO): 85
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 28 downstream targets (CollecTRI)
• MANE Select transcript: NM_144997

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27310
Approved symbol	FLCN
Name	folliculin
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	BHD, MGC17998, MGC23445, DENND8B
Ensembl gene	ENSG00000154803
Ensembl biotype	protein_coding
OMIM	607273
Entrez	201163

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 30 protein_coding, 6 retained_intron

ENST00000285071, ENST00000389168, ENST00000389169, ENST00000389171, ENST00000417064, ENST00000461699, ENST00000466317, ENST00000473853, ENST00000480316, ENST00000577591, ENST00000888042, ENST00000888043, ENST00000888044, ENST00000888045, ENST00000918780, ENST00000918781, ENST00000962727, ENST00000962728, ENST00000962729, ENST00000962730, ENST00000962731, ENST00000962732, ENST00000962733, ENST00000962734, ENST00000962735, ENST00000962736, ENST00000962737, ENST00000962738, ENST00000962739, ENST00000962740, ENST00000962741, ENST00000962742, ENST00000962743, ENST00000962744, ENST00000962745, ENST00000962746

RefSeq mRNA: 5 — MANE Select: NM_144997 NM_001353229, NM_001353230, NM_001353231, NM_144606, NM_144997

CCDS: CCDS32579, CCDS32580

Canonical transcript exons

ENST00000285071 — 14 exons

Exon	Start	End
ENSE00001017844	17226176	17226322
ENSE00001151512	17219019	17219209
ENSE00001261191	17221537	17221628
ENSE00001261249	17212212	17213856
ENSE00003493285	17215185	17215316
ENSE00003504847	17231794	17231882
ENSE00003577854	17232788	17232901
ENSE00003603499	17222501	17222661
ENSE00003611747	17217069	17217182
ENSE00003639824	17214985	17215090
ENSE00003669163	17216380	17216503
ENSE00003691829	17227889	17228161
ENSE00003791218	17223922	17224143
ENSE00003841959	17236912	17237168

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 98.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.1669 / max 339.7186, expressed in 1805 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164755	15.7805	1804
164756	0.2269	72
164754	0.1596	47

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	98.19	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.71	gold quality
cerebellar hemisphere	UBERON:0002245	97.61	gold quality
cerebellar cortex	UBERON:0002129	97.48	gold quality
cerebellum	UBERON:0002037	96.76	gold quality
apex of heart	UBERON:0002098	96.24	gold quality
endocervix	UBERON:0000458	95.87	gold quality
mucosa of stomach	UBERON:0001199	95.74	gold quality
body of uterus	UBERON:0009853	95.68	gold quality
left ovary	UBERON:0002119	95.20	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.84	gold quality
right ovary	UBERON:0002118	94.73	gold quality
oocyte	CL:0000023	94.35	gold quality
gall bladder	UBERON:0002110	94.22	gold quality
upper lobe of left lung	UBERON:0008952	94.09	gold quality
sural nerve	UBERON:0015488	94.05	gold quality
right lobe of thyroid gland	UBERON:0001119	93.98	gold quality
pituitary gland	UBERON:0000007	93.95	gold quality
right coronary artery	UBERON:0001625	93.95	gold quality
tendon of biceps brachii	UBERON:0008188	93.92	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.87	gold quality
ovary	UBERON:0000992	93.64	gold quality
lower esophagus	UBERON:0013473	93.64	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.61	gold quality
right uterine tube	UBERON:0001302	93.59	gold quality
vagina	UBERON:0000996	93.46	gold quality
left lobe of thyroid gland	UBERON:0001120	93.27	gold quality
upper lobe of lung	UBERON:0008948	93.27	gold quality
descending thoracic aorta	UBERON:0002345	93.16	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.16

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

28 targets.

Target	Regulation
ACP5	Repression
ANGPT2	Repression
ASAH1	Repression
CD8A	Activation
CDH1	Repression
CDH13	Activation
COX5A	Repression
DCDC2	Activation
DDIT3	Repression
FABP3	Activation
FNIP2	Repression
FYN	Activation
GPNMB	Repression
GREM1	Repression
INHBA	Activation
NDUFS8	Repression
PDK4	Repression
PPARGC1A	Repression
SMAD3	Activation
SOX9	Activation
SULT1C2	Repression
TFE3	Repression
TGFB2	Activation
THBS1	Activation
TNC	Activation
UCP3	Repression
VCAM1	Activation
VEGFB	Repression

Upstream regulators (CollecTRI, top): MTOR, PRKAA1, PRKAB1, PRKAG1, TFE3

miRNA regulators (miRDB)

5 targeting FLCN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-4286	97.20	64.37	1587

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Mutations lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome (PMID:12204536)
• Clinical and genetic studies of four sporadic BHD cases and four families with a total of 23 affected subjects (PMID:12471204)
• Mutations in sporadic colorectal carcinomas and colorectal carcinoma cell lines with microsatellite instability (PMID:12746401)
• BHD is involved in the entire spectrum of histological types of renal tumors, suggesting its major role in kidney cancer tumorigenesis. (PMID:12907635)
• potential role of BHD as a tumor suppressor gene (review) (PMID:15579035)
• Germ-line mutation spectrum and phenotype analysis were expanded in a large cohort of families with Birt-Hogg-Dube syndrome. (PMID:15852235)
• These results support a role for BHD as a tumor suppressor gene that predisposes to the development of renal tumors when both copies are inactivated. (PMID:15956655)
• May regulate tumorigenesis through modulating stem cells in human. (PMID:16636660)
• Findings show that the BHD gene is a rare target in microsatellite instability (MSI)-high gastric cancer, and BHD mutation tends to occur downstream in the mutational events of other major MSI-high target genes. (PMID:16870330)
• Results suggest that FLCN, mutated in Birt-Hogg-Dube syndrome, and its interacting partner FNIP1 may be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. (PMID:17028174)
• Germline mutations of the BHD gene are involved in some patients with multiple lung cysts & pneumothorax. 4 were new: 3 deletions or insertions in exons 6, 12 & 13, & a splice acceptor site mutation in intron 5 resulting in an in-frame deletion of exon 6. (PMID:17496196)
• The UOK 257 cell line: a novel model for studies of the human Birt-Hogg-Dube gene pathway. (PMID:18206534)
• The first germline missense mutation in BHD c.1978A>G (K508R) in a patient who presented with bilateral multifocal renal oncocytomas, is reported. (PMID:18234728)
• FLCN mutation contributes to not only familial but also ‘apparently sporadic’ patients with isolated primary spontaneous pneumothorax (PMID:18505456)
• Birt-Hogg-Dube (BHD) syndrome, showing the occurrence of two frameshift mutations located respectively in exons 5 (802insA) and 9 (1345delAAAG) of the FLCN gene. A novel homozygous sequence variant in the intron 9 (IVS9 +5C>T) was also found. (PMID:18573707)
• Mutations in the folliculin gene are associated with cystic lung lesions in an otherwise morphological normal lung and predispose to spontaneous pneumothorax [case report] (PMID:18579543)
• study reports an Asian family with Birt-Hogg-Dube syndrom with a BHD germline mutation (PMID:18709329)
• Genetic variation in folliculin does not appear to be a major risk factor for severe COPD (PMID:19116017)
• Folliculin regulates the activity of TORC1, and a new paradigm in which both inappropriately high and inappropriately low levels of TORC1 activity can be associated with renal tumorigenesis. (PMID:19234517)
• In the siblings reported, no FLCN mutations were identified (PMID:19327534)
• A family with lung cysts and spontaneous pneumothorax in 3 generations had a deletion mutation in exon 10 of the FLCN gene. (PMID:19483054)
• We report cases involving a new mutation in three unrelated families of Birt-Hogg-Dube syndrome. (PMID:20227563)
• An Birt-Hogg-Dube syndrome protein germline mutation was found in 23 (63.9%) of the 36 patients. A large genomic deletion was identified in two of the remaining 13 patients. (PMID:20413710)
• Data show that germline FLCN mutations were not detected in 50 patients with familial non-syndromic colorectal cancer. (PMID:20522427)
• Data show that FLCN mutations were found in 9 of 19 (47%) families. (PMID:20618353)
• plays role in tumor suppression and inhibition on rapamycin pathway (PMID:21079084)
• FLCN tumor suppressor gene inactivation induces TFE3 transcriptional activity by increasing its nuclear localization (PMID:21209915)
• Birt-Hogg-Dube (BHD) protein-deficient cells exhibited defects in cell-intrinsic apoptosis that correlated with reduced expression of the BH3-only protein Bim, which was similarly observed in all human and mouse BHD-related tumors examined. (PMID:21258407)
• This report confirms that large intragenic FLCN deletions can cause Birt-Hogg-Dube syndrome and documents the first large intragenic FLCN duplication in a Birt-Hogg-Dube syndrome patient (PMID:21412933)
• Genetic testing for Birt-Hogg-Dube should be considered in the treatment algorithm of patients with bilateral renal masses and known oncocytoma (PMID:21496834)
• FLCN mutations throughout the coding sequence, and suggest that multiple protein domains contribute to folliculin stability and tumor suppressor activity. (PMID:21538689)
• confirmed a high yield of FLCN mutations in clinically defined BHD families, we found a substantially increased lifetime risk of renal cancer of 16% for FLCN mutation carriers (PMID:22146830)
• Germline mutation analysis of the FCLN gene in mother and daughter cases with renal cell neoplasms showed a deletion of 18 bp in exon 5(c.332_349del/p.H111_Q116del), predicting an alteration of the amino acid sequence of “HPSHPQ” replaced by a single amino acid, “L”. (PMID:22211584)
• Study reports a novel in-frame deletion mutation p.F143del (c.427_429delTTC) in exon 6 of FLCN gene in a Korean proband and her two sisters. (PMID:22446046)
• The FLCN-FNIP complex deregulated in Birt-Hogg-Dube syndrome is absolutely required for B-cell differentiation. (PMID:22709692)
• Findings suggest that aspects of folliculin tumour suppressor function are linked to interaction with p0071 and the regulation of RhoA signalling. (PMID:22965878)
• Data indicate that folliculin-CT is structurally similar to the DENN domain of DENND1B. (PMID:22977732)
• FLCN functions as a tumor suppressor by negatively regulating rRNA synthesis. (PMID:23077212)
• These data support a model in which dysregulation of the FLCN-p0071 interaction leads to alterations in cell adhesion, cell polarity, and RhoA signaling. (PMID:23139756)
• FLCN deficiency and subsequent increased PPARGC1A expression result in increased mitochondrial function and oxidative metabolism as the source of cellular energy, which may drive hyperplastic transformation. (PMID:23150719)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	flcn	ENSDARG00000062385
mus_musculus	Flcn	ENSMUSG00000032633
rattus_norvegicus	Flcn	ENSRNOG00000003302
drosophila_melanogaster	BHD	FBGN0261111
caenorhabditis_elegans		WBGENE00017699

Protein

Protein identifiers

Folliculin — Q8NFG4 (reviewed: Q8NFG4)

Alternative names: BHD skin lesion fibrofolliculoma protein, Birt-Hogg-Dube syndrome protein

All UniProt accessions (4): Q8NFG4, A0A0S2Z5Y7, C9J4C4, J3QQZ7

UniProt curated annotations — full annotation on UniProt →

Function. Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis. GTPase-activating protein that plays a key role in the cellular response to amino acid availability through regulation of the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3. Activates mTORC1 by acting as a GTPase-activating protein: specifically stimulates GTP hydrolysis by RagC/RRAGC or RagD/RRAGD, promoting the conversion to the GDP-bound state of RagC/RRAGC or RagD/RRAGD, and thereby activating the kinase activity of mTORC1. The GTPase-activating activity is inhibited during starvation and activated in presence of nutrients. Acts as a key component for non-canonical mTORC1-dependent control of the MiT/TFE factors TFEB and TFE3, while it is not involved in mTORC1-dependent phosphorylation of canonical RPS6KB1/S6K1 and EIF4EBP1/4E-BP1. In low-amino acid conditions, the lysosomal folliculin complex (LFC) is formed on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, inactivates mTORC1 and maximizes nuclear translocation of TFEB and TFE3. Upon amino acid restimulation, RagA/RRAGA (or RagB/RRAGB) nucleotide exchange promotes disassembly of the LFC complex and liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3. Indirectly acts as a positive regulator of Wnt signaling by promoting mTOR-dependent cytoplasmic retention of MiT/TFE factor TFE3. Required for the exit of hematopoietic stem cell from pluripotency by promoting mTOR-dependent cytoplasmic retention of TFE3, thereby increasing Wnt signaling. Acts as an inhibitor of browning of adipose tissue by regulating mTOR-dependent cytoplasmic retention of TFE3. Involved in the control of embryonic stem cells differentiation; together with LAMTOR1 it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes, and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent TFE3 inactivation. In response to flow stress, regulates STK11/LKB1 accumulation and mTORC1 activation through primary cilia: may act by recruiting STK11/LKB1 to primary cilia for activation of AMPK resided at basal bodies, causing mTORC1 down-regulation. Together with FNIP1 and/or FNIP2, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy. Required for starvation-induced perinuclear clustering of lysosomes by promoting association of RILP with its effector RAB34. Regulates glycolysis by binding to lactate dehydrogenase LDHA, acting as an uncompetitive inhibitor.

Subunit / interactions. Interacts (via C-terminus) with FNIP1 or FNIP2 (via C-terminus). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator. Interaction with FNIP1 or FNIP2 mediates indirect interaction with the PRKAA1, PRKAB1 and PRKAG1 subunits of 5’-AMP-activated protein kinase (AMPK). Interacts with HSP90AA1 in the presence of FNIP1. Interacts with HSP70, STUB1, CDC37, AHSA1, CCT2, STIP1, PTGES3 and PPP5C. Interacts with GABARAP; interaction takes place in the presence of FNIP1 and/or FNIP2. Interacts with RILP; the interaction is direct and promotes association between RILP and RAB34. Interacts with KIF3A and KIF3B. Interacts with lactate dehydrogenase LDHA, but not LDHB; the interaction is direct, may preferentially bind LDHA dimers rather than tetramers, and regulates LDHA activity, acting as an uncompetitive inhibitor.

Subcellular location. Lysosome membrane. Cytoplasm. Cytosol. Cell projection. Cilium. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle. Nucleus.

Tissue specificity. Expressed in most tissues tested, including skin, lung, kidney, heart, testis and stomach.

Post-translational modifications. Phosphorylation by ULK1 modulates the interaction with GABARAP and is required to regulate autophagy.

Disease relevance. Birt-Hogg-Dube syndrome 1 (BHD1) [MIM:135150] A form of Birt-Hogg-Dube syndrome, a rare genodermatosis usually manifesting in adulthood and characterized by multiple fibrofolliculomas, trichodiscomas, and acrochordons. Patients with this syndrome have an increased susceptibility to develop renal cell carcinoma, lung cysts, and spontaneous pneumothorax. Inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Primary spontaneous pneumothorax (PSP) [MIM:173600] Condition in which air is present in the pleural space in the absence of a precipitating event, such as trauma or lung disease. This results in secondary collapse of the lung, either partially or completely, and some degree of hypoxia. PSP is relatively common, with an incidence between 7.4-18/100'000 for men and 1.2-6/100'000 for women and a dose-dependent, increased risk among smokers. Most cases are sporadic, typically occurring in tall, thin men aged 10-30 years and generally while at rest. Familial PSP is rarer and usually is inherited as an autosomal dominant condition with reduced penetrance, although X-linked recessive and autosomal recessive inheritance have also been suggested. The disease is caused by variants affecting the gene represented in this entry. Renal cell carcinoma (RCC) [MIM:144700] Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype. The gene represented in this entry may be involved in disease pathogenesis.

Activity regulation. GTPase-activating activity is inhibited in the folliculin complex (LFC), which stabilizes the GDP-bound state of RagA/RRAGA (or RagB/RRAGB), because Arg-164 is located far from the RagC/RRAGC or RagD/RRAGD nucleotide pocket. Disassembly of the LFC complex upon amino acid restimulation liberates the GTPase-activating activity.

Similarity. Belongs to the folliculin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NFG4-1	1	yes
Q8NFG4-2	2
Q8NFG4-3	3

RefSeq proteins (5): NP_001340158, NP_001340159, NP_001340160, NP_653207, NP_659434* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021713	Folliculin	Family
IPR032035	Folliculin_DENN	Domain
IPR037520	Folliculin/SMCR8_longin	Domain
IPR037521	FLCN/SMCR8_DENN	Domain
IPR044886	FLCN_DENN_C_sf	Homologous_superfamily

Pfam: PF11704, PF16692

UniProt features (88 total): sequence variant 22, strand 18, helix 17, modified residue 7, mutagenesis site 6, splice variant 4, domain 3, region of interest 3, turn 3, compositionally biased region 2, chain 1, site 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3V42	X-RAY DIFFRACTION	2
6ULG	ELECTRON MICROSCOPY	3.31
8DHB	ELECTRON MICROSCOPY	3.53
6NZD	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFG4-F1	79.14	0.60

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 164 (essential for gtpase activation (gap) activity)

Post-translational modifications (7): 62, 73, 302, 406, 537, 542, 571

Mutagenesis-validated functional residues (6):

Position	Phenotype
10	abolished gtpase activation (gap) activity.
118	does not assemble into a stable folliculin complex (lfc), preventing localization to the lysosomal membrane upon amino a
164	abolished gtpase activation (gap) activity.
406	impaired ability to regulate autophagy; when associated with a-537 and a-542.
537	impaired ability to regulate autophagy; when associated with a-406 and a-542.
542	impaired ability to regulate autophagy; when associated with a-406 and a-537.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9639288	Amino acids regulate mTORC1

MSigDB gene sets: 461 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_VACUOLE_ORGANIZATION, GOCC_VACUOLAR_MEMBRANE, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP

GO Biological Process (45): negative regulation of transcription by RNA polymerase II (GO:0000122), in utero embryonic development (GO:0001701), cell-cell junction assembly (GO:0007043), transforming growth factor beta receptor signaling pathway (GO:0007179), cellular response to starvation (GO:0009267), positive regulation of autophagy (GO:0010508), hemopoiesis (GO:0030097), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), TOR signaling (GO:0031929), regulation of TOR signaling (GO:0032006), negative regulation of TOR signaling (GO:0032007), positive regulation of TOR signaling (GO:0032008), lysosome localization (GO:0032418), cellular response to amino acid starvation (GO:0034198), negative regulation of Rho protein signal transduction (GO:0035024), intracellular signal transduction (GO:0035556), positive regulation of apoptotic process (GO:0043065), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), negative regulation of glycolytic process (GO:0045820), regulation of Ras protein signal transduction (GO:0046578), epithelial cell proliferation (GO:0050673), negative regulation of epithelial cell proliferation (GO:0050680), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), ERK1 and ERK2 cascade (GO:0070371), negative regulation of ERK1 and ERK2 cascade (GO:0070373), cell proliferation involved in kidney development (GO:0072111), energy homeostasis (GO:0097009), intrinsic apoptotic signaling pathway (GO:0097193), negative regulation of cold-induced thermogenesis (GO:0120163), negative regulation of cell proliferation involved in kidney development (GO:1901723), negative regulation of post-translational protein modification (GO:1901874), negative regulation of brown fat cell differentiation (GO:1903444), positive regulation of TORC1 signaling (GO:1904263), negative regulation of lysosome organization (GO:1905672), regulation of pro-B cell differentiation (GO:2000973), positive regulation of intrinsic apoptotic signaling pathway (GO:2001244), lysosome organization (GO:0007040), negative regulation of cell population proliferation (GO:0008285), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), protein destabilization (GO:0031648)

GO Molecular Function (5): enzyme inhibitor activity (GO:0004857), GTPase activator activity (GO:0005096), enzyme binding (GO:0019899), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (16): nucleus (GO:0005634), cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), mitotic spindle (GO:0072686), FNIP-folliculin RagC/D GAP (GO:1990877), spindle (GO:0005819), cytoskeleton (GO:0005856), membrane (GO:0016020), midbody (GO:0030496), cell projection (GO:0042995), cell-cell contact zone (GO:0044291)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cellular response to starvation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
TOR signaling	3
regulation of TOR signaling	2
intracellular anatomical structure	2
binding	2
intracellular membraneless organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
chordate embryonic development	1
cell junction assembly	1
cell-cell junction organization	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
cell development	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cellular response to transforming growth factor beta stimulus	1
intracellular signal transduction	1
regulation of intracellular signal transduction	1
negative regulation of intracellular signal transduction	1
positive regulation of intracellular signal transduction	1
vacuolar localization	1
cellular response to starvation	1
response to amino acid starvation	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
signal transduction	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
intracellular signaling cassette	1

Protein interactions and networks

STRING

1092 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FLCN	FNIP2	Q9P278	999
FLCN	FNIP1	Q8TF40	999
FLCN	RRAGC	Q9HB90	890
FLCN	MTOR	P42345	832
FLCN	RRAGB	Q5VZM2	819
FLCN	TSC2	P49815	796
FLCN	RRAGD	Q9NQL2	777
FLCN	RRAGA	Q7L523	772
FLCN	EFNA5	P52803	745
FLCN	PRKAG1	P54619	745
FLCN	SLC38A9	Q8NBW4	724
FLCN	NPRL2	Q8WTW4	717
FLCN	TFE3	P19532	712
FLCN	PRKAB1	Q9Y478	700
FLCN	LARS1	Q9P2J5	697

IntAct

79 interactions, top by confidence:

A	B	Type	Score
LAMTOR4	LAMTOR5	psi-mi:“MI:0914”(association)	0.960
LAMTOR3	LAMTOR5	psi-mi:“MI:0914”(association)	0.730
POLR3K	POLR3A	psi-mi:“MI:0914”(association)	0.640
FLCN	FNIP2	psi-mi:“MI:0915”(physical association)	0.630
FLCN	FNIP2	psi-mi:“MI:0403”(colocalization)	0.630
FNIP2	FLCN	psi-mi:“MI:0914”(association)	0.630
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
GABARAP	IPO5	psi-mi:“MI:0914”(association)	0.590
FLCN	FNIP1	psi-mi:“MI:0915”(physical association)	0.560
FNIP1	FLCN	psi-mi:“MI:0914”(association)	0.560
ORF	EIF3D	psi-mi:“MI:0914”(association)	0.560
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
LDLRAD4	WWP2	psi-mi:“MI:0914”(association)	0.530
FLCN	ZNF609	psi-mi:“MI:0914”(association)	0.530
VTA1	CHMP2A	psi-mi:“MI:0914”(association)	0.530
FNIP2	PRKAA1	psi-mi:“MI:0914”(association)	0.460
FLCN	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
HIBCH	FLCN	psi-mi:“MI:0915”(physical association)	0.400
HSPA8	FLCN	psi-mi:“MI:0915”(physical association)	0.400
ALDOB	FLCN	psi-mi:“MI:0915”(physical association)	0.370
FLCN	TSTD2	psi-mi:“MI:0915”(physical association)	0.370
FLCN	FBP1	psi-mi:“MI:0915”(physical association)	0.370
FLCN	HEMGN	psi-mi:“MI:0915”(physical association)	0.370
FLCN	CCDC180	psi-mi:“MI:0915”(physical association)	0.370
FLCN	NANS	psi-mi:“MI:0915”(physical association)	0.370
FLCN	TMEFF1	psi-mi:“MI:0915”(physical association)	0.370
FNIP1	PRKAG1	psi-mi:“MI:0914”(association)	0.350

BioGRID (146): FLCN (Affinity Capture-MS), FLCN (Affinity Capture-MS), FLCN (Affinity Capture-MS), FLCN (Proximity Label-MS), FLCN (Affinity Capture-MS), FLCN (Affinity Capture-Western), FLCN (Reconstituted Complex), FLCN (Affinity Capture-Western), FLCN (Affinity Capture-Western), FLCN (Biochemical Activity), FLCN (Reconstituted Complex), ULK1 (Affinity Capture-Western), SF3B1 (Affinity Capture-MS), SF3B3 (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS)

ESM2 similar proteins: A2A690, A2AWA9, A2RSQ0, A6QL63, F1LTE0, G3V7Q0, O60941, O70585, P40763, P42224, P42227, P42229, P42230, P42231, P52631, P52632, P84060, Q148V7, Q4V8I4, Q5R372, Q5R8N4, Q5RCW6, Q5ZJ17, Q62771, Q62784, Q6DFZ1, Q6DV79, Q6GQW0, Q6IQ26, Q6PAL8, Q6ZPY2, Q6ZUT9, Q7Z3J2, Q8BIK4, Q8CIQ7, Q8IZD9, Q8N122, Q8NFG4, Q92538, Q95115

Diamond homologs: Q3B7L5, Q5M7Q1, Q76JQ2, Q8NFG4, Q8QZS3

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
FLCN	“up-regulates activity”	RRAGC	“gtpase-activating protein”
FLCN	“up-regulates activity”	RRAGD	“gtpase-activating protein”
HSP90AA1	“up-regulates quantity by stabilization”	FLCN	binding
HSPA1A	“up-regulates quantity by stabilization”	FLCN	binding
HSP90AB1	“up-regulates quantity by stabilization”	FLCN	binding
TFE3	“up-regulates quantity by expression”	FLCN	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Energy dependent regulation of mTOR by LKB1-AMPK	7	54.0×	5e-09
MTOR signalling	8	41.7×	3e-09
TP53 Regulates Metabolic Genes	12	30.5×	1e-12
Amino acids regulate mTORC1	6	23.6×	1e-05
Macroautophagy	10	22.6×	3e-09
PTEN Regulation	5	22.4×	1e-04
Regulation of PTEN gene transcription	6	21.0×	2e-05
Autophagy	7	20.4×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of TOR signaling	5	39.3×	4e-05
positive regulation of TORC1 signaling	7	32.9×	1e-06
cellular response to amino acid stimulus	6	29.2×	2e-05
cellular response to glucose starvation	5	26.8×	2e-04
cellular response to xenobiotic stimulus	5	19.1×	8e-04
negative regulation of apoptotic process	9	5.0×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — LUAD.

Clinical variants and AI predictions

ClinVar

2943 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	354
Likely pathogenic	57
Uncertain significance	1216
Likely benign	670
Benign	77

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068460	NM_144997.7(FLCN):c.319_320del (p.Val107fs)	Pathogenic
1068469	NM_144997.7(FLCN):c.57_58del (p.Phe20fs)	Pathogenic
1068651	NM_144997.7(FLCN):c.367C>T (p.Gln123Ter)	Pathogenic
1069125	NM_144997.7(FLCN):c.826_842del (p.Gly276fs)	Pathogenic
1069356	NC_000017.10:g.(?17131193)(17140502_?)del	Pathogenic
1069357	NC_000017.10:g.(?17127226)(17140502_?)del	Pathogenic
1071535	NM_144997.7(FLCN):c.827_828insAG (p.Ala277fs)	Pathogenic
1071737	NM_144997.7(FLCN):c.995dup (p.Ser333fs)	Pathogenic
1071832	NM_144997.7(FLCN):c.1477C>T (p.Gln493Ter)	Pathogenic
1071978	NM_144997.7(FLCN):c.321dup (p.Ser108fs)	Pathogenic
1072796	NM_144997.7(FLCN):c.1333_1352del (p.Ala445fs)	Pathogenic
1073198	NM_144997.7(FLCN):c.1347_1353dup (p.Val452fs)	Pathogenic
1074043	NM_144997.7(FLCN):c.558G>A (p.Trp186Ter)	Pathogenic
1075238	NC_000017.10:g.(?17116969)(17140502_?)del	Pathogenic
1075239	NC_000017.10:g.(?17116969)(17117180_?)del	Pathogenic
1075380	NC_000017.10:g.(?17124841)(17125985_?)del	Pathogenic
1076910	NM_144997.7(FLCN):c.1153C>T (p.Gln385Ter)	Pathogenic
1206072	NM_144997.7(FLCN):c.610G>T (p.Ala204Ser)	Pathogenic
1319129	NM_144997.7(FLCN):c.1337_1343dup (p.Leu449fs)	Pathogenic
1349973	NM_144997.7(FLCN):c.1300+1G>C	Pathogenic
1361458	NM_144997.7(FLCN):c.810del (p.Glu271fs)	Pathogenic
1361582	NM_144997.7(FLCN):c.476_479dup (p.Asp160fs)	Pathogenic
1382685	NM_144997.7(FLCN):c.919del (p.Glu307fs)	Pathogenic
141706	NM_144997.7(FLCN):c.943G>T (p.Glu315Ter)	Pathogenic
141865	NM_144997.7(FLCN):c.499C>T (p.Gln167Ter)	Pathogenic
1451720	NM_144997.7(FLCN):c.1127G>A (p.Trp376Ter)	Pathogenic
1451945	NC_000017.10:g.(?17131193)(17131475_?)del	Pathogenic
1452894	NM_144997.7(FLCN):c.755del (p.Ala252fs)	Pathogenic
1454279	NM_144997.7(FLCN):c.67_79del (p.Glu23fs)	Pathogenic
1455402	NM_144997.7(FLCN):c.1321del (p.Val441fs)	Pathogenic

SpliceAI

2902 predictions. Top by Δscore:

Variant	Effect	Δscore
17:17213850:CACTT:C	acceptor_gain	1.0000
17:17213852:CTTTG:C	acceptor_gain	1.0000
17:17213853:TTTG:T	acceptor_gain	1.0000
17:17213854:T:TC	acceptor_gain	1.0000
17:17213854:TTG:T	acceptor_gain	1.0000
17:17213855:TG:T	acceptor_gain	1.0000
17:17213856:GC:G	acceptor_loss	1.0000
17:17213856:GCTGA:G	acceptor_loss	1.0000
17:17213857:C:CC	acceptor_gain	1.0000
17:17213857:C:T	acceptor_loss	1.0000
17:17213858:T:A	acceptor_loss	1.0000
17:17213858:T:C	acceptor_loss	1.0000
17:17214972:CA:C	donor_gain	1.0000
17:17214983:A:AC	donor_gain	1.0000
17:17214984:C:CA	donor_gain	1.0000
17:17214984:C:CC	donor_gain	1.0000
17:17214984:CTT:C	donor_gain	1.0000
17:17214986:T:TA	donor_gain	1.0000
17:17214997:T:TA	donor_gain	1.0000
17:17215086:GCCCA:G	acceptor_gain	1.0000
17:17215087:CCCA:C	acceptor_gain	1.0000
17:17215087:CCCAC:C	acceptor_gain	1.0000
17:17215088:CCA:C	acceptor_gain	1.0000
17:17215088:CCAC:C	acceptor_gain	1.0000
17:17215089:C:T	acceptor_gain	1.0000
17:17215089:CA:C	acceptor_gain	1.0000
17:17215089:CAC:C	acceptor_gain	1.0000
17:17215091:C:CC	acceptor_gain	1.0000
17:17215092:T:G	acceptor_loss	1.0000
17:17215105:A:T	acceptor_gain	1.0000

AlphaMissense

3834 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:17213709:C:A	K562N	1.000
17:17213709:C:G	K562N	1.000
17:17213728:C:T	G556D	1.000
17:17213738:A:G	W553R	1.000
17:17213738:A:T	W553R	1.000
17:17213847:C:A	K516N	1.000
17:17213847:C:G	K516N	1.000
17:17214992:A:G	W511R	1.000
17:17214992:A:T	W511R	1.000
17:17223984:A:G	W186R	1.000
17:17223984:A:T	W186R	1.000
17:17224007:T:A	D178V	1.000
17:17224027:G:C	S171R	1.000
17:17224027:G:T	S171R	1.000
17:17224029:T:G	S171R	1.000
17:17224037:C:G	R168P	1.000
17:17224046:C:A	G165V	1.000
17:17224046:C:T	G165D	1.000
17:17224047:C:A	G165C	1.000
17:17224047:C:G	G165R	1.000
17:17224048:C:A	R164S	1.000
17:17224048:C:G	R164S	1.000
17:17224049:C:A	R164M	1.000
17:17224049:C:G	R164T	1.000
17:17224052:G:T	A163D	1.000
17:17224061:T:A	D160V	1.000
17:17224061:T:G	D160A	1.000
17:17224062:C:A	D160Y	1.000
17:17224062:C:G	D160H	1.000
17:17224081:G:C	S153R	1.000

dbSNP variants (sampled 300 via entrez): RS1000136543 (17:17224160 G>A,C,T), RS1000234104 (17:17229417 C>T), RS1000269939 (17:17222016 A>G), RS1000406659 (17:17235056 G>A), RS1000464940 (17:17224370 C>T), RS1000672054 (17:17235325 C>T), RS1000781801 (17:17221746 A>G), RS1000796245 (17:17220724 T>C), RS1000850951 (17:17222951 G>A), RS1000910709 (17:17220428 G>A), RS1001071080 (17:17225577 T>C), RS1001084215 (17:17230844 G>A), RS1001173793 (17:17214378 G>A), RS1001223199 (17:17236865 G>A), RS1001272410 (17:17219894 G>A)

Disease associations

OMIM: gene MIM:607273 | disease phenotypes: MIM:135150, MIM:114500, MIM:144700, MIM:173600, MIM:610883, MIM:167000, MIM:258040

GenCC curated gene-disease

Disease	Classification	Inheritance
Birt-Hogg-Dube syndrome 1	Definitive	Autosomal dominant
Birt-Hogg-Dube syndrome	Definitive	Autosomal dominant
familial spontaneous pneumothorax	Strong	Autosomal dominant
renal carcinoma	Strong	Autosomal dominant
colorectal cancer	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
obsolete Birt-Hogg-Dube syndrome	Definitive	AD

Mondo (18): hereditary neoplastic syndrome (MONDO:0015356), Birt-Hogg-Dube syndrome (MONDO:0800444), Birt-Hogg-Dube syndrome 1 (MONDO:0800445), colorectal cancer (MONDO:0005575), nonpapillary renal cell carcinoma (MONDO:0007763), familial spontaneous pneumothorax (MONDO:0008259), Potocki-Lupski syndrome (MONDO:0012574), colon carcinoma (MONDO:0002032), ovarian cancer (MONDO:0008170), exstrophy-epispadias complex (MONDO:0017919), hypoparathyroidism (MONDO:0001220), pulmonary arterial hypertension (MONDO:0015924), chromophobe renal cell carcinoma (MONDO:0017885), hepatoblastoma (MONDO:0018666), pilocytic astrocytoma (MONDO:0016691)

Orphanet (15): Birt-Hogg-Dubé syndrome (Orphanet:122), Inherited cancer-predisposing syndrome (Orphanet:140162), 17p11.2 microduplication syndrome (Orphanet:1713), Familial spontaneous pneumothorax (Orphanet:2903), Hereditary clear cell renal cell carcinoma (Orphanet:422526), Rare ovarian cancer (Orphanet:213500), Exstrophy-epispadias complex (Orphanet:322), Cloacal exstrophy (Orphanet:93929), Pulmonary arterial hypertension (Orphanet:182090), Chromophobe renal cell carcinoma (Orphanet:319303), Hepatoblastoma (Orphanet:449), Pilocytic astrocytoma (Orphanet:251612), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667), Idiopathic/heritable pulmonary arterial hypertension (Orphanet:422)

HPO phenotypes

85 total (30 of 85 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000107	Renal cyst
HP:0000154	Wide mouth
HP:0000218	High palate
HP:0000243	Trigonocephaly
HP:0000252	Microcephaly
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000325	Triangular face
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000494	Downslanted palpebral fissures
HP:0000540	Hypermetropia
HP:0000678	Dental crowding
HP:0000689	Dental malocclusion
HP:0000717	Autism
HP:0000733	Motor stereotypy
HP:0000752	Hyperactivity
HP:0000817	Reduced eye contact
HP:0000821	Hypothyroidism
HP:0001012	Multiple lipomas
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001442	Typified by somatic mosaicism
HP:0001508	Failure to thrive
HP:0001518	Small for gestational age

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006979_809	Heel bone mineral density	1.000000e-14
GCST90002396_609	Mean reticulocyte volume	7.000000e-20

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D058249	Birt-Hogg-Dube Syndrome	C04.700.212; C16.320.700.212
D018197	Hepatoblastoma	C04.557.435.380
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D007011	Hypoparathyroidism	C19.642.482
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
FLCN c.1285dupC	Everolimus	Renal Cell Carcinoma	Sensitivity/Response	CIViC C	EID10137

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

75 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	2
sodium arsenite	increases abundance, increases expression	2
Arsenic	increases expression, increases abundance	2
Formaldehyde	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
sodium arsenate	increases abundance, increases expression	1
2-butenal	increases expression	1
dodecyldimethylamine oxide	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
boron nitride	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	increases expression	1
benzo(e)pyrene	decreases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1
aflatoxin B2	decreases methylation	1
coumarin	decreases phosphorylation	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
pinostrobin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment, decreases expression	1

Cellosaurus cell lines

19 cell lines: 17 cancer cell line, 1 induced pluripotent stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1219	FTC-133	Cancer cell line	Male
CVCL_1723	SW1990	Cancer cell line	Male
CVCL_1D69	UOK257-2	Cancer cell line	Male
CVCL_A4EN	CMCi009-A	Induced pluripotent stem cell	Female
CVCL_B9VJ	Abcam HeLa FLCN KO	Cancer cell line	Female
CVCL_D8LG	Ubigene HCT 116 FLCN KO	Cancer cell line	Male
CVCL_E1MW	HyCyte SW1990 KO-hLINC00511	Cancer cell line	Male
CVCL_E8T0	SW1990/GFP (Bsd)	Cancer cell line	Male
CVCL_E8T1	SW1990/GFP (Puro)	Cancer cell line	Male
CVCL_E8T2	SW1990/Luciferase	Cancer cell line	Male

Clinical trials (associated diseases)

335 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	PHASE4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	PHASE4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	PHASE4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	PHASE4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	PHASE4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	PHASE4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	PHASE4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
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