Affinage

FLCN

Folliculin · UniProt Q8NFG4

Length
579 aa
Mass
64.5 kDa
Annotated
2026-06-09
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FLCN (folliculin) is a tumor suppressor that operates at the lysosomal surface as the catalytic GTPase-activating protein (GAP) for RagC/D within the amino acid-sensing arm of the mTORC1 pathway, coupling nutrient status to a transcriptional program governed by the MiT/TFE factors TFE3 and TFEB (PMID:31704029, PMID:36103527, PMID:27913603). FLCN acts in an obligate heterodimer with FNIP1/FNIP2 and, in its active conformation, reorients to position a catalytic arginine finger (Arg164) for GTP hydrolysis on RagC/D; disruption of this active interface abolishes GAP activity and drives nuclear retention of TFE3 without affecting canonical S6K/4E-BP1 phosphorylation, defining a substrate-selective mode of mTORC1 control (PMID:31704029, PMID:36103527). Lysosomal recruitment of the FLCN-FNIP complex is gated by amino acid availability through GATOR1-dependent conversion of RagA/B to the GDP-bound state, and FLCN coordinates the nucleotide status of the two Rag subunits by binding RagA/B(GDP) while acting as GAP on RagC/D (PMID:29848618). Loss of FLCN relieves mTOR-dependent cytoplasmic sequestration of TFE3/TFEB, and the resulting nuclear MiT/TFE activity is the common driver of FLCN-deficiency phenotypes: induction of PGC-1α/PGC-1β driving mitochondrial biogenesis and adipose browning (PMID:27913603), chronic AMPK–PGC-1α/ERRα activation (PMID:27151976), glycogen accumulation (PMID:26439621, PMID:32049013), cardiac hypertrophy (PMID:24908670), a non-canonical interferon response (PMID:33459596), WNT pathway modulation (PMID:31272105), and ectopic Prox1 expression causing blood–lymphatic vessel misconnection through direct TFE3 binding to a Prox1 regulatory element (PMID:33298956). In vivo, FLCN loss activates mTORC1 (and PI3K-AKT) and produces polycystic kidneys and renal cell carcinoma that are rescued by rapamycin, establishing FLCN as an upstream suppressor of mTOR in the kidney (PMID:19850877, PMID:18974783). FLCN sits within feedback and stress-responsive circuits: AMPK–TFEB transcriptionally induces FLCN expression, TFE3 itself activates FLCN transcription, and PRDM10 directly drives FLCN promoter activity (PMID:31404503, PMID:32049013, PMID:36440963). FLCN activity is further tuned by phosphorylation—by the TSC2-mTORC1 axis at Ser62/Ser302, by ULK1 at Ser406/Ser537/Ser542, and by insulin-responsive mTORC2–AKT1 at Ser62, the latter inhibiting RagC GAP activity to promote insulin-induced mTORC1 activation and tumor growth (PMID:25126726, PMID:19695222, PMID:37083230). Beyond the lysosome, FLCN engages Rab11A through its C-terminal DENN-like domain to promote recycling of PAT1 and transferrin receptor 1, maintaining lysosomal amino acid levels and iron homeostasis (PMID:30446510, PMID:33609526).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2006 High

    Establishing that FLCN works through a defined protein complex and signaling axis was the first step in moving beyond its identification as a BHD disease gene; FNIP1 was shown to be its physical partner linking FLCN to AMPK-mTOR signaling.

    Evidence Yeast two-hybrid and reciprocal Co-IP with in vitro kinase assays and pharmacological inhibition in mammalian cells

    PMID:17028174

    Open questions at the time
    • Did not define the direction of FLCN's effect on mTOR
    • Kinase phosphorylating FLCN not identified
    • No structural or catalytic mechanism
  2. 2008 High

    Whether FLCN suppresses or promotes mTOR in vivo was resolved by tissue-specific knockout showing FLCN acts upstream to restrain mTOR in the kidney, with rapamycin reversing the cystic tumor phenotype.

    Evidence Kidney-specific conditional KO mice with rapamycin rescue and histology

    PMID:18974783

    Open questions at the time
    • Did not define the biochemical activity by which FLCN suppresses mTOR
    • Did not identify the relevant downstream effectors
  3. 2009 High

    Germline and heterozygous mouse models established FLCN as a bona fide tumor suppressor with LOH-driven kidney tumors and showed FLCN loss activates both mTORC1/mTORC2 and PI3K-AKT, placing it broadly in growth-signaling control.

    Evidence Conditional KO mice, LOH analysis, immunoblotting of human tumors

    PMID:19850877

    Open questions at the time
    • Mechanism connecting FLCN loss to AKT/mTORC2 not resolved
    • Essential embryonic role not mechanistically dissected
  4. 2010 High

    The key downstream effector of FLCN was identified as the MiT/TFE transcription factor TFE3, whose phosphorylation and cytoplasmic retention depend on FLCN, with TFE3 targets (e.g. GPNMB) induced upon FLCN loss.

    Evidence shRNA knockdown and re-expression with immunostaining, RT-PCR across cell lines, MEFs, and tumors

    PMID:21209915

    Open questions at the time
    • The biochemical step linking FLCN to TFE3 phosphorylation not yet defined
    • Relationship to canonical mTORC1 substrates unclear
  5. 2010 Medium

    Beyond mTOR, FLCN re-expression was shown to suppress tumor growth and modulate TGF-β pathway genes, with Activin A blocking anchorage-independent growth, broadening the tumor-suppressor output.

    Evidence Xenograft assays, differential gene expression, ELISA, anchorage-independent growth with FLCN re-expression

    PMID:20573232

    Open questions at the time
    • Direct mechanism linking FLCN to TGF-β gene expression not established
    • Relationship to the TFE3 axis not resolved
  6. 2012 High

    FLCN was linked to mitochondrial metabolism by showing its deficiency drives PGC-1α-dependent mitochondrial biogenesis and oxidative metabolism, with PGC-1α double-KO epistasis confirming the axis.

    Evidence Muscle-specific conditional KO mice, PPARGC1A double-KO epistasis, EM and metabolic profiling

    PMID:23150719

    Open questions at the time
    • How FLCN loss elevates PGC-1α not mechanistically traced
    • Connection to TFE3/mTOR left open
  7. 2014 Medium

    FLCN was tied directly to the core autophagy machinery via GABARAP binding and ULK1-mediated phosphorylation, embedding it in autophagy regulation.

    Evidence Co-IP, phospho-site mapping, ULK1 overexpression, autophagic flux assays

    PMID:25126726

    Open questions at the time
    • Functional consequence of ULK1 phosphorylation on GAP activity not defined here
    • Single-lab finding
  8. 2016 High

    The TFE3-PGC-1 connection was placed firmly downstream of FLCN's RagC/D activity in adipose browning, independent of TSC-mTOR-S6K, by multiple epistasis rescues.

    Evidence Adipose-specific KO mice with TFE3 and PGC-1β co-deletion epistasis and inducible overexpression

    PMID:27913603

    Open questions at the time
    • Did not yet provide structural proof of RagC/D GAP activity
    • Parallel AMPK contribution not reconciled
  9. 2016 High

    A parallel route to FLCN-deficiency metabolism was defined through chronic AMPK–PGC-1α–ERRα activation driving browning and oxidative metabolism.

    Evidence Adipose-specific KO mice, AMPK activity assays, metabolic phenotyping

    PMID:27151976

    Open questions at the time
    • Mechanistic integration of AMPK and TFE3 arms left unresolved
    • Cause of AMPK hyperactivation not fully traced
  10. 2016 Medium

    A biochemical role at the lysosome was proposed by showing FLCN maintains lysosomal leucine to stimulate mTORC1 by limiting lysosomal PAT1 accumulation.

    Evidence Knockdown/overexpression in HEK293, lysosomal amino acid measurement, mTORC1 assays, leucine rescue

    PMID:27280402

    Open questions at the time
    • Mechanism preventing PAT1 lysosomal accumulation not yet defined
    • Relationship to GAP activity unclear
  11. 2018 High

    The gating of FLCN-FNIP recruitment was resolved: GATOR1 GAP activity on RagA/B (GDP loading) recruits the complex, which then acts as GAP on RagC/D, coordinating nucleotide status across the Rag heterodimer with amino acid availability.

    Evidence Lysosomal fractionation, dominant-negative/constitutively active Rag mutants, GATOR1 depletion, microscopy

    PMID:29848618

    Open questions at the time
    • Atomic mechanism of catalysis not yet shown
    • How nutrient signals trigger reorientation unresolved
  12. 2018 Medium

    The PAT1-recycling mechanism was clarified by identifying FLCN's C-terminal DENN-like domain interaction with Rab11A that loads PAT1 onto recycling vesicles, with FLCN not acting as a direct Rab11A GEF.

    Evidence Co-IP, domain mapping, PAT1 localization, mTORC1 assays, in vitro GEF assay (negative)

    PMID:30446510

    Open questions at the time
    • Precise enzymatic role on Rab11A unresolved (no GEF activity)
    • Single-lab finding
  13. 2019 High

    Atomic-level mechanism was established: cryo-EM of the FLCN-FNIP2-Rag-Ragulator complex revealed the heterodimer architecture and a conserved catalytic arginine finger essential for RagC/D GAP activity.

    Evidence Cryo-EM structure with biochemical GAP assays and arginine-finger mutagenesis

    PMID:31704029

    Open questions at the time
    • Captured an inactive conformation; catalytic geometry not yet seen
    • How conformational switching is triggered not resolved
  14. 2019 High

    FLCN was extended into innate immunity and stress, acting with AMPK upstream of TFEB/TFE3 independently of mTORC1 to drive pro-inflammatory and pathogen-resistance programs across species.

    Evidence C. elegans genetic epistasis and mammalian KO cells with AMPK activation and LPS treatment

    PMID:30917316

    Open questions at the time
    • mTOR-independent route to TFEB activation not biochemically defined
    • Direct AMPK-FLCN-TFEB connectivity not mapped
  15. 2019 Medium

    A transcriptional feedback loop was uncovered whereby AMPK induces FLCN expression via TFEB binding a defined FLCN promoter element, independent of mTOR.

    Evidence Transcriptomics, AMPK-deficient MEFs, TFEB/TFE3 KO, FLCN promoter-luciferase with site mutation, zebrafish

    PMID:31404503

    Open questions at the time
    • Physiological contexts engaging the loop not fully defined
    • Single-lab reporter evidence
  16. 2019 Medium

    FLCN was linked to WNT signaling, with TFE3 silencing fully reversing the WNT-activity deficit of FLCN-deficient cells, identifying TFE3 as the key mediator.

    Evidence Flcn inactivation in MEFs/fibroblasts, RNA-seq, TCF/LEF reporter, TFE3 siRNA epistasis, β-catenin rescue

    PMID:31272105

    Open questions at the time
    • Direct TFE3 targets in the WNT pathway not mapped
    • Single-lab finding
  17. 2020 High

    A developmental role was defined: FLCN loss drives TFE3-dependent ectopic Prox1 expression in venous endothelium, causing blood-lymphatic vessel misconnection, with ChIP showing direct TFE3 binding to a Prox1 regulatory element.

    Evidence Endothelial-specific KO mice, ChIP for TFE3-Prox1, vascular anatomy in mice and humans

    PMID:33298956

    Open questions at the time
    • How FLCN loss is sensed specifically in venous endothelium not resolved
  18. 2020 Medium

    A FLCN-TFE3 feedback loop in hematopoietic cells was defined where TFE3 transcriptionally activates FLCN and FLCN loss amplifies TFE3-driven glycogenesis and lysosomal-storage-like phenotypes.

    Evidence Hematopoietic-specific KO mice with Tfe3 co-deletion epistasis and transcriptional target analysis

    PMID:32049013

    Open questions at the time
    • Generality of the feedback loop across tissues not established
    • Single-lab finding
  19. 2021 High

    A regulatory off-switch was identified: during selective autophagy (CASM/mitophagy/xenophagy), GABARAP conjugation sequesters FLCN-FNIP via a LIR motif, disrupting RagC/D GAP function to activate TFEB/TFE3.

    Evidence Co-IP, LIR motif mapping/mutagenesis, GABARAP lipidation assays, GAP and nuclear-localization assays

    PMID:34597140

    Open questions at the time
    • In vivo significance of GABARAP-mediated FLCN sequestration not quantified
    • LC3 vs GABARAP selectivity mechanism not fully defined
  20. 2021 Medium

    FLCN was connected to iron homeostasis by promoting Rab11A-TfR1 binding required for TfR1 recycling; FLCN loss causes iron deficiency and HIF activation rescued by dietary iron.

    Evidence Co-IP, TfR1 recycling and HIF reporter assays, Drosophila BHD model with iron rescue

    PMID:33609526

    Open questions at the time
    • Whether iron deficiency contributes to BHD tumorigenesis unresolved
    • Single-lab finding
  21. 2021 Medium

    A hepatic role was defined where FLCN loss activates TFEB/TFE3 to promote autophagy and reduce steatosis, fibrosis and inflammation in a fatty liver model.

    Evidence Liver-specific KO mice with autophagy, lipid, fibrosis and inflammation readouts

    PMID:34711912

    Open questions at the time
    • Direct transcriptional targets driving the protective phenotype not mapped
  22. 2022 High

    The catalytic mechanism of substrate-selective mTORC1 control was visualized: in the active FLCN complex, FLCN reorients 90° to break RagA contacts and engage RagC, positioning Arg164 for catalysis; disrupting this interface abolishes GAP activity and retains TFE3 in the nucleus without affecting S6K/4E-BP1.

    Evidence Cryo-EM of the active complex, interface mutagenesis, GAP and TFE3/S6K assays

    PMID:36103527

    Open questions at the time
    • Trigger for the inactive-to-active conformational switch not fully defined
    • Basis of TFE3 vs S6K substrate selectivity at the catalytic step incomplete
  23. 2023 Medium

    Insulin-responsive regulation of FLCN was defined: lysosomal RagD-recruited mTORC2-AKT1 phosphorylates FLCN at Ser62, inhibiting RagC GAP activity to enable insulin-induced mTORC1 activation and tumor growth.

    Evidence In vitro AKT1 kinase assay, lysosomal fractionation, RagD mutants, phospho-site mutagenesis, xenografts

    PMID:37083230

    Open questions at the time
    • Reconciliation of AKT1 Ser62 with TSC2-mTORC1 Ser62/Ser302 phosphorylation incomplete
    • Single-lab finding
  24. 2023 Medium

    Transcriptional control of FLCN was extended by showing PRDM10 directly binds the FLCN promoter, with a pathogenic Cys677Tyr variant abrogating FLCN expression.

    Evidence PRDM10 DNA binding and promoter reporter assays, inducible variant expression, RNA-seq, family co-segregation

    PMID:36440963

    Open questions at the time
    • Broader regulatory network controlling FLCN expression not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single FLCN-FNIP RagC/D GAP activity is mechanistically partitioned to selectively control MiT/TFE phosphorylation versus canonical mTORC1 substrates, and how the multiple inputs (ULK1, AKT1/mTORC2, TSC2-mTORC1 phosphorylation; GABARAP sequestration; GATOR1 gating) are integrated in a given tissue.
  • No unified model reconciling phosphorylation inputs with conformational switching
  • Substrate-selectivity mechanism at the catalytic step undefined
  • Tissue-specific weighting of mTOR-dependent vs AMPK/mTOR-independent TFE3/TFEB arms unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005764 lysosome 4 GO:0031410 cytoplasmic vesicle 2 GO:0005634 nucleus 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1643685 Disease 3 R-HSA-9612973 Autophagy 3
Partners
AKT1FNIP1FNIP2GABARAPRAB11ARAGARAGCTDP-43
Complex memberships
AMPK-FNIP2(MAPO1)-FLCN complexFLCN-FNIP1/2 heterodimerFLCN-FNIP2-Rag-Ragulator (active FLCN complex)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 FLCN (folliculin) physically interacts with a novel binding protein FNIP1, and this complex associates with AMPK. FNIP1 is phosphorylated by AMPK, and FLCN phosphorylation is reduced by AMPK inhibitors and rapamycin, and enhanced by FNIP1 overexpression, placing FLCN in the AMPK-mTOR signaling axis. Co-immunoprecipitation, yeast two-hybrid, in vitro phosphorylation assay, pharmacological inhibition (rapamycin, AMPK inhibitors), overexpression studies Proceedings of the National Academy of Sciences of the United States of America High 17028174
2009 Homozygous BHD/FLCN knockout in mice causes early embryonic lethality (E5.5–E6.5) with defects in visceral endoderm; heterozygous knockout mice develop kidney tumors with loss of heterozygosity. BHD inactivation leads to activation of both mTORC1 and mTORC2, and PI3K-AKT pathway activation with elevated total AKT protein in kidney tumors. Conditional knockout mouse model, immunoblotting, LOH analysis, histological analysis Proceedings of the National Academy of Sciences of the United States of America High 19850877
2008 Kidney-specific FLCN knockout in mice leads to polycystic kidneys, hyperplasia, and cystic renal cell carcinoma via activation of the mTOR pathway; rapamycin treatment rescues these phenotypes, demonstrating FLCN acts upstream to suppress mTOR signaling in kidney. Conditional knockout mouse model (Ksp-Cre), rapamycin treatment, histological analysis, BUN measurements PloS one High 18974783
2010 FLCN inactivation induces nuclear localization of TFE3 transcription factor (accompanied by decreased TFE3 phosphorylation), leading to increased TFE3 transcriptional activity and upregulation of its target GPNMB. Restoration of wild-type FLCN suppresses GPNMB expression and nuclear TFE3. shRNA knockdown, stable re-expression, immunostaining, quantitative RT-PCR, immunoblotting in cell lines, mouse embryo fibroblasts, and mouse/human renal tumors PloS one High 21209915
2019 Cryo-EM structure of the FLCN-FNIP2-Rag GTPase-Ragulator complex reveals that FLCN-FNIP2 adopts an extended conformation with heterodimerized Longin domains contacting Rag nucleotide-binding domains and DENN domains at the distal end. A conserved arginine on FLCN (catalytic arginine finger) is essential for its GAP activity toward RagC/D GTPases. Cryo-EM structure determination, biochemical GAP activity assays, mutagenesis of catalytic arginine Cell High 31704029
2022 Cryo-EM structure of the active FLCN complex (AFC) with FLCN, FNIP2, SLC38A9 N-terminal tail, RagA(GDP):RagC(GDP·BeFx), and Ragulator shows FLCN reorients 90° relative to its inactive lysosomal conformation, breaks contact with RagA, and makes new contacts with RagC that position Arg164 for catalytic GAP activity. Disruption of AFC-specific interfaces eliminates GAP activity and causes nuclear retention of TFE3 without affecting S6K or 4E-BP1 phosphorylation. Cryo-EM structure determination, interface mutagenesis, GAP activity assay, TFE3 nuclear localization assay, S6K/4E-BP1 phosphorylation assay Science advances High 36103527
2012 FLCN deficiency in muscle leads to increased mitochondrial biogenesis and a metabolic shift toward oxidative phosphorylation in a PGC-1α (PPARGC1A)-dependent manner. Re-expression of wild-type FLCN in FLCN-null kidney cancer cells suppresses mitochondrial metabolism and PPARGC1A expression. Tissue-specific conditional knockout mice (CKM-Cre, MYOG-Cre), electron microscopy (% mitochondrial area), metabolic profiling, immunoblotting, PPARGC1A double-knockout epistasis, oxygen consumption measurement Journal of the National Cancer Institute High 23150719
2016 Adipose-specific deletion of FLCN relieves mTOR-dependent cytoplasmic retention of TFE3, leading to TFE3 nuclear translocation and direct induction of PGC-1α/PGC-1β, driving mitochondrial biogenesis and adipose browning. This is mediated by RagC/D GTPases independently of TSC-mTOR-S6K signaling. Co-deletion of TFE3 or PGC-1β rescues the browning phenotype. Adipose-specific FLCN KO mice, TFE3 co-deletion epistasis, PGC-1β co-deletion epistasis, TFE3 nuclear localization assay, gene expression analysis, inducible PGC-1β overexpression Genes & development High 27913603
2016 Loss of FLCN in adipose tissue leads to chronic hyperactivation of AMPK, which induces PGC-1α and ERRα, driving mitochondrial biogenesis, oxidative metabolism, and browning of white adipose tissue. The AMPK/PGC-1α/ERRα molecular axis mediates these metabolic effects. Adipose-specific FLCN KO mice (Adipoq-FLCN), AMPK activity assays, gene expression analysis, mitochondrial biogenesis assays, metabolic phenotyping (energy expenditure, cold exposure, HFD resistance) Genes & development High 27151976
2018 FLCN-FNIP lysosomal recruitment during amino acid starvation requires GATOR1 GAP activity toward RagA/B (converting them to GDP-bound state). By binding RagA/B(GDP) and acting as GAP on RagC/D, FLCN-FNIP coordinates nucleotide status between Rag heterodimer subunits in response to amino acid availability. Lysosomal fractionation, dominant-negative and constitutively active Rag GTPase mutants, GATOR1 depletion, fluorescence microscopy, immunoblotting The Journal of cell biology High 29848618
2021 During autophagy-related processes (CASM, mitophagy, xenophagy), GABARAP (but not LC3) membrane conjugation is required for TFEB/TFE3 activation. GABARAP directly binds to a previously unidentified LIR motif in the FLCN/FNIP complex, sequestering it to GABARAP-conjugated membranes, disrupting FLCN/FNIP GAP function toward RagC/D and impairing mTOR-dependent phosphorylation of TFEB. Co-immunoprecipitation, LIR motif identification and mutagenesis, GABARAP lipidation assays, TFEB/TFE3 nuclear localization, RagC/D GAP activity assays, selective autophagy genetic models Science advances High 34597140
2014 FLCN interacts with GABARAP (GABA-A receptor-associated protein), a core autophagy component. FLCN is phosphorylated by ULK1 at Ser406, Ser537, and Ser542. Loss of FLCN moderately impairs basal autophagic flux. The FLCN-GABARAP interaction is modulated by presence of FNIP1 or FNIP2 and regulated by ULK1. Co-immunoprecipitation, phosphorylation site mapping, ULK1 overexpression, autophagic flux assays (SQSTM1, MAP1LC3B, GABARAP levels), siRNA knockdown Autophagy Medium 25126726
2009 FLCN phosphorylation at Ser62 and Ser302 is regulated by the Tsc2-mTORC1 pathway downstream of tuberin and Rheb. Downregulation of tuberin or overexpression of Rheb induces multiple FLCN phosphorylations. FLCN phosphorylation modulates its complex formation with AMPK. Immunoblotting with phospho-specific approaches, siRNA knockdown of TSC2, Rheb overexpression, AMPK co-immunoprecipitation Biochemical and biophysical research communications Medium 19695222
2011 Pathogenic FLCN missense and in-frame deletion mutations that impair folliculin tumor suppressor function significantly disrupt protein stability (assessed in vitro). Mutations that did not impair protein stability also did not impair growth suppression activity or intracellular localization, indicating protein stability is a functional correlate. Cycloheximide chase assay, protein stability measurement, growth suppression assay in cell lines, intracellular localization by immunofluorescence, evolutionary analysis Human mutation Medium 21538689
2010 Wild-type FLCN suppresses tumor development in FLCN-null renal cancer cells in nude mice in a dose-dependent manner. FLCN loss leads to downregulation of key TGF-β signaling genes including TGFB2, INHBA, THBS1, GREM1, and SMAD3. Activin A (INHBA homodimer) completely suppresses anchorage-independent growth of FLCN-null cells. Xenograft tumor assay, differential gene expression, ELISA for secreted proteins, anchorage-independent growth assay, FLCN stable re-expression Molecular cancer Medium 20573232
2019 FLCN and AMPK act upstream of TFEB/TFE3 in the innate immune response independently of the mTORC1 signaling pathway. In C. elegans, loss of FLCN confers pathogen resistance via AMPK-dependent TFEB/TFE3 activation. In mammalian cells, loss of FLCN or AMPK activation induces TFEB/TFE3-dependent pro-inflammatory cytokine expression. LPS treatment of macrophages reduces ATP and activates AMPK with concomitant TFEB nuclear localization. C. elegans genetic epistasis (flcn-1 deletion, AMPK overexpression/deletion), mammalian FLCN KO cells, pharmacological AMPK activation, LPS treatment, nuclear localization assays, cytokine expression measurement Cell reports High 30917316
2015 In C. elegans, FLCN-1 (FLCN ortholog) loss leads to constitutive AMPK-dependent accumulation of glycogen stores, conferring resistance to hyperosmotic stress. Upon stress, glycogen is degraded to produce glycerol through GPDH enzymes. This resistance requires AMPK, glycogen synthase, and glycogen phosphorylase. Glycogen accumulates in kidneys of FLCN-deficient mice and renal tumors from BHD patients. C. elegans genetics (loss-of-function mutations, epistasis), glycogen measurement, glycerol production assay, GPDH enzyme inhibition, mouse kidney histology, human tumor tissue analysis PLoS genetics Medium 26439621
2011 The AMPK-MAPO1(FNIP2)-FLCN complex is required for apoptosis triggered by O6-methylguanine DNA damage. siRNA knockdown of FLCN or FNIP2/MAPO1 suppresses sub-G1 accumulation after MNU treatment. AMPK phosphorylation after MNU occurs in an MLH1-dependent manner and requires both MAPO1 and FLCN for normal AMPK activation. siRNA knockdown, cell cycle analysis (sub-G1), AMPK phosphorylation immunoblotting, AICAR treatment, mitochondrial membrane potential assay DNA repair Medium 22209521
2014 Loss of FLCN in cardiomyocytes causes severe cardiac hypertrophy via mTORC1 upregulation. Flcn-deficient hearts show reduced phospho-AMPK-α (T172), elevated ATP, and increased mitochondrial function. Upregulated PPARGC1A (PGC-1α) drives excess mitochondrial metabolism, leading to AMPK inactivation and mTORC1 activation. Inactivation of PPARGC1A in Flcn-deficient hearts reduces heart mass, restores phospho-AMPK, and suppresses mTORC1. Cardiac-specific FLCN KO mice, PPARGC1A double KO epistasis, rapamycin treatment, AMPK activity assays, ATP measurement, mitochondrial function assays, echocardiography Human molecular genetics High 24908670
2006 Drosophila BHD homolog (DBHD) is required for germline stem cell (GSC) maintenance in fly testis. RNAi-mediated reduction of DBHD suppresses the GSC overproliferation phenotype caused by overexpression of the JAK/STAT ligand unpaired (upd) or the Dpp pathway, placing DBHD downstream or in parallel of JAK/STAT and Dpp signaling in GSC regulation. RNAi knockdown, genetic epistasis with JAK/STAT and Dpp pathway components, germline stem cell counting in fly testis Oncogene Medium 16636660
2019 AMPK promotes expression of the FLCN tumor suppressor gene through activation of TFEB independently of mTOR. AMPK-induced FLCN expression is abolished in cells lacking TFEB/TFE3, and mutation of the putative TFEB-binding site in the FLCN promoter abrogates promoter activity, defining an AMPK-TFEB-FLCN transcriptional axis. Transcriptomic profiling, AMPK-deficient MEFs, pharmacological AMPK activators, TFEB/TFE3 double KO, FLCN promoter-luciferase reporter assay with TFEB site mutation, zebrafish exercise model FASEB journal Medium 31404503
2020 FLCN loss in hematopoietic cells disrupts a FLCN-TFE3 feedback loop: TFE3 normally transcriptionally activates FLCN expression, and loss of FLCN amplifies TFE3 activity. TFE3 stimulates glycogenesis by promoting expression of glycogenesis genes (Gys1, Gyg). TFE3 deletion in Flcn-KO mice reduces phagocyte expansion and lysosomal storage disorder-like phenotypes. Hematopoietic-specific Flcn KO mice, Tfe3 co-deletion epistasis, transcriptional target analysis (ChIP/gene expression), glycogen accumulation assays, histological analysis Cell reports Medium 32049013
2020 Genetic deficiency of Folliculin in mice causes misconnection of blood and lymphatic vessels due to ectopic expression of Prox1 in venous endothelial cells. Mechanistically, FLCN loss leads to nuclear translocation of TFE3, which binds a regulatory element of the Prox1 gene to enhance its venous expression. Endothelial-specific FLCN KO mice, TFE3 nuclear localization by immunofluorescence, ChIP assay for TFE3 binding to Prox1 regulatory element, Prox1 expression analysis, vascular anatomy analysis in mice and humans Nature communications High 33298956
2016 FLCN maintains the leucine level within lysosomes to stimulate mTORC1. FLCN suppression reduces lysosomal leucine content and mTORC1 activity; both effects are reversed by high leucine supplementation but not other amino acids. FLCN exerts this function by inhibiting accumulation of the amino acid transporter PAT1 on the lysosome surface. FLCN knockdown/overexpression in HEK293 cells, lysosomal amino acid measurement, mTORC1 activity assay (S6K phosphorylation), PAT1 localization by immunofluorescence, leucine rescue experiments PloS one Medium 27280402
2018 FLCN interacts with Rab11A through its C-terminal DENN-like domain. FLCN promotes loading of the amino acid transporter PAT1 onto Rab11A vesicles for recycling to the plasma membrane, preventing PAT1 accumulation on lysosomes and maintaining lysosomal amino acid levels for mTORC1 activation. In vitro GEF activity assay does not support direct FLCN-mediated modification of Rab11A nucleotide state. Co-immunoprecipitation, domain-mapping pulldown, PAT1 localization by immunofluorescence, mTORC1 activity assay, in vitro GEF assay (negative result for direct GEF activity on Rab11A), siRNA knockdown Journal of cell science Medium 30446510
2021 FLCN promotes Rab11A binding with transferrin receptor 1 (TfR1), which is required for TfR1 recycling between cell surface and cytoplasm. Loss of FLCN attenuates Rab11A-TfR1 interaction, delays TfR1 recycling, causes iron deficiency, and induces HIF activity. Iron supplementation reverses the HIF activation, and iron-rich diet rescues BHD phenotypes in Drosophila. Co-immunoprecipitation (Rab11A-TfR1), TfR1 recycling assay, HIF activity reporter, iron measurement, siRNA knockdown, Drosophila BHD model with dietary iron rescue The Journal of biological chemistry Medium 33609526
2015 FLCN-null cells exhibit dysregulated cofilin de/phosphorylation pathways. SSH2 serine phosphatase knockdown specifically induces Caspase3/7-dependent apoptosis in FLCN-deficient cells but not in isogenic FLCN-expressing cells, identifying a synthetic lethal interaction between FLCN loss and SSH2. siRNA library screening, Caspase3/7 activity assay, cell cycle analysis, SSH1/2/3 expression measurement, FLCN isogenic cell line comparison Oncogene Medium 23416984
2019 Loss of FLCN in human renal tubular epithelial cells activates TFE3 and upregulates its E-box targets RRAGD and GPNMB without modifying mTORC1 activity. FLCN loss or loss of its binding partners FNIP1/FNIP2 induces a non-canonical interferon response independently of interferon, involving STAT2 recruitment to chromatin and slowed cellular proliferation. FLCN/FNIP1/FNIP2 CRISPR knockout in RPTEC/TERT1 cells, RNA-seq, ChIP for STAT2, mTORC1 activity assays, TFE3 target gene expression, proliferation assays eLife Medium 33459596
2019 Loss of FLCN inhibits canonical WNT signaling via TFE3. FLCN deficiency decreases expression of Wnt2, Wnt7b, TCF4, LEF1, BCL9, AXIN2, and BMP4. Constitutively active β-catenin only partially rescues decreased WNT activity, whereas silencing TFE3 completely reverses the WNT activity deficit in FLCN-deficient cells, placing TFE3 as a key mediator of FLCN-dependent WNT regulation. Flcn inactivation in MEFs and human fetal lung fibroblasts, RNA-seq, TCF/LEF luciferase reporter assay, TFE3 siRNA epistasis, constitutively active β-catenin rescue Human molecular genetics Medium 31272105
2015 FLCN is a novel modifier of TDP-43 cytoplasmic translocation and aggregation. FLCN directly interacts with TDP-43 through FLCN amino acids 202-299 and the RNA-recognition motif domains of TDP-43. Both exogenous and endogenous FLCN are required for TDP-43 cytoplasmic accumulation, protein aggregation, and stress granule formation. Co-immunoprecipitation, domain-mapping truncation assays, siRNA knockdown, overexpression, immunofluorescence for TDP-43 localization and aggregation, stress granule assay Human molecular genetics Medium 26516189
2023 AKT1 phosphorylates FLCN at a conserved site (Ser62) in an insulin-responsive manner. mTORC2-AKT1 is recruited to lysosomes by RagD, and this lysosomal RagD-mTORC2-AKT1 recruitment is an essential step for insulin-stimulated FLCN phosphorylation. FLCN phosphorylation inhibits RagC GAP activity and is required for insulin-induced mTORC1 activation and promotes tumor growth in an mTORC1-dependent manner. In vitro kinase assay (AKT1 phosphorylation of FLCN), lysosomal fractionation, RagD mutant studies, mTORC1 activity assay, FLCN phospho-site mutagenesis, xenograft tumor model Advanced science Medium 37083230
2021 Loss of hepatic FLCN activates TFEB and TFE3, promoting autophagy, reducing triglyceride accumulation, fibrosis, and inflammation in a methionine- and choline-deficient diet liver disease model. Liver-specific FLCN KO mice, TFEB/TFE3 nuclear localization assay, autophagic flux measurement, lipid accumulation assay, fibrosis scoring, inflammatory marker assessment Scientific reports Medium 34711912
2017 FLCN missense mutants H255Y and K508R promote aberrant kidney cell proliferation. H255Y mutant transgene expression fails to rescue the multi-cystic kidney phenotype of Flcn-deficient mice. K508R mutant transgene partially rescues the phenotype in full KO mice but induces multi-cystic kidneys and cardiac hypertrophy in heterozygous KO mice, suggesting dominant negative activity of K508R on wild-type FLCN. BAC recombineering transgenic mice, Flcn-KO kidney phenotype rescue assay, histological analysis, cardiac phenotyping Human molecular genetics Medium 28007907
2017 FNIP2 protein stability is regulated by SCFβ-TRCP E3 ubiquitin ligase and Casein Kinase 1 (CK1) in a nutrition-dependent manner. Degradation of FNIP2 leads to lysosomal dissociation of FLCN and subsequent lysosomal association of mTOR, promoting renal cancer cell proliferation. Proteasome inhibitor experiments, β-TRCP and CK1 inhibition/knockdown, ubiquitination assays, lysosomal fractionation for FLCN and mTOR localization, proliferation assays Oncotarget Medium 28039480
2023 PRDM10 directly binds a regulatory motif in the FLCN promoter and controls FLCN transcription. The PRDM10 Cys677Tyr variant loses affinity for this FLCN promoter element, abrogating FLCN mRNA and protein levels in human cells. DNA binding assay for PRDM10 at FLCN promoter, promoter reporter assay, inducible PRDM10 Cys677Tyr overexpression, RNA-seq, FLCN protein quantification Human molecular genetics Medium 36440963

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proceedings of the National Academy of Sciences of the United States of America 397 17028174
2008 BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports. Journal of medical genetics 362 18234728
2005 Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome. American journal of human genetics 305 15852235
2009 Homozygous loss of BHD causes early embryonic lethality and kidney tumor development with activation of mTORC1 and mTORC2. Proceedings of the National Academy of Sciences of the United States of America 192 19850877
2005 High frequency of somatic frameshift BHD gene mutations in Birt-Hogg-Dubé-associated renal tumors. Journal of the National Cancer Institute 185 15956655
2010 Inactivation of the FLCN tumor suppressor gene induces TFE3 transcriptional activity by increasing its nuclear localization. PloS one 144 21209915
2017 FLCN: The causative gene for Birt-Hogg-Dubé syndrome. Gene 135 28970150
2011 Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families. British journal of cancer 129 22146830
2003 A mutation in the canine BHD gene is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in the German Shepherd dog. Human molecular genetics 120 14532326
2008 Deficiency of FLCN in mouse kidney led to development of polycystic kidneys and renal neoplasia. PloS one 113 18974783
2016 The tumor suppressor FLCN mediates an alternate mTOR pathway to regulate browning of adipose tissue. Genes & development 111 27913603
2019 Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex. Cell 109 31704029
2021 GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis. Science advances 106 34597140
2005 A 4-bp deletion in the Birt-Hogg-Dubé gene (FLCN) causes dominantly inherited spontaneous pneumothorax. American journal of human genetics 97 15657874
2019 The Transcription Factors TFEB and TFE3 Link the FLCN-AMPK Signaling Axis to Innate Immune Response and Pathogen Resistance. Cell reports 94 30917316
2003 Inactivation of BHD in sporadic renal tumors. Cancer research 94 12907635
2016 Chronic AMPK activation via loss of FLCN induces functional beige adipose tissue through PGC-1α/ERRα. Genes & development 90 27151976
2010 A new locus-specific database (LSDB) for mutations in the folliculin (FLCN) gene. Human mutation 88 19802896
2012 Regulation of mitochondrial oxidative metabolism by tumor suppressor FLCN. Journal of the National Cancer Institute 78 23150719
2010 Investigation of the Birt-Hogg-Dube tumour suppressor gene (FLCN) in familial and sporadic colorectal cancer. Journal of medical genetics 73 20522427
2010 Tumor suppressor FLCN inhibits tumorigenesis of a FLCN-null renal cancer cell line and regulates expression of key molecules in TGF-beta signaling. Molecular cancer 73 20573232
2004 A germ-line insertion in the Birt-Hogg-Dubé (BHD) gene gives rise to the Nihon rat model of inherited renal cancer. Proceedings of the National Academy of Sciences of the United States of America 69 14769940
2008 Mutation analysis of the FLCN gene in Chinese patients with sporadic and familial isolated primary spontaneous pneumothorax. Clinical genetics 65 18505456
2006 Novel mutations in the BHD gene and absence of loss of heterozygosity in fibrofolliculomas of Birt-Hogg-Dubé patients. The Journal of investigative dermatology 65 17124507
2014 FLCN, a novel autophagy component, interacts with GABARAP and is regulated by ULK1 phosphorylation. Autophagy 62 25126726
2018 GATOR1-dependent recruitment of FLCN-FNIP to lysosomes coordinates Rag GTPase heterodimer nucleotide status in response to amino acids. The Journal of cell biology 58 29848618
2006 Mutations in BHD and TP53 genes, but not in HNF1beta gene, in a large series of sporadic chromophobe renal cell carcinoma. British journal of cancer 58 17133269
2003 Analysis of the Birt-Hogg-Dubé (BHD) tumour suppressor gene in sporadic renal cell carcinoma and colorectal cancer. Journal of medical genetics 58 14627671
2019 AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 56 31404503
2008 Familial non-VHL clear cell (conventional) renal cell carcinoma: clinical features, segregation analysis, and mutation analysis of FLCN. Clinical cancer research : an official journal of the American Association for Cancer Research 51 18794106
2014 Folliculin (Flcn) inactivation leads to murine cardiac hypertrophy through mTORC1 deregulation. Human molecular genetics 50 24908670
2011 Identification of intragenic deletions and duplication in the FLCN gene in Birt-Hogg-Dubé syndrome. Genes, chromosomes & cancer 47 21412933
2015 FLCN and AMPK Confer Resistance to Hyperosmotic Stress via Remodeling of Glycogen Stores. PLoS genetics 46 26439621
2006 The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance. Oncogene 43 16636660
2017 Dihydromyricetin prevents obesity-induced slow-twitch-fiber reduction partially via FLCN/FNIP1/AMPK pathway. Biochimica et biophysica acta. Molecular basis of disease 36 28363698
2011 Constitutional FLCN mutations in patients with suspected Birt-Hogg-Dubé syndrome ascertained for non-cutaneous manifestations. Clinical genetics 34 20618353
2011 Birt Hogg-Dubé syndrome-associated FLCN mutations disrupt protein stability. Human mutation 33 21538689
2022 Structural basis for FLCN RagC GAP activation in MiT-TFE substrate-selective mTORC1 regulation. Science advances 31 36103527
2017 The ABCs of BHD: An In-Depth Review of Birt-Hogg-Dubé Syndrome. AJR. American journal of roentgenology 31 28981362
2006 Natural history of the Nihon (Bhd gene mutant) rat, a novel model for human Birt-Hogg-Dubé syndrome. Virchows Archiv : an international journal of pathology 25 16447066
2015 Disruption of tubular Flcn expression as a mouse model for renal tumor induction. Kidney international 23 26083655
2011 Familial multiple discoid fibromas: a look-alike of Birt-Hogg-Dubé syndrome not linked to the FLCN locus. Journal of the American Academy of Dermatology 22 21794948
2009 Regulation of folliculin (the BHD gene product) phosphorylation by Tsc2-mTOR pathway. Biochemical and biophysical research communications 22 19695222
2020 Blood and lymphatic systems are segregated by the FLCN tumor suppressor. Nature communications 21 33298956
2008 Birt-Hogg-Dubé (BHD) syndrome: report of two novel germline mutations in the folliculin (FLCN) gene. European journal of dermatology : EJD 21 18573707
2016 FLCN Maintains the Leucine Level in Lysosome to Stimulate mTORC1. PloS one 20 27280402
2021 Loss of FLCN-FNIP1/2 induces a non-canonical interferon response in human renal tubular epithelial cells. eLife 19 33459596
2019 Loss of FLCN inhibits canonical WNT signaling via TFE3. Human molecular genetics 19 31272105
2023 Comparative analyses define differences between BHD-associated renal tumour and sporadic chromophobe renal cell carcinoma. EBioMedicine 18 37182269
2020 A FLCN-TFE3 Feedback Loop Prevents Excessive Glycogenesis and Phagocyte Activation by Regulating Lysosome Activity. Cell reports 18 32049013
2017 H255Y and K508R missense mutations in tumour suppressor folliculin (FLCN) promote kidney cell proliferation. Human molecular genetics 18 28007907
2013 A de novo FLCN mutation in a patient with spontaneous pneumothorax and renal cancer; a clinical and molecular evaluation. Familial cancer 18 23264078
2011 Activation of AMP-activated protein kinase by MAPO1 and FLCN induces apoptosis triggered by alkylated base mismatch in DNA. DNA repair 18 22209521
2023 PRDM10 directs FLCN expression in a novel disorder overlapping with Birt-Hogg-Dubé syndrome and familial lipomatosis. Human molecular genetics 17 36440963
2021 A systematic review assessing the existence of pneumothorax-only variants of FLCN. Implications for lifelong surveillance of renal tumours. European journal of human genetics : EJHG 17 34267338
2018 BHD-associated kidney cancer exhibits unique molecular characteristics and a wide variety of variants in chromatin remodeling genes. Human molecular genetics 17 29767721
2016 Case Report of Birt-Hogg-Dubé Syndrome: Germline Mutations of FLCN Detected in Patients With Renal Cancer and Thyroid Cancer. Medicine 17 27258496
2015 FLCN intragenic deletions in Chinese familial primary spontaneous pneumothorax. American journal of medical genetics. Part A 17 25807935
2015 Folliculin, a tumor suppressor associated with Birt-Hogg-Dubé (BHD) syndrome, is a novel modifier of TDP-43 cytoplasmic translocation and aggregation. Human molecular genetics 16 26516189
2012 Novel in-frame deletion mutation in FLCN gene in a Korean family with recurrent primary spontaneous pneumothorax. Gene 16 22446046
2004 Natural history of the Nihon rat model of BHD. Current molecular medicine 16 15579036
2019 Genotypic characteristics of Chinese patients with BHD syndrome and functional analysis of FLCN variants. Orphanet journal of rare diseases 15 31615547
2016 Bilateral renal tumors in an adult man with Smith-Magenis syndrome: The role of the FLCN gene. European journal of medical genetics 15 27633572
2016 Genetic screening of the FLCN gene identify six novel variants and a Danish founder mutation. Journal of human genetics 15 27734835
2018 Early onset renal cell carcinoma in an adolescent girl with germline FLCN exon 5 deletion. Familial cancer 14 28623476
2017 Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN complex localization and promotes renal cancer progression. Oncotarget 14 28039480
2011 The impact of germline BHD mutation on histological concordance and clinical treatment of patients with bilateral renal masses and known unilateral oncocytoma. The Journal of urology 14 21496834
2015 Flcn-deficient renal cells are tumorigenic and sensitive to mTOR suppression. Oncotarget 13 26418749
2018 Birt-Hogg-Dubé syndrome in two Chinese families with mutations in the FLCN gene. BMC medical genetics 12 29357828
2017 Characterization of a splice-site mutation in the tumor suppressor gene FLCN associated with renal cancer. BMC medical genetics 12 28499369
2023 Germline- and Somatic-Inactivating FLCN Variants in Parathyroid Cancer and Atypical Parathyroid Tumors. The Journal of clinical endocrinology and metabolism 11 36935552
2018 Splice-site mutation causing partial retention of intron in the FLCN gene in Birt-Hogg-Dubé syndrome: a case report. BMC medical genomics 11 29720200
2018 FLCN is a novel Rab11A-interacting protein that is involved in the Rab11A-mediated recycling transport. Journal of cell science 11 30446510
2021 Loss of hepatic Flcn protects against fibrosis and inflammation by activating autophagy pathways. Scientific reports 10 34711912
2011 FLCN gene-mutated renal cell neoplasms: mother and daughter cases with a novel germline mutation. International journal of urology : official journal of the Japanese Urological Association 10 22211584
2009 Novel intronic germline FLCN gene mutation in a patient with multiple ipsilateral renal neoplasms. Human pathology 10 19733897
2006 Transgenic rescue from embryonic lethality and renal carcinogenesis in the Nihon rat model by introduction of a wild-type Bhd gene. Oncogene 10 16369488
2023 Role of FLCN Phosphorylation in Insulin-Mediated mTORC1 Activation and Tumorigenesis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 37083230
2023 Exons 1-3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome. Orphanet journal of rare diseases 9 37170274
2009 Loss of heterozygosity at the FLCN locus in early renal cystic lesions in dogs with renal cystadenocarcinoma and nodular dermatofibrosis. Mammalian genome : official journal of the International Mammalian Genome Society 9 19387735
2008 Second hits in the FLCN gene in a hereditary renal cancer syndrome in dogs. Mammalian genome : official journal of the International Mammalian Genome Society 9 18219524
2024 The Prevalence and Radiologic Features of Renal Cancers Associated with FLCN, BAP1, SDH, and MET Germline Mutations. Radiology. Imaging cancer 8 38456787
2024 Integrated systems pharmacology, molecular docking, and MD simulations investigation elucidating the therapeutic mechanisms of BHD in Alzheimer's disease treatment. Metabolic brain disease 8 39556154
2020 FLCN-regulated miRNAs suppressed reparative response in cells and pulmonary lesions of Birt-Hogg-Dubé syndrome. Thorax 8 32184379
2020 Quantitative genetic screening reveals a Ragulator-FLCN feedback loop that regulates the mTORC1 pathway. Science signaling 8 32934076
2017 Birt-Hogg-Dubé syndrome: a literature review and case study of a Chinese woman presenting a novel FLCN mutation. BMC pulmonary medicine 8 28222720
2023 FLCN-Driven Functional Adrenal Cortical Carcinoma with High Mitotic Tumor Grade: Extending the Endocrine Manifestations of Birt-Hogg-Dubé Syndrome. Endocrine pathology 7 36701047
2022 A retrospective two centre study of Birt-Hogg-Dubé syndrome reveals a pathogenic founder mutation in FLCN in the Swedish population. PloS one 7 35176117
2019 FLCN alteration drives metabolic reprogramming towards nucleotide synthesis and cyst formation in salivary gland. Biochemical and biophysical research communications 7 31806376
2013 Knockdown of Slingshot 2 (SSH2) serine phosphatase induces Caspase3 activation in human carcinoma cell lines with the loss of the Birt-Hogg-Dubé tumour suppressor gene (FLCN). Oncogene 7 23416984
2007 Postoperative fibromatosis-type fibromas in the Bhd gene mutant (Nihon) rat. Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie 7 18036795
2022 Minigene Assay as an Effective Molecular Diagnostic Strategy in Determining the Pathogenicity of Noncanonical Splice-Site Variants in FLCN. The Journal of molecular diagnostics : JMD 6 36410626
2021 FLCN regulates transferrin receptor 1 transport and iron homeostasis. The Journal of biological chemistry 6 33609526
2021 A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review. Frontiers in genetics 6 33927747
2019 Unilateral renal cystadenocarcinoma and nodular dermatofibrosis in a mixed-breed dog carrying a FLCN gene mutation. Veterinary dermatology 6 30672048
2017 Birt-Hogg-Dube Syndrome with a Novel Mutation in the FLCN Gene. Genetic testing and molecular biomarkers 6 28805452
2016 Birt-Hogg-Dubé syndrome: novel FLCN frameshift deletion in daughter and father with renal cell carcinomas. Familial cancer 6 26342594
2017 Novel germline mutations in FLCN gene identified in two Chinese patients with Birt-Hogg-Dubé syndrome. Chinese journal of cancer 5 28069055
2016 Are lung cysts in renal cell cancer (RCC) patients an indication for FLCN mutation analysis? Familial cancer 5 26603437
2016 Novel folliculin (FLCN) mutation and familial spontaneous pneumothorax. QJM : monthly journal of the Association of Physicians 5 27486260

Missed literature

Know a paper Affinage missed for FLCN? Flag it for the maintainers and the community.

No submissions yet.