FLCN report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0050673Biological processepithelial cell proliferation
GO_0097009Biological processenergy homeostasis
GO_0030511Biological processpositive regulation of transforming growth factor beta receptor signaling pathway
GO_0035024Biological processnegative regulation of Rho protein signal transduction
GO_0007043Biological processcell-cell junction assembly
GO_2000973Biological processregulation of pro-B cell differentiation
GO_0030097Biological processhemopoiesis
GO_0001701Biological processin utero embryonic development
GO_0046578Biological processregulation of Ras protein signal transduction
GO_0031929Biological processTOR signaling
GO_0032007Biological processnegative regulation of TOR signaling
GO_0070373Biological processnegative regulation of ERK1 and ERK2 cascade
GO_1901874Biological processnegative regulation of post-translational protein modification
GO_2001244Biological processpositive regulation of intrinsic apoptotic signaling pathway
GO_0072111Biological processcell proliferation involved in kidney development
GO_0000122Biological processnegative regulation of transcription by RNA polymerase II
GO_0009267Biological processcellular response to starvation
GO_0050680Biological processnegative regulation of epithelial cell proliferation
GO_0051898Biological processnegative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO_0045820Biological processnegative regulation of glycolytic process
GO_1905672Biological processnegative regulation of lysosome organization
GO_0097193Biological processintrinsic apoptotic signaling pathway
GO_0070371Biological processERK1 and ERK2 cascade
GO_0035556Biological processintracellular signal transduction
GO_0010508Biological processpositive regulation of autophagy
GO_0032418Biological processlysosome localization
GO_0034198Biological processcellular response to amino acid starvation
GO_0043491Biological processphosphatidylinositol 3-kinase/protein kinase B signal transduction
GO_1901723Biological processnegative regulation of cell proliferation involved in kidney development
GO_1903444Biological processnegative regulation of brown fat cell differentiation
GO_1904263Biological processpositive regulation of TORC1 signaling
GO_0007179Biological processtransforming growth factor beta receptor signaling pathway
GO_0043065Biological processpositive regulation of apoptotic process
GO_0032006Biological processregulation of TOR signaling
GO_0032008Biological processpositive regulation of TOR signaling
GO_0120163Biological processnegative regulation of cold-induced thermogenesis
GO_0030496Cellular componentmidbody
GO_0005886Cellular componentplasma membrane
GO_0072686Cellular componentmitotic spindle
GO_0005813Cellular componentcentrosome
GO_0005764Cellular componentlysosome
GO_0044291Cellular componentcell-cell contact zone
GO_0005929Cellular componentcilium
GO_0005829Cellular componentcytosol
GO_0005737Cellular componentcytoplasm
GO_1990877Cellular componentFNIP-folliculin RagC/D GAP
GO_0005765Cellular componentlysosomal membrane
GO_0005634Cellular componentnucleus
GO_0019899Molecular functionenzyme binding
GO_0004857Molecular functionenzyme inhibitor activity
GO_0044877Molecular functionprotein-containing complex binding
GO_0005096Molecular functionGTPase activator activity
GO_0005515Molecular functionprotein binding

IV. Literature review

[source]
Gene nameFLCN
Protein nameFolliculin isoform 1 (Folliculin, isoform CRA_a)
Folliculin isoform 3
Folliculin (BHD skin lesion fibrofolliculoma protein) (Birt-Hogg-Dube syndrome protein)
Folliculin
SynonymshCG_1775424
BHD
DescriptionFUNCTION: 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 (By similarity). 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 (By similarity). 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 . .

AccessionsA0A0S2Z5Y7
A0A0S2Z643
J3QQZ7
C9J4C4
ENST00000389169.9 [Q8NFG4-2]
ENST00000417064.1
ENST00000285071.9 [Q8NFG4-1]
ENST00000461699.1
Q8NFG4