FLCN
FLCN (Folliculin) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Renal cell carcinoma, Colorectal cancer, Gastric & gastro-oesophageal junction cancer and 3 more.
Overview
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 signalling 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.
CIViC holds 3 clinical evidence items and 0 assertions across 3 variants, naming Everolimus and Sirolimus. Open Targets scores its association with cancer at 0.84 (direct and indirect evidence; datatypes genetic literature 0.75, affected pathway 0.76, literature 0.67, genetic association 0.75, somatic mutation 0.87, animal model 0.62). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Lung Adenocarcinoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · FLCN (Folliculin) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Renal cell carcinoma, Colorectal cancer, Gastric & gastro-oesophageal junction cancer and 3 more.
- 1 · What it is
FLCN (Folliculin) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Renal cell carcinoma, Colorectal cancer, Gastric & gastro-oesophageal junction cancer and 3 more.
- 2 · What goes wrong in cancer
Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis.
- 3 · How drugs use it
No product in this corpus aims at FLCN yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:27310 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q8NFG4 (protein name, function text, keywords and locations (REST API)); CIViC gene FLCN (3 evidence items, 0 assertions, 3 variants; diseases: Renal Cell Carcinoma, Renal Carcinoma, Papillary Renal Cell Carcinoma (GraphQL API, CC0)); Open Targets ENSG00000154803 (association with cancer (MONDO_0004992) 0.84; per-cancer scores at or above 0.5: colorectal cancer 0.73, gastric cancer 0.51, renal cell carcinoma 0.74, skin cancer 0.50 (GraphQL API, CC0)); IntOGen FLCN (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
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 signalling 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 maximises nuclear translocation of TFEB and TFE3. Location: Lysosome membrane; Cytoplasm, cytosol; Cell projection, cilium; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome (UniProt). Locus 17p11.2 (HGNC).
- Renal cell carcinoma: Open Targets association 0.74 with renal cell carcinoma (MONDO_0005086); CIViC evidence names this disease
- Colorectal cancer: Open Targets association 0.73 with colorectal cancer (MONDO_0005575)
- Gastric & gastro-oesophageal junction cancer: Open Targets association 0.51 with gastric cancer (MONDO_0001056)
- Skin cancer: Open Targets association 0.50 with skin cancer (MONDO_0002898)
- Papillary renal cell carcinoma: CIViC evidence names this disease
- Non-small-cell lung cancer: IntOGen driver in 1 cohort (LUAD)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 2 therapies; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 3 clinical evidence items on its variants. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Renal Carcinoma.
Latest papers
topQuery for this target: (TITLE:"FLCN" OR ABSTRACT:"FLCN" OR TITLE:"folliculin" OR ABSTRACT:"folliculin" OR TITLE:"Folliculin" OR ABSTRACT:"Folliculin" OR TITLE:"MGC17998" OR ABSTRACT:"MGC17998" OR TITLE:"MGC23445" OR ABSTRACT:"MGC23445" OR TITLE:"DENND8B" OR ABSTRACT:"DENND8B") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about FLCN, not a curated reading list.
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