{"entity":{"id":"flcn","kind":"target","name":"FLCN","aka":["folliculin","Folliculin","MGC17998","MGC23445","DENND8B"],"tldr":"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.","summary":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:27310","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:27310"},{"label":"UniProt Q8NFG4","url":"https://www.uniprot.org/uniprotkb/Q8NFG4/entry"},{"label":"NCBI Gene 201163","url":"https://www.ncbi.nlm.nih.gov/gene/201163"},{"label":"Ensembl ENSG00000154803","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000154803"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["rcc","colorectal","gastric","skin-cancer","papillary-rcc","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"FLCN","role":["drug-target","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:27310","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:27310","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q8NFG4","url":"https://www.uniprot.org/uniprotkb/Q8NFG4/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene FLCN","url":"https://civicdb.org/features/19959","note":"3 evidence items, 0 assertions, 3 variants; diseases: Renal Cell Carcinoma, Renal Carcinoma, Papillary Renal Cell Carcinoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000154803","url":"https://platform.opentargets.org/target/ENSG00000154803/associations","note":"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)"},{"label":"IntOGen FLCN","url":"https://www.intogen.org/search?gene=FLCN","note":"driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:27310","ensembl":"ENSG00000154803","uniprot":"Q8NFG4","entrez":"201163","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).","whereFound":["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)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/flcn/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"papillary-rcc","kind":"cancer","name":"Papillary renal cell carcinoma","route":"/cancers/papillary-rcc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}]}}