# FLCN

Source: https://onco.cc/targets/flcn/  
OnCo record `flcn` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: folliculin; Folliculin; MGC17998; MGC23445; DENND8B
- Tags: cancer-genes-wave
- Symbol: FLCN
- Class: tumor-suppressor
- 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).
- Where found: 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

- 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.

## Sources

- HGNC HGNC:27310: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:27310
- UniProt Q8NFG4: https://www.uniprot.org/uniprotkb/Q8NFG4/entry
- NCBI Gene 201163: https://www.ncbi.nlm.nih.gov/gene/201163
- Ensembl ENSG00000154803: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000154803

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Papillary renal cell carcinoma](https://onco.cc/cancers/papillary-rcc/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)

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JSON: https://onco.cc/api/v1/entities/flcn.json