FLCN Gene (Folliculin)
Tumor suppressor gene associated with Birt-Hogg-Dubé syndrome and renal cell carcinoma
Gene Information Card
| Symbol | FLCN |
|---|---|
| Full Name | Folliculin |
| Gene Type | Protein coding |
| Chromosomal Location | 17p11.2 |
| NCBI Gene ID | 201163 ncbi.nlm.nih.gov/gene/201163 |
| Ensembl ID | ENSG00000139567 |
| UniProt ID | Q8NFG4 |
| OMIM ID | 607273 |
| HGNC ID | 27310 |
| Aliases | BHD, FLCL, MGC17998 |
Description
The FLCN gene encodes folliculin, a tumor suppressor protein involved in mTOR signaling and cellular energy sensing. Germline mutations in FLCN cause Birt-Hogg-Dubé syndrome (BHD), characterized by fibrofolliculomas, lung cysts, and increased risk of renal cell carcinoma. The protein interacts with FNIP1 and FNIP2 to regulate AMPK and mTOR pathways.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Birt-Hogg-Dubé syndrome | Loss-of-function mutations in FLCN disrupt folliculin-mediated mTOR regulation, leading to benign skin tumors, lung cysts, and renal tumors. | OMIM #135150 |
| Renal cell carcinoma (chromophobe, oncocytic, clear cell) | Biallelic inactivation of FLCN in kidney cells promotes uncontrolled cell growth via mTOR pathway activation. | ClinVar, COSMIC |
| Pneumothorax (spontaneous) | Lung cysts in BHD patients result from FLCN deficiency in alveolar epithelial cells, causing cyst formation and rupture. | OMIM #135150 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Lung | 8.3 | Medium |
| Skin | 6.1 | Low |
| Prostate | 9.7 | Medium |
| Testis | 15.2 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.0 | Embryonic kidney cells |
| A549 | 7.5 | Lung carcinoma cells |
| HeLa | 6.8 | Cervical carcinoma cells |
| MCF7 | 5.2 | Breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1285dupC (p.His429Profs*27) | Frameshift | Common in BHD | Loss of function |
| c.1733delC (p.Pro578Leufs*21) | Frameshift | Recurrent | Loss of function |
| c.469_471del (p.Phe157del) | In-frame deletion | Rare | Loss of function |
| c.610G>A (p.Gly204Arg) | Missense | Rare | Likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Majority of FLCN mutations are loss-of-function (frameshift, nonsense, splice-site), leading to truncated or absent folliculin protein and mTOR pathway dysregulation.
Gain of Function (GOF)
No gain-of-function mutations reported in FLCN.
Dominant Negative (DN)
No dominant-negative mutations reported; BHD follows autosomal dominant inheritance with second-hit somatic inactivation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• mTOR signaling pathway (Reactome: R-HSA-165159)
• AMPK signaling (KEGG: hsa04152)
• Energy sensing and metabolism (UniProt)
Protein Summary
Folliculin is a 579-amino acid protein with a DENN domain and a C-terminal coiled-coil region. It forms complexes with FNIP1/FNIP2 and interacts with AMPK and mTORC1/2 to regulate cell growth, metabolism, and autophagy. Loss of folliculin leads to constitutive mTOR activation and tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FLCN Knockout HEK293 Cell Line | EDJ-KQ1150 | Human | 201163 | Details Get a Quote |
| FLCN Knockout HCT 116 Cell Line | EDJ-KQ17925 | Human | 201163 | Details Get a Quote |
| FLCN Knockout A-549 Cell Line | EDJ-KQ20377 | Human | 201163 | Details Get a Quote |
| FLCN Knockout HeLa Cell Line | EDJ-KQ20378 | Human | 201163 | Details Get a Quote |
| FLCN (c.1177-165C>T )Point Mutation in HAP1 Cell Line | EDC03491 | Human | 201163 | Details Get a Quote |
| FLCN (c.396+59T>C )Point Mutation in HAP1 Cell Line | EDC03492 | Human | 201163 | Details Get a Quote |
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