Birt-Hogg-Dube syndrome: genes and variants
Birt-Hogg-Dube syndrome is linked to 1 analyzed protein (FLCN). 11 DNA variants are known to cause it; 798 more are uncertain, and 2 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: Birt-Hogg-Dube syndrome 1; Birt-Hogg-Dubé syndrome
Genes linked to Birt-Hogg-Dube syndrome
FLCN: Folliculin
It couples lysosomal nutrient sensing to AMPK, mTOR, and related pathways and helps regulate cell growth and metabolism. Germline loss-of-function variants cause Birt-Hogg-Dube syndrome with fibrofolliculomas, pulmonary cysts, pneumothorax, and renal-tumor predisposition.
11 disease-causing and 798 uncertain variants in FLCN are linked to Birt-Hogg-Dube syndrome.
Known disease-causing variants in Birt-Hogg-Dube syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| FLCN M1I | 1 | Disease-causing (★★) | |
| FLCN M1T | 1 | Disease-causing (★★) | |
| FLCN M1V | 1 | Disease-causing (★★) | |
| FLCN C11W | 11 | Disease-causing (★★) | |
| FLCN E434Q | 434 | cDENN FLCN/SMCR8-type | Disease-causing (★★) |
| FLCN E434K | 434 | cDENN FLCN/SMCR8-type | Disease-causing (★) |
| FLCN H255Y | 255 | Disease-causing (★) | |
| FLCN K462R | 462 | cDENN FLCN/SMCR8-type | Disease-causing (★) |
| FLCN L536P | 536 | dDENN FLCN/SMCR8-type | Disease-causing |
| FLCN T22K | 22 | Disease-causing | |
| FLCN L518P | 518 | dDENN FLCN/SMCR8-type | Disease-causing |
Uncertain variants in Birt-Hogg-Dube syndrome that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| FLCN H255P | 255 | Conflicting reports (★) | +7: H255Y at the same position is pathogenic; seen in 6.6e-06 of gnomAD DNA copies; REVEL 0.950 | |
| FLCN T22M | 22 | Conflicting reports (★) | +6: T22K at the same position is pathogenic; REVEL 0.945 |
Which prediction tools work for Birt-Hogg-Dube syndrome
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- PolyPhen-2: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Diseases related to Birt-Hogg-Dube syndrome
- Ovarian cancer, also linked to FLCN
- Colorectal cancer, also linked to FLCN
- Nonpapillary renal cell carcinoma, also linked to FLCN
Frequently asked questions
Which genes are linked to Birt-Hogg-Dube syndrome?
In CATVariant, Birt-Hogg-Dube syndrome is linked to 1 analyzed protein: FLCN (Folliculin).
How many genetic variants are linked to Birt-Hogg-Dube syndrome?
847 variants: 11 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 798 are of uncertain significance or have conflicting reports.
Which uncertain variants in Birt-Hogg-Dube syndrome look disease-causing?
2 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example FLCN H255P and FLCN T22M. These are leads for expert review, not diagnoses.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
Download every variant as CSV · Browse all diseases · Methods · About the Center