FLCN

Chr 17AD

folliculin

Also known as: BHD, DENND8B, FLCL

NCBI Gene: 201163ENSG00000154803UniProt: Q8NFG4OMIM: 607273

Folliculin is a GTPase-activating protein that regulates cellular response to amino acid availability through mTORC1 signaling and also inhibits glycolysis by binding to lactate dehydrogenase. Mutations cause Birt-Hogg-Dubé syndrome, an autosomal dominant condition characterized by fibrofolliculomas, renal tumors, lung cysts, and spontaneous pneumothorax. The gene is highly constrained against loss-of-function variants (LOEUF 0.388), reflecting its essential cellular functions.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.394 OMIM phenotypes
Clinical Summary— FLCN
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Gene-Disease Validity (ClinGen)
obsolete Birt-Hogg-Dube syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.79) — some intolerance to loss-of-function variants.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — FLCN
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.789
Z-score 3.94
OE 0.18 (0.10–0.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.13Z-score
OE missense 0.83 (0.75–0.92)
293 obs / 352.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.10–0.39)
0≤0.351.4
Missense OE0.83 (0.75–0.92)
0≤0.61.4
Synonymous OE1.10
0≤1.21.6
LoF obs/exp: 5 / 27.1Missense obs/exp: 293 / 352.7Syn Z: -0.92
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFLCN-related Birt-Hogg-Dube syndromeLOFAD
DN
0.3395th %ile
GOF
0.4480th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.39

Literature Evidence

LOFRenal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD familiesPMID:22146830

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

FLCN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Folliculin: A Regulator of Transcription Through AMPK and mTOR Signaling Pathways
Ramirez Reyes JMJ et al.·Front Cell Dev Biol
2021
Folliculin (FLCN) in Thyroid Tumors: Incidence, Significance, and Role as a Driver Gene and Secondary Alteration
Hassan FA et al.·Curr Oncol
2025
Clinic Examination and Gene Diagnosis for a Birt-Hogg-Dube Syndrome Family With a Novel flcn Frameshift Mutation Causing Nonsense-Mediated mRNA Degradation
Xu Y et al.·Hum Mutat
2025
Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors
van de Beek I et al.·Mol Genet Genomic Med
2022
First published report of the FLCN c.1222 C > T (p.Gln408Ter) variant in a Chinese family with Birt-Hogg-Dube syndrome and literature review
Huang S et al.·BMC Med Genomics
2026Review
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Renal tumors harboring FLCN mutations: Case series from clinical practice.
Ding CC et al.·Hum Pathol
2026Cohort
FLCN-mutated oncocytic tumor in the thyroid defines a biologically distinct subset characterized by metabolic remodeling and canonical oncogenic signaling suppression.
Kong W et al.·Virchows Arch
2026Functional
FLCN-Mutated Tumors in Smith-Magenis Syndrome: A Case Report of FLCN-Associated Pathogenesis.
Pichette É et al.·Int J Surg Pathol
2026Case report
Select updates in the pathology of kidney, testis, and penile cancer for 2026: Including FLCN-mutated (kidney) tumors, paratesticular mesothelial tumors, and TP53/HPV status in penile squamous cell carcinoma.
Tekin B et al.·Hum Pathol
2026
Phenotypic expansion of retinal abnormalities in folliculin (FLCN) variant-related pathology (Birt-Hogg-Dubé syndrome).
August AH et al.·Ophthalmic Genet
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients