This gene is located within the Smith-Magenis syndrome region on chromosome 17. Mutations in this gene are associated with Birt-Hogg-Dube syndrome, which is characterized by fibrofolliculomas, renal tumors, lung cysts, and pneumothorax. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008] See more...

Aliases for FLCN Gene

Aliases for FLCN Gene

  • Folliculin 2 3 4 5
  • BHD Skin Lesion Fibrofolliculoma Protein 3 4
  • Birt-Hogg-Dube Syndrome Protein 3 4
  • BHD 3 4
  • DENND8B 3
  • FLCL 3

External Ids for FLCN Gene

Previous GeneCards Identifiers for FLCN Gene

  • GC17M017056
  • GC17M016868
  • GC17M017115

Summaries for FLCN Gene

Entrez Gene Summary for FLCN Gene

  • This gene is located within the Smith-Magenis syndrome region on chromosome 17. Mutations in this gene are associated with Birt-Hogg-Dube syndrome, which is characterized by fibrofolliculomas, renal tumors, lung cysts, and pneumothorax. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

CIViC Summary for FLCN Gene

GeneCards Summary for FLCN Gene

FLCN (Folliculin) is a Protein Coding gene. Diseases associated with FLCN include Pneumothorax, Primary Spontaneous and Birt-Hogg-Dube Syndrome. Among its related pathways are mTOR signaling pathway (KEGG) and Translational Control. An important paralog of this gene is ENSG00000264187.

UniProtKB/Swiss-Prot Summary for FLCN Gene

  • May be a tumor suppressor. May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. May regulate phosphorylation of RPS6KB1.

Additional gene information for FLCN Gene

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FLCN Gene

Genomics for FLCN Gene

GeneHancer (GH) Regulatory Elements for FLCN Gene

Promoters and enhancers for FLCN Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FLCN on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FLCN

Top Transcription factor binding sites by QIAGEN in the FLCN gene promoter:
  • AML1a
  • AP-2alpha
  • FOXJ2
  • FOXJ2 (long isoform)
  • GR
  • GR-alpha
  • MIF-1
  • Nkx2-5
  • p53

Genomic Locations for FLCN Gene

Genomic Locations for FLCN Gene
chr17:17,206,924-17,237,188
(GRCh38/hg38)
Size:
30,265 bases
Orientation:
Minus strand
chr17:17,115,526-17,140,502
(GRCh37/hg19)
Size:
24,977 bases
Orientation:
Minus strand

Genomic View for FLCN Gene

Genes around FLCN on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FLCN Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FLCN Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FLCN Gene

Proteins for FLCN Gene

  • Protein details for FLCN Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8NFG4-FLCN_HUMAN
    Recommended name:
    Folliculin
    Protein Accession:
    Q8NFG4
    Secondary Accessions:
    • A6NJJ8
    • Q6ZRX1
    • Q96BD2
    • Q96BE4

    Protein attributes for FLCN Gene

    Size:
    579 amino acids
    Molecular mass:
    64473 Da
    Quaternary structure:
    • Interacts (via C-terminus) with FNIP1 and FNIP2 (via C-terminus). This mediates indirect interaction with the PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-activated protein kinase (PubMed:17028174, PubMed:18403135, PubMed:18663353, PubMed:27353360). Interacts with HSP90AA1 in the presence of FNIP1. Interacts with HSP70, STUB1, CDC37, AHSA1, CCT2, STIP1, PTGES3 and PPP5C (PubMed:27353360).

    Three dimensional structures from OCA and Proteopedia for FLCN Gene

    Alternative splice isoforms for FLCN Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FLCN Gene

Post-translational modifications for FLCN Gene

  • Phosphorylated. Several different phosphorylated forms exist.
  • Ubiquitination at Lys206 and Lys559
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for FLCN Gene

Domains & Families for FLCN Gene

Gene Families for FLCN Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for FLCN Gene

Suggested Antigen Peptide Sequences for FLCN Gene

GenScript: Design optimal peptide antigens:
  • Birt-Hogg-Dube syndrome protein (FLCN_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8NFG4

UniProtKB/Swiss-Prot:

FLCN_HUMAN :
  • Belongs to the folliculin family.
Family:
  • Belongs to the folliculin family.
genes like me logo Genes that share domains with FLCN: view

Function for FLCN Gene

Molecular function for FLCN Gene

UniProtKB/Swiss-Prot Function:
May be a tumor suppressor. May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. May regulate phosphorylation of RPS6KB1.

Phenotypes From GWAS Catalog for FLCN Gene

Gene Ontology (GO) - Molecular Function for FLCN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity IEA --
GO:0005096 contributes_to GTPase activator activity IBA 21873635
GO:0005515 protein binding IPI 17028174
GO:0044877 protein-containing complex binding IDA 17028174
genes like me logo Genes that share ontologies with FLCN: view
genes like me logo Genes that share phenotypes with FLCN: view

Human Phenotype Ontology for FLCN Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for FLCN Gene

MGI Knock Outs for FLCN:
  • Flcn Flcn<tm1.1Lss>
  • Flcn Flcn<tm1.1Btt>

miRNA for FLCN Gene

miRTarBase miRNAs that target FLCN

Clone Products

  • Addgene plasmids for FLCN

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for FLCN Gene

Localization for FLCN Gene

Subcellular locations from UniProtKB/Swiss-Prot for FLCN Gene

Cytoplasm. Nucleus. Note=Mainly localized in the nucleus. Colocalizes with FNIP1 and FNIP2 in the cytoplasm. {ECO:0000269 PubMed:17028174, ECO:0000269 PubMed:18663353}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FLCN gene
Compartment Confidence
plasma membrane 5
nucleus 5
cytosol 5
lysosome 4
mitochondrion 2
endosome 2
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Plasma membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FLCN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 17028174
GO:0005737 cytoplasm IDA,IEA 17028174
GO:0005764 lysosome TAS 25126726
GO:0005829 cytosol IBA,IDA --
GO:0005886 plasma membrane IDA --
genes like me logo Genes that share ontologies with FLCN: view

Pathways & Interactions for FLCN Gene

genes like me logo Genes that share pathways with FLCN: view

Pathways by source for FLCN Gene

2 KEGG pathways for FLCN Gene
1 Cell Signaling Technology pathway for FLCN Gene

SIGNOR curated interactions for FLCN Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for FLCN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IMP 21209915
GO:0001701 in utero embryonic development ISS --
GO:0001932 regulation of protein phosphorylation IDA 18663353
GO:0001934 positive regulation of protein phosphorylation ISS --
GO:0007043 cell-cell junction assembly ISS --
genes like me logo Genes that share ontologies with FLCN: view

Drugs & Compounds for FLCN Gene

(1) Drugs for FLCN Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with FLCN: view

Transcripts for FLCN Gene

mRNA/cDNA for FLCN Gene

5 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

  • Addgene plasmids for FLCN

Alternative Splicing Database (ASD) splice patterns (SP) for FLCN Gene

No ASD Table

Relevant External Links for FLCN Gene

GeneLoc Exon Structure for
FLCN

Expression for FLCN Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for FLCN Gene

Protein differential expression in normal tissues from HIPED for FLCN Gene

This gene is overexpressed in Bone (52.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for FLCN Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for FLCN

SOURCE GeneReport for Unigene cluster for FLCN Gene:

Hs.31652

mRNA Expression by UniProt/SwissProt for FLCN Gene:

Q8NFG4-FLCN_HUMAN
Tissue specificity: Expressed in most tissues tested, including skin, lung, kidney, heart, testis and stomach.

Evidence on tissue expression from TISSUES for FLCN Gene

  • Skin(4.6)
  • Lung(4.5)
  • Spleen(4.2)
  • Kidney(2.6)
  • Thyroid gland(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for FLCN Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • urinary
Regions:
Head and neck:
  • ear
  • eye
  • face
  • head
  • outer ear
Thorax:
  • chest wall
  • diaphragm
  • lung
Abdomen:
  • intestine
  • kidney
  • large intestine
  • stomach
Pelvis:
  • anus
  • rectum
  • ureter
  • urethra
  • urinary bladder
  • uterus
General:
  • hair
  • skin
genes like me logo Genes that share expression patterns with FLCN: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Protein tissue co-expression partners for FLCN Gene

Orthologs for FLCN Gene

This gene was present in the common ancestor of animals.

Orthologs for FLCN Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia FLCN 30
  • 99.89 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 92 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 90 (a)
OneToMany
dog
(Canis familiaris)
Mammalia FLCN 31 30
  • 88.66 (n)
OneToMany
cow
(Bos Taurus)
Mammalia FLCN 31 30
  • 87.62 (n)
OneToMany
mouse
(Mus musculus)
Mammalia Flcn 17 31 30
  • 87.39 (n)
rat
(Rattus norvegicus)
Mammalia Flcn 30
  • 86.59 (n)
chicken
(Gallus gallus)
Aves -- 31
  • 88 (a)
OneToMany
FLCN 30
  • 78.74 (n)
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 73 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia flcn 30
  • 76.03 (n)
zebrafish
(Danio rerio)
Actinopterygii flcn 31 30
  • 63.73 (n)
OneToMany
wufe38g11 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007579 30
  • 47.28 (n)
fruit fly
(Drosophila melanogaster)
Insecta BHD 31 30
  • 45.89 (n)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea F22D3.2 30
  • 40.76 (n)
flcn-1 31
  • 20 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2717 31
  • 43 (a)
OneToMany
Species where no ortholog for FLCN was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for FLCN Gene

ENSEMBL:
Gene Tree for FLCN (if available)
TreeFam:
Gene Tree for FLCN (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FLCN: view image

Paralogs for FLCN Gene

Paralogs for FLCN Gene

genes like me logo Genes that share paralogs with FLCN: view

Variants for FLCN Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FLCN Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
638865 Pathogenic: Multiple fibrofolliculomas 17,214,984(-) CTTCATCCACTCCTCC SPLICE_ACCEPTOR_VARIANT,SPLICE_DONOR_VARIANT
639059 Uncertain Significance: Multiple fibrofolliculomas 17,228,004(-) G/T MISSENSE_VARIANT
639998 Uncertain Significance: Multiple fibrofolliculomas 17,216,478(-) C/T MISSENSE_VARIANT
640135 Uncertain Significance: Multiple fibrofolliculomas 17,227,989(-) C/T MISSENSE_VARIANT
641105 Uncertain Significance: Multiple fibrofolliculomas 17,215,081(-) G/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for FLCN Gene

Structural Variations from Database of Genomic Variants (DGV) for FLCN Gene

Variant ID Type Subtype PubMed ID
dgv893e212 CNV loss 25503493
esv1004208 CNV deletion 20482838
esv3582552 CNV loss 25503493
esv3582555 CNV loss 25503493
nsv155 OTHER inversion 15895083
nsv469777 CNV gain 16826518
nsv499114 OTHER inversion 21111241
nsv833380 CNV loss 17160897
nsv833382 CNV loss 17160897

Variation tolerance for FLCN Gene

Residual Variation Intolerance Score: 40.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.97; 20.03% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FLCN Gene

Human Gene Mutation Database (HGMD)
FLCN
SNPedia medical, phenotypic, and genealogical associations of SNPs for
FLCN

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FLCN Gene

Disorders for FLCN Gene

MalaCards: The human disease database

(36) MalaCards diseases for FLCN Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search FLCN in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

FLCN_HUMAN
  • Birt-Hogg-Dube syndrome (BHD) [MIM:135150]: A rare autosomal dominant genodermatosis characterized by hair follicle hamartomas (fibrofolliculomas), kidney tumors, and spontaneous pneumothorax. Fibrofolliculomas are part of the triad of Birt-Hogg-Dube syndrome skin lesions that also includes trichodiscomas and acrochordons. Onset of this dermatologic condition is invariably in adulthood. Birt-Hogg-Dube syndrome is associated with a variety of histologic types of renal tumors, including chromophobe renal cell carcinoma (RCC), benign renal oncocytoma, clear-cell RCC and papillary type I RCC. Multiple lipomas, angiolipomas, and parathyroid adenomas are also seen in Birt-Hogg-Dube syndrome patients. {ECO:0000269 PubMed:12204536, ECO:0000269 PubMed:15852235, ECO:0000269 PubMed:18234728, ECO:0000269 PubMed:19785621}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Primary spontaneous pneumothorax (PSP) [MIM:173600]: Condition in which air is present in the pleural space in the absence of a precipitating event, such as trauma or lung disease. This results in secondary collapse of the lung, either partially or completely, and some degree of hypoxia. PSP is relatively common, with an incidence between 7.4-18/100'000 for men and 1.2-6/100'000 for women and a dose-dependent, increased risk among smokers. Most cases are sporadic, typically occurring in tall, thin men aged 10-30 years and generally while at rest. Familial PSP is rarer and usually is inherited as an autosomal dominant condition with reduced penetrance, although X-linked recessive and autosomal recessive inheritance have also been suggested. {ECO:0000269 PubMed:15657874, ECO:0000269 PubMed:18505456, ECO:0000269 PubMed:18579543}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype. {ECO:0000269 PubMed:18794106}. Note=The gene represented in this entry may be involved in disease pathogenesis.

Additional Disease Information for FLCN

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with FLCN: view

No data available for Genatlas for FLCN Gene

Publications for FLCN Gene

  1. Mutation analysis of the FLCN gene in Chinese patients with sporadic and familial isolated primary spontaneous pneumothorax. (PMID: 18505456) Ren HZ … Yi L (Clinical genetics 2008) 3 4 23 41 54
  2. Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. (PMID: 17028174) Baba M … Zbar B (Proceedings of the National Academy of Sciences of the United States of America 2006) 2 3 4 23 54
  3. Folliculin mutations are not associated with severe COPD. (PMID: 19116017) Cho MH … Raby BA (BMC medical genetics 2008) 3 23 41 54
  4. Interaction of folliculin (Birt-Hogg-Dubé gene product) with a novel Fnip1-like (FnipL/Fnip2) protein. (PMID: 18663353) Takagi Y … Hino O (Oncogene 2008) 3 4 23 54
  5. Identification and characterization of a novel folliculin-interacting protein FNIP2. (PMID: 18403135) Hasumi H … Schmidt LS (Gene 2008) 3 4 23 54

Products for FLCN Gene

  • Signalway ELISA kits for FLCN
  • Signalway Proteins for FLCN

Sources for FLCN Gene