FLCN folliculin [Homo sapiens (human)] - Gene

Summary

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Official Symbol: FLCNprovided by HGNC
Official Full Name: folliculinprovided by HGNC
Primary source: HGNC:27310
See related: Ensembl:ENSG00000154803; HPRD:06278; MIM:607273; Vega:OTTHUMG00000059275
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BHD; FLCL
Summary: 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]

Genomic context

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Location :: 17p11.2

Sequence :: Chromosome: 17; NC_000017.10 (17115526..17140502, complement)

See FLCN in Epigenomics, MapViewer

Chromosome 17 - NC_000017.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

These data support a model in which dysregulation of the FLCN-p0071 interaction leads to alterations in cell adhesion, cell polarity, and RhoA signaling.
Title: Folliculin, the product of the Birt-Hogg-Dube tumor suppressor gene, interacts with the adherens junction protein p0071 to regulate cell-cell adhesion.
These findings identify novel pathways and targets linked to folliculin tumour suppressor activity.
Title: Gene expression and protein array studies of folliculin-regulated pathways.
FLCN deficiency and subsequent increased PPARGC1A expression result in increased mitochondrial function and oxidative metabolism as the source of cellular energy, which may drive hyperplastic transformation.
Title: Regulation of mitochondrial oxidative metabolism by tumor suppressor FLCN.
The FLCN-FNIP complex deregulated in Birt-Hogg-Dube syndrome is absolutely required for B-cell differentiation.
Title: The folliculin-FNIP1 pathway deleted in human Birt-Hogg-Dubé syndrome is required for murine B-cell development.
Study reports a novel in-frame deletion mutation p.F143del (c.427_429delTTC) in exon 6 of FLCN gene in a Korean proband and her two sisters.
Title: Novel in-frame deletion mutation in FLCN gene in a Korean family with recurrent primary spontaneous pneumothorax.
confirmed a high yield of FLCN mutations in clinically defined BHD families, we found a substantially increased lifetime risk of renal cancer of 16% for FLCN mutation carriers
Title: Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families.
FLCN mutations throughout the coding sequence, and suggest that multiple protein domains contribute to folliculin stability and tumor suppressor activity.
Title: Birt Hogg-Dubé syndrome-associated FLCN mutations disrupt protein stability.
Birt-Hogg-Dube (BHD) protein-deficient cells exhibited defects in cell-intrinsic apoptosis that correlated with reduced expression of the BH3-only protein Bim, which was similarly observed in all human and mouse BHD-related tumors examined.
Title: Loss of the Birt-Hogg-Dubé tumor suppressor results in apoptotic resistance due to aberrant TGFβ-mediated transcription.
Data show that FLCN mutations were found in 9 of 19 (47%) families.
Title: Constitutional FLCN mutations in patients with suspected Birt-Hogg-Dubé syndrome ascertained for non-cutaneous manifestations.
This report confirms that large intragenic FLCN deletions can cause Birt-Hogg-Dube syndrome and documents the first large intragenic FLCN duplication in a Birt-Hogg-Dube syndrome patient
Title: Identification of intragenic deletions and duplication in the FLCN gene in Birt-Hogg-Dubé syndrome.

Submit: New GeneRIF Correction See all (38)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

The clinical characteristics of Birt-Hogg-Dube syndrome (BHDS) include cutaneous manifestations (fibrofolliculomas, trichodiscomas/angiofibromas, perifollicular fibromas, and acrochordons), pulmonary cysts/history of pneumothorax, and various types of renal tumors. Disease severity can vary significantly even within the same family. Skin lesions typically appear during the third and fourth decades of life and typically increase in size and number with age. Lung cysts are mostly bilateral and multifocal; most individuals are asymptomatic but have a high risk for spontaneous pneumothorax. Individuals with BHDS have an increased risk of renal tumors that are typically bilateral and multifocal and usually slow growing; median age of tumor diagnosis is 48 years. The most common renal tumors are renal hybrids of oncocytoma and chromophobe histologic cell types. Some families have renal tumor and/or autosomal dominant spontaneous pneumothorax without cutaneous manifestations.

Diagnosis Testing

BHDS is diagnosed by clinical findings and by molecular genetic testing. FLCN (also known as BHD) is the only gene known to be associated with BHDS. Sequence analysis, available on a clinical basis, detects mutations in FLCN in 88% of affected individuals; therefore, some affected individuals who fulfill clinical diagnostic criteria do not have an identifiable mutation.

Genetic Counseling

BHDS is inherited in an autosomal dominant manner. The offspring of an individual with BHDS have a 50% chance of inheriting the mutation. Prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing allele of an affected family member has been identified.

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
pol	gag-pol	HIV-1 PR is identified to have a physical interaction with folliculin (FLCN) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
BioGRID:128366	BioGRID:106848	APP	BioGRID	PubMed	Reconstituted Complex
BioGRID:128366	BioGRID:125175	FNIP1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex
BioGRID:128366	BioGRID:111550	PRKAA2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:128366	BioGRID:113011	TP53BP1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:128366	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:128366	BioGRID:1205538	gag-pol	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Renal cell carcinoma, organism-specific biosystem (from KEGG)
Renal cell carcinoma, organism-specific biosystemRenal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal canc...
Renal cell carcinoma, conserved biosystem (from KEGG)
Renal cell carcinoma, conserved biosystemRenal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal canc...

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

D10S275 (e-PCR)
- UniSTS:147992

D8S2279 (e-PCR)
- UniSTS:473907

RH98335 (e-PCR)
- UniSTS:86095

D17S740 (e-PCR), detects polymorphism
- UniSTS:37725

D10S16 (e-PCR)
- UniSTS:155756

D15S1477 (e-PCR)
- UniSTS:474482

D1S1423 (e-PCR)
- UniSTS:149619

D17S2196 (e-PCR), detects polymorphism
- UniSTS:29299

RH36905 (e-PCR)
- UniSTS:87932

D11S3114 (e-PCR)
- UniSTS:152207

D3S1674 (e-PCR)
- UniSTS:148451

Genotypes

See FLCN SNP Geneview Report
See FLCN SNP Genotype Report
See FLCN SNP Variation Viewer Report

Homology

Homologs of the FLCN gene: The FLCN gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and C.elegans.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

FLJ45004, FLJ99377, MGC17998, MGC23445, DKFZp547A118

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein complex binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
TOR signaling cascade	IMP Inferred from Mutant Phenotype more info	PubMed
cell-cell junction assembly	ISS Inferred from Sequence or Structural Similarity more info
hemopoiesis	ISS Inferred from Sequence or Structural Similarity more info
in utero embryonic development	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of ATP biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of Rho protein signal transduction	IMP Inferred from Mutant Phenotype more info
negative regulation of TOR signaling cascade	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of cell growth	IDA Inferred from Direct Assay more info
negative regulation of cell migration	IMP Inferred from Mutant Phenotype more info
negative regulation of cell proliferation involved in kidney development	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of energy homeostasis	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of mitochondrion organization	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of protein kinase B signaling cascade	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of protein localization to nucleus	IDA Inferred from Direct Assay more info
negative regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info
negative regulation of transcription from RNA polymerase II promoter	IMP Inferred from Mutant Phenotype more info
positive regulation of TOR signaling cascade	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cell adhesion	IMP Inferred from Mutant Phenotype more info
positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info
positive regulation of transcription from RNA polymerase II promoter	IMP Inferred from Mutant Phenotype more info
positive regulation of transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info
positive regulation of transforming growth factor beta receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
regulation of TOR signaling cascade	ISS Inferred from Sequence or Structural Similarity more info
regulation of cytokinesis	IMP Inferred from Mutant Phenotype more info
regulation of histone acetylation	ISS Inferred from Sequence or Structural Similarity more info
regulation of pro-B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
response to stress	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
colocalizes_with cell-cell contact zone	IDA Inferred from Direct Assay more info
cytoplasm	IDA Inferred from Direct Assay more info
colocalizes_with midbody	IDA Inferred from Direct Assay more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: folliculin

Names: folliculin; birt-Hogg-Dube syndrome protein; BHD skin lesion fibrofolliculoma protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008001.2 RefSeqGene

Range

5001..29977

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_144606.5 → NP_653207.1 folliculin isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, as compared to variant 1. Isoform 2 has a shorter and distinct C-terminus, as compared to isoform 1.

Source sequence(s)

BC015687, CX759825, DA461022, DA944035

Consensus CDS

CCDS32580.1

UniProtKB/Swiss-Prot

Q8NFG4

Related

ENSP00000373821, OTTHUMP00000065504, ENST00000389169, OTTHUMT00000131578

Conserved Domains (1) summary

pfam11704
Location:104 – 267
Blast Score: 615

Folliculin; Vesicle coat protein involved in Golgi to plasma membrane transport
NM_144997.5 → NP_659434.2 folliculin isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC055811, AF517523, CX759825, DA461022, DA944035

Consensus CDS

CCDS32579.1

UniProtKB/Swiss-Prot

Q8NFG4

Related

ENSP00000285071, OTTHUMP00000065503, ENST00000285071, OTTHUMT00000131577

Conserved Domains (1) summary

pfam11704
Location:104 – 267
Blast Score: 615

Folliculin; Vesicle coat protein involved in Golgi to plasma membrane transport

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000017.10 Reference GRCh37.p10 Primary Assembly

Range

17115526..17140502, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000149.1 Alternate HuRef

Range

16868444..16893256, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018928.1 Alternate CHM1_1.0

Range

17104372..17129344, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01009767.1 (1494..4321)	None
genomic	ABBA01009768.1	None
genomic	AC055811.20 (74626..99596)	None
genomic	AMYH01008155.1 (169402..194374)	None
genomic	CH471196.2	EAW55715.1
		EAW55716.1
genomic	CS478258.1	CAM35387.1
mRNA	AF517523.1	AAM94803.1
mRNA	AK126951.1	BAC86760.1
mRNA	AK127912.1	BAC87186.1
mRNA	AK309336.1	None
mRNA	AL831885.1	CAD38565.1
mRNA	BC015687.2	AAH15687.1
mRNA	BC015725.2	AAH15725.2
mRNA	BQ423946.1	None
mRNA	CX759825.1	None
mRNA	DA461022.1	None
mRNA	DA944035.1	None
other-genetic	HQ447198.1	ADQ31685.1