FLCN folliculin [Homo sapiens (human)] - Gene

Summary

Official Symbol: FLCNprovided by HGNC
Official Full Name: folliculinprovided by HGNC
Primary source: HGNC:HGNC:27310
See related: Ensembl:ENSG00000154803 MIM:607273; AllianceGenome:HGNC:27310
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; DENND8B
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]
Expression: Ubiquitous expression in endometrium (RPKM 9.4), ovary (RPKM 9.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17p11.2

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (17212212..17237330, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (17158255..17183608, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (17115526..17140482, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Germline- and Somatic-Inactivating FLCN Variants in Parathyroid Cancer and Atypical Parathyroid Tumors.
Title: Germline- and Somatic-Inactivating FLCN Variants in Parathyroid Cancer and Atypical Parathyroid Tumors.
Progress in Adrenal Cortical Neoplasms: From Predictive Histomorphology to FLCN-Driven Germline Pathogenesis and the Prognostic Performance of Multiparameter Scoring Systems in Pediatric Adrenal Cortical Neoplasms.
Title: Progress in Adrenal Cortical Neoplasms: From Predictive Histomorphology to FLCN-Driven Germline Pathogenesis and the Prognostic Performance of Multiparameter Scoring Systems in Pediatric Adrenal Cortical Neoplasms.
Role of FLCN Phosphorylation in Insulin-Mediated mTORC1 Activation and Tumorigenesis.
Title: Role of FLCN Phosphorylation in Insulin-Mediated mTORC1 Activation and Tumorigenesis.
Folliculin Prevents Lysosomal Degradation of Human Papillomavirus To Support Infectious Cell Entry.
Title: Folliculin Prevents Lysosomal Degradation of Human Papillomavirus To Support Infectious Cell Entry.
Exons 1-3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dube syndrome.
Title: Exons 1-3 deletion in FLCN is associated with increased risk of pneumothorax in Chinese patients with Birt-Hogg-Dubé syndrome.
PRDM10 directs FLCN expression in a novel disorder overlapping with Birt-Hogg-Dube syndrome and familial lipomatosis.
Title: PRDM10 directs FLCN expression in a novel disorder overlapping with Birt-Hogg-Dubé syndrome and familial lipomatosis.
Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors.
Title: Combined germline pathogenic variants in FLCN and TP53 are associated with early onset renal cell carcinoma and brain tumors.
Phosphoproteomic Analysis of FLCN Inactivation Highlights Differential Kinase Pathways and Regulatory TFEB Phosphoserines.
Title: Phosphoproteomic Analysis of FLCN Inactivation Highlights Differential Kinase Pathways and Regulatory TFEB Phosphoserines.
Frequency of truncating FLCN variants and Birt-Hogg-Dube-associated phenotypes in a health care system population.
Title: Frequency of truncating FLCN variants and Birt-Hogg-Dubé-associated phenotypes in a health care system population.
A systematic review assessing the existence of pneumothorax-only variants of FLCN. Implications for lifelong surveillance of renal tumours.
Title: A systematic review assessing the existence of pneumothorax-only variants of FLCN. Implications for lifelong surveillance of renal tumours.

Submit: New GeneRIF Correction See all GeneRIFs (107)

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

Associated conditions

Description	Tests
Birt-Hogg-Dube syndrome MedGen: C0346010 GeneReviews: Birt-Hogg-Dube Syndrome	not available
Birt-Hogg-Dube syndrome 1 MedGen: CN375946 OMIM: 135150 GeneReviews: Birt-Hogg-Dube Syndrome	not available
Colorectal cancer MedGen: C0346629 OMIM: 114500 GeneReviews: Lynch Syndrome	not available
Familial spontaneous pneumothorax MedGen: C1868193 OMIM: 173600 GeneReviews: Not available	not available
Nonpapillary renal cell carcinoma MedGen: CN074294 OMIM: 144700 GeneReviews: Not available	not available
Potocki-Lupski syndrome MedGen: C2931246 OMIM: 610883 GeneReviews: Potocki-Lupski Syndrome	not available

Copy number response

Description
Copy number response Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2023-01-11) ClinGen Genome Curation PagePubMed Triplosensitivity No evidence available (Last evaluated 2023-01-11) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
retropepsin	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 Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

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

Clone Names

FLJ45004, FLJ99377, MGC17998, MGC23445, DKFZp547A118

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTPase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables enzyme inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
involved_in TOR signaling	IEA Inferred from Electronic Annotation more info
involved_in cell proliferation involved in kidney development	IEA Inferred from Electronic Annotation more info
involved_in cell-cell junction assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to amino acid starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in energy homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in hemopoiesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in in utero embryonic development	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in intrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in lysosome localization	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of Rho protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of TOR signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of brown fat cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cell proliferation involved in kidney development	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of glycolytic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of lysosome organization	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of post-translational protein modification	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of TOR signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of TOR signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of TORC1 signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of TORC1 signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of autophagy	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of intrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transforming growth factor beta receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of transforming growth factor beta receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of Ras protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of TOR signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of pro-B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in transforming growth factor beta receptor signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of FNIP-folliculin RagC/D GAP	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with cell-cell contact zone	IDA Inferred from Direct Assay more info	PubMed
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
located_in cilium	IDA Inferred from Direct Assay more info	PubMed
located_in cilium	TAS Traceable Author Statement more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	TAS Traceable Author Statement more info	PubMed
colocalizes_with midbody	IDA Inferred from Direct Assay more info	PubMed
located_in mitotic spindle	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: folliculin

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

NP_001340158.1

EC 2.7.1.21

NP_001340159.1

EC 2.7.1.21

NP_001340160.1

EC 2.7.1.21

NP_653207.1

EC 2.7.1.21

NP_659434.2

EC 2.7.1.21

XP_011522016.1

EC 2.7.1.21

XP_011522020.1

EC 2.7.1.21

XP_011522023.1

EC 2.7.1.21

XP_016879794.1

EC 2.7.1.21

XP_016879797.1

EC 2.7.1.21

XP_016879798.1

EC 2.7.1.21

XP_047291487.1

EC 2.7.1.21

XP_047291488.1

EC 2.7.1.21

XP_047291489.1

EC 2.7.1.21

XP_047291490.1

EC 2.7.1.21

XP_047291491.1

EC 2.7.1.21

XP_047291492.1

EC 2.7.1.21

XP_047291493.1

EC 2.7.1.21

XP_047291494.1

EC 2.7.1.21

XP_047291495.1

EC 2.7.1.21

XP_047291496.1

EC 2.7.1.21

XP_047291497.1

EC 2.7.1.21

XP_047291498.1

EC 2.7.1.21

XP_054171308.1

EC 2.7.1.21

XP_054171309.1

EC 2.7.1.21

XP_054171310.1

EC 2.7.1.21

XP_054171311.1

EC 2.7.1.21

XP_054171312.1

EC 2.7.1.21

XP_054171313.1

EC 2.7.1.21

XP_054171314.1

EC 2.7.1.21

XP_054171315.1

EC 2.7.1.21

XP_054171316.1

EC 2.7.1.21

XP_054171317.1

EC 2.7.1.21

XP_054171318.1

EC 2.7.1.21

XP_054171319.1

EC 2.7.1.21

XP_054171320.1

EC 2.7.1.21

XP_054171321.1

EC 2.7.1.21

XP_054171322.1

EC 2.7.1.21

XP_054171323.1

EC 2.7.1.21

XP_054171324.1

EC 2.7.1.21

XP_054171325.1

EC 2.7.1.21

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), LRG_325

mRNA and Protein(s)

NM_001353229.2 → NP_001340158.1 folliculin isoform 3

Status: REVIEWED

Source sequence(s)

AC055811

Conserved Domains (2) summary

pfam11704
Location:106 → 283

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

pfam16692
Location:367 → 581

Folliculin_C; Folliculin C-terminal domain
NM_001353230.2 → NP_001340159.1 folliculin isoform 1

Status: REVIEWED

Source sequence(s)

AC055811

Consensus CDS

CCDS32579.1

UniProtKB/Swiss-Prot

A6NJJ8, Q6ZRX1, Q8NFG4, Q96BD2, Q96BE4

Conserved Domains (2) summary

pfam11704
Location:106 → 265

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

pfam16692
Location:344 → 566

Folliculin_C; Folliculin C-terminal domain
NM_001353231.2 → NP_001340160.1 folliculin isoform 1

Status: REVIEWED

Source sequence(s)

AC055811

Consensus CDS

CCDS32579.1

UniProtKB/Swiss-Prot

A6NJJ8, Q6ZRX1, Q8NFG4, Q96BD2, Q96BE4

Conserved Domains (2) summary

pfam11704
Location:106 → 265

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

pfam16692
Location:344 → 566

Folliculin_C; Folliculin C-terminal domain
NM_144606.7 → NP_653207.1 folliculin isoform 2

See identical proteins and their annotated locations for NP_653207.1

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)

AC055811, BC015687, CX759825, DA461022

Consensus CDS

CCDS32580.1

UniProtKB/TrEMBL

A0A0S2Z5Y7

Related

ENSP00000373821.5, ENST00000389169.9

Conserved Domains (1) summary

pfam11704
Location:106 → 265

Folliculin; Vesicle coat protein involved in Golgi to plasma membrane transport
NM_144997.7 → NP_659434.2 folliculin isoform 1

See identical proteins and their annotated locations for NP_659434.2

Status: REVIEWED

Description

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

Source sequence(s)

AC055811, AF517523, CX759825, DA461022

Consensus CDS

CCDS32579.1

UniProtKB/Swiss-Prot

A6NJJ8, Q6ZRX1, Q8NFG4, Q96BD2, Q96BE4

Related

ENSP00000285071.4, ENST00000285071.9

Conserved Domains (2) summary

pfam11704
Location:106 → 265

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

pfam16692
Location:344 → 566

Folliculin_C; Folliculin C-terminal domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

17212212..17237330 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047435536.1 → XP_047291492.1 folliculin isoform X2

UniProtKB/Swiss-Prot

A6NJJ8, Q6ZRX1, Q8NFG4, Q96BD2, Q96BE4
XM_047435531.1 → XP_047291487.1 folliculin isoform X1
XM_047435541.1 → XP_047291497.1 folliculin isoform X3
XM_047435538.1 → XP_047291494.1 folliculin isoform X2

UniProtKB/Swiss-Prot

A6NJJ8, Q6ZRX1, Q8NFG4, Q96BD2, Q96BE4
XM_011523718.4 → XP_011522020.1 folliculin isoform X1

See identical proteins and their annotated locations for XP_011522020.1

Conserved Domains (2) summary

pfam11704
Location:106 → 283

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

pfam16692
Location:367 → 581

Folliculin_C; Folliculin C-terminal domain
XM_017024309.3 → XP_016879798.1 folliculin isoform X3

Conserved Domains (2) summary

pfam11704
Location:106 → 190

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

pfam16692
Location:275 → 489

Folliculin_C; Folliculin C-terminal domain
XM_011523714.4 → XP_011522016.1 folliculin isoform X1

See identical proteins and their annotated locations for XP_011522016.1

Conserved Domains (2) summary

pfam11704
Location:106 → 283

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

pfam16692
Location:367 → 581

Folliculin_C; Folliculin C-terminal domain
XM_017024305.3 → XP_016879794.1 folliculin isoform X1

Conserved Domains (2) summary

pfam11704
Location:106 → 283

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

pfam16692
Location:367 → 581

Folliculin_C; Folliculin C-terminal domain
XM_047435534.1 → XP_047291490.1 folliculin isoform X1
XM_047435537.1 → XP_047291493.1 folliculin isoform X2

UniProtKB/Swiss-Prot

A6NJJ8, Q6ZRX1, Q8NFG4, Q96BD2, Q96BE4
XM_047435532.1 → XP_047291488.1 folliculin isoform X1
XM_047435540.1 → XP_047291496.1 folliculin isoform X3
XM_047435535.1 → XP_047291491.1 folliculin isoform X2

UniProtKB/Swiss-Prot

A6NJJ8, Q6ZRX1, Q8NFG4, Q96BD2, Q96BE4
XM_017024308.2 → XP_016879797.1 folliculin isoform X2

UniProtKB/Swiss-Prot

A6NJJ8, Q6ZRX1, Q8NFG4, Q96BD2, Q96BE4

Conserved Domains (2) summary

pfam11704
Location:106 → 265

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

pfam16692
Location:344 → 566

Folliculin_C; Folliculin C-terminal domain
XM_047435533.1 → XP_047291489.1 folliculin isoform X1
XM_011523721.4 → XP_011522023.1 folliculin isoform X1

See identical proteins and their annotated locations for XP_011522023.1

Conserved Domains (2) summary

pfam11704
Location:106 → 283

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

pfam16692
Location:367 → 581

Folliculin_C; Folliculin C-terminal domain
XM_047435539.1 → XP_047291495.1 folliculin isoform X1
XM_047435542.1 → XP_047291498.1 folliculin isoform X4