ID:FLCN_HUMAN DESCRIPTION: RecName: Full=Folliculin; AltName: Full=BHD skin lesion fibrofolliculoma protein; AltName: Full=Birt-Hogg-Dube syndrome protein; FUNCTION: May play a role in the pathogenesis of an uncommon form of kidney cancer through its association with an inherited disorder of the hair follicle (fibrofolliculomas). May be a tumor suppressor. May be involved in colorectal tumorigenesis. May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. May regulate phosphorylation of RPS6KB1. SUBUNIT: 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. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Mainly localized in the nucleus. Co-localizes with FNIP1 and FNIP2 in the cytoplasm. TISSUE SPECIFICITY: Expressed in most tissues tested, including skin, lung, kidney, heart, testis and stomach. DEVELOPMENTAL STAGE: Expressed in fetal lung, kidney, liver, and brain. PTM: Phosphorylated. Several different phosphorylated forms exist. DISEASE: Defects in FLCN are the cause of Birt-Hogg-Dube syndrome (BHD) [MIM:135150]. BHD is a rare autosomal dominant genodermatosis characterized by hair follicle hamartomas (fibrofolliculomas), kidney tumors, and spontaneous pneumothorax. Fibrofolliculomas are part of the triad of BHD skin lesions that also includes trichodiscomas and acrochordons. Onset of this dermatologic condition is invariably in adulthood. BHD 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 patients affected with this disease. The majority of mutations are predicted to prematurely terminate the protein. DISEASE: Defects in FLCN are in some cases a cause of primary spontaneous pneumothorax (PSP) [MIM:173600]. PSP is a 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. DISEASE: Defects in FLCN may be a cause of 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. SIMILARITY: Belongs to the folliculin family. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FLCN"; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/FLCNID789ch17p11.html"; WEB RESOURCE: Name=Leiden Open Variation Database; Note=Folliculin (FLCN); URL="http://grenada.lumc.nl/LOVD2/shared1/home.php?select_db=FLCN";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q8NFG4
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001701 in utero embryonic development GO:0001932 regulation of protein phosphorylation GO:0001934 positive regulation of protein phosphorylation GO:0007043 cell-cell junction assembly GO:0010508 positive regulation of autophagy GO:0010629 negative regulation of gene expression GO:0010823 negative regulation of mitochondrion organization GO:0030097 hemopoiesis GO:0030308 negative regulation of cell growth GO:0030336 negative regulation of cell migration GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway GO:0031929 TOR signaling GO:0032006 regulation of TOR signaling GO:0032007 negative regulation of TOR signaling GO:0032008 positive regulation of TOR signaling GO:0032465 regulation of cytokinesis GO:0035024 negative regulation of Rho protein signal transduction GO:0035065 regulation of histone acetylation GO:0043065 positive regulation of apoptotic process GO:0045785 positive regulation of cell adhesion GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0051898 negative regulation of protein kinase B signaling GO:0070373 negative regulation of ERK1 and ERK2 cascade GO:0097009 energy homeostasis GO:1900181 negative regulation of protein localization to nucleus GO:1901723 negative regulation of cell proliferation involved in kidney development GO:2000973 regulation of pro-B cell differentiation GO:2001170 negative regulation of ATP biosynthetic process
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
