FLCN
folliculin, the group of DENN domain containing
Basic information
Region (hg38): 17:17212212-17237188
Links
Phenotypes
GenCC
Source:
- Birt-Hogg-Dube syndrome (Strong), mode of inheritance: AD
- renal carcinoma (Strong), mode of inheritance: AD
- familial spontaneous pneumothorax (Strong), mode of inheritance: AD
- Birt-Hogg-Dube syndrome (Strong), mode of inheritance: AD
- familial spontaneous pneumothorax (Moderate), mode of inheritance: AD
- Birt-Hogg-Dube syndrome 1 (Definitive), mode of inheritance: AD
- familial spontaneous pneumothorax (Supportive), mode of inheritance: AD
- Birt-Hogg-Dube syndrome (Supportive), mode of inheritance: AD
- colorectal cancer (Limited), mode of inheritance: AD
- Birt-Hogg-Dube syndrome 1 (Definitive), mode of inheritance: AD
- Birt-Hogg-Dube syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Birt-Hogg-Dube syndrome 1; Pneumothorax, primary spontaneous | AD | Oncologic; Pulmonary | Individuals are at risk for a number of types of neoplasms, and surveillance and early diagnosis/treatment may be beneficial; Some individuals may demonstrate isolated pneumothorax, but may be at elevated risk for malignancies; Affected individuals commonly have recurrent pneumothoraces, and early pleurodesis may beneficial) | Dermatologic; Oncologic; Pulmonary | 596896; 10522666; 11533913; 12471204; 12204536; 15657874; 15852235; 17496196; 18505456; 18234728; 19320655; 20413710; 20618353; 22146830; 23264078; 23414156; 23542717; 23715758; 23846428; 23995526 |
ClinVar
This is a list of variants' phenotypes submitted to
- Birt-Hogg-Dube_syndrome (1915 variants)
- Hereditary_cancer-predisposing_syndrome (1503 variants)
- Birt-Hogg-Dube_syndrome_1 (608 variants)
- not_provided (456 variants)
- Familial_spontaneous_pneumothorax (228 variants)
- Nonpapillary_renal_cell_carcinoma (192 variants)
- Colorectal_cancer (187 variants)
- not_specified (167 variants)
- FLCN-related_disorder (112 variants)
- 17p11.2_microduplication_syndrome (97 variants)
- Ovarian_cancer (12 variants)
- Carcinoma_of_colon (8 variants)
- Hereditary_breast_ovarian_cancer_syndrome (2 variants)
- Spontaneous_pneumothorax (1 variants)
- See_cases (1 variants)
- Multiple_monogenic_benign_skin_tumours (1 variants)
- Hypoparathyroidism (1 variants)
- Chromophobe_renal_cell_carcinoma (1 variants)
- Exstrophy-epispadias_complex (1 variants)
- Hereditary_renal_cancer (1 variants)
- Pilocytic_astrocytoma (1 variants)
- Hepatoblastoma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FLCN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000144997.7. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 541 | 28 | 582 | |||
| missense | 18 | 16 | 1010 | 135 | 1184 | |
| nonsense | 73 | 10 | 86 | |||
| start loss | 3 | 3 | 6 | |||
| frameshift | 203 | 37 | 244 | |||
| splice donor/acceptor (+/-2bp) | 23 | 41 | 67 | |||
| Total | 325 | 108 | 1025 | 678 | 33 |
Highest pathogenic variant AF is 0.0000688434
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FLCN | protein_coding | protein_coding | ENST00000285071 | 11 | 24977 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.789 | 0.211 | 125723 | 0 | 25 | 125748 | 0.0000994 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.13 | 293 | 353 | 0.831 | 0.0000245 | 3818 |
| Missense in Polyphen | 50 | 81.857 | 0.61082 | 910 | ||
| Synonymous | -0.917 | 163 | 149 | 1.10 | 0.0000114 | 1132 |
| Loss of Function | 3.94 | 5 | 27.1 | 0.184 | 0.00000135 | 293 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000290 | 0.0000290 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000272 | 0.000272 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000123 | 0.000123 |
| Middle Eastern | 0.000272 | 0.000272 |
| South Asian | 0.000131 | 0.000131 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- 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. {ECO:0000269|PubMed:12204536, ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18663353}.;
- Disease
- DISEASE: 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.; DISEASE: 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.; DISEASE: 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.;
- Pathway
- mTOR signaling pathway - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human)
(Consensus)
Recessive Scores
- pRec
- 0.172
Intolerance Scores
- loftool
- 0.0936
- rvis_EVS
- -0.2
- rvis_percentile_EVS
- 39.17
Haploinsufficiency Scores
- pHI
- 0.216
- hipred
- Y
- hipred_score
- 0.647
- ghis
- 0.614
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.276
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Flcn
- Phenotype
- renal/urinary system phenotype; immune system phenotype; neoplasm; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- flcn
- Affected structure
- post-vent region
- Phenotype tag
- abnormal
- Phenotype quality
- bent
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;in utero embryonic development;regulation of protein phosphorylation;positive regulation of protein phosphorylation;cell-cell junction assembly;positive regulation of autophagy;negative regulation of gene expression;negative regulation of mitochondrion organization;hemopoiesis;negative regulation of cell growth;negative regulation of cell migration;positive regulation of transforming growth factor beta receptor signaling pathway;TOR signaling;regulation of TOR signaling;negative regulation of TOR signaling;positive regulation of TOR signaling;regulation of cytokinesis;negative regulation of Rho protein signal transduction;regulation of histone acetylation;positive regulation of apoptotic process;positive regulation of cell adhesion;positive regulation of transcription by RNA polymerase II;negative regulation of protein kinase B signaling;negative regulation of ERK1 and ERK2 cascade;energy homeostasis;negative regulation of cold-induced thermogenesis;negative regulation of protein localization to nucleus;negative regulation of cell proliferation involved in kidney development;regulation of pro-B cell differentiation;negative regulation of ATP biosynthetic process
- Cellular component
- nucleus;cytoplasm;lysosome;cytosol;plasma membrane;cilium;midbody;cell-cell contact zone
- Molecular function
- guanyl-nucleotide exchange factor activity;protein binding;protein-containing complex binding