BHD
MCID: BRT002
MIFTS: 64

Birt-Hogg-Dube Syndrome (BHD)

Categories: Cancer diseases, Genetic diseases, Nephrological diseases, Rare diseases, Respiratory diseases, Skin diseases

Aliases & Classifications for Birt-Hogg-Dube Syndrome

MalaCards integrated aliases for Birt-Hogg-Dube Syndrome:

Name: Birt-Hogg-Dube Syndrome 57 12 73 20 58 72 36 13 54 44 15 39
Fibrofolliculomas with Trichodiscomas and Acrochordons 57 20 43 58 72
Birt-Hogg-Dubé Syndrome 73 25 43 29 6
Hornstein-Knickenberg Syndrome 57 25 20 43
Bhd 57 20 43 72
Bhd Syndrome 20 6
Hornstein-Birt-Hogg-Dubé Syndrome 43
Multiple Fibrofolliculomas 70
Birt Hogg Dube Syndrome 20
Birt-Hogg-Dub Syndrome 6

Characteristics:

Orphanet epidemiological data:

58
birt-hogg-dube syndrome
Inheritance: Autosomal dominant; Age of onset: Adult;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
intrafamilial variability
features usually appear during adulthood
mean age of presentation of renal cancer is 50 years, but earlier onset has been reported
see also isolated pneumothorax , an allelic disorder that may represent a mild form of the bhd syndrome


HPO:

31
birt-hogg-dube syndrome:
Inheritance autosomal dominant inheritance


GeneReviews:

25
Penetrance Based on the three major clinical manifestations, penetrance of bhds is considered to be very high. approximately 90%-95% of individuals with a heterozygous germline flcn pathogenic variant develop at least one feature of bhds.

Classifications:

Orphanet: 58  
Rare renal diseases
Rare respiratory diseases
Rare skin diseases


External Ids:

Disease Ontology 12 DOID:0050676
OMIM® 57 135150
KEGG 36 H00818
MeSH 44 D058249
MESH via Orphanet 45 D058249
ICD10 via Orphanet 33 D23.9
UMLS via Orphanet 71 C0346010
Orphanet 58 ORPHA122
MedGen 41 C0346010
UMLS 70 C0346010

Summaries for Birt-Hogg-Dube Syndrome

MedlinePlus Genetics : 43 Birt-Hogg-Dubé syndrome is a rare disorder that affects the skin and lungs and increases the risk of certain types of tumors. Its signs and symptoms vary among affected individuals.Birt-Hogg-Dubé syndrome is characterized by multiple noncancerous (benign) skin tumors, particularly on the face, neck, and upper chest. These growths typically first appear in a person's twenties or thirties and become larger and more numerous over time. Affected individuals also have an increased chance of developing cysts in the lungs and an abnormal accumulation of air in the chest cavity (pneumothorax) that may result in the collapse of a lung. Additionally, Birt-Hogg-Dubé syndrome is associated with an elevated risk of developing cancerous or noncancerous kidney tumors. Other types of cancer have also been reported in affected individuals, but it is unclear whether these tumors are actually a feature of Birt-Hogg-Dubé syndrome.

MalaCards based summary : Birt-Hogg-Dube Syndrome, also known as fibrofolliculomas with trichodiscomas and acrochordons, is related to renal cell carcinoma, nonpapillary and fibroma. An important gene associated with Birt-Hogg-Dube Syndrome is FLCN (Folliculin), and among its related pathways/superpathways are mTOR signaling pathway and Regulation of TP53 Activity. The drugs Clotrimazole and Miconazole have been mentioned in the context of this disorder. Affiliated tissues include kidney, lung and thyroid, and related phenotypes are emphysema and papule

Disease Ontology : 12 A skin disease that is characterized by the development of skin papules on the head, face and upper torso, has material basis in heterozygous mutation in the gene encoding folliculin on chromosome 17p11.

GARD : 20 Birt-Hogg-Dube syndrome (BHDS) is a rare, complex, genetic disorder with three main clinical findings: non-cancerous (benign) skin tumors ; lung cysts and/or history of pneumothorax (collapsed lung); and various types of renal tumors. Fibrofolliculomas are a type of benign skin tumor specific to BHDS. They typically occur on the face, neck, and upper torso. Most people with BHDS also have multiple cysts in both lungs that can be seen on high-resolution chest CT scan. While these cysts usually do not cause any symptoms, they put people at increased risk for spontaneous pneumothorax. BHDS is caused by mutations in the FLCN gene. The condition is inherited in an autosomal dominant fashion.

OMIM® : 57 Birt-Hogg-Dube syndrome is an autosomal dominant genodermatosis characterized by hair follicle hamartomas, kidney tumors, and spontaneous pneumothorax (Nickerson et al., 2002). BHD is similar to, but histologically and genetically distinct from, familial multiple discoid fibromas (FMDF; 190340). (135150) (Updated 05-Apr-2021)

KEGG : 36 Birt-Hogg-Dube syndrome is an autosomal dominant condition characterized by skin fibrofolliculomas, multiple pulmonary cysts, and renal cancer. Skin lesions usually appear after the age of 20 years with multiple white papules in the midface. The disease is caused by mutations in the FLCN gene coding for folliculin.

UniProtKB/Swiss-Prot : 72 Birt-Hogg-Dube syndrome: 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.

Wikipedia : 73 Birt-Hogg-Dubé syndrome (BHD), also Hornstein-Birt-Hogg-Dubé syndrome, Hornstein-Knickenberg syndrome,... more...

GeneReviews: NBK1522

Related Diseases for Birt-Hogg-Dube Syndrome

Diseases related to Birt-Hogg-Dube Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 215)
# Related Disease Score Top Affiliating Genes
1 renal cell carcinoma, nonpapillary 31.2 TSC2 TFE3 PTEN MTOR KRT7 FLCN
2 fibroma 31.0 PTCH1 FLCN CTNNB1
3 tuberous sclerosis 1 30.6 TSC2 PTEN MTOR
4 kidney cancer 30.5 TSC2 PTEN MTOR FLCN FH
5 thyroid gland cancer 30.4 PTEN PTCH1 KRT7 CTNNB1
6 congenital heart defects, hamartomas of tongue, and polysyndactyly 30.4 TSC2 PTEN FLCN
7 tuberous sclerosis 30.4 TSC2 PTEN MTOR FLCN
8 clear cell renal cell carcinoma 30.3 TFE3 PTEN MTOR KRT7 FLCN CTNNB1
9 oncocytoma 30.3 KRT7 FNIP2 FLCN FH
10 kidney angiomyolipoma 30.2 TSC2 TFE3 MTOR FNIP1 FLCN
11 polycystic liver disease 1 with or without kidney cysts 30.0 TSC2 PTCH1 KRT7 FLCN
12 rhabdomyosarcoma 30.0 PTEN PTCH1 MTOR KRT7 CTNNB1
13 tuberous sclerosis 2 29.9 TSC2 PTEN MTOR
14 angiomyolipoma 29.9 TSC2 TFE3 MTOR KRT7 FLCN
15 renal cell carcinoma, papillary, 1 29.6 TFE3 PTEN MTOR KRT7 FNIP2 FNIP1
16 hereditary renal cell carcinoma 29.6 TSC2 FNIP2 FNIP1 FLCN FH
17 familial renal oncocytoma 29.5 RRAGC RAB35 FNIP2 FNIP1 FLCN
18 pneumothorax, primary spontaneous 11.7
19 beukes hip dysplasia 11.6
20 discoid fibromas, familial multiple 11.4
21 renal oncocytoma 11.4
22 pneumothorax 10.9
23 erythrokeratoderma ''en cocardes'' 10.6
24 cystic disease of lung 10.6
25 lung disease 10.6
26 chromophil renal cell carcinoma 10.6
27 rare genetic skin disease 10.6
28 tumor predisposition syndrome 10.5
29 cutaneous telangiectasia and cancer syndrome, familial 10.5
30 adenoma 10.5
31 inherited cancer-predisposing syndrome 10.5
32 goiter 10.5
33 lymphangioleiomyomatosis 10.4
34 chromophobe renal cell carcinoma 10.4
35 multinodular goiter 10.4
36 cystic kidney disease 10.4
37 skin disease 10.4
38 parathyroid adenoma 10.4
39 virus-associated trichodysplasia spinulosa 10.4
40 nodular medulloblastoma 10.3 PTCH1 CTNNB1
41 autosomal dominant non-syndromic intellectual disability 19 10.3 TFE3 CTNNB1
42 endometrioid ovary carcinoma 10.3 PTEN CTNNB1
43 hereditary leiomyomatosis and renal cell cancer 10.3 PTCH1 FH
44 beckwith-wiedemann syndrome 10.3
45 thyroid carcinoma, familial medullary 10.3
46 retinoblastoma 10.3
47 pancreatic cancer 10.3
48 pulmonary arteriovenous fistulas 10.3
49 incontinentia pigmenti 10.3
50 langerhans cell histiocytosis 10.3

Graphical network of the top 20 diseases related to Birt-Hogg-Dube Syndrome:



Diseases related to Birt-Hogg-Dube Syndrome

Symptoms & Phenotypes for Birt-Hogg-Dube Syndrome

Human phenotypes related to Birt-Hogg-Dube Syndrome:

58 31 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 emphysema 58 31 hallmark (90%) Very frequent (99-80%) HP:0002097
2 papule 58 31 hallmark (90%) Very frequent (99-80%) HP:0200034
3 skin tags 58 31 hallmark (90%) Very frequent (99-80%) HP:0010609
4 abnormality of retinal pigmentation 58 31 frequent (33%) Frequent (79-30%) HP:0007703
5 multiple lipomas 58 31 frequent (33%) Frequent (79-30%) HP:0001012
6 pulmonary sequestration 58 31 frequent (33%) Frequent (79-30%) HP:0100632
7 renal cell carcinoma 58 31 very rare (1%) Occasional (29-5%) HP:0005584
8 pneumothorax 58 31 occasional (7.5%) Occasional (29-5%) HP:0002107
9 medullary thyroid carcinoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0002865
10 parathyroid adenoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0002897
11 spontaneous pneumothorax 31 very rare (1%) HP:0002108
12 colon cancer 31 very rare (1%) HP:0003003
13 cutaneous leiomyoma 31 very rare (1%) HP:0007620
14 cutaneous leiomyosarcoma 31 very rare (1%) HP:0006755
15 fibrofolliculoma 31 very rare (1%) HP:0030436
16 sebaceous hyperplasia 31 very rare (1%) HP:0032227
17 trichodiscoma 31 very rare (1%) HP:0032228
18 large intestinal polyposis 31 HP:0030255
19 renal neoplasm 31 HP:0009726
20 renal cyst 31 HP:0000107
21 multiple pulmonary cysts 31 HP:0005948

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Genitourinary Kidneys:
renal cysts
renal tumors (in about 27% of patients)

Respiratory Lung:
lung cysts (in about 80% of patients)
bullous disease
spontaneous pneumothorax (in about 30% of patients)

Skin Nails Hair Skin:
fibrofolliculomas
acrochordons (skin tag)

Neoplasia:
renal carcinoma
parotid oncocytomas
neural tissue tumors
lipomas
angiolipomas

Head And Neck Face:
facial papules

Abdomen Gastrointestinal:
colonic polyps
colorectal adenomas

Skin Nails Hair Hair:
trichodiscomas (tumor of the hair disc)

Clinical features from OMIM®:

135150 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Birt-Hogg-Dube Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.18 CTNNB1 FH FLCN FNIP1 FNIP2 KRT7
2 homeostasis/metabolism MP:0005376 10.17 CTNNB1 FH FLCN FNIP1 FNIP2 KRT7
3 hematopoietic system MP:0005397 10.11 CTNNB1 FLCN FNIP1 MTOR PTCH1 PTEN
4 mortality/aging MP:0010768 10.07 CTNNB1 FH FLCN FNIP1 FNIP2 MADD
5 neoplasm MP:0002006 9.76 CTNNB1 FLCN FNIP1 FNIP2 PTCH1 PTEN
6 normal MP:0002873 9.56 CTNNB1 FNIP2 MTOR PTCH1 PTEN RRAGB
7 renal/urinary system MP:0005367 9.32 CTNNB1 FH FLCN FNIP1 FNIP2 KRT7

Drugs & Therapeutics for Birt-Hogg-Dube Syndrome

Drugs for Birt-Hogg-Dube Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Clotrimazole Approved, Vet_approved Phase 3 23593-75-1 2812
2
Miconazole Approved, Investigational, Vet_approved Phase 3 22916-47-8 4189
3
Sirolimus Approved, Investigational Phase 3 53123-88-9 6436030 5284616
4 Antibiotics, Antitubercular Phase 3
5 Pharmaceutical Solutions Phase 3
6 Anti-Bacterial Agents Phase 3
7 Anti-Infective Agents Phase 3
8 Antifungal Agents Phase 3
9
Everolimus Approved Phase 2 159351-69-6 6442177 70789204
10
Lactitol Approved, Investigational Phase 2 585-86-4 157355
11 Immunosuppressive Agents Phase 2
12 Immunologic Factors Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Topical Rapamycin to Treat Fibrofolliculomas in Birt-Hogg-Dubé Syndrome Completed NCT00928798 Phase 3 Rapamycin;placebo
2 Phase 2 Study of Everolimus Therapy in Patients With Birt-Hogg-Dube Syndrome (BHD)-Associated Kidney Cancer or Sporadic Chromophobe Renal Cancer Terminated NCT02504892 Phase 2 Everolimus
3 Prevalence of Birt-Hogg-Dubé Syndrome Among Patients With (Hereditary) Spontaneous Pneumothorax Unknown status NCT02916992 Phase 1
4 Assessment of Safety of Air Travel in Patients With Birt-Hogg-Dube Syndrome Unknown status NCT03040115
5 The Birt Hogg-Dube Syndrome: Identification of the Disease Gene and Characterization of the Predisposition of Renal Cancer Recruiting NCT00033137
6 MyVHL: Patient Natural History Study Recruiting NCT03749980

Search NIH Clinical Center for Birt-Hogg-Dube Syndrome

Cochrane evidence based reviews: birt-hogg-dube syndrome

Genetic Tests for Birt-Hogg-Dube Syndrome

Genetic tests related to Birt-Hogg-Dube Syndrome:

# Genetic test Affiliating Genes
1 Birt-Hogg-Dubé Syndrome 29

Anatomical Context for Birt-Hogg-Dube Syndrome

MalaCards organs/tissues related to Birt-Hogg-Dube Syndrome:

40
Kidney, Lung, Thyroid, Colon, Skin, Adrenal Gland, Breast

Publications for Birt-Hogg-Dube Syndrome

Articles related to Birt-Hogg-Dube Syndrome:

(show top 50) (show all 211)
# Title Authors PMID Year
1
Clinical and genetic spectrum of Birt-Hogg-Dube syndrome patients in whom pneumothorax and/or multiple lung cysts are the presenting feature. 25 6 57 61
20413710 2010
2
Constitutional FLCN mutations in patients with suspected Birt-Hogg-Dubé syndrome ascertained for non-cutaneous manifestations. 6 25 57
20618353 2011
3
BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports. 25 57 6
18234728 2008
4
Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome. 6 57 25
15852235 2005
5
Clinical and genetic studies of Birt-Hogg-Dubé syndrome. 6 57 25
12471204 2002
6
Birt-Hogg-Dube syndrome presenting as multiple oncocytic parotid tumors. 61 25 6
23050938 2012
7
Early onset of renal cancer in a family with Birt-Hogg-Dubé syndrome. 6 57
19320655 2009
8
Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome. 57 6
12204536 2002
9
Cutaneous melanoma in Birt-Hogg-Dubé syndrome: part of the clinical spectrum? 6 25
28869776 2018
10
Genetic screening of the FLCN gene identify six novel variants and a Danish founder mutation. 25 6
27734835 2017
11
Genetic, epidemiologic and clinicopathologic studies of Japanese Asian patients with Birt-Hogg-Dubé syndrome. 6 25
27220747 2016
12
Risk of spontaneous pneumothorax due to air travel and diving in patients with Birt-Hogg-Dubé syndrome. 25 6
27652079 2016
13
Molecular genetics and clinical features of Birt-Hogg-Dubé syndrome. 25 6
26334087 2015
14
Topical rapamycin as a treatment for fibrofolliculomas in Birt-Hogg-Dubé syndrome: a double-blind placebo-controlled randomized split-face trial. 25 6
24910976 2014
15
Birt-Hogg-Dubé syndrome in a patient with melanoma and a novel mutation in the FCLN gene. 25 6
23414156 2013
16
Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families. 25 6
22146830 2011
17
Investigation of the Birt-Hogg-Dube tumour suppressor gene (FLCN) in familial and sporadic colorectal cancer. 6 25
20522427 2010
18
Birt-Hogg-Dubé syndrome: clinical and genetic studies of 10 French families. 25 6
19785621 2010
19
Risk of renal and colonic neoplasms and spontaneous pneumothorax in the Birt-Hogg-Dubé syndrome. 57 25
11927500 2002
20
Birt-Hogg-Dubé syndrome: a novel marker of kidney neoplasia. 25 57
10522666 1999
21
Birt-Hogg-Dubé syndrome and Hornstein-Knickenberg syndrome are the same. Different sectioning technique as the cause of different histology. 57 25
10189247 1999
22
Perifollicular fibromatosis cutis with polyps of the colon--a cutaneo-intestinal syndrome sui generis. 25 57
1200700 1975
23
Birt-Hogg-Dube syndrome prospectively detected by review of chest computed tomography scans. 6 61
28151982 2017
24
Renal angiomyolipoma in Birt-Hogg-Dube syndrome: A case study supporting overlap with tuberous sclerosis complex. 6 61
27643397 2016
25
A rapid NGS strategy for comprehensive molecular diagnosis of Birt-Hogg-Dubé syndrome in patients with primary spontaneous pneumothorax. 6 61
27229674 2016
26
Recurrent spontaneous pneumothoraces and bullous emphysema. A novel mutation causing Birt-Hogg-Dube syndrome. 6 61
27642565 2016
27
Birt-Hogg-Dube syndrome is a novel ciliopathy. 61 6
23784378 2013
28
Spontaneous pneumothorax due to Birt-Hogg-Dube syndrome in a Chinese family. 6 61
19659657 2009
29
Identification and characterization of a novel folliculin-interacting protein FNIP2. 61 6
18403135 2008
30
Multiple lipomas, angiolipomas, and parathyroid adenomas in a patient with Birt-Hogg-Dube syndrome. 57 61
8734663 1996
31
Multiple fibrofolliculomas with trichodiscomas and acrochordons. 57 61
7458379 1981
32
Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. 61 57
596896 1977
33
A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dubé syndrome. 57
32612235 2020
34
Birt-Hogg-Dube Syndrome with a Novel Mutation in the FLCN Gene. 25 61
28805452 2017
35
Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. 6
28724667 2017
36
Medullary thyroid carcinoma in a patient with Birt-Hogg-Dube syndrome. 25 61
28242119 2017
37
Clinical and genetic characteristics of chinese patients with Birt-Hogg-Dubé syndrome. 6
28558743 2017
38
Characterization of a splice-site mutation in the tumor suppressor gene FLCN associated with renal cancer. 6
28499369 2017
39
Multiple chromophobe and clear cell renal cancer in a patient affected by Birt-Hogg-Dubè syndrome: a case report. 6
28009417 2017
40
An 18-year-old man with recurrent pneumothorax since he was 10-year-old. 6
27257988 2016
41
Haploinsufficiency of the folliculin gene leads to impaired functions of lung fibroblasts in patients with Birt-Hogg-Dubé syndrome. 6
27905298 2016
42
Familial pneumothoraces: Birt-Hogg-Dubé syndrome. 6
27906882 2016
43
Undefined familial colorectal cancer and the role of pleiotropism in cancer susceptibility genes. 6
27356891 2016
44
Birt-Hogg-Dubé Syndrome Presenting as a Nevus Comedonicus-Like Lesion in an 8-Year-Old Boy. 6
27470329 2016
45
Capture-based high-coverage NGS: a powerful tool to uncover a wide spectrum of mutation types. 6
26402642 2016
46
Are lung cysts in renal cell cancer (RCC) patients an indication for FLCN mutation analysis? 6
26603437 2016
47
Birt-Hogg-Dubé syndrome detected incidentally by asymptomatic bilateral pneumothorax in health screening: a case of a young Japanese woman. 6
26943385 2015
48
Genetic analysis of familial spontaneous pneumothorax in an Indian family. 6
25827758 2015
49
Renal cell tumour characteristics in patients with the Birt-Hogg-Dubé cancer susceptibility syndrome: a retrospective, multicentre study. 6
25519458 2014
50
Characterization of pulmonary cysts in Birt-Hogg-Dubé syndrome: histopathological and morphometric analysis of 229 pulmonary cysts from 50 unrelated patients. 6
24393238 2014

Variations for Birt-Hogg-Dube Syndrome

ClinVar genetic disease variations for Birt-Hogg-Dube Syndrome:

6 (show top 50) (show all 795)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FLCN FLCN, 2-BP DEL/2-BP INS, NT610 Indel Pathogenic 3378 GRCh37:
GRCh38:
2 FLCN NM_144997.7(FLCN):c.987del (p.Ser330fs) Deletion Pathogenic 241933 rs878855221 GRCh37: 17:17122408-17122408
GRCh38: 17:17219094-17219094
3 FLCN NM_144997.7(FLCN):c.202del (p.Ser68fs) Deletion Pathogenic 409389 rs1060502370 GRCh37: 17:17131250-17131250
GRCh38: 17:17227936-17227936
4 FLCN NM_144997.7(FLCN):c.433del (p.Asp145fs) Deletion Pathogenic 431057 rs1135401752 GRCh37: 17:17127421-17127421
GRCh38: 17:17224107-17224107
5 FLCN NC_000017.10:g.(?_17116047)_(17118400_?)del Deletion Pathogenic 460576 GRCh37: 17:17116047-17118400
GRCh38:
6 FLCN NM_144997.7(FLCN):c.121C>T (p.Gln41Ter) SNV Pathogenic 571073 rs1254608489 GRCh37: 17:17131331-17131331
GRCh38: 17:17228017-17228017
7 FLCN NM_144997.7(FLCN):c.1177-169_1538del Deletion Pathogenic 638865 GRCh37: 17:17118299-17119986
GRCh38: 17:17214985-17216672
8 FLCN NM_144997.7(FLCN):c.273del (p.His92fs) Deletion Pathogenic 838883 GRCh37: 17:17129613-17129613
GRCh38: 17:17226299-17226299
9 FLCN NC_000017.11:g.(?_17216370)_(17228161_?)del Deletion Pathogenic 831982 GRCh37: 17:17119684-17131475
GRCh38:
10 FLCN NC_000017.11:g.(?_17214975)_(17215326_?)del Deletion Pathogenic 832607 GRCh37: 17:17118289-17118640
GRCh38:
11 FLCN NM_144997.7(FLCN):c.523_535del (p.Ile175fs) Deletion Pathogenic 857729 GRCh37: 17:17127319-17127331
GRCh38: 17:17224005-17224017
12 FLCN NM_144997.7(FLCN):c.1054_1055del (p.Met352fs) Deletion Pathogenic 863926 GRCh37: 17:17122340-17122341
GRCh38: 17:17219026-17219027
13 FLCN NM_144997.7(FLCN):c.1397del (p.Val466fs) Deletion Pathogenic 864273 GRCh37: 17:17118534-17118534
GRCh38: 17:17215220-17215220
14 FLCN NC_000017.11:g.(?_17221527)_(17224153_?)del Deletion Pathogenic 830501 GRCh37: 17:17124841-17127467
GRCh38:
15 FLCN Insertion Pathogenic 870301 GRCh37:
GRCh38:
16 FLCN NM_144997.7(FLCN):c.1440del (p.Thr481fs) Deletion Pathogenic 664632 rs1597579055 GRCh37: 17:17118397-17118397
GRCh38: 17:17215083-17215083
17 FLCN NM_144997.7(FLCN):c.167del (p.Ser56fs) Deletion Pathogenic 649905 rs1597617757 GRCh37: 17:17131285-17131285
GRCh38: 17:17227971-17227971
18 FLCN NM_144997.7(FLCN):c.312del (p.Lys105fs) Deletion Pathogenic 655361 rs1597612985 GRCh37: 17:17129574-17129574
GRCh38: 17:17226260-17226260
19 FLCN NM_144997.7(FLCN):c.1326del (p.His442fs) Deletion Pathogenic 657432 rs1597580340 GRCh37: 17:17118605-17118605
GRCh38: 17:17215291-17215291
20 FLCN NM_144997.7(FLCN):c.239del (p.Asp80fs) Deletion Pathogenic 409393 rs1060502371 GRCh37: 17:17131213-17131213
GRCh38: 17:17227899-17227899
21 FLCN NM_144997.7(FLCN):c.563del (p.Phe188fs) Deletion Pathogenic 659786 rs1597606551 GRCh37: 17:17127291-17127291
GRCh38: 17:17223977-17223977
22 FLCN NM_144997.7(FLCN):c.913del (p.Glu305fs) Deletion Pathogenic 935431 GRCh37: 17:17122482-17122482
GRCh38: 17:17219168-17219168
23 FLCN NM_144997.7(FLCN):c.228del (p.Lys78fs) Deletion Pathogenic 946478 GRCh37: 17:17131224-17131224
GRCh38: 17:17227910-17227910
24 FLCN NM_144997.7(FLCN):c.576_586del (p.Lys192fs) Deletion Pathogenic 963006 GRCh37: 17:17127268-17127278
GRCh38: 17:17223954-17223964
25 FLCN NM_144997.7(FLCN):c.1318del (p.Glu440fs) Deletion Pathogenic 529989 rs1555607273 GRCh37: 17:17118613-17118613
GRCh38: 17:17215299-17215299
26 FLCN NM_144997.7(FLCN):c.1358_1374del (p.Gly453fs) Deletion Pathogenic 529992 rs1555607179 GRCh37: 17:17118557-17118573
GRCh38: 17:17215243-17215259
27 FLCN NM_144997.7(FLCN):c.1128G>A (p.Trp376Ter) SNV Pathogenic 960732 GRCh37: 17:17120431-17120431
GRCh38: 17:17217117-17217117
28 FLCN NM_144997.7(FLCN):c.1359del (p.Cys454fs) Deletion Pathogenic 529979 rs1555607212 GRCh37: 17:17118572-17118572
GRCh38: 17:17215258-17215258
29 FLCN NM_144997.7(FLCN):c.510C>A (p.Tyr170Ter) SNV Pathogenic 565561 rs1567819834 GRCh37: 17:17127344-17127344
GRCh38: 17:17224030-17224030
30 FLCN NM_144997.7(FLCN):c.365_372del (p.Arg122fs) Deletion Pathogenic 565562 rs1567822638 GRCh37: 17:17129514-17129521
GRCh38: 17:17226200-17226207
31 FLCN NM_144997.7(FLCN):c.804del (p.Arg268_Leu269insTer) Deletion Pathogenic 575582 rs1567816285 GRCh37: 17:17124918-17124918
GRCh38: 17:17221604-17221604
32 FLCN NM_144997.7(FLCN):c.1451del (p.Asn484fs) Deletion Pathogenic 575959 rs1567807238 GRCh37: 17:17118386-17118386
GRCh38: 17:17215072-17215072
33 FLCN NM_144997.7(FLCN):c.887C>G (p.Ser296Ter) SNV Pathogenic 571069 rs1490424623 GRCh37: 17:17122508-17122508
GRCh38: 17:17219194-17219194
34 FLCN NM_144997.7(FLCN):c.828delinsAGA (p.Ala277fs) Indel Pathogenic 241931 rs878855220 GRCh37: 17:17124894-17124894
GRCh38: 17:17221580-17221580
35 FLCN NM_144997.7(FLCN):c.1451_1458dup (p.Glu487fs) Duplication Pathogenic 460596 rs757197845 GRCh37: 17:17118378-17118379
GRCh38: 17:17215064-17215065
36 FLCN NM_144997.7(FLCN):c.979dup (p.Ala327fs) Duplication Pathogenic 460642 rs1555608552 GRCh37: 17:17122415-17122416
GRCh38: 17:17219101-17219102
37 FLCN NM_144997.7(FLCN):c.991_992TC[3] (p.Ser333fs) Microsatellite Pathogenic 529991 rs1555608515 GRCh37: 17:17122397-17122398
GRCh38: 17:17219083-17219084
38 FLCN NM_144997.7(FLCN):c.942_943AG[2] (p.Ser316fs) Microsatellite Pathogenic 662576 rs1597591875 GRCh37: 17:17122448-17122449
GRCh38: 17:17219134-17219135
39 FLCN NM_144997.7(FLCN):c.808dup (p.Thr270fs) Duplication Pathogenic 835373 GRCh37: 17:17124913-17124914
GRCh38: 17:17221599-17221600
40 FLCN NM_144997.7(FLCN):c.420dup (p.Ile141fs) Duplication Pathogenic 845558 GRCh37: 17:17127433-17127434
GRCh38: 17:17224119-17224120
41 FLCN NM_144997.7(FLCN):c.739_761delinsCAGCGAG (p.Asp247fs) Indel Pathogenic 845669 GRCh37: 17:17125833-17125855
GRCh38: 17:17222519-17222541
42 FLCN NM_144997.7(FLCN):c.634C>T (p.Gln212Ter) SNV Pathogenic 253232 rs558699420 GRCh37: 17:17125960-17125960
GRCh38: 17:17222646-17222646
43 FLCN NM_144997.7(FLCN):c.1532G>A (p.Trp511Ter) SNV Pathogenic 253257 rs879255682 GRCh37: 17:17118305-17118305
GRCh38: 17:17214991-17214991
44 FLCN NM_144997.7(FLCN):c.735_738del (p.Ser246fs) Deletion Pathogenic 253234 rs879255662 GRCh37: 17:17125856-17125859
GRCh38: 17:17222542-17222545
45 FLCN NM_144997.7(FLCN):c.853C>T (p.Gln285Ter) SNV Pathogenic 253239 rs879255667 GRCh37: 17:17124869-17124869
GRCh38: 17:17221555-17221555
46 FLCN NM_144997.7(FLCN):c.1188del (p.Val397fs) Deletion Pathogenic 618131 rs1567809782 GRCh37: 17:17119806-17119806
GRCh38: 17:17216492-17216492
47 FLCN NM_144997.7(FLCN):c.1528del (p.Glu510fs) Deletion Pathogenic 253255 rs879255680 GRCh37: 17:17118309-17118309
GRCh38: 17:17214995-17214995
48 FLCN NM_144997.7(FLCN):c.1124_1139del (p.Ile375fs) Deletion Pathogenic 253245 rs879255673 GRCh37: 17:17120420-17120435
GRCh38: 17:17217106-17217121
49 FLCN NM_144997.7(FLCN):c.1483_1486CTGT[3] (p.Asp498fs) Microsatellite Pathogenic 253254 rs879255679 GRCh37: 17:17118346-17118347
GRCh38: 17:17215032-17215033
50 FLCN NM_144997.7(FLCN):c.453del (p.Phe152fs) Deletion Pathogenic 253230 rs879255660 GRCh37: 17:17127401-17127401
GRCh38: 17:17224087-17224087

UniProtKB/Swiss-Prot genetic disease variations for Birt-Hogg-Dube Syndrome:

72
# Symbol AA change Variation ID SNP ID
1 FLCN p.Ser108Ile VAR_066023
2 FLCN p.Lys508Arg VAR_066029 rs199643834

Cosmic variations for Birt-Hogg-Dube Syndrome:

9 (show top 50) (show all 2860)
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM122741017 TP53 skin,trunk,carcinoma,NS c.440G>A p.G147E 17:7673784-7673784 15
2 COSM144653327 TP53 skin,face,carcinoma,NS c.*131C>T p.? 17:7670685-7670685 15
3 COSM144659648 TP53 skin,chest,carcinoma,NS c.716C>T p.P239L 17:7673787-7673787 15
4 COSM112254631 TP53 skin,face,carcinoma,NS c.586C>T p.R196* 17:7674945-7674945 15
5 COSM143371865 TP53 skin,face,carcinoma,NS c.469C>T p.R157* 17:7674945-7674945 15
6 COSM93183824 TP53 skin,face,carcinoma,NS c.680C>T p.S227F 17:7674283-7674283 15
7 COSM143943797 TP53 skin,neck,carcinoma,NS c.266G>A p.R89Q 17:7674220-7674220 15
8 COSM121875437 TP53 skin,face,carcinoma,NS c.178C>T p.Q60* 17:7674957-7674957 15
9 COSM143388508 TP53 skin,face,carcinoma,NS c.629G>C p.R210T 17:7674217-7674217 15
10 COSM111758868 TP53 skin,face,carcinoma,NS c.742C>T p.R248W 17:7674221-7674221 15
11 COSM142570304 TP53 skin,face,carcinoma,NS c.715C>T p.P239S 17:7673788-7673788 15
12 COSM142560384 TP53 skin,face,carcinoma,NS c.616G>T p.G206C 17:7674230-7674230 15
13 COSM142742951 TP53 skin,face,carcinoma,NS c.315G>A p.Q105= 17:7675180-7675180 15
14 COSM105639284 TP53 skin,face,carcinoma,NS c.712T>A p.C238S 17:7674251-7674251 15
15 COSM112253879 TP53 skin,face,carcinoma,NS c.742C>T p.R248W 17:7674221-7674221 15
16 COSM112253698 TP53 skin,chest,carcinoma,NS c.853G>A p.E285K 17:7673767-7673767 15
17 COSM121878773 TP53 skin,face,carcinoma,NS c.241C>T p.R81* 17:7674894-7674894 15
18 COSM111776406 TP53 skin,face,carcinoma,NS c.993+1G>A p.? 17:7673534-7673534 15
19 COSM142837551 TP53 skin,face,carcinoma,NS c.742C>T p.R248W 17:7674221-7674221 15
20 COSM122742188 TP53 skin,face,carcinoma,NS c.58C>T p.P20S 17:7675158-7675158 15
21 COSM122735020 TP53 skin,face,carcinoma,NS c.190C>T p.R64* 17:7674945-7674945 15
22 COSM88272290 TP53 skin,trunk,carcinoma,NS c.480G>C p.M160I 17:7675132-7675132 15
23 COSM144028845 TP53 skin,face,carcinoma,NS c.679T>A p.C227S 17:7674251-7674251 15
24 COSM144021997 TP53 skin,face,carcinoma,NS c.421C>T p.P141S 17:7675158-7675158 15
25 COSM144015364 TP53 skin,face,carcinoma,NS c.604C>T p.R202* 17:7674894-7674894 15
26 COSM143944858 TP53 skin,trunk,carcinoma,NS c.109C>T p.R37* 17:7674945-7674945 15
27 COSM143156879 TP53 skin,trunk,carcinoma,NS c.245C>T p.S82F 17:7674241-7674241 15
28 COSM144316210 TP53 skin,trunk,carcinoma,NS c.716C>T p.P239L 17:7673787-7673787 15
29 COSM121877621 TP53 skin,face,carcinoma,NS c.190C>T p.R64* 17:7674945-7674945 15
30 COSM93201188 TP53 skin,face,carcinoma,NS c.993+1G>A p.? 17:7673534-7673534 15
31 COSM106455733 TP53 skin,trunk,carcinoma,NS c.853G>C p.E285Q 17:7673767-7673767 15
32 COSM144658487 TP53 skin,face,carcinoma,NS c.143C>A p.P48Q 17:7676109-7676109 15
33 COSM142639459 TP53 skin,face,carcinoma,NS c.597T>A p.C199* 17:7674249-7674249 15
34 COSM105620390 TP53 skin,face,carcinoma,NS c.733G>T p.G245C 17:7674230-7674230 15
35 COSM144014436 TP53 skin,face,carcinoma,NS c.553C>T p.R185* 17:7674945-7674945 15
36 COSM112253194 TP53 skin,face,carcinoma,NS c.833C>G p.P278R 17:7673787-7673787 15
37 COSM112263720 TP53 skin,face,carcinoma,NS c.832C>T p.P278S 17:7673788-7673788 15
38 COSM122272676 TP53 skin,face,carcinoma,NS c.190C>T p.R64* 17:7674945-7674945 15
39 COSM143157606 TP53 skin,trunk,carcinoma,NS c.109C>T p.R37* 17:7674945-7674945 15
40 COSM144310437 TP53 skin,trunk,carcinoma,NS c.727C>T p.R243W 17:7673776-7673776 15
41 COSM111766659 TP53 skin,chest,carcinoma,NS c.833C>T p.P278L 17:7673787-7673787 15
42 COSM93239210 TP53 skin,face,carcinoma,NS c.706T>C p.Y236H 17:7674257-7674257 15
43 COSM144651436 TP53 skin,face,carcinoma,NS c.625C>T p.R209W 17:7674221-7674221 15
44 COSM105620642 TP53 skin,face,carcinoma,NS c.742C>T p.R248W 17:7674221-7674221 15
45 COSM144013959 TP53 skin,face,carcinoma,NS c.502C>T p.H168Y 17:7675077-7675077 15
46 COSM143949062 TP53 skin,face,carcinoma,NS c.263A>C p.N88T 17:7674223-7674223 15
47 COSM112571322 TP53 skin,trunk,carcinoma,NS c.480G>C p.M160I 17:7675132-7675132 15
48 COSM112253674 TP53 skin,trunk,carcinoma,NS c.722C>T p.S241F 17:7674241-7674241 15
49 COSM121876459 TP53 skin,face,carcinoma,NS c.346C>T p.R116W 17:7674221-7674221 15
50 COSM111775215 TP53 skin,face,carcinoma,NS c.746G>C p.R249T 17:7674217-7674217 15

Expression for Birt-Hogg-Dube Syndrome

Search GEO for disease gene expression data for Birt-Hogg-Dube Syndrome.

Pathways for Birt-Hogg-Dube Syndrome

Pathways related to Birt-Hogg-Dube Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 mTOR signaling pathway hsa04150

Pathways related to Birt-Hogg-Dube Syndrome according to GeneCards Suite gene sharing:

(show all 17)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.82 TSC2 RRAGC RRAGB RRAGA PTEN MTOR
2 12.68 PTEN PTCH1 MTOR FH CTNNB1
3
Show member pathways
12.46 TFE3 PTEN MTOR FLCN FH
4 12.24 RRAGC RRAGB RRAGA MTOR
5
Show member pathways
12.23 TSC2 RRAGC RRAGB RRAGA MTOR
6
Show member pathways
12.09 TSC2 PTEN PTCH1 MTOR CTNNB1
7 12.02 TSC2 RRAGC RRAGB RRAGA MTOR FLCN
8 11.98 TSC2 PTEN MTOR CTNNB1
9 11.83 TSC2 MTOR CTNNB1
10 11.8 TSC2 PTEN MTOR CTNNB1
11
Show member pathways
11.74 TSC2 RRAGC RRAGB RRAGA PTEN MTOR
12
Show member pathways
11.72 TSC2 RRAGC RRAGB RRAGA MTOR
13 11.67 TSC2 RRAGB PTEN FNIP2
14 11.64 TSC2 SMCR8 RRAGC RRAGB RRAGA PTEN
15 11.56 TSC2 RRAGC RRAGB RRAGA PTEN MTOR
16 11.44 TSC2 MTOR CTNNB1
17 11.13 TSC2 PTEN MTOR

GO Terms for Birt-Hogg-Dube Syndrome

Cellular components related to Birt-Hogg-Dube Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 10.22 TSC2 TFE3 SMCR8 RRAGC RRAGB RRAGA
2 cytoplasm GO:0005737 10.22 TSC2 TFE3 SMCR8 RRAGC RRAGB RRAGA
3 cytosol GO:0005829 10.13 TSC2 TFE3 RRAGC RRAGB RRAGA RAB35
4 lysosomal membrane GO:0005765 9.85 RRAGB RRAGA MTOR FNIP2 FNIP1 FLCN
5 postsynaptic cytosol GO:0099524 9.46 PTEN MTOR
6 cell projection membrane GO:0031253 9.43 RAB35 CTNNB1
7 Gtr1-Gtr2 GTPase complex GO:1990131 9.33 RRAGC RRAGB RRAGA
8 lysosome GO:0005764 9.23 TSC2 RRAGC RRAGB RRAGA MTOR FNIP2
9 EGO complex GO:0034448 9.13 RRAGC RRAGB RRAGA

Biological processes related to Birt-Hogg-Dube Syndrome according to GeneCards Suite gene sharing:

(show all 26)
# Name GO ID Score Top Affiliating Genes
1 cell cycle arrest GO:0007050 9.84 RRAGC RRAGB RRAGA MTOR
2 response to estradiol GO:0032355 9.79 PTEN PTCH1 CTNNB1
3 cellular protein localization GO:0034613 9.76 RRAGC RRAGB RRAGA CTNNB1
4 negative regulation of protein kinase B signaling GO:0051898 9.75 TSC2 PTEN FLCN
5 regulation of macroautophagy GO:0016241 9.73 RRAGC RRAGB RRAGA MTOR
6 negative regulation of TOR signaling GO:0032007 9.7 TSC2 FNIP1 FLCN
7 regulation of TOR signaling GO:0032006 9.69 RRAGC RRAGB FLCN
8 TOR signaling GO:0031929 9.67 MTOR FNIP1 FLCN
9 regulation of protein phosphorylation GO:0001932 9.67 MTOR FNIP2 FNIP1 FLCN
10 positive regulation of TORC1 signaling GO:1904263 9.65 RRAGB RRAGA FLCN
11 regulation of autophagy GO:0010506 9.65 SMCR8 RRAGC RRAGB RRAGA MTOR
12 cell fate determination GO:0001709 9.63 PTCH1 CTNNB1
13 regulation of protein kinase B signaling GO:0051896 9.62 PTEN MTOR
14 cellular response to amino acid stimulus GO:0071230 9.62 RRAGC RRAGB RRAGA MTOR
15 negative regulation of phosphatidylinositol 3-kinase signaling GO:0014067 9.61 TSC2 PTEN
16 negative regulation of macroautophagy GO:0016242 9.61 SMCR8 MTOR
17 anoikis GO:0043276 9.6 TSC2 MTOR
18 cellular response to leucine starvation GO:1990253 9.59 RRAGB MTOR
19 negative regulation of cell size GO:0045792 9.58 PTEN MTOR
20 regulation of osteoclast differentiation GO:0045670 9.58 TFE3 MTOR CTNNB1
21 regulation of TORC1 signaling GO:1903432 9.57 SMCR8 RRAGC
22 negative regulation of mitochondrion organization GO:0010823 9.56 FNIP1 FLCN
23 regulation of pro-B cell differentiation GO:2000973 9.55 FNIP1 FLCN
24 cellular response to amino acid starvation GO:0034198 9.55 RRAGC RRAGB RRAGA MTOR FLCN
25 cellular response to starvation GO:0009267 9.43 RRAGC RRAGB RRAGA MTOR FNIP1 FLCN
26 positive regulation of TOR signaling GO:0032008 9.1 SMCR8 RRAGC RRAGB RRAGA FNIP1 FLCN

Molecular functions related to Birt-Hogg-Dube Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 GTPase activity GO:0003924 9.46 RRAGC RRAGB RRAGA RAB35
2 guanyl-nucleotide exchange factor activity GO:0005085 9.26 SMCR8 MADD FNIP1 FLCN
3 ATPase inhibitor activity GO:0042030 8.62 FNIP2 FNIP1

Sources for Birt-Hogg-Dube Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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