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FB2026_01
,
released March 12, 2026
This report describes Birt-Hogg-Dube syndrome (BHD); BHD exhibits autosomal dominant inheritance. The human gene implicated in this disease is FLCN, which encodes a GTPase-activating protein with roles in diverse metabolic pathways and cellular processes. There is a single orthologous gene in Drosophila, Dmel\BHD, for which an amorphic mutation, overexpression constructs, and RNAi targeting constructs have been generated.
A UAS construct of the human Hsap\FLCN has been introduced into flies; partial heterologous rescue (functional complementation) of Dmel\BHD loss-of-function phenotypes has been demonstrated.
Animals homozygous for a null mutation of Dmel\BHD typically die during the larval stage; larvae grow slowly and stop development before pupation, displaying various characteristics of malnutrition. Growth delay, but not viablity, can be rescued by high levels of yeast or supplementation with leucine (but not other amino acids). Work in Drosophila supports a role for FLCN in iron metabolism: partial rescue of the larval BHD null phenotypes is observed for larvae fed iron-rich food.
[updated Jul. 2021 by FlyBase; FBrf0222196]
[BIRT-HOGG-DUBE SYNDROME 1; BHD1](https://omim.org/entry/135150)
[FOLLICULIN; FLCN](https://omim.org/entry/607273)
Birt-Hogg-Dube 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-Dube syndrome is characterized by multiple noncancerous 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-Dube syndrome is associated with an elevated risk of developing cancerous or noncancerous kidney tumors. [MedlinePlus, Birt-Hogg-Dube syndrome; 2021.07.18]
Birt-Hogg-Dube syndrome is characterized by hair follicle hamartomas, kidney tumors, and spontaneous pneumothorax (Nickerson et al., 2002; pubmed:12204536). Primary spontaneous pneumothorax (MIM:173600) is an allelic disorder that may represent a milder part of the clinical spectrum of the BHD syndrome. [from MIM:135150; 2021.07.18]
Birt-Hogg-Dube syndrome (BHD) is caused by heterozygous mutation in the FLCN gene.[from MIM:135150; 2021.07.18]
Functional studies support a role for FLCN in diverse metabolic pathways and cellular processes that include modulation of the mTOR pathway, regulation of PGC1α and mitochondrial biogenesis, cell-cell adhesion and RhoA signaling, control of TFE3/TFEB transcriptional activity, amino acid-dependent activation of mTORC1 on lysosomes through Rag GTPases, and regulation of autophagy (Schmidt and Linehan, 2018; pubmed:28970150).
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human FLCN (1 Drosophila to 1 human). Dmel\BHD shares 60% identity and 71% similarity with the human gene.