FLCN

Cilia effects upon perturbation of FLCN

Cilia number / % ciliated:

Little effect

Loss-of-function effect:

Shorter (under flow stress) / no effect (no-flow)

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-9.51) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-3.15) PMID:29459680
• Pusapati et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, neg_rank=264, lfc=-0.66) PMID:30270045

Phenotypes

Human ciliopathy phenotype:

nonpapillary renal cell carcinoma; renal carcinoma; kidney oncocytoma

Ciliopathy associations

• Birt-Hogg-Dubé Syndrome

Subcellular localization

basal body, nucleus, transition zone

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Metabolism
• T cell biology
• Signaling (Hedgehog, GPCRs, ion channels)
• Transition zone

Function

Part of the mechanosensory machinery of primary cilia. Tumor suppressor associated with Birt-Hogg-Dub茅 (BHD) syndrome. Down-regulation of mTORC1 sig ling pathway through primary cilia, it recruits and associates with LKB1 and recruits the ki se to primary cilia for activation of AMPK (27072130). FLCN expression levels are critically important for correct timing of ciliogenesis and intracellular transport events involved in ciliogenesis (23784378).