TSC1

Cilia effects upon perturbation of TSC1

Cilia number / % ciliated:

Unknown

Loss-of-function effect:

Shorter cilia

Overexpression effect:

Unknown

Ciliogenesis screen results (5 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-1.54) PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381
• Pusapati et al. 2018 (CRISPR) [CRISPR]: Negative Regulator (Hh signaling, pos_rank=30, lfc=1.19) PMID:30270045

Phenotypes

Mouse phenotype:

abnormal thymus morphology, increased startle reflex, preweaning lethality, complete penetrance, enlarged thymus

Ciliopathy associations

• Autosomal Recessive Polycystic Kidney Disease

References: PMID:19692352

Subcellular localization

basal body, cytosol, transition zone

References: PMID:41005307, PMID:19008302, PMID:18845692, PMID:29396625, PMID:19321600

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Metabolism
• Protein processing & maturation
• Cell migration & adhesion
• Cardiac & muscle development
• Transition zone

Function

Regulates the length of cilia. Form a complex with TSC2 that negatively regulates the nTOR pathway and, in turn, cell growth, proliferation and survival (19008302). Mutations have been associated with Tuberous sclerosis complex and polycystic kidney disease. Loss of Tsc1 or Tsc2 enhances ciliary formation and elongation (18845692). Required for activation of canonical TGF-β signaling. Regulates Smoothened (SMO)- dependent HH signaling in cilia (29396625). Role in maintaining cell polarity (19321600).