GAS8

Cilia effects upon perturbation of GAS8

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-1.94) PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Mouse phenotype:

preweaning lethality, complete penetrance

Human ciliopathy phenotype:

primary ciliary dyskinesia

Ciliopathy associations

• Primary Ciliary Dyskinesia

Subcellular localization

cilia

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• T cell biology
• Reproduction & sperm
• Cell migration & adhesion
• Signaling (Hedgehog, GPCRs, ion channels)

Function

Role in ciliary motility. Implicated in the Hh sig ling pathway by binding to Smo and regulating its traficking into the cilium (21659505). Mutations are associated with human disease as a cause of severe PCD phenotypes (27472056). GAS8 is required for motile cilia function. Loss of GAS8 causes shorter and structurally abnormal cilia. It interacts with the dynein regulatory complex and regulates Hedgehog signaling via Smoothened localization. (27472056, 21659505)