VPS4A

Cilia effects upon perturbation of VPS4A

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Hyper-ciliogenesis (z=2.09) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Mouse phenotype:

protruding tongue, preweaning lethality, complete penetrance, unresponsive to tactile stimuli, abnormal body wall morphology, abnormal embryo size, increased spleen weight, abnormal skin morphology, enlarged spleen

Human ciliopathy phenotype:

cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome

Subcellular localization

basal body, cytosol

References: PMID:29463826, PMID:33186545

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• Metabolism
• Viral interactions
• Protein processing & maturation

Function

Dynamic component of both centrioles. Regulates centrosome localisation and levels of gamma-tubulin, centriolar satellite stability and ciliogenesis. Rssential for activation of membrane remodeling during cilium extention. Depletion alters centrosome numbers and size (29463826).De Novo VPS4A Mutations Cause Multisystem Disease with Abnormal Neurodevelopment, with mutations affecting Mutations affected other ESCRT-dependent cellular processes, including regulation of centrosome number, primary cilium morphology, nuclear membrane morphology, chromosome segregation, mitotic spindle formation, and cell cycle progression (33186545)