PIK3C2A

Cilia effects upon perturbation of PIK3C2A

Cilia number / % ciliated:

No effect

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (4 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.67) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381
• Pusapati et al. 2018 (CRISPR) [CRISPR]: Negative Regulator (Hh signaling, pos_rank=128, lfc=0.77) PMID:30270045

Phenotypes

Mouse phenotype:

increased neutrophil cell number, decreased lymphocyte cell number, embryonic growth retardation, abnormal embryo size, embryonic lethality prior to tooth bud stage, preweaning lethality, complete penetrance, enlarged lymph nodes, decreased locomotor activity

Ciliopathy associations

• Oculoskeletodental Syndrome

Subcellular localization

basal body, cilia, cytosol, endosome, nucleus

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Cell migration & adhesion
• Signaling (Hedgehog, GPCRs, ion channels)
• Cardiac & muscle development
• Muscle contraction & physiology

Function

Mutations cause syndromic short stature, skeletal abnormalities, and cataracts associated with ciliary dysfunction (31034465). Critical for the formation of cilia and for receptor mediated endocytosis. Promotes the activation and pericentriolar localisation of Rab11+ vesicles, triggers the Rab8- dependent pathway and translocation of Smo to the primary cilium. Controls the production of PtdIns3P at the endocytic recycling compartment located at the base of the primary cilium (24697898). PI3KC2伪- dependent and VPS34- independent generation of PI3P controls primary cilium- mediated autophagy in response to shear stress (31941925). Oculoskeletodental syndrome (OCSKD) is a rare autosomal recessive ciliopathy caused by PIK3C2A loss-of-function variants, characterized by ocular, skeletal, and dental anomalies(41703929).