FSD1L

Cilia effects upon perturbation of FSD1L

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.81) 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:

preweaning lethality; complete penetrance

Human ciliopathy phenotype:

Bi-allelic pathogenic variants cause severe hydrocephalus, corpus callosum agenesis, and absent pyramid decussation OR neurodevelopmental syndrome with severe intellectual disability, spastic tetraparesis, reduced vision, epilepsy, and corpus callosum agenesis/hypoplasia (11 individuals from 6 families).

Ciliopathy associations

• Hydrocephalus with Corpus Callosum Agenesis

Subcellular localization

golgi apparatus, plasma membrane, transition zone, vesicles

Functional category

• Non-motile cilium / primary cilium; Ciliary assembly/disassembly; Cilia???cytoskeleton/adhesion links

Function

In neural progenitors, FSD1L localized with microtubules of the mitotic spindle during M phase and to the transition zone and along the axoneme of the primary cilium during interphase. In line with this, fibroblasts from affected individuals exhibited marked alterations of the mitotic spindle and reduced ciliogenesis and ciliary length compared to control cells(PMID: 41720098).