VPS13B

Cilia effects upon perturbation of VPS13B

Loss-of-function effect:

Longer cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Elliott et al. 2025 (CRISPRa) [CRISPRa]: Disassembly Trigger (casTLE Effect=-2.67) PMID:41160700

Phenotypes

Mouse phenotype:

spermatogenesis defect, vacuolation, dysplasia, aspermia, decreased lymphocyte cell number, hydropic degeneration, decreased circulating alkaline phosphatase level, abnormal eye morphology, decreased exploration in new environment, decreased lean body mass, steatosis, increased startle reflex, impaired glucose tolerance, decreased leukocyte cell number, abnormal skin morphology, increased total body fat amount, decreased body length, germ cell defect, increased grip strength, small heart, lens extrusion, small spleen, increased mean corpuscular volume, enlarged lymph nodes

Human ciliopathy phenotype:

Intellectual disability

Subcellular localization

cilia, nucleus

References: PMID:41005307

Function

VPS13B, mutated in Cohen syndrome, is a Golgi-associated member of the VPS13 lipid-transfer protein family. VPS13B knockdown lowers PI(4,5)P2 at the ciliary base, lengthens primary cilia and blocks Hedgehog pathway activation, and neural progenitor cells from Cohen syndrome iPSC-derived neural rosettes have longer, abnormal cilia (Lovera Ulecia, PhD thesis, Universitat de Barcelona, 2023, https://www.tdx.cat/handle/10803/688471). VPS13B localizes to cilia (PMID 41005307).