ZFYVE19

Cilia effects upon perturbation of ZFYVE19

Cilia number / % ciliated:

Decrease

Loss-of-function effect:

Decrease

Overexpression effect:

Unknown

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: Hyper-ciliogenesis (z=2.17) 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:

decreased exploration in new environment, abnormal behavior, decreased locomotor activity, decreased thigmotaxis, increased circulating glucose level Zfyve19-/- mice: cilia abnormalities, cell division failure, biliary fibrosis (with chemical challenge).

Ciliopathy associations

• Progressive Familial Intrahepatic Cholestasis

Subcellular localization

cilia associated gene

Functional category

• Ciliary assembly/disassembly
• T cell biology

Function

The Zfyve19-/- mice were normal overall, particularly with respect to hepatobiliary features. However, when challenged with α-naphthyl isothiocyanate, Zfyve19-/- mice developed changes resembling those in ZFYVE19-deficient patients, including elevated serum liver injury markers, increased numbers of bile duct profiles with abnormal cholangiocyte polarity and biliary fibrosis. Failure of cell division, centriole and cilia abnormalities, and increased cell death were observed in knockdown/knockout cells(PMID: 38816193). Zfyve19-/- mice show centriole and cilia abnormalities, cell division failure, and biliary fibrosis via TGF-β pathway. Cholangiocyte polarity disrupted. ZFYVE19 confirmed as liver-restricted ciliopathy gene.