PSKH1

Cilia effects upon perturbation of PSKH1

Cilia number / % ciliated:

No effect

Loss-of-function effect:

Increase

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-3.84) 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:

edema, increased fasting circulating glucose level, preweaning lethality, complete penetrance, hemorrhage, improved glucose tolerance Pskh1 homozygous KO: abnormally long cilia, recapitulates human hepatorenal ciliopathy phenotype (cholestasis + kidney disease).

Mouse ciliopathy phenotype:

increased heart weight

Human ciliopathy phenotype:

Pediatric cholestasis, kidney involvement (hepatorenal ciliopathy)

Ciliopathy associations

• Progressive Familial Intrahepatic Cholestasis

Subcellular localization

cilia, nucleus

Functional category

• Ciliary assembly/disassembly

Function

PSKH1 has localized in cilia. Biallelic PSKH1 variants cause hepatorenal ciliopathy. Patient fibroblasts: abnormally long cilia with abnormal IFT transport. Pskh1 KO mouse: abnormally long cilia recapitulating human phenotype.