GPC4

Cilia effects upon perturbation of GPC4

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-6.18) 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 circulating creatinine level; abnormal cholesterol homeostasis; increased mean corpuscular hemoglobin concentration; increased circulating bilirubin level; abnormal snout morphology; decreased fasting circulating glucose level; decreased blood urea nitrogen level; preweaning lethality; incomplete penetrance; increased mean corpuscular hemoglobin; decreased grip strength; cornea opacity

Ciliopathy associations

• Simpson-Golabi-Behmel Syndrome

Subcellular localization

cilia, nucleoplasm, plasma membrane

Functional category

• Metabolism; Signaling (Hedgehog, GPCRs, ion channels)

Function

The role of Glypican 4 (Gpc4) during mouse brain development, a loss-of-function line was created which shows severe forebrain defects including holoprosencephaly and cyclopia. The loss of Gpc4 causes a truncation of Sonic hedgehog expression domains in the forebrain and impaired Hedgehog signaling activity in vitro. Furthermore, Gpc4 knockdown in mouse embryonic stem cells impairs the exit from the pluripotent state which is phenocopied by the inhibition of Fgf-signaling. These data suggest a role of Gpc4 as a positive modulator of Hedgehog- and Fgf-signaling during forebrain development (Weiss, Stefan). Simpson-Golabi-Behmel syndrome (SGBS) is a X-linked neonatal overgrowth syndrome caused by mutations in the GPC3 or GPC4 genes (PMID: 30371035).