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Table1 Information of the detected CIC rare missense variants in infants
with NTDs
Figure 1 Identification of CIC rare missense variants in infants with
NTDs. (A) Protein amino acid locus of CIC missense variants. (B) Amino
Acid conservation of identified variants among different species.
Figure 2 Subcellular localization and protein abundance of CIC wildtype
and CIC variants. (A) Hela cells were transfected with mutated and
wildtype constructs of GFP-tagged CIC and pEGFP backbone vector for 36h
and were imaged under deconvolution microscope. Scale bar 5um. (B)
Western Blotting was performed in Hela cells 48h after transfection.
GAPDH was used as loading control. (C) Western Blotting was repeated for
three times and student t-test was performed to compare the protein
level between wildtype and mutant.
Figure 3 Overexpression of CIC mutants affected FOLR1 protein level and
folate binding ability of Hela cells. (A) Hela cells were transfected
with mutated and wildtype constructs of GFP-tagged CIC and pEGFP
backbone vector for 48h, and western blotting was performed to quantify
FOLR1 protein level in each group. GAPDH was used as loading control.
(B) Western blotting was repeated for three times and Student’s t-test
was performed to compare the protein level between wildtype and mutant.
(C) Folate of Hela cells transfected with CIC wildtype and variants were
collected and quantified in triplicates.
Figure 4 Overexpression of CIC mutants affected core PCP protein Vangl2
and its downstream protein RhoA in Hela cells. (A) Hela cells were
transfected with mutated and wildtype constructs of GFP-tagged CIC and
pEGFP backbone vector for 48h, and western blotting was performed to
quantify Vangl2 and RhoA protein level in each group. GAPDH was used as
loading control. (B) Western blotting was repeated for three times and
Student’s t-test was performed to compare Vangl2 and RhoA protein level
between wildtype and mutant.
Figure 5 CIC loss of function diminished core PCP protein Vangl2 and its
downstream protein RhoA in NIH3T3 cells. (A) NIH3T3 cells were
transfected with CIC wildtype, CIC-R353X construct and pEGFP backbone
vector for 48h, and Western Blotting was performed to quantify GFP-CIC,
Vangl2 and RhoA protein level in each group. GAPDH was used as loading
control. (B) Western Blotting was repeated for three times and student
t-test was performed to compare Vangl2 and RhoA protein level between
wildtype and R353X.