Table 2.

Functional analysis of CLDN16 mutations (expressed in LLC-PK1 cells)a

MutationPositionTERDilution PotentialPNa/PClPNa (10−6 cm/s)PCl (10−6 cm/s)LocalizationFunction
Vector61.0 ± 2.1−8.13 ± 0.19b0.296 ± 0.010b6.866 ± 0.184b23.220 ± 0.182
WT33.0 ± 1.52.97 ± 0.191.500 ± 0.03833.363 ± 0.34622.257 ± 0.346TJ+
M71TN terminus60.0 ± 2.5−7.83 ± 0.12b0.313 ± 0.007b7.282 ± 0.121b23.307 ± 0.123LysosomeCL
G88EFirst TMD50.7 ± 2.9−7.13 ± 0.09b0.354 ± 0.005b9.398 ± 0.105b26.590 ± 0.106TJCL
S110RFirst ECL38.3 ± 0.9−3.30 ± 0.12b0.637 ± 0.010b18.787 ± 0.188b29.513 ± 0.188TJPL
R114QFirst ECL34.7 ± 3.7−2.33 ± 0.09b0.728 ± 0.009b22.100 ± 0.153b30.340 ± 0.153TJPL
C131RFirst ECL60.7 ± 3.0−7.50 ± 0.06b0.332 ± 0.003b7.493 ± 0.057b22.597 ± 0.055ERCL
I137delFirst ECL41.7 ± 2.3−4.57 ± 0.09b0.530 ± 0.007b15.143 ± 0.130b28.557 ± 0.130TJPL
H141DFirst ECL39.3 ± 2.6−3.17 ± 0.09b0.649 ± 0.008b18.513 ± 0.141b28.547 ± 0.141TJPL
L151WFirst ECL39.7 ± 0.9−1.97 ± 0.18b0.766 ± 0.018b19.903 ± 0.271b25.983 ± 0.273TJPL
R216CSecond ECL44.3 ± 2.7−5.10 ± 0.20b0.490 ± 0.015b13.710 ± 0.280b28.003 ± 0.277TJCL
G227RSecond ECL39.0 ± 1.0−3.20 ± 0.06b0.646 ± 0.005b18.460 ± 0.092b28.600 ± 0.092TJPL
  • a Number of independent monolayers, n = 3. TER, transepithelial resistance; P, permeability; TMD, transmembrane domain; ECL, extracellular loop; ER, endoplasmic reticulum.

  • b P < 0.05, mutant versus WT.