Table 5 The reported pathogenic missense mutations in other classic CLDNs
From: The CLDN5 gene at the blood-brain barrier in health and disease
Identified mutation | Position in CLDN-5 | Homology level | Estimated or validated changes | Ref. |
|---|---|---|---|---|
CLDN-1 (R81H) | R81 | Very High | Mis-localization due to the structural instability | [144] |
CLDN-2 (G161R) | G161 | Very high | In silico docking study indicates it may affect oligomer formations | [233] |
CLDN-9 (E159K) | E159 | Very High | Incorporation into the TJs or barrier-forming ability were not impaired. But this position needs for cis-interaction | [234] |
CLDN-10a (R78G) | R81 | Very High | Mis-localization due to the structural instability | [143] |
CLDN-10b (N48K) | G48 | High | TJs were not formed correctly due to the disturbance of classic CLDN signature | [235] |
CLDN-10b (D73N) | S74 | Low | Incorporation into the TJs was partially impaired by attenuation of CLDN-10b specific intra-molecule interaction | |
CLDN-10b (P149R) | P150 | Very High | Incorporation into the TJs was partially impaired by impaired cis-oligomerization | |
CLDN-10b (S131L) | A132 | Low | Mis-localization | [237] |
CLDN-10b (G165A) | G167 | Very high | Incorporation into the TJs was partially impaired and trans-interaction ability was clearly attenuated | [238] |
CLDN-14 (V85D) | V85 | High | Mis-localization | [239] |
CLDN-14 (G101R) | G101 | Very high | It localized at the cell border, but TJs were not formed correctly | |
CLDN-14 (R81H) | R81 | Very High | Mis-localization due to the structural instability | [145] |
CLDN-19 (Q57E) | Q57 | High | Mis-localization | [161] |
CLDN-19 (G20D) | G20 | High | Mis-localization | |
CLDN-19 (L90P) | L90 | High | Incorporation into the TJs was not impaired but its function was partially impaired. | |
CLDN-19 (G123R) | G122 | Very high | Incorporation into the TJs was not impaired but its function was partially impaired. |