Table 3.
Functional characterization of CARD14 variants.
| Protein Change | CARD14 domain | NF-κB reporter | Pathogenic signature upon O/E | Other functional testing |
|---|---|---|---|---|
| R38C | CARD | 0.11 | no | |
| R62Q | CARD | 1.06 | no | |
| R69W | CARD | 0.144 | nd | |
| G117S | Between CARD-CC | 3.71 | yes | - over expressed in EC in psoriatic skin - no spontaneous oligomerization - increased interaction with MALT1 and BCL10, increased ERK/p38 activation |
| M119R | Between CARD-CC | nd | nd | |
| M119T | Between | nd | nd | |
| CARD-CC | ||||
| M119V | Between | nd | nd | |
| CARD-CC | ||||
| L124P | Between CARD-CC | nd | nd | |
| C127S | Between CARD-CC | nd | nd | |
| Q136L | CC | nd | nd | |
| E138K | CC | nd | nd | |
| E138A | CC | 8.95 | yes | - increased CARD14 staining and proinfl. gene expression in lesional skin - over expressed in EC in psoriatic skin - spontaneous CARD14 oligomerization - increased interaction with MALT1 and BCL10, increased ERK/p38 activation |
| E138del | CC | ≈2.5 | yes (mouse) | - spontaneous CARD14 oligomerization - increased interaction with BCL10 |
| E142G | CC | 5 | yes | |
| E142K | CC | 4.03 | yes | - increased interaction with MALT1 and BCL10, increased ERK/p38 activation |
| L150R | CC | 1.79 | no | |
| R151Q | CC | 0.576 | nd | |
| R151W | CC | 1.766 | nd | |
| L156P | CC | ≈1.2 | nd | - spontaneous CARD14 oligomerization |
| Q157P | CC | nd | nd | |
| R166H | CC | nd | nd | |
| H171N | CC | 0.68 | no | - increased interaction with MALT1 and BCL10, increased ERK/p38 activation |
| D176H | CC | 2.78 | no | - spontaneous CARD14 oligomerization |
| R179H | CC | 1.38 | no | |
| V191L | CC | 1.02 | no | |
| E197K | CC | 1.667 | nd | |
| S200N | CC | 0.67 | no | |
| L209P | CC | 0.575 | nd | |
| A216T | CC | nd | nd | |
| L228R | CC | 1.5 | nd | |
| D285G | CC | 1.14 | no | |
| M338V | CC | 0.914 | nd | |
| T420A | linker | 0.663 | nd | |
| E422K | linker | nd | nd | |
| R430W | linker | nd | nd | |
| R547S | linker | 1 | no | |
| V585I | linker | nd | nd | |
| T591M | PDZ | nd | nd | |
| I593N | PDZ | 1.3 | no | |
| S602L | PDZ | 1.1 | nd | |
| R682W | SH3 | 0.95 | no | |
| G714S | SH3 | 1.02 | no | |
| S802R | none | nd | nd | |
| R820W | GUK | nd | nd | |
| D973E | none | nd | nd |
Summary of functional studies performed on CARD14 variants depicting ability to activate NF-κB and interaction with binding partners, BCL10 and MALT1.
CC, coiled-coil; GuK, guanylate-kinase domain; PDZ, PSD-95, discs-large, zona occludens-1 domain; SH3, Src homology 3 domain; O/E, overexpression.