Table 3.
The effect of APECED-causing mutations on the function and subcellular localization of the AIRE protein. In addition, the effect of mutations designed to disrupt the structure of the PHD zinc fingers are shown. C1/2G and C3/4G denote changing the first and second, or third and fourth, cysteines of the conserved PHD fingers to glycines, respectively. Adapted from Björses et al. Pitkänen et al. and Halonen (M. Halonen, 2003. Ph.D. thesis. University of Helsinki) [38,66]
| Mutation | Domain | Activation | Fibrils | Nuclear dots |
|---|---|---|---|---|
| Wild type | + + | + + | + + | |
| R15L | HSR | + | + + | + + |
| T16M | HSR | + | – | + |
| A21V | HSR | + | – | + |
| L28P | HSR | – | ++/–‡ | – |
| L29P | HSR | – | – | – |
| W78R | HSR | – | + + | + |
| V80L | HSR | + | + + | + + |
| K83E | HSR | + | + + | ++/–‡ |
| Y85C | HSR | + + | – | + + |
| Y90C | HSR | + | + + | + + |
| L93R | HSR | – | – | – |
| G228W | SAND | – | – | + |
| R257X | SAND | – | + + | – |
| C302P† | PHD1 | – | + + | + |
| C1/2G PHD1† | PHD1 | – | N.D. | N.D. |
| C3/4G PHD1† | PHD1 | – | N.D. | N.D. |
| C311Y | PHD1 | + | – | + |
| P326Q | PHD1 | + | + + | + + |
| L397fsX478 | PHD1 | – | – | – |
| C437P† | PHD2 | – | + + | + |
| C302P/C437P† | PHD1/2 | – | + + | – |
| C1/2G PHD2† | PHD2 | – | N.D. | N.D. |
†
not patientmutations
‡
difference in results between authors; N.D. no data available.