Table 3.
Mechanisms leading to GOF or LOF activities of the PCSK9 variants analyzed in this study.
| LDLR Expression | LDL Uptake | Mature/Inmature PCSK9 | Secreted PCSK9 | Furin Cleavage | Extracellular Activity | Affinity for LDLR | Intracellular Activity | Classification | |
|---|---|---|---|---|---|---|---|---|---|
| wt | - | - | - | - | - | - | - | - | wt |
| E32K | ↓ | ↓ | - | - | - | ↑ | ↑ | - | GOF |
| R46L | ↑ | ↑ | - | ↓ | - | ↓ | ↓ | - | LOF |
| L108R | ↓ | ↓ | - | - | - | ↑ | ↑ | - | GOF |
| S127R | ↓ | ↓ | ↓ | ↓ | - | ↑ | ↑ | ↑ | GOF |
| D129G | ↓ | ↓ | ↓ | ↓ | - | ↑ | ↑ | ↑ | GOF |
| D129N | ↓ | ↓ | - | - | - | ↑ | ↑ | - | GOF |
| R194A | ↑ | ↑ | - | - | - | ↓ | ↓ | - | LOF |
| R218S | ↓ | ↓ | - | - | ↓ | ↑ | - | - | GOF |
| D374Y | ↓ | ↓ | - | - | - | ↑ | ↑ | ↑ | GOF |
Blue bar: normal activity; arrow pointing up: increased activity compared to wt; arrow pointing down: decreased activity compared to wt.