Table 1.
List of key findings of TBK1 activities affected by TBK1 ALS missense mutations in this study
| Domain and mutations | Kinase activity | Protein dimerization | OPTN interaction | Stability | |||
| TBK1 | IRF3 | OPTN | p62 | ||||
| KD | |||||||
| L11S* | +++ | +++ | ++ | +++ | +++ | ++ | |
| N22H* | +++ | ++ | +++ | + | +++ | +++ | |
| N22D* | +++ | +++ | +++ | +++ | +++ | +++ | |
| R25H† | + | − | + | − | +++ | +++ | |
| R47H†‡ | + | − | − | − | +++ | +++ | |
| T77W* | +++ | +++ | +++ | + | +++ | +++ | |
| Y105C* | +++ | ++ | ++ | + | +++ | + | |
| N129D§ | − | − | − | − | +++ | ++ | |
| V132E§ | − | − | − | − | +++ | +++ | |
| R134H† | ± | − | − | − | +++ | +++ | |
| S151F* | +++ | +++ | +++ | +++ | + | ++ | |
| S151C* | +++ | +++ | +++ | ± | + | ++ | |
| G217R‡§ | − | − | ± | − | + | ++ | Less stable |
| R228H† | ++ | − | ± | ± | +++ | +++ | |
| I257T* | +++ | ++ | ++ | ± | ++ | +++ | |
| ULD | |||||||
| L306I* | +++ | +++ | +++ | +++ | +++ | +++ | |
| R308Q* | +++ | +++ | ++ | +++ | +++ | + | |
| T320Q* | +++ | +++ | +++ | +++ | +++ | +++ | |
| R357Q*‡ | +++ | +++ | +++ | ± | − | ++ | Less stable |
| SDD | |||||||
| K401E* | +++ | +++ | +++ | +++ | +++ | +++ | |
| I450K§ | − | − | ± | − | − | ++ | Less stable |
| V479E* | +++ | +++ | +++ | + | ++ | +++ | |
| M559R‡§ | − | − | ± | − | − | ++ | Less stable |
| Q565P* | +++ | +++ | +++ | − | − | ++ | |
| CTD | |||||||
| E696K*‡ | +++ | +++ | +++ | +++ | +++ | − | |
*
Group I.
†
Group II.
§
Group III.
‡
Familial ALS mutation.
+++, Normal activity.
++, Slightly reduced activity.
+, Significantly reduced activity.
±, Very weak activity.
−, No activity.