Table 1.
Results of TDP-43 co-aggregation screening with ALS/FTLD causative genes.
| Functions | Gene symbol | Mutations | Localization | Aggregation | Co-aggregation with TDP-43 | TDP-43 inclusions in inherited ALS cases | Co-localization with TDP-43 inclusions | References |
|---|---|---|---|---|---|---|---|---|
| RNA-binding proteins | TARDBP | Wild-type | Nuclear | − | − | Yes43–45 | − |
1. Pamphlett et al.43 2. Van Deerlin et al.44 3. Yokoseki et al.45 |
| (ALS10) | M337V | Nuclear | − | − | ||||
| G348C | Nuclear | − | − | |||||
| ∆NLS | Nuclear | − | − | |||||
| FUS | Wild-type | Nuclear | − | − | No46,47 |
− (Yes in sporadic ALS32) |
1. Kwiatkowski et al.46 2. Vance et al.47 3. Ikenaka et al.32 |
|
| (ALS6) | R521C | Nuclear | − | − | ||||
| P525L | Cytosol | ++ | ++ | |||||
| HNRNPA1 | Wild-type | Nuclear | − | − | Yes | Yes | 1. Kim et al.48 | |
| (ALS20) | D314V | Nuclear | − | − | ||||
| N319S | Nuclear | − | − | |||||
| MATR3 | Wild-type | Nuclear | − | − | Yes49,50 | Yes49,50 |
1. Johnson et al.49 2. Tada et al.50 |
|
| (ALS21) | S85C | Nuclear | − | − | ||||
| F115C | Nuclear + cytosol | + | + | |||||
| TAF15 | Wild-type | Nuclear + cytosol | + | ++ | Not reported | − | ||
| G391E | Nuclear + cytosol | + | ++ | |||||
| R408C | Nuclear + cytosol | + | + | |||||
| TIA1 | Wild-type | Nuclear + cytosol | + | ++ | Yes34,35 | Yes34/No35 |
1. Hirsch-Reinshagen et al.34 2. Mackenzie et al.25 |
|
| P362L | Nuclear + cytosol | + | + | |||||
| A381T | Nuclear + cytosol | + | + | |||||
| Intracellular trafficking | FIG4 | Wild-type | Cytosol | + | − | Not reported | − | |
| (ALS11) | Q403X | Cytosol | + | − | ||||
| V654A | Cytosol | + | − | |||||
| CHMP2B | wild-type | Cytosol | + | + | No | − | 1. Cairns et al.51 | |
| (ALS17) | I29V | Cytosol | + | + | ||||
| Q206H | Nuclear + cytosol | + | + | |||||
| TFG | Wild-type | Cytosol | +++ | − | Not reported | − | ||
| G269V | Cytosol | +++ | − | |||||
| P285L | Cytosol | +++ | − | |||||
| Protein degradation | VCP | Wild-type | Cytosol | − | − | Yes51–53 | Not reporter (Yes in cultured cells53) |
1. Cairns et al.51 2. Neumann et al.52 3. Gitcho et al.53 |
| (ALS14) | R155H | Cytosol | − | − | ||||
| A232E | Cytosol | − | − | |||||
| UBQLN2 | Wild-type | Cytosol | +++ | ++ | Yes54–56 | Yes56 (Yes in cultured cells54) |
1. Deng et al.54 2. Williams et al.55 3. Fahed et al.56 |
|
| (ALS15) | P497H | Cytosol | +++ | ++ | ||||
| P506T | Cytosol | +++ | ++ | |||||
| SQSTM1 | Wild-type | Cytosol | ++ | − | Yes | Yes | 1. Kovacs et al.57 | |
| (FTLD-ALS3) | P392L | Cytosol | ++ | − | ||||
| G425R | Cytosol | ++ | − | |||||
| TBK1 | Wild-type | Cytosol | − | − | Yes58,59 | Not reported |
1. Freischmidt et al.58 2. Gijselinck et al.59 |
|
| (FTLS-ALS4) | K401E | Cytosol | − | − | ||||
| ∆690–713 | Cytosol | − | − | |||||
| CCNF | Wild-type | Nuclear | − | − | Not reported | − | ||
| S509P | Nuclear | − | − | |||||
| S621G | Nuclear | − | − | |||||
| Cytoskelton | PFN1 | Wild-type | Cytosol | − | − | Yes60,61 | Not reported (Yes in cultured cells61) |
1. Wu et al.60 2. Smith et al.61 |
| (ALS18) | C71G | Cytosol | ++ | ++ | ||||
| M114T | cytosol | − | − | |||||
| TUBA4A | Wild-type | Cytosol | ++ | ++ | Not reported | − | ||
| (ALS22) | R320H | Cytosol | ++ | ++ | ||||
| W407X | Cytosol | ++ | ++ | |||||
| ER stress response | VAPB | Wild-type | er | − | − | Not reported | − | |
| (ALS8) | T46I | er | + | − | ||||
| P56S | er | ++ | − | |||||
| Growth hormone receptor | ERBB4 | Wild-type | er + cell surface | − | − | Not reported | − | |
| (ALS19) | R927Q | er + cell surface | − | − | ||||
| R1275W | er + cell surface | − | − | |||||
| Mitochondrial homeostasis | CHCHD10 | Wild-type | Mito | − | − | Not reported | − | |
| (FTLD-ALS2) | P34S | Mito | − | − | ||||
| S59L | Mito | − | − |
“Aggregation” was evaluated by ratio with intracellar aggregates of each gene product. +: mild (<30%), ++: medium (30–70%), +++: severe (>70%).
“Co-aggregation with TDP-43” was evaluated co-localization of TDP-43 aggregates and aggregates of each gene product. +: partially, ++: completely.
More than 50 cells were counted in each trial (n = 3 each).
er endoplasmic reticullum, mito mitochondria.