TABLE 1.
Major genes associated with ALS and FTD.
| Locus | Genes | ALS/FTD | Gene frequency | Mutations | Protein inclusions | Sources |
| 14q11.2 | ANG | ALS | <1% ALS | Missense | TDP43 | Greenway et al., 2006 |
| 5q31.2 | MATR3 | ALS | 1% sALS 1-2% fALS | Missense | TDP43 | Johnson et al., 2014; Nguyen et al., 2018 |
| 21q22.11 | SOD1 | ALS | 5% sALS 20% fALS | Missense | SOD1/p62 | Rosen et al., 1993; Shaw et al., 1998 |
| 20q13.32 | VAPB | ALS | <1% ALS | Missense | Nishimura et al., 2004; Millecamps et al., 2010 | |
| 12q24.12 | ATXN2 | ALS-FTD | 4.7% ALS | CAG repeat | TDP-43 | Elden et al., 2010; Bäumer et al., 2014; Rubino et al., 2019 |
| 16p13.3 | CCNF | ALS-FTD | <1% sALS 0.6–3.3% fALS <4% FTD | Missense | TDP43 | Williams et al., 2016; Nguyen et al., 2018 |
| 22q11.23 | CHCHD10 | ALS-FTD | <1% sALS 2% fALS <1% FTD | Missense/nonsense | TDP43 | Bannwarth et al., 2014; Nguyen et al., 2018 |
| 9p21.2 | C9orf72 | ALS-FTD | 6% sALS 37% fALS 5% sFTD 25% fFTD | G4C2 repeat expansion | TDP43/p62/dipeptides repeat/ubiquitin | DeJesus-Hernandez et al., 2011; Renton et al., 2011; Majounie et al., 2012 |
| 2p13.1 | DCTN1 | ALS-FTD | <1% sALS <1% fALS | Missense | TDP43 | Puls et al., 2003; Münch et al., 2004, 2005 |
| 16p11.2 | FUS | ALS-FTD | ∼1% sALS 3% fALS <1% FTD | Missense/nonsense | FUS/p62 | Kwiatkowski et al., 2009; Vance et al., 2009; Van Langenhove et al., 2012 |
| 10p13 | OPTN | ALS-FTD | <1% ALS 4% FTD | Missense/deletion/nonsense | TDP43/p62 | Maruyama et al., 2010; Van Langenhove et al., 2012; Pottier et al., 2015 |
| 5q35 | SQSTM1/p62 | ALS-FTD | 2–3% ALS 2–3% FTD | Missense/nonsense/deletion | TDP43/p62 | Fecto and Siddique, 2011; Elisa et al., 2012; Le Ber et al., 2013 |
| 12q14.2 | TBK1 | ALS-FTD | <1% sALS 3% fALS <1% FTD | Missense/nonsense | TDP43/p62 | Cirulli et al., 2015; Freischmidt et al., 2015; Nguyen et al., 2018; Lamb et al., 2019 |
| 2p13.3 | TIA1 | ALS-FTD | <1% sALS 2.2% fALS <1% FTD | Missense | TDP43/p62 | Mackenzie et al., 2017; Nguyen et al., 2018 |
| 2q35 | TUBA4A | ALS-FTD | <1% sALS 1% fALS <1% FTD | Missense/nonsense | TDP43 | Smith et al., 2014; Nguyen et al., 2018 |
| 9p13.3 | VCP | ALS-FTD | 1–2% fALS <1% FTD | Missense | TDP43/p62 | Watts et al., 2004; Johnson et al., 2010 |
| Xp11.21 | UBQLN2 | ALS-FTD | 2% ALS <1% FTD | Missense | TDP43/p62/ubiquitin/FUS/OPTN | Deng et al., 2011; Synofzik et al., 2012 |
| 3p11.2 | CHMP2B | FTD | <1% ALS <1% FTD | Missense/nonsense | Ubiquitin/P62 | Skibinski et al., 2005; Parkinson et al., 2006; Van Langenhove et al., 2012 |
| 17q21.31 | GRN | FTD | 1–5% sFTD 5–20% fFTD | Missense/nonsense/splice site/frameshift | TDP-43 | Baker et al., 2006; Cruts et al., 2006; Rademakers et al., 2012 |
| 17q21.2 | MAPT | FTD | 5–20% fFTD | Missense/splice site/deletion | Tau | Hutton et al., 1998; Rademakers et al., 2012 |
Characteristics of major genes associated with ALS or FTD. Table is adapted from Hardy and Rogaeva (2014).