Table 1.
Genetic mutations identified in familial and sporadic forms of amyotrophic lateral sclerosis (ALS).
| Gene | Locus | Protein encoded | sALS (%) Frequency | fALS (%) Frequency | Cellular function | References |
|---|---|---|---|---|---|---|
| SOD1 | 21q22.1 | Superoxide dismutase 1 | 1–2 | 12–23.5 | Redox regulation and antioxidant activity | Rosen et al. (1993) and Andersen et al. (2003) |
| DAO | 12q22-23 | D-amino acid oxidase | NA | Unknown | Enzyme that catalyzes the oxidative deamination of D-amino acids | Mitchell et al. (2010) |
| C9orf72 | 9p21.2 | Chromosome 9 open reading frame72 | 7 | 30–50 | Rab mediated cellular trafficking, autophagy, autoimmunity, indirect oxidative stress, and vesicular trafficking | Dejesus-Hernandez et al. (2011) and Renton et al. (2011) |
| TARDBP | 1p36.22 | TAR DNA-binding protein-43 | 1 | 2–5 | RNA metabolism, DNA repair | Rutherford et al. (2008), Sreedharan et al. (2008), and Kirby et al. (2010) |
| FUS | 16p11.2 | Fused in Sarcoma | 1 | 5 | RNA metabolism, DNA repair | Kwiatkowski et al. (2009) and Vance et al. (2009) |
| VCP | 9p13.3 | Valosin-containing protein | 1 | <1 | Protein degradation, intracellular membrane fusion and protein quality control | Shaw (2010) |
| TBK1 | 12q14.2 | Tank-binding kinase1 | <1 | <1–5 | Kinase involved in autophagy, inflammation | Cirulli et al. (2015), Freischmidt et al. (2015) and Gijselinck et al. (2015) |
| CHCHD10 | 22q11.23 | Coiled-coil-helix-coiled-coil-helix domain containing 10 | <1 | 3.6 | Mitochondrial regulation | Bannwarth et al. (2014) and Zhang et al. (2015) |
| SQSTM1/p62 | 5q35 | Sequestosome 1/p62 | <1 | 1.8 | Autophagy receptor involved in selective autophagy, UPS | Fecto et al. (2011) and Le Ber et al. (2013) |
| CCNF | 16p13.3 | Cyclin F | 2 | 0.6–3.3 | Regulator of cell cyclin transitions, a component of the E3 Ubiquitin protein ligase linked to protein homeostasis, UPS | Williams et al. (2016) |
| PFN1 | 17p13 | Profilin-1 | <1 | <1 | Actin binding protein involved in regulating actin dynamics | Wu et al. (2012) |
| ALS2 | 2q33 | Alsin | NA | Unknown | Cellular trafficking, neuroinflammation, redox regulation | Yang et al. (2001) |
| KIF5A | 12q13.3 | Kinesin family of proteins | NA | <1 | Molecular motor protein involved in axonal transport | Brenner et al. (2018) and Nicolas et al. (2018) |
| OPTN | 10p13 | Optineurin | <1 | 2.6 | Maintenance of Golgi complex, membrane trafficking, and autophagy receptor | Maruyama et al. (2010) and Pottier et al. (2015) |
| UBQLN2 | Xp11.21 | Ubiquilin 2 | <1 | 0.5–2 | Macroautophagy and the UPS | Deng et al. (2011), Synofzik et al. (2012), Williams et al. (2012), and Gellera et al. (2013) |
| NEFH | 22q12 | Neurofilament heavy chain | Rare | Component of the cytoskeleton that provides structural support and facilitates axonal transport | Figlewicz et al. (1994) | |
| TUBA4A | 2q36.1 | Tubulin α-4A chain | <1 | <1 | Microtubule subunit involved in intracellular transport and DNA segregation | Smith et al. (2014) |