TABLE 1.
Genes thought to be causative of ALS.
| Involved in | Gene | Protein | Functions include | References |
| RNA processing | TARDBP | TAR DNA-Binding Protein, 43-Kd | Splicing regulation, RNA transport, miRNA biogenesis | Rutherford et al., 2008; Sreedharan et al., 2008; Neumann, 2009 |
| FUS | Fused in sarcoma | Splicing regulation, RNA transport, maintenance of genomic integrity, miRNA processing | Kwiatkowski et al., 2009; Vance et al., 2009 | |
| ANG | Angiogenin | RNA processing, neurite outgrowth, vascularisation, stress granule formation | Greenway et al., 2006; Wu et al., 2007 | |
| SETX | Senataxin | DNA/RNA metabolism and helicase activity | Chen et al., 2004; Hirano et al., 2011 | |
| MATR3 | Matrin 3 | RNA processing, chromatin organization | Johnson et al., 2014b | |
| ATXN2 | Ataxin 2 | RNA processing (interacts with TDP-43), endocytosis, modulates mTOR signaling | Elden et al., 2010; Sproviero et al., 2016 | |
| TAF15 | TATA-binding protein-associated factor 2N | transcription initiation; RNA polymerase II | Couthouis et al., 2011; Ticozzi et al., 2011 | |
| EWSR1 | EWS RNA Binding Protein 1 | RNA splicing, transcriptional repressor, | Couthouis et al., 2012 | |
| hnRNPa1 | Heterogeneous nuclear ribonucleoprotein A1 | mRNA processing, splicing, and transport | Kim et al., 2013; Naruse et al., 2018 | |
| hnRNPA2B1 | Heterogeneous nuclear ribonucleoproteins A2/B1 | mRNA processing, splicing, and transport | Kim et al., 2013; Fifita et al., 2017 | |
| ELP3 | Elongator complex protein 3 | Protein synthesis, maturation of projection neurons | Simpson et al., 2009 | |
| Protein Trafficking and degradation | C9ORF72 | Guanine nucleotide exchange C9orf72 | Transcription, splicing regulation, endosomal trafficking, autophagy | DeJesus-Hernandez et al., 2011; Renton et al., 2011 |
| ALS2 | Alsin | Endosomal dynamics and trafficking, neurite outgrowth | Hadano et al., 2001; Yang et al., 2001 | |
| VAPB | Vesicle-associated membrane protein-associated protein B/C | Vesicle trafficking | Nishimura et al., 2004; Sanhueza et al., 2013 | |
| CHMP2B | Charged multivesicular body protein 2b | Multivesicular body formation, protein trafficking to lysosomes | Parkinson et al., 2006; Cox et al., 2010 | |
| FIG4 | Polyphosphoinositide phosphatase | Endosomal trafficking to Golgi network, autophagy regulation | Chow et al., 2009; Osmanovic et al., 2017; Bertolin et al., 2018 | |
| UBQLN2 | Ubiquilin-2 | Protein degradation via UPS | Deng et al., 2011; Gellera et al., 2013 | |
| SQSTM1 | Sequestosome-1 (p62) | Protein degradation via UPS and autophagy | Fecto et al., 2011; Rubino et al., 2012; Hirano et al., 2013 | |
| SIGMAR1 | Sigma non-opioid intracellular receptor 1 | Lipid transport from ER, mitochondrial axonal transport, BDNF and EGF signaling | Luty et al., 2010; Al-Saif et al., 2011; Ullah et al., 2015 | |
| OPTN | Optineurin | Golgi maintenance, membrane trafficking, exocytosis, autophagy | Maruyama et al., 2010; Tümer et al., 2012; Pottier et al., 2018 | |
| VCP | Valosin Containing Protein | Protein degradation via UPS, autophagy, membrane fusion | Forman et al., 2006; Johnson et al., 2010 | |
| TBK1 | Tank Binding Kinase 1 | Autophagy, innate immunity signaling | Borghero et al., 2015; Cirulli et al., 2015; Oakes et al., 2017 | |
| Cytoskeletal and axonal dynamics | DCTN1 | Dynactin subunit 1 | Axonogenesis, microtubule anchoring, ER to Golgi transport, spindle formation, vesicle transport, cilia formation | Münch et al., 2004, 2005; Takahashi et al., 2008; Liu et al., 2014 |
| PFN1 | Profilin 1 | Cytoskeletal signaling, regulates actin polymerization | Wu et al., 2012; Smith et al., 2015 | |
| SPG11 | Spatacsin | Cytoskeletal stability, regulating synaptic vesicle transport | Orlacchio et al., 2010; Daoud et al., 2012 | |
| TUBA4A | Tubulin α-4A chain | Component of microtubules | Smith et al., 2014; Pensato et al., 2015 | |
| NEFH | Neurofilament heavy polypeptide | Maintenance of neuronal caliber, intracellular transport | Figlewicz et al., 1994; Al-Chalabi et al., 1999 | |
| PRPH | Peripherin | Cytoskeletal protein, neurite elongation, axonal regeneration | Gros-Louis et al., 2004; Leung et al., 2004; Corrado et al., 2011 | |
| NEK1 | NIMA (Never In Mitosis Gene A)-Related Kinase 1 | Cilia formation, DNA-damage response, microtubule stability, neuronal morphology, axonal polarity | Brenner et al., 2016; Kenna et al., 2016; Nguyen et al., 2018; Shu et al., 2018 | |
| Mitochondria | CHCHD10 | Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10 | Mitochondrial protein, cristae morphology, oxidative phosphorylation | Bannwarth et al., 2014; Chaussenot et al., 2014; Johnson et al., 2014a |
| C19ORF12 | Protein C19orf12 | Mitochondrial protein | Deschauer et al., 2012 | |
| Other | SOD1 | Superoxide dismutase [Cu-Zn] | Cytosolic Antioxidant | Rosen et al., 1993 |
| ERBB4 | Receptor tyrosine-protein kinase erbB-4 | Neuronal cell mitogenesis and differentiation | Takahashi et al., 2013 | |
| SS18L1 | Calcium-responsive transactivator | Neuron specific chromatin remodeling | Teyssou et al., 2014 | |
| PNPLA6 | Neuropathy target esterase | Regulation of neuronal membrane composition | Rainier et al., 2008 | |
| PON1-3 | Paraoxonase 1-3 | Enzymatic breakdown of nerve toxins | Saeed et al., 2006; Wills et al., 2009; Ticozzi et al., 2010 | |
| DAO | D-amino-acid oxidase | Regulates D-serine levels, N-methyl-D-aspartate receptor regulation | Mitchell et al., 2010; Morgan et al., 2017 | |
| CHRNA3,4,B4 | Neuronal acetylcholine receptor subunit α-3, α-4, β-4 | Cholinergic Neurotransmission | Sabatelli et al., 2009, 2012 | |
| ALS3 | ALS3 | Disulfide redox protein | Hand et al., 2002 | |
| Unknown | ALS7 | Unknown | Unknown | Sapp et al., 2003 |
| ALS6-21 | Unknown | Unknown | Butterfield et al., 2009 | |
| ALS-FTD | Unknown | Unknown | Dobson-Stone et al., 2013 |