Table 1.
Gene mutations in clinical ALS.
| Clinical subtype | Locus | Gene | Onset/inheritance | Phenotype |
|---|---|---|---|---|
| Removal of reactive oxygen species | ||||
| ALS1 | 21q22 | Superoxide dismutase-1 (SOD1) | Adult/AD | Classical |
| RNA binding and processing | ||||
| ALS4 | 9q34 | Senataxin (SETX) | Juvenile/AD | Classical |
| ALS6 | 16p11.2 | Fused in sarcoma (FUS) | Adult/AD | Classical |
| ALS9 | 14q11.2 | Angiogenin (ANG) | Adult/AD | Classical |
| ALS10 | 1p36.2 | TAR DNA-binding protein 43 (TARDBP) | Adult/AD | Classical |
| ALS13 | 12q24.12 | ATXN2 | Adult | Classical |
| Endosomal trafficking and cell signaling | ||||
| ALS2 | 2q33 | Alsin (ALS2) | Juvenile/AR | Classical |
| ALS11 | 6q21 | Polyphosphoinositide phosphatase (Figure 4) | Adult/AD | |
| ALS8 | 20q13.3 | Vesicle-associated membrane protein-associated protein B (VAP-B) | Adult/AD | Classical |
| ALS12 | 10p13 | Optineurin (OPTN) | Adult/AD and AR | Atypical |
| ALS–FTD | 9q21–q22 | Chromosome 9 open reading frame 72 (C9ORF72) | Adult/AD | Atypical |
| Glutamate excitotoxicity | ||||
| ND | 12q24 | d-amino acid oxidase (DAO) | Adult/AD | Atypical |
| Ubiquitin/protein degradation | ||||
| ND | 9p13–p12 | Valosin-containing protein (VCP) | Adult/AD | Atypical |
| ALSX | Xp11 | Ubiquilin 2 (UBQLN2) | Adult/X-linked | Classical |
| Cytoskeleton | ||||
| ALS–dementia–PD | 17q21 | Microtubule-associated protein tau (MAPT) | Adult/AD | Atypical |
| Other processes | ||||
| ALS5 | 15q15–q21 | Spatacsin (SPG11) | Juvenile/AR | Classical |
| ALS–FTD | 9p13.3 | σ Non-opioid receptor 1 (SIGMAR1) | Adult/AD Juvenile/AR | Atypical |
| Unknown processes | ||||
| ALS3 | 18q21 | Unknown | Adult/AD | Classical |
| ALS7 | 20ptel–p13 | Unknown | Adult/AD | Classical |
A list of genes associated with classical and atypical ALS. The left column groups the genes according to their cellular functions, the second to left column lists the corresponding chromosomal locus, and the middle column gives the gene name, if applicable. In the second to right column the time of disease onset and means of inheritance are displayed, while the right column links each gene to the disease phenotype in the clinic. AD, autosomal dominant; AR, autosomal recessive; FTD, frontotemporal dementia; PD, Parkinson’s disease.