Table 1.
list of genes claimed to be involved in ALS etiology and pathogenesis
| Gene | Location | FALS locus |
Strategy | Suggested role in ALS* |
Associated phenotypes | OMIM nr |
Refs |
|---|---|---|---|---|---|---|---|
| SOD1 | 21q22.11 | ALS 1 | Linkage analysis | AD, AR, main gene | - | 147450 | Rosen et al., 1993 |
| ALS2 | 2q33.2 | ALS 2 | Linkage analysis | AR, main gene? | Hereditary spastic paraplegia | 606352 | Hadano et al., 2001 |
| Unknown | 18q21 | ALS 3 | Linkage analysis | AD? | ? | (606640) | Hand et al., 2002 |
| SETX | 9q34.13 | ALS 4 | Linkage analysis | AR, main gene? | Spinocerebellar ataxia | 608465 | Chen et al., 2004 |
| SPG11 | 15q21.1 | ALS 5 | Linkage analysis, family study, candidate gene, WES | AR, main gene? | Hereditary spastic paraplegia | 610844 | Orlacchio et al., 2010; Daoud et al., 2012 |
| FUS | 16p11.2 | ALS 6 | Linkage analysis, candidate gene | AD, AR, main gene | - | 137070 | Vance et al., 2009; Kwiatkowski et al., 2009 |
| Unknown | 20p13 | ALS 7 | Linkage analysis | AD? | ? | (608031) | Sapp et al., 2003 |
| VAPB | 20q13.33 | ALS 8 | Linkage analysis | AD, main gene? | Spinal muscular atrophy, late-onset | 605704 | Nishimura et al., 2004 |
| ANG | 14q11.1 | ALS 9 | Candidate gene, association study | AD?, main gene? modifier gene? | - | 105850 | Greenway et al., 2006 |
| TARDBP | 1p36.22 | ALS 10 | Linkage analysis, candidate gene | AD, main gene | FTD | 605078 | Gitcho et al., 2008; Kabashi et al., 2008; Sreedharan et al., 2008 |
| FIG4 | 6q21 | ALS 11 | Candidate gene | AD, AR, main gene? | Charcot-Marie-Tooth disease, type 4J; Yunis-Varon syndrome | 609390 | Chow et al., 2009 |
| OPTN | 10p13 | ALS 12 | Family study: homozygosity mapping | AD, AR, main gene | Open angle glaucoma | 602432 | Maruyama et al., 2010 |
| ATXN2 | 12q24.12 | ALS 13 | Candidate gene | Susceptibility gene | Spinocerebellar ataxia | 601517 | Elden et al., 2010; Daoud et al., 2011 |
| VCP | 9p13.3 | ALS 14 | Family study: WES | AD, main gene | FTD, inclusion body myopathy, Paget’s disease | 601023 | Johnson et al., 2010 |
| UBQLN2 | Xp11.21 | ALS 15 | Linkage analysis | XL, main gene | FTD | 300264 | Deng et al., 2011 |
| SIGMAR1 | 9p13.3 | ALS 16 | Family study: homozygosity mapping | AR, main gene | - | 601978 | Al-Saif et al., 2011 |
| CHMP2B | 3p11.2 | ALS 17 (ALS-FTD3) | Linkage analysis, candidate gene | AD, main gene | FTD | 609512 | Parkinson et al., 2006 |
| PFN1 | 17p13.3 | ALS 18 | Family study: WES | AD, main gene | - | 176610 | Wu et al., 2012 |
| Unknown | 9q21-q22 | ALS-FTD 1 | Linkage analysis | AD? | FTD | Hosler et al.,, 2000 | |
| C9orf72 | 9p21.2 | ASL-FTD 2 | GWAS, linkage analysis | AD, main gene | FTD | 614260 | Renton et al., 2011; DeJesus-Henrnandez et al., 2011 |
| MATR3 | 5q31.2 | Family study: WES | AD, main gene | - | 164015 | Johnson et al., 2014 | |
| CHCHD10 | 22q11.23 | Family study: WES | AD, main gene | FTD, cerebellar ataxia, myopathy | 615903 | Bannwarth et al., 2014; Chaussenot et al., 2014 | |
| SQSTM1 | 5q35.3 | Candidate gene | AD, main gene | FTD, inclusion body myopathy, Paget’s disease | 601530 | Fecto et al., 2011 | |
| TAF15 | 17q12 | Candidate gene | AD, main gene? | - | 601574 | Couthouis et al., 2011 | |
| EWSR1 | 22q12.2 | Candidate gene | AD?, main gene? | - | 133450 | Couthouis et al., 2012 | |
| HNRNPA1 | 12q13.13 | Family study, WES | AD, main gene | FTD, inclusion body myopathy, Paget’s disease | 164017 | Kim et al., 2013 | |
| HNRNPA2B1 | 7p15.2 | Family study, WES | AD, main gene | FTD, inclusion body myopathy, Paget’s disease | 600124 | Kim et al., 2013 | |
| SPAST | 2q22.3 | Candidate gene | AD, main gene? | Hereditary spastic paraplegia | 604277 | Meyer et al., 2005 | |
| VEGF | 6p21.1 | Candidate gene, association study | Susceptibility gene | - | 192240 | Lambrechts et al., 2009 | |
| HFE | 6p22.2 | Candidate gene, association study | Susceptibility gene | Hemochromatosis | 613609 | Goodall et al., 2005 | |
| NEFH | 22q12.2 | Candidate gene, association study | Susceptibility gene? | - | 162230 | Al-Chalabi et al., 1999; Figlewicz et al., 1994 | |
| PRPH | 12q13.12 | Candidate gene | AD?, main gene? | - | 170710 | Leung et al., 2004 | |
| PON1, 2, 3 | 7q21.3 | Candidate gene, association study | Susceptibility gene? | - | 168820 | Wills et al., 2009 | |
| DCTN1 | 2p13.1 | Linkage analysis | AD, main gene? | Perry syndrome | 601143 | Puls et al., 2003 | |
| CHRNA4 | 20q13.33 | Candidate gene, association study | Susceptibility gene | Nocturnal frontal lobe epilepsy | 118504 | Sabatelli et al., 2012 | |
| CHRNA3 CHRNB4 | 15q25.1 | Candidate gene, association study | Susceptibility gene? | - | 118509 118503 | Sabatelli et al., 2009 | |
| ERLIN2 | 8p11.23 | Family study: homozygosity mapping | AR, main gene | Hereditary spastic paraplegia | 611605 | Al-Saif et al., 2012 | |
| UNC13A | 19p13.11 | GWAS | Susceptibility gene, modifier gene | - | 609894 | Chiò et al., 2013a; Diekstra et al., 2012a | |
| DPP6 | 7q36.2 | GWAS | Susceptibility gene? | Ventricular fibrillation | 126141 | Van Es et al., 2008 | |
| ELP3 | 8p21.1 | GWAS | Susceptibility gene? | - | 612722 | Simpson et al., 2009 | |
| ZNF512B | 20q13.33 | GWAS | Susceptibility gene, modifier gene | - | - | Iida et al. 2011; Tetsuka et al., 2013 | |
| ITPR2 | 12p12.1 | GWAS | Susceptibility gene? | - | 600144 | Chiò et al., 2009b | |
| FGGY | 1p32.1 | GWAS | Susceptibility gene? | - | - | Chiò et al., 2009b | |
| CHGB | 20p12.3 | Candidate gene, association study | Susceptibility gene? | - | 118920 | Gros-Louis et al., 2009 | |
| DPYSL3 | 5q32 | Candidate gene, association study | Susceptibility gene? | - | 601168 | Blasco et al., 2013 | |
| GRN | 17q21.31 | Candidate gene, association study | Susceptibility gene, modifier gene | - | 138945 | Sleegers et al., 2008 | |
| KIFAP3 | 1q24.2 | GWAS | Modifier gene | - | 601836 | Landers et al., 2009 | |
| EPHA4 | 2q36.1 | Candidate gene | Modifier gene | - | 602188 | Van Hoecke et al., 2012 | |
| PPARGC1A | 4p15.2 | Candidate gene, association study | Modifier gene | - | 604517 | Eschbach et al., 2013 | |
| APOE | 19q13.32 | Candidate gene, association study | Modifier gene | Alzheimer disease | 107741 | Zetterberg et al., 2008 | |
| MAOB | Xp11.3 | Candidate gene, association study | Modifier gene | - | 309860 | Orrù et al., 1999 | |
| CX3CR1 | 3p22.2 | Candidate gene, association study | Modifier gene | - | 601470 | Lopez-Lopez et al., 2014 | |
| SMN1 (SMN2) | 5q13.2 | Candidate gene, association study | Susceptibility gene | Spinal muscular atrophy | 600354 | Corcia et al., 2002 | |
| EPHA3 | 1q22 | GWAS | Protective factor | - | 601381 | Uyan et al., 2013 | |
| SS18L1 | 20q13.33 | WES (trios study) | AD, main gene | - | 606472 | Chesi et al., 2013 | |
| DAO | 13q33.2 | Linkage analysis | AD, main gene? | - | 124050 | Mitchell et al., 2010 | |
| PNPLA6 | 19p13.2 | Family study: homozygosity mapping | AR, main gene? | Hereditary spastic paraplegia, Boucher-Neuhäuser and Gordon Holmes syndromes | 603197 | Rainier et al., 2008 | |
| MAPT | 17q21.31 | Candidate gene, association study | Susceptibility gene | FTD | 157140 | Fang et al., 2013 | |
| TREM2 | 6p21.1 | Candidate gene, association study | Susceptibility gene | Alzheimer disease | 605086 | Cady et al., 2014 |
GWAS: genome wide association study; WES: whole exome sequencing
AD: autosomal dominant inheritance; AR: autosomal recessive inheritance; X-linked inheritance
OMIM: Online Mendelian Inheritance in Men database (www.omim.org)