Table 3.
Characteristics of the genes encompassed by the commercial clinical genetic tests offered globally specific to amyotrophic lateral sclerosis (ALS), as well as potential genes of interest missing from clinical genetic tests
| Gene | Relationship with ALS Identified | Year of First Discovery | Onset | Inheritance Pattern | Method of First Discovery | Protein Function | PMID of First Discovery | No. Tests |
|---|---|---|---|---|---|---|---|---|
| ABCD1 | No | NA | NA | NA | NA | Mitochondrial function | NA | 1 |
| ABHD12 | No | NA | NA | NA | NA | Stress response | NA | 1 |
| ALS2 | Yes | 2001 | Juvenile | AD | Linkage | Endosomal trafficking | 11586298; 11586297 | 12 |
| ANG | Yes | 2006 | Adult | AD | Candidate gene | RNA processing | 16501576 | 14 |
| ANXA11 | Yes | 2017 | Adult | AD | Rare variant association (familial and/or case-control studies) | Intracellular cargo transport | 28469040 | 3 |
| ARHGEF28 | Yes | 2013 | Adult | Unclear | Candidate gene | RNA processing | 23286752 | 4 |
| ATL1 | No | NA | NA | NA | NA | Cell maintenance | NA | 1 |
| ATXN1 | Yes | 2012 | Adult | AD | Candidate gene | Endosomal trafficking | 23197749 | 1 |
| ATXN2 | Yes | 2012 | Adult | AD | Candidate gene | Endosomal trafficking | 23197749 | 5 |
| BSCL2 | No | NA | NA | NA | NA | Cell maintenance | NA | 1 |
| C9orf72 | Yes | 2011 | Adult | AD | Linkage | RNA processing | 21944778 | 5 |
| CCNF | Yes | 2016 | Adult | AD | Linkage | Ubiquitination | 27080313 | 1 |
| CFAP410 | Yes | 2016 | Adult | Unclear | GWAS | Cytoskeleton | 27455348 | 1 |
| CHCHD10 | Yes | 2014 | Adult | AD | Rare variant association (familial and/or case-control studies) | Mitochondrial function | 24934289 | 9 |
| CHGB | Yes | 2009 | Adult | Unclear | Candidate gene | Exosomal trafficking | 20007371 | 1 |
| CHMP2B | Yes | 2006 | Adult | AD | Candidate gene | Cell maintenance | 16807408 | 12 |
| CHRM1 | Yes | 2015 | Adult | AD | Rare variant association (familial and/or case-control studies) | Cell maintenance | 25773295 | 1 |
| CHRNA4 | Yes | 2009 | Adult | AD | Rare variant association (familial and/or case-control studies) | Cell maintenance | 19628475 | 1 |
| CRYM | Yes | 2011 | Adult | Unclear | Candidate gene | Intracellular cargo transport | 21220648 | 1 |
| DAO | Yes | 2010 | Adult | Unclear | Candidate gene | Stress response | 20368421 | 5 |
| DCTN1 | Yes | 2003 | Adult | Unclear | Candidate gene | Intracellular cargo transport | 12627231 | 10 |
| DPP6 | Yes | 2008 | Adult | Unclear | GWAS | Cell maintenance | 18057069 | 2 |
| ELP3 | Yes | 2009 | Adult | Unclear | GWAS | RNA processing | 18996918 | 2 |
| ERBB4 | Yes | 2013 | Adult | AD | Linkage | Neuronal development | 24119685 | 8 |
| ERGIC1 | Yes | 2020 | Adult | Unclear | GWAS | Intracellular cargo transport | 32968195 | 0 |
| EWSR1 | Yes | 2012 | Adult | AD | Candidate gene | RNA processing | 22454397 | 1 |
| FGGY | Yes | 2007 | Adult | Unclear | GWAS | Cell maintenance | 17671248 | 1 |
| FIG4 | Yes | 2009 | Adult | AD | Candidate gene | Endosomal trafficking | 19118816 | 11 |
| FUS | Yes | 2009 | Adult | AD/AR | Linkage | RNA processing | 19251627 | 13 |
| GBE1 | No | NA | NA | NA | NA | Cell maintenance | NA | 1 |
| GLE1 | Yes | 2015 | Adult | AD | Candidate gene | RNA processing | 25343993 | 1 |
| GLT8D1 | Yes | 2019 | Adult | AD | Rare variant association (familial and/or case-control studies) | Cell maintenance | 30811981 | 1 |
| GRN | Yes | 2007 | Adult | AD | Candidate gene | Stress response | 17371905 | 6 |
| HEXA | No | NA | NA | NA | NA | Cell maintenance | NA | 3 |
| HFE | Yes | 2004 | Adult | AD | Candidate gene | Cell maintenance | 15546588 | 1 |
| HNRNPA1 | Yes | 2013 | Adult | AD | Rare variant association (familial and/or case-control studies) | RNA processing | 23455423 | 9 |
| HNRNPA2B1 | Yes | 2014 | Adult | AD | Rare variant association (familial and/or case-control studies) | RNA processing | 24119545 | 7 |
| HNRNPD | No | NA | NA | NA | NA | RNA processing | NA | 1 |
| HSPD1 | No | NA | NA | NA | NA | Mitochondrial function | NA | 1 |
| ITPR2 | Yes | 2007 | Adult | Unclear | GWAS | Cell maintenance | 17827064 | 1 |
| KIF5A | Yes | 2018 | Adult | AD | Rare variant association (familial and/or case-control studies) | Cytoskeleton | 29342275 | 4 |
| LMNB1 | No | NA | NA | NA | NA | Cytoskeleton | NA | 1 |
| LUM | Yes | 2011 | Adult | Unclear | Candidate gene | Extracellular matrix | 21220648 | 1 |
| MAPT | Yes | 2005 | Adult | Unclear | Candidate gene | Cytoskeleton | 16005901 | 5 |
| MATR3 | Yes | 2014 | Adult | AD | Rare variant association (familial and/or case-control studies) | RNA processing | 24686783 | 8 |
| MFN2 | Yes | 2019 | Adult | AD/AR | Rare variant association (familial and/or case-control studies) | Mitochondrial function | 31108397 | 1 |
| MOBP | Yes | 2016 | Adult | Unclear | GWAS | Cytoskeleton | 27455348 | 1 |
| NEFH | Yes | 1994 | Adult | Unclear | Candidate gene | Intracellular cargo transport | 7849698 | 7 |
| NEK1 | Yes | 2016 | Adult | Unclear | Rare variant association (familial and/or case-control studies) | Cell maintenance | 26945885 | 5 |
| OPTN | Yes | 2010 | Adult | AD | Linkage | Cell maintenance | 20428114 | 13 |
| PARK7 | Yes | 2005 | Adult | AR | Rare variant association (familial and/or case-control studies) | Stress response | 16240358 | 2 |
| PFN1 | Yes | 2012 | Adult | AD | Rare variant association (familial and/or case-control studies) | Cytoskeleton | 22801503 | 11 |
| PMP22 | Yes | 2009 | Adult | AD | Candidate gene | Neuronal development | 19238316 | 1 |
| PON1 | Yes | 2006 | Adult | AD | Candidate gene | Cell maintenance | 16822964 | 1 |
| PON2 | Yes | 2006 | Adult | AD | Candidate gene | Cell maintenance | 16822964 | 1 |
| PON3 | Yes | 2006 | Adult | AD | Candidate gene | Cell maintenance | 16822964 | 1 |
| PRF1 | No | NA | NA | NA | NA | Stress response | NA | 1 |
| PRPH | Yes | 2004 | Adult | Unclear | Candidate gene | Cytoskeleton | 15322088 | 5 |
| PRPH2 | No | NA | NA | NA | NA | Cell adhesion | NA | 2 |
| PSEN1 | No | NA | NA | NA | NA | Cell maintenance | NA | 3 |
| REEP1 | No | NA | NA | NA | NA | Mitochondrial function | NA | 1 |
| SETX | Yes | 2002 | Juvenile | AD | Linkage | RNA processing | 12023320 | 13 |
| SIGMAR1 | Yes | 2011 | Juvenile | AD/AR | Linkage | Stress response | 21842496 | 9 |
| SLC52A2 | Yes | 2012 | Juvenile | AR | Rare variant association (familial and/or case-control studies)? | Cell maintenance | 22740598 | 1 |
| SLC52A3 | Yes | 2010 | Juvenile | AR | Linkage | Cell maintenance | 20206331 | 2 |
| SMN1 | Yes | 2002 | Adult | Unclear | Candidate gene | RNA processing | 11835381 | 1 |
| SMN2 | Yes | 2001 | Adult | AR | Candidate gene | RNA processing | 11274309 | 1 |
| SOD1 | Yes | 1993 | Adult | AD | Linkage | Stress response | 8446170 | 14 |
| SPART | No | NA | NA | NA | NA | Endosomal trafficking | NA | 5 |
| SPAST | Yes | 2005 | Adult | AD | Candidate gene | Intracellular cargo transport | 16009903 | 2 |
| SPG11 | Yes | 2010 | Juvenile | AR | Linkage | Intracellular cargo transport | 20110243 | 9 |
| SQSTM1 | Yes | 2011 | Adult | AD | Candidate gene | Cell maintenance | 22084127 | 11 |
| SRCAP | Yes | 2013 | Adult | AD | Candidate gene | Histone regulation | 23708140 | 1 |
| SS18L1 | Yes | 2013 | Adult | AD | Rare variant association (familial and/or case-control studies) | Neuronal development | 23708140 | 1 |
| STMN2 | Yes | 2021 | Adult | AD | Candidate gene | Cytoskeleton | 33841129 | 1 |
| TAF15 | Yes | 2011 | Adult | AD | Candidate gene | RNA processing | 21438137 | 6 |
| TARDBP | Yes | 2008 | Adult | AD | Linkage | RNA processing | 18309045 | 14 |
| TBK1 | Yes | 2015 | Adult | AD | Rare variant association (familial and/or case-control studies) | Cell maintenance | 25700176 | 9 |
| TFG | Yes | 2013 | Adult | AD | Candidate gene | Intracellular cargo transport | 24291928 | 1 |
| TIA1 | Yes | 2017 | Adult | AD | Rare variant association (familial and/or case-control studies) | RNA processing | 28817800 | 1 |
| TREM2 | Yes | 2014 | Adult | AD | Candidate gene | Stress response | 24535663 | 2 |
| TRPM7 | Yes | 2005 | Adult | AD | Candidate gene | Cell maintenance | 16051700 | 2 |
| TUBA4A | Yes | 2014 | Adult | AD | Rare variant association (familial and/or case-control studies) | Cytoskeleton | 25374348 | 8 |
| UBQLN2 | Yes | 2011 | Adult | X-LD | Linkage | Cell maintenance | 21857683 | 13 |
| UNC13A | Yes | 2009 | Adult | Unclear | GWAS | Exosomal trafficking | 19734901 | 4 |
| VAPB | Yes | 2004 | Adult | AD | Linkage | Stress response | 15372378 | 14 |
| VCP | Yes | 2010 | Adult | AD | Rare variant association (familial and/or case-control studies) | Cell maintenance | 21145000 | 13 |
| VEGFA | Yes | 2003 | Adult | AR | Candidate gene | Cell maintenance | 12847526 | 4 |
| VPS54 | Yes | 2008 | Adult | Unclear | Candidate gene | Intracellular cargo transport | 18574757 | 2 |
| VRK1 | Yes | 2015 | Juvenile | AR | Rare variant association (familial and/or case-control studies) | Cell maintenance | 26583493 | 1 |
| WASHC5 | Yes | 2019 | Adult | AD | Candidate gene | Endosomal trafficking | 30778698 | 1 |
Genes recently associated with ALS using large-scale association studies, but not included on any clinical tests were included in the list of genes. Relationship with ALS Identified indicates whether a publication has previously described a relationship between the gene and ALS using genetic evidence of any methodology. Abbreviations: AD, autosomal dominant; AR, autosomal recessive; NA, not applicable; X-LD, x-linked dominant.