Please consider the following changes in Table
Mendelian and non-Mendelian loci known to cause FALS or confer risk for SALS. Information in this table reproduces content in Tables 7 and 8 from Lill and Bertram, 2011 ([2], and databases therein). Polymorphisms in the VEGF promoter that were originally associated with increased ALS risk have not been confirmed in subsequent studies but may act as modifiers of disease onset or progression in subsets of ALS cases [58].
Mendelian genes for heritable ALS (FALS) | ||||
---|---|---|---|---|
Gene | Location | Heritance | Protein | Pathway or effect |
|
14q11.2 | Dominant | Angiogenin | rRNA transcription |
|
2q33 | Recessive | Alsin | Endosome/membrane trafficking |
|
9p21.2 | Dominant | Uncharacterized | Altered C9ORF72 RNA splicing, formation of nuclear RNA foci |
|
6q21 | Recessive | FIG4 homolog | Endosomal trafficking |
|
16p11.2 | Both | Fused in sarcoma | Altered RNA processing, formation of inclusion bodies |
|
10p13 | Both | Optineurin | Golgi maintenance, membrane trafficking and exocytosis, formation of inclusion bodies |
|
9q34.12 | Dominant | Senataxin | DNA and RNA processing |
|
21q22.11 | Almost always | Superoxide dismutase-1 | Protein aggregation, possible gains of redox function, impaired axonal transport |
|
15q21.2 | Recessive | spatacsin | Impaired axonal transport |
|
1p36.22 | Dominant | TAR DNA binding | RNA processing, formation of protein inclusion bodies |
|
Xp11.231 dominant | X-linked | Ubiquilin-2 | Proteosomal protein degradation, inclusion body formation |
|
20q13.32 | Dominant | Vesicle-associated membrane protein VAMP | Vesicle trafficking |
|
9p13.3 | Dominant | Valosin-containing protein | Proteosomal degradation, endosomal trafficking, vesicle sorting |
|
17p13.3 | Dominant | Profilin-1 | Actin polymerization regulator |
| ||||
Susceptibility loci for sporadic ALS (SALS) | ||||
Gene | Location | Polymorphism | Protein | OR (95% CI) |
| ||||
|
9p21.2 | rs2814707 | Unknown | 1.25 (1.19–1.32) |
|
19p13.1 | rs12608932 homolog | Unc-13 vesicle protein | 1.18 (1.13–1.24) |
|
12q24.12 | Poly-Q | Ataxin-2 | N.a. |