Progress in Therapy Development for Amyotrophic Lateral Sclerosis

Table 1

Mendelian and non-Mendelian loci known to cause FALS or confer risk for SALS. 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 [4].

Mendelian genes for heritable ALS (FALS)
Gene	Location	Heritance	Protein	Pathway or effect
ANG	14q11.2	Dominant	Angiogenin	rRNA transcription
ALS2	2q33	Recessive	Alsin	Endosome/membrane trafficking
C9ORF72	9p21.2	Dominant	Uncharacterized	Altered C9ORF72 RNA splicing, formation of nuclear RNA foci
FIG4	6q21	Recessive	FIG4 homolog	Endosomal trafficking
FUS	16p11.2	Both	Fused in sarcoma	Altered RNA processing, formation of inclusion bodies
OPTN	10p13	Both	Optineurin	Golgi maintenance, membrane trafficking and exocytosis, formation of inclusion bodies
SETX	9q34.12	Dominant	Senataxin	DNA and RNA processing
SOD1	21q22.11	Almost; always	Superoxide; dismutase-1	Protein aggregation, possible gains of redox function, impaired axonal transport
SPG11	15q21.2	Recessive	Spatacsin	Impaired axonal transport
TARDPB	1p36.22	Dominant	TAR DNA binding	RNA processing, formation of protein inclusion bodies
UBQLN2	Xp11.231; dominant	X-linked	Ubiquilin-2	Proteasomal protein degradation, inclusion body formation
VAPB	20q13.32	Dominant	Vesicle-associated; membrane protein VAMP	Vesicle trafficking
VCP	9p13.3	Dominant	Valosin-containing; protein	Proteasomal degradation, endosomal trafficking, vesicle sorting
Susceptibility loci for sporadic ALS (SALS)
Gene	Location	Polymorphism	Protein	OR (95% CI)
GWA_9p21.2	9p21.2	rs2814707	Unknown	1.25 (1.19–1.32)
UNC13A	19p13.1	rs12608932; homolog	Unc-13; Vesicle protein	1.18 (1.13–1.24)
ATXN2	12q24.12	Poly-Q	Ataxin-2	n.a.