Amyotrophic lateral sclerosis: update and new developments

Figures & data

Table 1 Common genes involved in ALS

Gene	Locus	Protein	Found in cellular inclusions	ALS subtype	Other
Autosomal dominant FALS genes also implicated in SALS
SOD1	21q22.1	Cu,Zn superoxide dismutase (SOD)	+	ALS1	Can be recessive in FALS
FUS	16p11.2	Fused in sarcoma (FUS)	+	ALS6	Can be recessive in FALS
ANG	14q11.1	Angiogenin (ANG)		ALS9	Autosomal Dominant or Haploinsufficient
TARDBP	1p36.22	TAR DNA Binding Protein-43 (TDP-43)	+	ALS10
OPTN	10p13	Optineurin	+	ALS12	Can be recessive in FALS
C9ORF72	9p21	C9ORF72	?	‘ALS-FTD’	Newly characterized
Autosomal dominant FALS genes
ALS3	18q21	ALS3		ALS3
SETX	9q34.13	Senataxin		ALS4	Can cause juvenile onset
ALS7	20p13	ALS7		ALS7
VAPB	20q13.33	VAMP-associated protein B	+	ALS8	Can cause juvenile onset
FIG4	6q21	Phosphoinositide 5-phosphatase		ALS11
VCP	9p13.3	Valosin-containing protein		ALS14
Autosomal recessive FALS genes
ALS2	2q33.1	Alsin		ALS2	Can cause juvenile onset
SPG11	15q15.1	Spatacsin		ALS5	Can cause juvenile onset
X-linked dominant FALS gene
UBQLN2	Xp11.2	Ubiquilin-2	+	ALS15	Can cause juvenile onset
Other genes
ATXN2	12q24.1	Ataxin-2		ALS13	Increases ALS susceptibility

Note: Gene products discussed in the main text, as well as additional FALS and susceptibility genes and relevant characteristics are noted.

Abbreviations: FALS, familial amyotrophic lateral sclerosis; SALS, sporadic amyotrophic lateral sclerosis.

Figure 1 Known mutations in FALS and SALS-associated proteins.

Notes: Known mutations are mapped onto their corresponding proteins. Single mutations can include point mutations, premature stop codons, deletions, or insertions. For simplicity, one of the SOD dimers contains the mapped mutations. Structural and Domain Organization is indicated. Solved structures of domains or entire proteins are shown as ribbon diagrams: Cu,ZnSOD (1PU0); TDP-43 RRM1 (1CQG); TDP-43 RRM2 (1WF0); FUS RRM (1LA6); Angiogenin (1B1I). Clothespins indicate that the tertiary structure and inter-domain associations are not entirely known, so protein is stretched out to better show mutations sites. Schematic depictions of conserved domains without solved structures are shown in grey. Where applicable, known or putative oligomeric state and molecular weights are indicated.
Abbreviations: FALS, familial amyotrophic lateral sclerosis; SALS, sporadic amyotrophic lateral sclerosis; NLS, nuclear localization sequence; NES, nuclear export sequence; Sec, cleaved signal sequence; RRM, RNA regnition motif; X rich, X (amino acid residue) rich motifs; UBD, ubiquitin binding domain; ZnF, zinc finger; UBL, ubiquitin like domain; STI1, heat-shock-chaperonin-binding motifs; UBA, ubiquitin associated domain.