ALS2

Summary

ALS2 (alsin Rho guanine nucleotide exchange factor ALS2, HGNC:443) is a protein-coding gene on chromosome 2q33.1, encoding Alsin (Q96Q42). May act as a GTPase regulator.

The protein encoded by this gene contains an ATS1/RCC1-like domain, a RhoGEF domain, and a vacuolar protein sorting 9 (VPS9) domain, all of which are guanine-nucleotide exchange factors that activate members of the Ras superfamily of GTPases. The protein functions as a guanine nucleotide exchange factor for the small GTPase RAB5. The protein localizes with RAB5 on early endosomal compartments, and functions as a modulator for endosomal dynamics. Mutations in this gene result in several forms of juvenile lateral sclerosis and infantile-onset ascending spastic paralysis. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 57679 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ALS2-related motor neuron disease (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,200 total — 72 pathogenic, 39 likely-pathogenic
• Phenotypes (HPO): 98
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_020919

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:443
Approved symbol	ALS2
Name	alsin Rho guanine nucleotide exchange factor ALS2
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000003393
Ensembl biotype	protein_coding
OMIM	606352
Entrez	57679

Gene structure

Transcript identifiers

Ensembl transcripts: 79 — 29 protein_coding, 21 retained_intron, 19 nonsense_mediated_decay, 10 protein_coding_CDS_not_defined

ENST00000264276, ENST00000409632, ENST00000410052, ENST00000439495, ENST00000462747, ENST00000467448, ENST00000482789, ENST00000482891, ENST00000483703, ENST00000489440, ENST00000494017, ENST00000496244, ENST00000679409, ENST00000679416, ENST00000679427, ENST00000679435, ENST00000679503, ENST00000679516, ENST00000679549, ENST00000679550, ENST00000679618, ENST00000679630, ENST00000679635, ENST00000679686, ENST00000679701, ENST00000679728, ENST00000679916, ENST00000679939, ENST00000679949, ENST00000680000, ENST00000680135, ENST00000680149, ENST00000680163, ENST00000680174, ENST00000680188, ENST00000680236, ENST00000680287, ENST00000680404, ENST00000680441, ENST00000680497, ENST00000680508, ENST00000680569, ENST00000680630, ENST00000680634, ENST00000680644, ENST00000680722, ENST00000680723, ENST00000680726, ENST00000680737, ENST00000680759, ENST00000680814, ENST00000680819, ENST00000680828, ENST00000680861, ENST00000680927, ENST00000680939, ENST00000681144, ENST00000681152, ENST00000681250, ENST00000681256, ENST00000681279, ENST00000681303, ENST00000681307, ENST00000681312, ENST00000681378, ENST00000681461, ENST00000681495, ENST00000681558, ENST00000681619, ENST00000681663, ENST00000681692, ENST00000681716, ENST00000681758, ENST00000681768, ENST00000681808, ENST00000905985, ENST00000925368, ENST00000942930, ENST00000942931

RefSeq mRNA: 3 — MANE Select: NM_020919 NM_001135745, NM_001410975, NM_020919

CCDS: CCDS42800, CCDS46492, CCDS92925

Canonical transcript exons

ENST00000264276 — 34 exons

Exon	Start	End
ENSE00000934613	201700267	201701889
ENSE00001932788	201780877	201780933
ENSE00003469997	201723043	201723120
ENSE00003498649	201768866	201768945
ENSE00003505470	201738670	201738735
ENSE00003513641	201727212	201727278
ENSE00003525905	201715672	201715839
ENSE00003526371	201726664	201726866
ENSE00003537621	201753146	201753242
ENSE00003546342	201710991	201711108
ENSE00003553880	201705416	201705461
ENSE00003554077	201718077	201718210
ENSE00003567371	201704122	201704218
ENSE00003569651	201725356	201725454
ENSE00003595325	201724295	201724459
ENSE00003600534	201704454	201704603
ENSE00003602119	201706846	201707022
ENSE00003608497	201729052	201729183
ENSE00003615171	201757402	201757759
ENSE00003617570	201754503	201754671
ENSE00003619728	201767229	201767383
ENSE00003629440	201760881	201761818
ENSE00003631470	201746566	201746748
ENSE00003636929	201727705	201727775
ENSE00003644854	201749712	201749789
ENSE00003653809	201707869	201707991
ENSE00003656488	201723330	201723441
ENSE00003659416	201728512	201728640
ENSE00003661001	201741674	201741854
ENSE00003662379	201744258	201744429
ENSE00003667861	201709881	201710038
ENSE00003667933	201726484	201726549
ENSE00003673437	201733276	201733438
ENSE00003692637	201705139	201705200

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 96.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.3030 / max 372.8987, expressed in 1785 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33262	14.5581	1784
33263	0.2087	94
33264	0.1752	63
33265	0.1660	62
33259	0.1478	34
33260	0.0264	3
33261	0.0207	7

Top tissues by expression

260 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cerebellum	UBERON:0002037	96.76	gold quality
cerebellar cortex	UBERON:0002129	96.72	gold quality
cerebellar hemisphere	UBERON:0002245	96.71	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.21	gold quality
cerebellar vermis	UBERON:0004720	95.08	gold quality
tibialis anterior	UBERON:0001385	93.64	gold quality
left ventricle myocardium	UBERON:0006566	93.12	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.53	gold quality
deltoid	UBERON:0001476	90.36	gold quality
sural nerve	UBERON:0015488	90.26	gold quality
middle temporal gyrus	UBERON:0002771	89.48	gold quality
cortical plate	UBERON:0005343	89.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.95	gold quality
myocardium	UBERON:0002349	88.89	gold quality
calcaneal tendon	UBERON:0003701	88.51	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.60	gold quality
adrenal tissue	UBERON:0018303	87.44	gold quality
oviduct epithelium	UBERON:0004804	87.37	gold quality
ileal mucosa	UBERON:0000331	86.95	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.56	gold quality
biceps brachii	UBERON:0001507	86.41	gold quality
secondary oocyte	CL:0000655	86.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.31	gold quality
islet of Langerhans	UBERON:0000006	86.20	gold quality
skeletal muscle tissue	UBERON:0001134	86.03	gold quality
ventricular zone	UBERON:0003053	85.88	gold quality
colonic epithelium	UBERON:0000397	85.78	gold quality
muscle tissue	UBERON:0002385	85.71	gold quality
postcentral gyrus	UBERON:0002581	85.71	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.59	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	12.88
E-MTAB-9067	yes	11.78
E-ANND-3	yes	10.65
E-MTAB-9801	yes	6.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF1, NFE2L2

miRNA regulators (miRDB)

98 targeting ALS2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-323A-3P	99.79	70.30	1739

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• causative genes for familial amyotrophic lateral sclerosis (PMID:12138710)
• Infantile-onset ascending hereditary spastic paralysis is associated with mutations in the alsin gene. (PMID:12145748)
• 16 patients from 11 unrelated families were studied with a phenotype of infantile ascending hereditary spastic paralysis (IAHSP); Alsin mutations were found in 4 of the 10 families, whereas haplotype analysis excluded the ALS2 locus in one family (PMID:12601111)
• Perturbation of endosomal dynamics caused by loss of ALS2 rab5GEF activity might underlie neuronal dysfunction and degeneration. (PMID:12837691)
• deletion mutations in ALS2 gene detected in ALS2 patients seem to be uncommon in Japanese AR-ALS, and that SNPs in uncoding regions might possibly be relevant to predisposition to ALS. (PMID:12866199)
• A nonsense mutation in alsin was found in infantile spastic paraplegia. Full-length alsin is probably required for the proper development and/or functioning of upper motor neurons. (PMID:12919135)
• Mutations in the ALS2 gene linked to early-onset motor neuron disease uniformly produce loss of activity through decreased protein stability of this endosomal protein. (PMID:14668431)
• Mutations of ALS2 are not a common cause of ALS. (PMID:14676054)
• Expression of alsin LF, but not alsin short form, protected motor neuronal cells from toxicity induced by mutants of the Cu/Zn-superoxide dismutase (SOD1) gene, which cause autosomal dominant ALS (PMID:14970233)
• oligomerization of the ALS2 protein is one of the fundamental features for its physiological function involving endosome dynamics in vivo (PMID:15247254)
• A peptide derived from the ALS2 protein is selectively localized to the somatodendritic compartment of motor neurons in human spinal cord. (PMID:15371724)
• These results suggest that amyotrophic lateral sclerosis 2 C-terminal like (ALS2CL), a novel ALS2 homologue, modulates Rab5-mediated endosome dynamics in HeLa cells. (PMID:15388334)
• Rac1, PI3 kinase, and Akt3 have roles in an anti-apoptotic pathway triggered by ALS2 that antagonizes SOD1 mutant-induced motoneuronal cell death (PMID:15579468)
• ALS2/Alsin has a role in regulating Rac-PAK signaling and neurite outgrowth (PMID:16049005)
• colocalization of Alsin with the centrosomal markers gamma-tubulin and A kinase anchoring protein. (PMID:16085057)
• ALS2 mutations are not implicated in the pathogenesis of adult-onset primary lateral sclerosis. (PMID:17698795)
• Autosomal recessive mutations in the ALS2 gene lead to a clinical spectrum of motor dysfunction including juvenile onset amyotrophic lateral sclerosis. [REVIEW] (PMID:17955197)
• mutations in ALS2 also need to be considered in patients from northwestern Europe with early-onset spastic paralysis and amyotrophic or primary lateral sclerosis. (PMID:18523452)
• Results suggest at least four recombination events in the ALS2 gene during maternal meiosis followed by a meiosis I error and postzygotic trisomy rescue or gamete complementation, in a patient with infantile-onset ascending spastic paralysis. (PMID:18810511)
• A structural model for the N-terminal 690-residue region of alsin through comparative modelling based on regulator of chromosome condensation 1 was created. (PMID:19023603)
• This novel ALS2 splice-site mutation is causing the loss of exon 18 in the transcript which results in a frameshift after exon 17. (PMID:19122027)
• these results suggest that Als2 is a binding partner of Uxt and Als2/Uxt interaction could be important for the activation of Nf-kappaB pathway. (PMID:21907703)
• ALS2 sequencing revealed two heterozygous mutations: the missense variant c.299 G>T, leading to the replacement of a serine with an isoleucine (p.S100I), and the splicing variant c.2580-2 A>G in brothers with juvenile amyotrophic lateral sclerosis. (PMID:23282280)
• The ALS2 mutation c.2761C>T leading to infantile-onset hereditary spastic paraplegia resides in the pleckstrin domain, which is involved in the overall neuronal development or maintenance. (PMID:24315819)
• The ALS2 gene should be screened for mutations in patients who present with generalized dystonia and cerebellar signs. (PMID:24562058)
• Data indicate a splice-site mutation of the amyotrophic lateral sclerosis 2 (juvenile) protein (ALS2) in four children of a consanguineous family with infantile-onset ascending hereditary spastic paraplegia. (PMID:24704789)
• novel compound heterozygous ALS2 deletion mutations were identified in two siblings with infantile ascending hereditary spastic paraplegia. (PMID:25433428)
• We identified a novel homozygous splice-site mutation (c.3512+1G>A) in the ALS2 gene (NM_020919.3) encoding alsin that segregated with the disease in this family (PMID:25474699)
• This study identified two novel ALS2 mutations in two Pakistani families with infantile-onset ascending hereditary spastic paraplegia cosegregating with the disease. (PMID:26751646)
• We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family (PMID:27601211)
• Nonsense mutation in ALS2 gene is associated with severe and progressive infantile onset of spastic paralysis. (PMID:28502191)
• These findings define a novel pathway whereby Alsin catalyzes the assembly of the Rab5 endocytic machinery on mitochondria. Defects in stress-sensing by endosomes could be crucial for mitochondrial quality control during the onset of amyotrophic lateral sclerosis. (PMID:29469808)
• This study identified a novel ALS2 pathogenic founder variant in Iran that further adds to the allelic heterogeneity of infantile-onset ascending hereditary spastic paralysis. (PMID:30128655)
• Disorganized higher structures of ALS2 variants impaired endosomal localization and the stability, leading to loss of the ALS2 function. (PMID:30224357)
• ALS2, the small GTPase Rab17-interacting protein, regulates maturation and sorting of Rab17-associated endosomes. (PMID:31959474)
• Genotype-phenotype correlation in seven motor neuron disease families with novel ALS2 mutations. (PMID:33155358)
• ALS2-related disorders in Spanish children. (PMID:33409823)
• The N-terminal intrinsically disordered region mediates intracellular localization and self-oligomerization of ALS2. (PMID:34243065)
• Tumor-derived hypoxic small extracellular vesicles promote endothelial cell migration and tube formation via ALS2/Rab5/beta-catenin signaling. (PMID:38847490)
• Conformational Dynamics and Molecular Characterization of Alsin MORN Monomer and Dimeric Assemblies. (PMID:39023312)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	als2a	ENSDARG00000075111
danio_rerio	als2b	ENSDARG00000076924
mus_musculus	Als2	ENSMUSG00000026024
rattus_norvegicus	Als2	ENSRNOG00000023280
drosophila_melanogaster	ca	FBGN0000247
drosophila_melanogaster	Rcc1	FBGN0002638
drosophila_melanogaster	CG7420	FBGN0031344
caenorhabditis_elegans		WBGENE00004304

Paralogs (9): HERC1 (ENSG00000103657), SERGEF (ENSG00000129158), RCBTB1 (ENSG00000136144), RCBTB2 (ENSG00000136161), RPGR (ENSG00000156313), RCCD1 (ENSG00000166965), RCC2 (ENSG00000179051), RCC1 (ENSG00000180198), RCC1L (ENSG00000274523)

Protein

Protein identifiers

Alsin — Q96Q42 (reviewed: Q96Q42)

Alternative names: Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 6 protein, Amyotrophic lateral sclerosis 2 protein

All UniProt accessions (32): Q96Q42, A0A0S2Z5I4, A0A0S2Z5Q7, A0A7P0T813, A0A7P0T8F3, A0A7P0T8P3, A0A7P0T8R1, A0A7P0T8T2, A0A7P0T8W6, A0A7P0T951, A0A7P0T958, A0A7P0T976, A0A7P0T980, A0A7P0T993, A0A7P0T9K3, A0A7P0T9P3, A0A7P0T9R1, A0A7P0T9U5, A0A7P0T9V4, A0A7P0TAC4, A0A7P0TAH8, A0A7P0TAM1, A0A7P0TBB0, A0A7P0TBK0, A0A7P0Z499, A0A7P0Z4F3, A0A7P0Z4I4, A0A7P0Z4J9, A0A7P0Z4M6, H0Y696, J3KQ33, J3KQ43

UniProt curated annotations — full annotation on UniProt →

Function. May act as a GTPase regulator. Controls survival and growth of spinal motoneurons.

Subunit / interactions. Forms a heteromeric complex with ALS2CL. Interacts with ALS2CL.

Disease relevance. Amyotrophic lateral sclerosis 2 (ALS2) [MIM:205100] A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. The disease is caused by variants affecting the gene represented in this entry. Juvenile primary lateral sclerosis (JPLS) [MIM:606353] A neurodegenerative disorder which is closely related to but clinically distinct from amyotrophic lateral sclerosis. It is a progressive paralytic disorder which results from dysfunction of the upper motor neurons while the lower neurons are unaffected. The disease is caused by variants affecting the gene represented in this entry. Infantile-onset ascending spastic paralysis (IAHSP) [MIM:607225] Characterized by progressive spasticity and weakness of limbs. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96Q42-1	1	yes
Q96Q42-2	2
Q96Q42-3	3

RefSeq proteins (3): NP_001129217, NP_001397904, NP_065970* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR000408	Reg_chr_condens	Repeat
IPR003123	VPS9	Domain
IPR003409	MORN	Repeat
IPR009091	RCC1/BLIP-II	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR037191	VPS9_dom_sf	Homologous_superfamily
IPR051984	Alsin	Family
IPR057248	Alsin-like_PH	Domain
IPR059093	HA_Alsin	Domain

Pfam: PF00415, PF02204, PF02493, PF25383, PF25582, PF26202

UniProt features (39 total): repeat 13, modified residue 7, sequence variant 6, splice variant 4, domain 3, compositionally biased region 2, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96Q42-F1	74.69	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 465, 466, 483, 492, 510, 533, 1335

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9007101	Rab regulation of trafficking
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 434 (showing top): GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_LYSOSOMAL_TRANSPORT, GOBP_BEHAVIOR, GOBP_ENDOSOME_ORGANIZATION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_VESICLE_ORGANIZATION, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_VACUOLAR_TRANSPORT, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE, REACTOME_MEMBRANE_TRAFFICKING

GO Biological Process (19): behavioral fear response (GO:0001662), receptor recycling (GO:0001881), response to oxidative stress (GO:0006979), endosome organization (GO:0007032), lysosomal transport (GO:0007041), neuromuscular junction development (GO:0007528), locomotory behavior (GO:0007626), intracellular protein localization (GO:0008104), endosomal transport (GO:0016197), positive regulation of Rac protein signal transduction (GO:0035022), synaptic transmission, glutamatergic (GO:0035249), positive regulation of GTPase activity (GO:0043547), positive regulation of protein kinase activity (GO:0045860), neuron projection morphogenesis (GO:0048812), regulation of endosome size (GO:0051036), protein homooligomerization (GO:0051260), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072), vesicle organization (GO:0016050), regulation of biological quality (GO:0065008)

GO Molecular Function (7): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein serine/threonine kinase activator activity (GO:0043539), protein binding (GO:0005515)

GO Cellular Component (14): ruffle (GO:0001726), nucleus (GO:0005634), cytoplasm (GO:0005737), early endosome (GO:0005769), centrosome (GO:0005813), cytosol (GO:0005829), postsynaptic density (GO:0014069), lamellipodium (GO:0030027), dendrite (GO:0030425), growth cone (GO:0030426), vesicle (GO:0031982), protein-containing complex (GO:0032991), dendritic spine (GO:0043197), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Rab regulation of trafficking	1
RHO GTPase cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Vesicle-mediated transport	1
Membrane Trafficking	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	2
GTPase regulator activity	2
cell leading edge	2
plasma membrane bounded cell projection	2
cellular anatomical structure	2
behavioral defense response	1
fear response	1
endocytosis	1
receptor metabolic process	1
response to stress	1
endomembrane system organization	1
vesicle organization	1
vacuolar transport	1
synapse organization	1
behavior	1
macromolecule localization	1
vesicle-mediated transport	1
intracellular transport	1
Rac protein signal transduction	1
regulation of Rac protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
chemical synaptic transmission	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
positive regulation of protein phosphorylation	1
protein kinase activity	1
positive regulation of kinase activity	1
regulation of protein kinase activity	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
regulation of vesicle size	1
protein complex oligomerization	1
regulation of biological quality	1
organelle organization	1
biological regulation	1
GTP binding	1
GDP binding	1
enzyme activator activity	1
GTPase binding	1
protein binding	1

Protein interactions and networks

STRING

2554 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALS2	SETX	Q7Z333	909
ALS2	RAB5A	P20339	893
ALS2	SOD1	P00441	888
ALS2	VAPB	O95292	878
ALS2	FIG4	Q92562	854
ALS2	TARDBP	Q13148	826
ALS2	FUS	P35637	820
ALS2	C9orf72	Q96LT7	819
ALS2	GAPVD1	Q14C86	799
ALS2	DCTN1	Q14203	792
ALS2	CHMP2B	Q9UQN3	790
ALS2	SPG11	Q96JI7	788
ALS2	OPTN	Q96CV9	771
ALS2	RABIF	P47224	748
ALS2	NEK1	Q96PY6	746

IntAct

53 interactions, top by confidence:

A	B	Type	Score
ALS2	YWHAB	psi-mi:“MI:0915”(physical association)	0.860
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
NEURL4	APBB1	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
SDF2	ALS2	psi-mi:“MI:0914”(association)	0.530
ALS2	NEK1	psi-mi:“MI:0915”(physical association)	0.500
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
IQSEC1	ALS2	psi-mi:“MI:2364”(proximity)	0.470
IQSEC1	ALS2	psi-mi:“MI:0915”(physical association)	0.470
ALS2	RAC1	psi-mi:“MI:0915”(physical association)	0.400
RAB5A	ALS2	psi-mi:“MI:0915”(physical association)	0.400
ALS2	ALS2	psi-mi:“MI:0915”(physical association)	0.400
ALS2	CDC37	psi-mi:“MI:0915”(physical association)	0.400
NEURL4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
DNAAF2	DNM1L	psi-mi:“MI:0914”(association)	0.350
STXBP6	SNAP23	psi-mi:“MI:0914”(association)	0.350
ALS2	CFAP410	psi-mi:“MI:0914”(association)	0.350
SDF2	HSPA5	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
ALS2	CHN2	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): ALS2 (Affinity Capture-MS), ALS2 (Affinity Capture-MS), ALS2 (Affinity Capture-MS), NEK1 (Affinity Capture-MS), ALS2 (Affinity Capture-MS), C21orf2 (Affinity Capture-MS), RBM6 (Affinity Capture-MS), CHN2 (Affinity Capture-MS), PDCD10 (Affinity Capture-MS), CHN1 (Affinity Capture-MS), ZYX (Affinity Capture-MS), ALS2 (Phenotypic Enhancement), ALS2 (Phenotypic Enhancement), ALS2 (Affinity Capture-MS), YWHAZ (Affinity Capture-MS)

ESM2 similar proteins: A0A140LI67, B5KFD7, D4A7V9, M0R4F8, O08774, O35827, O43187, O70167, O70173, O88866, O88900, O95398, O95704, P0C5Y8, Q0P5I2, Q13322, Q14449, Q4QQS0, Q5BIW4, Q5ICW4, Q5JV73, Q5PQS0, Q5R810, Q60760, Q68DX3, Q6IFT4, Q6IRN0, Q6P4K6, Q6REY9, Q6S5L8, Q6TXD4, Q7TSI1, Q80TQ5, Q80VA5, Q8BW88, Q8CFA1, Q8IWE5, Q8R1C9, Q8R2S1, Q8VCC8

Diamond homologs: A6QP75, P0C5Y8, Q5BIW4, Q60I26, Q60I27, Q920R0, Q96Q42, A6NED2, D3ZGQ5, F1RD40, O75592, O95199, O95714, P18754, P23800, P25171, P25183, P58544, Q15034, Q15751, Q4R828, Q4U2R1, Q52KW8, Q5DX34, Q5GLZ8, Q5PQN1, Q5RCZ7, Q6NRS1, Q6NXM2, Q6NYE2, Q6PAV2, Q6ZPR6, Q7TPH6, Q7ZZC8, Q86SG6, Q8BK67, Q8BTU7, Q8IVU3, Q8K1R7, Q8K2J9

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ALS2	“up-regulates activity”	RAB5A	binding
RAC1	“up-regulates activity”	ALS2	binding
RAB7A	“down-regulates activity”	ALS2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	6	142.8×	2e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	126.0×	2e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	126.0×	2e-10
Activation of BH3-only proteins	6	93.1×	1e-09
RHO GTPases activate PKNs	7	69.4×	3e-10
Intrinsic Pathway for Apoptosis	6	54.9×	3e-08
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	38.6×	9e-10
SARS-CoV-1-host interactions	6	32.9×	5e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	53.6×	4e-07
intracellular protein localization	6	15.3×	4e-04
endocytosis	5	11.6×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1200 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	72
Likely pathogenic	39
Uncertain significance	499
Likely benign	378
Benign	94

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100653	NM_020919.4(ALS2):c.2761C>T (p.Arg921Ter)	Pathogenic
1066545	NM_020919.4(ALS2):c.3624+1G>A	Pathogenic
1323101	NM_020919.4(ALS2):c.3513-2del	Pathogenic
1443530	NM_020919.4(ALS2):c.1622del (p.His541fs)	Pathogenic
1446510	NM_020919.4(ALS2):c.4528C>T (p.Arg1510Ter)	Pathogenic
1454451	NM_020919.4(ALS2):c.4368del (p.Lys1457fs)	Pathogenic
1455318	NM_020919.4(ALS2):c.864del (p.Val289fs)	Pathogenic
1460001	NC_000002.11:g.(?202587756)(202589192_?)del	Pathogenic
147402	GRCh38/hg38 2q33.1(chr2:198767347-202353840)x1	Pathogenic
1678521	NM_020919.4(ALS2):c.4223T>A (p.Leu1408Ter)	Pathogenic
1678522	NM_020919.4(ALS2):c.2707dup (p.Met903fs)	Pathogenic
1679834	NM_020919.4(ALS2):c.4270C>T (p.Gln1424Ter)	Pathogenic
1693001	NM_020919.4(ALS2):c.347G>A (p.Gly116Glu)	Pathogenic
1693002	NM_020919.4(ALS2):c.2580+2T>C	Pathogenic
1693003	NM_020919.4(ALS2):c.2417+1G>C	Pathogenic
1693004	NM_020919.4(ALS2):c.2713-2A>C	Pathogenic
1693005	NM_020919.4(ALS2):c.158_160del (p.Gly53del)	Pathogenic
1693006	NM_020919.4(ALS2):c.3517delG	Pathogenic
1805070	NM_020919.4(ALS2):c.3829A>T (p.Lys1277Ter)	Pathogenic
183239	NM_020919.4(ALS2):c.2002G>T (p.Gly668Ter)	Pathogenic
2007382	NM_020919.4(ALS2):c.977del (p.Gly326fs)	Pathogenic
2115520	NM_020919.4(ALS2):c.3070C>T (p.Gln1024Ter)	Pathogenic
2155448	NM_020919.4(ALS2):c.2839C>T (p.Gln947Ter)	Pathogenic
2184611	NM_020919.4(ALS2):c.2527C>T (p.Arg843Ter)	Pathogenic
241308	NM_020919.4(ALS2):c.1425_1428del (p.Gly477fs)	Pathogenic
2444743	NM_020919.4(ALS2):c.2110C>T (p.Arg704Ter)	Pathogenic
2503048	NM_020919.4(ALS2):c.3703-2A>C	Pathogenic
2796368	NM_020919.4(ALS2):c.114G>A (p.Trp38Ter)	Pathogenic
2808755	NM_020919.4(ALS2):c.460C>T (p.Gln154Ter)	Pathogenic
2822022	NM_020919.4(ALS2):c.641T>G (p.Leu214Ter)	Pathogenic

SpliceAI

5071 predictions. Top by Δscore:

Variant	Effect	Δscore
2:201701885:CATGC:C	acceptor_gain	1.0000
2:201704118:TCA:T	donor_loss	1.0000
2:201704119:CA:C	donor_loss	1.0000
2:201704121:C:A	donor_loss	1.0000
2:201704607:T:TC	acceptor_gain	1.0000
2:201705135:TTAC:T	donor_loss	1.0000
2:201705136:TA:T	donor_loss	1.0000
2:201705138:C:CT	donor_loss	1.0000
2:201705197:AAAC:A	acceptor_gain	1.0000
2:201705198:AACC:A	acceptor_loss	1.0000
2:201705199:AC:A	acceptor_gain	1.0000
2:201705199:ACCT:A	acceptor_loss	1.0000
2:201705200:CC:C	acceptor_gain	1.0000
2:201705200:CCTG:C	acceptor_loss	1.0000
2:201705201:C:CC	acceptor_gain	1.0000
2:201705201:C:CG	acceptor_loss	1.0000
2:201706841:CTTA:C	donor_loss	1.0000
2:201706842:TTA:T	donor_loss	1.0000
2:201706843:TA:T	donor_loss	1.0000
2:201706844:A:AC	donor_gain	1.0000
2:201706844:ACCTC:A	donor_loss	1.0000
2:201706845:C:CC	donor_gain	1.0000
2:201706845:C:G	donor_loss	1.0000
2:201706845:CCT:C	donor_gain	1.0000
2:201706941:C:CT	acceptor_gain	1.0000
2:201707018:CATAA:C	acceptor_gain	1.0000
2:201707020:TAA:T	acceptor_gain	1.0000
2:201707021:AA:A	acceptor_gain	1.0000
2:201707023:C:CC	acceptor_gain	1.0000
2:201707023:C:T	acceptor_loss	1.0000

AlphaMissense

10815 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:201704189:A:G	L1623P	1.000
2:201704207:A:G	L1617S	1.000
2:201704457:G:T	A1612D	1.000
2:201704458:C:G	A1612P	1.000
2:201704460:C:G	R1611P	1.000
2:201704506:A:G	W1596R	1.000
2:201704506:A:T	W1596R	1.000
2:201704577:A:G	L1572P	1.000
2:201705151:A:G	L1559P	1.000
2:201706870:A:G	L1519P	1.000
2:201706903:A:T	V1508D	1.000
2:201709963:C:G	G1400R	1.000
2:201715799:A:G	W1293R	1.000
2:201715799:A:T	W1293R	1.000
2:201718203:A:G	L1237P	1.000
2:201724344:A:G	W1155R	1.000
2:201724344:A:T	W1155R	1.000
2:201726689:A:G	W1053R	1.000
2:201726689:A:T	W1053R	1.000
2:201726860:A:G	W996R	1.000
2:201726860:A:T	W996R	1.000
2:201727739:A:G	W960R	1.000
2:201727739:A:T	W960R	1.000
2:201727773:G:C	F948L	1.000
2:201727773:G:T	F948L	1.000
2:201727775:A:G	F948L	1.000
2:201728516:G:T	A946D	1.000
2:201728522:A:T	V944D	1.000
2:201728560:A:C	F931L	1.000
2:201728560:A:T	F931L	1.000

dbSNP variants (sampled 300 via entrez): RS1000035295 (2:201703890 T>C), RS1000046889 (2:201751081 G>A), RS1000082388 (2:201703378 C>T), RS1000085932 (2:201750860 T>C), RS1000145105 (2:201725869 A>G), RS1000181592 (2:201719941 T>G), RS1000224325 (2:201708033 A>C), RS1000255413 (2:201775530 C>A,T), RS1000317752 (2:201719596 T>A,C), RS1000341721 (2:201739339 A>G), RS1000354519 (2:201712758 A>G), RS1000365740 (2:201782408 C>T), RS1000432084 (2:201757025 A>G), RS1000511760 (2:201777030 T>C), RS1000548982 (2:201709236 T>C,G)

Disease associations

OMIM: gene MIM:606352 | disease phenotypes: MIM:607225, MIM:205100, MIM:606353, MIM:303350

GenCC curated gene-disease

Disease	Classification	Inheritance
ALS2-related motor neuron disease	Definitive	Autosomal recessive
amyotrophic lateral sclerosis type 2, juvenile	Strong	Autosomal recessive
juvenile primary lateral sclerosis	Strong	Autosomal recessive
infantile-onset ascending hereditary spastic paralysis	Strong	Autosomal recessive
juvenile amyotrophic lateral sclerosis	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
ALS2-related motor neuron disease	Definitive	AR

Mondo (9): infantile-onset ascending hereditary spastic paralysis (MONDO:0011797), amyotrophic lateral sclerosis type 2, juvenile (MONDO:0008780), juvenile primary lateral sclerosis (MONDO:0011663), amyotrophic lateral sclerosis (MONDO:0004976), hereditary spastic paraplegia (MONDO:0019064), juvenile amyotrophic lateral sclerosis (MONDO:0017593), ALS2-related motor neuron disease (MONDO:0100227), axonal neuropathy (MONDO:0004183), microcephaly (MONDO:0001149)

Orphanet (5): Infantile-onset ascending hereditary spastic paralysis (Orphanet:293168), Juvenile amyotrophic lateral sclerosis (Orphanet:300605), Juvenile primary lateral sclerosis (Orphanet:247604), Amyotrophic lateral sclerosis (Orphanet:803), Hereditary spastic paraplegia (Orphanet:685)

HPO phenotypes

98 total (30 of 98 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000014	Abnormality of the bladder
HP:0000020	Urinary incontinence
HP:0000183	Tongue muscle weakness
HP:0000252	Microcephaly
HP:0000271	Abnormality of the face
HP:0000478	Abnormality of the eye
HP:0000496	Abnormality of eye movement
HP:0000514	Slow saccadic eye movements
HP:0000605	Supranuclear gaze palsy
HP:0000639	Nystagmus
HP:0000708	Atypical behavior
HP:0000763	Sensory neuropathy
HP:0000980	Pallor
HP:0001152	Saccadic smooth pursuit interruptions
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001264	Spastic diplegia
HP:0001270	Motor delay
HP:0001276	Hypertonia
HP:0001285	Spastic tetraparesis
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001317	Abnormal cerebellum morphology
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001347	Hyperreflexia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008764_1	Perceived intensity of neohesperidin dihydrochalcone	6.000000e-06
GCST008766_1	Perceived intensity of sweet substances	6.000000e-06

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C565957	Amyotrophic Lateral Sclerosis 2, Juvenile (supp.)
C537217	Hereditary spastic paralysis, infantile onset ascending (supp.)
C536416	Primary lateral sclerosis juvenile (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	4
sodium arsenite	increases reaction, increases abundance, increases expression, affects binding, affects reaction	3
Cisplatin	affects expression, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
FR900359	affects phosphorylation	1
trichostatin A	affects expression	1
cinnamaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	increases abundance, increases expression	1
cupric oxide	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Acetaldehyde	increases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Caffeine	affects phosphorylation	1
Calcitriol	increases expression	1
Catechin	increases expression, affects cotreatment	1
Copper	increases expression, affects binding	1
Coumestrol	decreases expression	1
Estradiol	affects expression	1
Ethyl Methanesulfonate	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C7HF	HAP1 ALS2 (-) 1	Cancer cell line	Male
CVCL_C7HG	HAP1 ALS2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	PHASE3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	PHASE3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	PHASE3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	PHASE3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	PHASE3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	PHASE3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS