SPG11

Summary

SPG11 (SPG11 vesicle trafficking associated, spatacsin, HGNC:11226) is a protein-coding gene on chromosome 15q21.1, encoding Spatacsin (Q96JI7). May play a role in neurite plasticity by maintaining cytoskeleton stability and regulating synaptic vesicle transport.

The protein encoded by this gene is a potential transmembrane protein that is phosphorylated upon DNA damage. Defects in this gene are a cause of spastic paraplegia type 11 (SPG11). Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 80208 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary spastic paraplegia 11 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 3,694 total — 395 pathogenic, 132 likely-pathogenic
• Phenotypes (HPO): 136
• Druggable target: yes
• MANE Select transcript: NM_025137

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11226
Approved symbol	SPG11
Name	SPG11 vesicle trafficking associated, spatacsin
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21439
Ensembl gene	ENSG00000104133
Ensembl biotype	protein_coding
OMIM	610844
Entrez	80208

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 14 retained_intron, 13 protein_coding, 12 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 1 non_stop_decay

ENST00000261866, ENST00000427534, ENST00000535302, ENST00000557866, ENST00000558080, ENST00000558093, ENST00000558138, ENST00000558253, ENST00000558319, ENST00000558561, ENST00000558790, ENST00000558988, ENST00000558989, ENST00000559193, ENST00000559347, ENST00000559511, ENST00000559933, ENST00000560299, ENST00000561268, ENST00000561391, ENST00000682065, ENST00000682410, ENST00000682460, ENST00000682495, ENST00000682648, ENST00000682669, ENST00000682788, ENST00000682877, ENST00000682915, ENST00000683121, ENST00000683186, ENST00000683255, ENST00000683496, ENST00000683573, ENST00000683734, ENST00000683753, ENST00000683838, ENST00000684038, ENST00000684235, ENST00000684490, ENST00000684676, ENST00000920240, ENST00000920241, ENST00000920242

RefSeq mRNA: 3 — MANE Select: NM_025137 NM_001160227, NM_001411132, NM_025137

CCDS: CCDS10112, CCDS53939, CCDS91991

Canonical transcript exons

ENST00000261866 — 40 exons

Exon	Start	End
ENSE00000684706	44564547	44564698
ENSE00000684735	44565854	44566009
ENSE00000884381	44562696	44563301
ENSE00001047590	44595259	44595459
ENSE00001047603	44596083	44596355
ENSE00001047605	44610840	44610985
ENSE00001047607	44583814	44584558
ENSE00001047612	44606025	44606091
ENSE00001047617	44608444	44608605
ENSE00001047619	44596784	44596943
ENSE00001047622	44598265	44598373
ENSE00001105923	44628669	44628844
ENSE00001105929	44633505	44633637
ENSE00001105933	44629233	44629388
ENSE00001105941	44626331	44626507
ENSE00001123435	44573547	44573745
ENSE00001183204	44620190	44620403
ENSE00001183208	44621759	44621934
ENSE00001183213	44622220	44622347
ENSE00001183220	44622728	44622799
ENSE00001183236	44648866	44649011
ENSE00001183238	44651491	44651939
ENSE00001183241	44652129	44652266
ENSE00001183246	44657095	44657296
ENSE00001183250	44659079	44659303
ENSE00001183253	44660432	44660616
ENSE00001287244	44613430	44613536
ENSE00001940948	44663391	44663662
ENSE00003459787	44566217	44566305
ENSE00003522763	44569398	44569505
ENSE00003534865	44600467	44600632
ENSE00003538379	44574902	44575041
ENSE00003576804	44567424	44567592
ENSE00003582020	44615363	44615566
ENSE00003622334	44572683	44572820
ENSE00003634381	44570525	44570658
ENSE00003660987	44592331	44592438
ENSE00003667183	44598631	44598836
ENSE00003690738	44585636	44585850
ENSE00003693147	44589252	44589414

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.2906 / max 325.6449, expressed in 1815 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149657	17.8079	1810
149656	0.7966	498
149650	0.5812	163
149651	0.1050	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	97.07	gold quality
granulocyte	CL:0000094	96.74	gold quality
calcaneal tendon	UBERON:0003701	96.36	gold quality
epithelium of bronchus	UBERON:0002031	96.34	gold quality
bronchus	UBERON:0002185	96.30	gold quality
epithelium of nasopharynx	UBERON:0001951	96.12	gold quality
upper leg skin	UBERON:0004262	96.02	gold quality
colonic epithelium	UBERON:0000397	95.89	gold quality
corpus callosum	UBERON:0002336	95.84	gold quality
pylorus	UBERON:0001166	95.77	gold quality
spleen	UBERON:0002106	95.72	gold quality
right lobe of thyroid gland	UBERON:0001119	95.62	gold quality
left lobe of thyroid gland	UBERON:0001120	95.51	gold quality
parietal pleura	UBERON:0002400	95.49	gold quality
thyroid gland	UBERON:0002046	95.41	gold quality
tonsil	UBERON:0002372	95.36	gold quality
bone marrow cell	CL:0002092	95.35	gold quality
ventricular zone	UBERON:0003053	95.32	gold quality
pleura	UBERON:0000977	95.30	gold quality
body of pancreas	UBERON:0001150	95.29	gold quality
adrenal tissue	UBERON:0018303	95.22	gold quality
skin of hip	UBERON:0001554	95.17	gold quality
right uterine tube	UBERON:0001302	95.08	gold quality
visceral pleura	UBERON:0002401	95.00	gold quality
monocyte	CL:0000576	94.99	gold quality
mononuclear cell	CL:0000842	94.93	gold quality
leukocyte	CL:0000738	94.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.79	gold quality
urethra	UBERON:0000057	94.70	gold quality
seminal vesicle	UBERON:0000998	94.60	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.47
E-GEOD-100618	no	840.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting SPG11, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-3923	99.52	69.21	446
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-3169	96.40	67.58	698
HSA-MIR-5579-5P	96.32	68.54	730

Literature-anchored findings (GeneRIF, showing 40)

• mutations in the SPG11 gene causes spastic paraplegia with thin corpus callosum (PMID:17322883)
• Frameshift, nonsense mutations, and splice mutations in SPG11. Mutations are major cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum associated with severe motor and cognitive impairment. (PMID:18067136)
• The study reveals the high frequency of SPG11 mutations in patients with HSP, a TCC and cognitive impairment, including in isolated patients, and extends the associated phenotype. (PMID:18079167)
• Autosomal recessive HSP-TCC is a frequent subtype of complicated HSP in Tunisia and is clinically and genetically heterogeneous. SPG11 and SPG15 are the major loci for this entity. (PMID:18332254)
• Mutations on KIAA1840 are frequent in complex autosomal recessive hereditary spastic paraplegia, but they are an infrequent cause of sporadic complex hereditary spastic paraplegia. (PMID:18337587)
• Mutations of the SPG11 gene encoding the spatacsin protein have been identified as a major cause of hereditary spastic paraplegia. (PMID:18361476)
• Genetic and phenotypic data on five patients from two Taiwanese/Chinese families with ARHSP-TCC. (PMID:18408091)
• SPG11 mutations should be suspected in patients with isolated or recessive HSP, thin corpus callosum and mental retardation. (PMID:18439221)
• Loss-of-function SPG11 mutations are the major cause of autosomal recessive hereditary spastic paraparesis with thin corpus callosum in Southern Europe, even in apparently sporadic cases. (PMID:18663179)
• 5 new spatacsin mutations were found in complex autosomal recessive hereditary spastic paraplegia:p.C133LfsX154, p.Q1875X, p.K2386QfsX2393,c.2834 + 1G > T & c.6754 + 4insTG. (PMID:18717728)
• This study widens the mutation spectrum of the SPG11 gene and the mutations in the SPG11 gene are also the major causative gene for HSP-TCC in the Chinese Hans. (PMID:18835492)
• Abnormal MRI signal in the region of the forceps minor of the corpus callosum is a characteristic early imaging finding of HSP-TCC with SPG11 mutations. (PMID:19040626)
• ZFYVE26 is the second gene responsible for spastic paraplegia with thinning of the corpus callosum in the Italian population (PMID:19084844)
• This study confirms heterogeneity amongst Italian families with hereditary spastic paraplegia/thin corpus callosum and reports a new mutation predicted to affect splicing in the spatacsin gene. (PMID:19087158)
• While expanding the spectrum of mutations in SPG11, this larger series also corroborated the notion that even within apparently homogeneous population a molecular diagnosis cannot be achieved without full gene sequencing. (PMID:19105190)
• Degeneration of the central retina is a common and previously unrecognized feature in SPG11 related disease. (PMID:19194956)
• Findings expand the mutation spectrum of SPG11 and suggest that SPG11 mutations may occur more frequently in familial than sporadic forms of cHSP without TCC. (PMID:19196735)
• Evidence that parkinsonism may initiate SPG11-linked HSP TCC and that SPG11 may cause juvenile parkinsonism. (PMID:19224311)
• we report three novel and one known heterozygous compound SPG11 mutations in patients with hereditary spastic paraplegia with thin corpus callosum; these are the first cases of genetically confirmed SPG11 mutations in the Korean population. (PMID:19513778)
• phenotype and mutation frequency compared with SPG15 in complicated hereditary spastic paraplegia (PMID:19917823)
• Up to 12 sequence alterations in the spatacsin gene have been identified in unrelated pedigrees with autosomal recessive juvenile amyotrophic lateral sclerosis. (PMID:20110243)
• analysis of SPG11 mutations in Asian kindreds and disruption of spatacsin function in the zebrafish (PMID:20390432)
• We identified genetic deficits in spatacsin that were associated with Levodopa responsive parkinsonism with pyramidal signs. (PMID:20669327)
• Data support the importance of SPG11 as a frequent cause for ARHSP-TCC, and expands the clinical SPG11 spectrum. (PMID:20971220)
• Retinal changes, an integral part of SPG11 mutations in this series of patients, are only observed once the paraplegia has become apparent. (PMID:21035867)
• SPG11, the most frequent gene associated with hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) encodes spatacsin, demonstrating the extensive genetic heterogeneity of this condition. (PMID:21440262)
• Spatacsin was strongly expressed in cortical and spinal motor neurons and in embryos. It partially co-localized with multiple organelles, particularly with protein-trafficking vesicles, endoplasmic reticulum and microtubules. (PMID:21545838)
• This study confirmed that SPG11 as a genetic cause of juvenile amyotrophic lateral sclerosis and indicate that SPG11 mutations could be associated with 2 different clinical phenotypes within the same family. (PMID:22154821)
• The analysis shows that the high number of repeated elements in SPG11 together with the presence of recombination hotspots and the high intrinsic instability of the 15q locus all contribute toward making this genomic region more prone to large gene rearrangements. (PMID:22237444)
• mutations result in white and grey matter abnormalities (PMID:22696581)
• This study widens the spectrum of mutations in SPG11 (PMID:23121729)
• There was a characteristic gradation in the reduction of microstructural integrity among fiber types and within the CC in patients with the SPG11 mutation (PMID:23221952)
• A novel homozygous nonsense mutation in exon 15 of the SPG11 gene (c.2678G>A; p.W893X) found in two Spanish siblings with a complicated forms of hereditary spastic paraplegia. (PMID:23438842)
• We propose AP-5, SPG15, SPG11 form a coat-like complex, with AP-5 involved in protein sorting, SPG15 facilitating docking of the coat onto membranes by interacting with PI3P via its FYVE domain, and SPG11 (possibly together with SPG15) forming a scaffold. (PMID:23825025)
• SPG11 mutations were identified in autosomal recessive juvenile Amyotrophic lateral sclerosis. (PMID:24085347)
• This study identified novel compound heterozygous mutations in the SPG11 gene of the patients as follows: a nonsense mutation c.6856C>T (p.R2286X) in exon 38 and a deletion mutation c.2863delG (p.Glu955Lysfs*8) in exon 16. (PMID:24090761)
• widespread accumulation of spatacsin observed in pathologic alpha-synuclein-containing inclusions suggests that spatacsin may be involved in the pathogenesis of alpha-synucleinopathies (PMID:24112408)
• We have identified an Hereditary spastic paraplegia patient who inherited the c.5121_5122insAG mutation from his mother and the c.6859C>T mutation from his father (PMID:24315199)
• Study provides evidence that SPG11 is implicated in axonal maintenance and cargo trafficking. (PMID:24794856)
• spastizin and spatacsin were essential components for the initiation of lysosomal tubulation. Together, these results link dysfunction of the autophagy/lysosomal biogenesis machinery to neurodegeneration. (PMID:25365221)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	spg11	ENSDARG00000045968
mus_musculus	Spg11	ENSMUSG00000033396
rattus_norvegicus	Spg11	ENSRNOG00000021954
drosophila_melanogaster	CG13531	FBGN0034786

Protein

Protein identifiers

Spatacsin — Q96JI7 (reviewed: Q96JI7)

Alternative names: Colorectal carcinoma-associated protein, Spastic paraplegia 11 protein

All UniProt accessions (20): A0A075B718, A0A804HI84, A0A804HI99, A0A804HID9, A0A804HIM5, Q96JI7, A0A804HIP5, A0A804HJG2, A0A804HJL9, A0A804HK59, A0A804HKQ8, A0A804HKV6, A0A804HLC5, A0A804HLE6, A0A804HLF9, A0A804HLG4, C4B7M2, H0YLK7, H0YLR8, H0YN34

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in neurite plasticity by maintaining cytoskeleton stability and regulating synaptic vesicle transport.

Subunit / interactions. Interacts with AP5Z1, AP5B1, AP5S1 and ZFYVE26.

Subcellular location. Cytoplasm. Cytosol. Nucleus. Cell projection. Axon. Dendrite.

Tissue specificity. Expressed in all structures of brain, with a high expression in cerebellum. Expressed in cortical projection neurons.

Disease relevance. Spastic paraplegia 11, autosomal recessive (SPG11) [MIM:604360] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. The disease is caused by variants affecting the gene represented in this entry. Amyotrophic lateral sclerosis 5, juvenile (ALS5) [MIM:602099] A form of amyotrophic lateral sclerosis, 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. ALS5 is an autosomal recessive, juvenile form characterized by onset of upper and lower motor neuron signs before age 25. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, axonal, type 2X (CMT2X) [MIM:616668] An autosomal recessive, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2X patients manifest a slowly progressive, peripheral neuropathy affecting the lower limbs and resulting in gait difficulties and distal sensory impairment. Some patients also have upper limb involvement. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96JI7-1	1	yes
Q96JI7-2	2
Q96JI7-3	3

RefSeq proteins (3): NP_001153699, NP_001398061, NP_079413* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028103	Spatacsin	Family
IPR028107	Spatacsin_C_dom	Domain

Pfam: PF14649

UniProt features (19 total): sequence variant 9, sequence conflict 5, splice variant 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8YAB	ELECTRON MICROSCOPY	3.26
8YAH	ELECTRON MICROSCOPY	3.3
8YAD	ELECTRON MICROSCOPY	4.02

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JI7-F1	67.06	0.00

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 (1): 1955

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 487 (showing top): GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_MEMORY, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_COGNITION, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_BEHAVIOR, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_VACUOLE_ORGANIZATION, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, BASSO_B_LYMPHOCYTE_NETWORK, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, GOBP_MEMBRANE_FUSION

GO Biological Process (24): protein import into nucleus (GO:0006606), lysosome organization (GO:0007040), chemical synaptic transmission (GO:0007268), axonogenesis (GO:0007409), neuromuscular junction development (GO:0007528), memory (GO:0007613), axo-dendritic transport (GO:0008088), corticospinal tract morphogenesis (GO:0021957), protein catabolic process (GO:0030163), cholesterol efflux (GO:0033344), vesicle transport along microtubule (GO:0047496), synaptic vesicle transport (GO:0048489), axon extension (GO:0048675), skeletal muscle fiber development (GO:0048741), localization within membrane (GO:0051668), motor behavior (GO:0061744), phagosome-lysosome fusion involved in apoptotic cell clearance (GO:0090389), walking behavior (GO:0090659), motor neuron apoptotic process (GO:0097049), autophagosome organization (GO:1905037), regulation of store-operated calcium entry (GO:2001256), intracellular protein transport (GO:0006886), intracellular protein localization (GO:0008104), neuron apoptotic process (GO:0051402)

GO Molecular Function (2): protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (12): nucleolus (GO:0005730), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), axon (GO:0030424), dendrite (GO:0030425), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202), nucleus (GO:0005634), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron projection	3
cellular anatomical structure	3
cytoplasm	3
intracellular membrane-bounded organelle	2
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
lytic vacuole organization	1
anterograde trans-synaptic signaling	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
synapse organization	1
learning or memory	1
transport along microtubule	1
central nervous system projection neuron axonogenesis	1
macromolecule catabolic process	1
protein metabolic process	1
cholesterol transport	1
organelle transport along microtubule	1
vesicle cytoskeletal trafficking	1
transport	1
cellular process	1
establishment of vesicle localization	1
synaptic vesicle localization	1
axonogenesis	1
neuron projection extension	1
skeletal muscle tissue development	1
myotube cell development	1
cellular localization	1
behavior	1
phagosome-lysosome fusion	1
phagolysosome assembly involved in apoptotic cell clearance	1
locomotory behavior	1
neuron apoptotic process	1
vacuole organization	1
macroautophagy	1
kinase binding	1
binding	1

Protein interactions and networks

STRING

1432 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPG11	AP5Z1	O43299	994
SPG11	ZFYVE26	Q68DK2	983
SPG11	AP5B1	Q2VPB7	966
SPG11	SPG7	Q9UQ90	957
SPG11	AP5S1	Q9NUS5	952
SPG11	SPG21	Q9NZD8	949
SPG11	SPAST	Q9UBP0	936
SPG11	PNPLA6	Q8IY17	856
SPG11	SPART	Q8N0X7	851
SPG11	ALS2	Q96Q42	788
SPG11	GJC2	Q5T442	779
SPG11	SEMA6D	Q8NFY4	758
SPG11	REEP1	Q9H902	741
SPG11	SETX	Q7Z333	737
SPG11	ATL1	Q8WXF7	734

IntAct

189 interactions, top by confidence:

A	B	Type	Score
SNX6	SNX2	psi-mi:“MI:0914”(association)	0.800
SPG11	AP5B1	psi-mi:“MI:0915”(physical association)	0.750
ZFYVE26	SPG11	psi-mi:“MI:2364”(proximity)	0.700
SPG11	ZFYVE26	psi-mi:“MI:0915”(physical association)	0.700
ZFYVE26	SPG11	psi-mi:“MI:0915”(physical association)	0.700
SPG11	Ap5z1	psi-mi:“MI:0914”(association)	0.640
SPG11	Ap5z1	psi-mi:“MI:0915”(physical association)	0.640
Ap5z1	SPG11	psi-mi:“MI:0915”(physical association)	0.640
DNM1	SPG11	psi-mi:“MI:0915”(physical association)	0.630
SPG11	DNM1	psi-mi:“MI:0915”(physical association)	0.630
SPG11	AP5Z1	psi-mi:“MI:0914”(association)	0.620
SPG11	AP5Z1	psi-mi:“MI:0915”(physical association)	0.620
SPG11	YWHAH	psi-mi:“MI:0407”(direct interaction)	0.590
YWHAH	SPG11	psi-mi:“MI:0915”(physical association)	0.590
AP5B1	Ap5z1	psi-mi:“MI:0915”(physical association)	0.570
SPG11	SERTAD3	psi-mi:“MI:0915”(physical association)	0.560
SERTAD3	SPG11	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (70): SPG11 (Two-hybrid), SPG11 (Affinity Capture-MS), SPG11 (Affinity Capture-MS), SPG11 (Affinity Capture-MS), SPG11 (Affinity Capture-MS), SPG11 (Affinity Capture-MS), SPG11 (Affinity Capture-MS), SPG11 (Affinity Capture-MS), SPG11 (Affinity Capture-RNA), SPG11 (Affinity Capture-MS), SPG11 (Proximity Label-MS), SPG11 (Proximity Label-MS), SPG11 (Affinity Capture-MS), SPG11 (Positive Genetic), SPG11 (Proximity Label-MS)

ESM2 similar proteins: A0A0M3U1B0, A0A1L8EYB2, A0FKI7, A1A5R8, A2AHC3, A2BE28, A5WUN7, A8DZJ1, B7ZS37, D3Z6S9, D3Z8E6, O55036, O60281, O75113, P54274, P62932, P70278, Q08AD1, Q13129, Q16533, Q2T9I9, Q3UMB5, Q5BLK4, Q5H9M0, Q5T4T6, Q5T5Y3, Q5VYS8, Q640U0, Q641E3, Q6DRL4, Q6IRN6, Q6PUR7, Q7Z2Z1, Q7Z7J5, Q86WZ0, Q8BQ33, Q8IZM8, Q8K0S9, Q8NEM2, Q8TEV9

Diamond homologs: Q3UHA3, Q55GD2, Q96JI7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 163 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	44.8×	5e-07
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	39.5×	7e-07
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	39.5×	7e-07
Activation of BH3-only proteins	6	29.2×	3e-06
RHO GTPases activate PKNs	6	18.7×	4e-05
Intrinsic Pathway for Apoptosis	6	17.2×	5e-05
RHOU GTPase cycle	5	13.7×	8e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	9	13.6×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

3694 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	395
Likely pathogenic	132
Uncertain significance	1434
Likely benign	1353
Benign	60

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068457	NM_025137.4(SPG11):c.1654_1655insGGAAAATCTTTTTTTTTTTTTTTTTTTTTNNNNNNNNGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGAGAGGGGA (p.Ser551_Lys552insArgLysIlePhePhePhePhePhePhePheXaaXaaXaaGlyGluGlyGluGlyGluGlyGluGlyGluGlyGluGlyGluGly)	Pathogenic
1070626	NM_025137.4(SPG11):c.4109del (p.Asp1370fs)	Pathogenic
1070834	NM_025137.4(SPG11):c.6317_6335del (p.Ser2106fs)	Pathogenic
1071204	NM_025137.4(SPG11):c.7138G>T (p.Glu2380Ter)	Pathogenic
1071977	NM_025137.4(SPG11):c.4939C>T (p.Gln1647Ter)	Pathogenic
1072015	NM_025137.4(SPG11):c.4432C>T (p.Gln1478Ter)	Pathogenic
1072253	NC_000015.9:g.(?44876002)(44876766_?)del	Pathogenic
1072337	NM_025137.4(SPG11):c.7055_7058dup (p.Gln2354fs)	Pathogenic
1072750	NM_025137.4(SPG11):c.4621C>T (p.Gln1541Ter)	Pathogenic
1074115	NC_000015.9:g.(?44862713)(44867249_?)del	Pathogenic
1074116	NC_000015.9:g.(?44941054)(44944474_?)del	Pathogenic
1074117	NC_000015.9:g.(?44918519)(44921596_?)del	Pathogenic
1074118	NC_000015.9:g.(?44881444)(44925841_?)dup	Pathogenic
1074526	NM_025137.4(SPG11):c.5322del (p.Leu1775fs)	Pathogenic
1075394	NM_025137.4(SPG11):c.7093_7094insCTT (p.Glu2365delinsAlaTer)	Pathogenic
1075471	NM_025137.4(SPG11):c.3909del (p.Lys1303fs)	Pathogenic
1075919	NC_000015.9:g.(?44862703)(44862876_?)del	Pathogenic
1109	NM_025137.4(SPG11):c.6100C>T (p.Arg2034Ter)	Pathogenic
1110	NM_025137.4(SPG11):c.529_533del (p.Ile177fs)	Pathogenic
1111	NM_025137.4(SPG11):c.118C>T (p.Gln40Ter)	Pathogenic
1112	NM_025137.4(SPG11):c.733_734del (p.Met245fs)	Pathogenic
1113	NM_025137.4(SPG11):c.2472_2473insT (p.Lys825Ter)	Pathogenic
1114	NM_025137.4(SPG11):c.442+1G>C	Pathogenic
1115	NM_025137.4(SPG11):c.7152-1G>C	Pathogenic
1116	NM_025137.4(SPG11):c.5623C>T (p.Gln1875Ter)	Pathogenic
1117	NM_025137.4(SPG11):c.3075dup (p.Glu1026fs)	Pathogenic
1180685	NM_025137.4(SPG11):c.6811_6812del (p.Leu2271fs)	Pathogenic
1180843	NM_025137.4(SPG11):c.6520_6521del (p.Tyr2174fs)	Pathogenic
1256320	NM_025137.4(SPG11):c.2471del (p.Phe824fs)	Pathogenic
1325833	NM_025137.4:c.(5866+1_5867-1)_(6477+1_6478-1)del	Pathogenic

SpliceAI

7780 predictions. Top by Δscore:

Variant	Effect	Δscore
15:44557483:CTACA:C	acceptor_loss	1.0000
15:44557484:TACA:T	acceptor_loss	1.0000
15:44557486:CA:C	acceptor_loss	1.0000
15:44557487:A:C	acceptor_loss	1.0000
15:44557488:GGT:G	acceptor_gain	1.0000
15:44557559:A:T	donor_gain	1.0000
15:44557573:A:G	donor_gain	1.0000
15:44557620:G:GT	donor_gain	1.0000
15:44557646:TTCAT:T	donor_gain	1.0000
15:44557648:CATG:C	donor_loss	1.0000
15:44557650:TG:T	donor_loss	1.0000
15:44557651:G:A	donor_loss	1.0000
15:44557651:G:GG	donor_gain	1.0000
15:44560243:TTTAA:T	acceptor_loss	1.0000
15:44560244:TTAAG:T	acceptor_loss	1.0000
15:44560245:TAA:T	acceptor_loss	1.0000
15:44560246:A:AG	acceptor_gain	1.0000
15:44560246:AAG:A	acceptor_loss	1.0000
15:44560246:AAGT:A	acceptor_gain	1.0000
15:44560246:AAGTG:A	acceptor_gain	1.0000
15:44560247:AGT:A	acceptor_gain	1.0000
15:44560247:AGTG:A	acceptor_gain	1.0000
15:44560247:AGTGG:A	acceptor_loss	1.0000
15:44560248:GT:G	acceptor_gain	1.0000
15:44560248:GTG:G	acceptor_gain	1.0000
15:44560248:GTGG:G	acceptor_gain	1.0000
15:44560248:GTGGA:G	acceptor_gain	1.0000
15:44560318:AAAAG:A	donor_loss	1.0000
15:44560319:AAAG:A	donor_loss	1.0000
15:44560320:AAGG:A	donor_loss	1.0000

AlphaMissense

16242 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:44567483:C:T	G2232D	0.999
15:44566237:C:G	A2275P	0.998
15:44610960:G:C	S1057R	0.998
15:44610960:G:T	S1057R	0.998
15:44610962:T:G	S1057R	0.998
15:44565954:A:G	L2300P	0.997
15:44567483:C:A	G2232V	0.997
15:44567484:C:G	G2232R	0.997
15:44567503:G:C	F2225L	0.997
15:44567503:G:T	F2225L	0.997
15:44567505:A:G	F2225L	0.997
15:44567513:G:T	A2222D	0.997
15:44567570:A:G	L2203P	0.997
15:44566226:A:C	S2278R	0.995
15:44566226:A:T	S2278R	0.995
15:44566228:T:G	S2278R	0.995
15:44567463:C:G	A2239P	0.995
15:44567475:G:C	H2235D	0.995
15:44567510:A:G	L2223P	0.995
15:44596104:A:C	S1471R	0.995
15:44596104:A:T	S1471R	0.995
15:44596106:T:G	S1471R	0.995
15:44600533:C:G	R1207P	0.995
15:44608451:A:G	L1149P	0.995
15:44567474:T:G	H2235P	0.994
15:44567518:C:A	M2220I	0.994
15:44567518:C:G	M2220I	0.994
15:44567518:C:T	M2220I	0.994
15:44567519:A:G	M2220T	0.994
15:44569495:A:G	L2163P	0.994

dbSNP variants (sampled 300 via entrez): RS1000023827 (15:44587717 A>C), RS1000063658 (15:44604108 C>G,T), RS1000076104 (15:44587919 A>C,G), RS1000169012 (15:44614975 T>G), RS1000178176 (15:44624877 G>A), RS1000198085 (15:44614803 A>G), RS1000228327 (15:44656149 A>C,G), RS1000241152 (15:44650247 G>A), RS1000278173 (15:44566487 C>G,T), RS1000304290 (15:44615353 C>T), RS1000307458 (15:44644453 C>A), RS1000323844 (15:44594200 G>T), RS1000340186 (15:44574383 A>C), RS1000392837 (15:44600892 G>A,T), RS1000394755 (15:44566690 A>C,T)

Disease associations

OMIM: gene MIM:610844 | disease phenotypes: MIM:604360, MIM:602099, MIM:616668, MIM:303350, MIM:605714, MIM:118220, MIM:162200, MIM:108600, MIM:615530

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spastic paraplegia 11	Definitive	Autosomal recessive
amyotrophic lateral sclerosis type 5	Strong	Autosomal recessive
Charcot-Marie-Tooth disease axonal type 2X	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
hereditary spastic paraplegia 11	Definitive	AR

Mondo (14): hereditary spastic paraplegia 11 (MONDO:0011445), amyotrophic lateral sclerosis type 5 (MONDO:0011196), Charcot-Marie-Tooth disease axonal type 2X (MONDO:0014726), hereditary spastic paraplegia (MONDO:0019064), juvenile amyotrophic lateral sclerosis (MONDO:0017593), cerebral amyloid angiopathy, APP-related (MONDO:0011583), amyotrophic lateral sclerosis (MONDO:0004976), intellectual disability (MONDO:0001071), Charcot-Marie-Tooth disease (MONDO:0015626), metabolic disease (MONDO:0005066), neurofibromatosis type 1 (MONDO:0018975), spastic ataxia (MONDO:0017845), early-onset Parkinson disease 20 (MONDO:0014233), autism spectrum disorder (MONDO:0005258)

Orphanet (18): Autosomal recessive spastic paraplegia type 11 (Orphanet:2822), Juvenile amyotrophic lateral sclerosis (Orphanet:300605), Autosomal recessive Charcot-Marie-Tooth disease type 2X (Orphanet:466775), Hereditary spastic paraplegia (Orphanet:685), ABeta amyloidosis, Dutch type (Orphanet:100006), ABetaL34V amyloidosis (Orphanet:324703), ABeta amyloidosis, Iowa type (Orphanet:324708), ABeta amyloidosis, Italian type (Orphanet:324713), ABetaA21G amyloidosis (Orphanet:324718), ABeta amyloidosis, Arctic type (Orphanet:324723), Hereditary cerebral amyloid angiopathy (Orphanet:85458), Amyotrophic lateral sclerosis (Orphanet:803), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Neurofibromatosis type 1 (Orphanet:636), Spastic ataxia (Orphanet:316226)

HPO phenotypes

136 total (30 of 136 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000252	Microcephaly
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000546	Retinal degeneration
HP:0000605	Supranuclear gaze palsy
HP:0000608	Macular degeneration
HP:0000639	Nystagmus
HP:0000640	Gaze-evoked nystagmus
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000712	Emotional lability
HP:0000726	Dementia
HP:0000736	Short attention span
HP:0000763	Sensory neuropathy
HP:0001004	Lymphedema
HP:0001152	Saccadic smooth pursuit interruptions
HP:0001239	Wrist flexion contracture
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001264	Spastic diplegia
HP:0001268	Mental deterioration

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007726_4	Anti-Toxoplasma gondii IgG seropositivity	5.000000e-06
GCST010241_150	Apolipoprotein A1 levels	3.000000e-20
GCST010242_280	HDL cholesterol levels	2.000000e-29

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007047	Toxoplasma gondii seropositivity
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (8)

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
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008659	Metabolic Diseases	C18.452
D009456	Neurofibromatosis 1	C04.557.580.600.580.590.650; C04.700.631.650; C10.562.600.500; C10.574.500.549.400; C10.668.829.675; C16.320.400.560.400; C16.320.700.633.650
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
C566576	Amyotrophic Lateral Sclerosis 5 (supp.)
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067204 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.16	Kd	692.5	nM	CHEMBL5653589
6.02	ED50	961.2	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149472: Binding affinity to human SPG11 incubated for 45 mins by Kinobead based pull down assay	kd	0.6925	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, affects cotreatment, increases abundance	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
chromium hexavalent ion	decreases expression	1
K 7174	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Vehicle Emissions	affects expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Lead	affects expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Methotrexate	affects expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	decreases expression, increases abundance, affects cotreatment	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652514	Binding	Binding affinity to human SPG11 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

11 cell lines: 9 induced pluripotent stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2H6	Abcam HeLa SPG11 KO	Cancer cell line	Female
CVCL_C6IE	HAP1 SPG11 (-)	Cancer cell line	Male
CVCL_E4W2	KOLF2.1J SPG11 PTC PTC/PTC	Induced pluripotent stem cell	Male
CVCL_E4W4	KOLF2.1J SPG11 Q1875X SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E4W5	KOLF2.1J SPG11 Q1875X SNV/WT	Induced pluripotent stem cell	Male
CVCL_VE48	SPG11-11	Induced pluripotent stem cell	Female
CVCL_VE49	SPG11-12	Induced pluripotent stem cell	Female
CVCL_VE50	SPG11-21	Induced pluripotent stem cell	Female
CVCL_VE51	SPG11-22	Induced pluripotent stem cell	Female
CVCL_VE52	SPG11-31	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
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