SETX

Summary

SETX (senataxin, HGNC:445) is a protein-coding gene on chromosome 9q34.13, encoding Helicase senataxin (Q7Z333). ATP-dependent 5’->3’ DNA/RNA helicase that preferentially unwinds RNA substrates over DNA, playing a crucial role in resolving R-loops and promoting transcription termination.

This gene encodes a protein named for its homology to the Sen1p protein of fungi which has RNA helicase activity encoded by a domain at the C-terminal end of the protein. The protein encoded by this gene contains a DNA/RNA helicase domain at its C-terminal end which suggests that it may be involved in both DNA and RNA processing. Mutations in this gene have been associated with ataxia-ocular apraxia-2 (AOA2) and an autosomal dominant form of juvenile amyotrophic lateral sclerosis (ALS4).

Source: NCBI Gene 23064 — RefSeq curated summary.

At a glance

• Gene–disease (curated): distal hereditary motor neuropathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 2,204 total — 58 pathogenic, 51 likely-pathogenic
• Phenotypes (HPO): 69
• MANE Select transcript: NM_015046

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:445
Approved symbol	SETX
Name	senataxin
Location	9q34.13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0625, AOA2, Sen1, STEX
Ensembl gene	ENSG00000107290
Ensembl biotype	protein_coding
OMIM	608465
Entrez	23064

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000224140, ENST00000436441, ENST00000464133, ENST00000474172, ENST00000477049, ENST00000905305, ENST00000905306, ENST00000923215, ENST00000923216, ENST00000923217, ENST00000923218, ENST00000923219, ENST00000947394

RefSeq mRNA: 3 — MANE Select: NM_015046 NM_001351527, NM_001351528, NM_015046

CCDS: CCDS6947

Canonical transcript exons

ENST00000224140 — 26 exons

Exon	Start	End
ENSE00000732865	132275256	132275420
ENSE00000732873	132278070	132278257
ENSE00000732877	132281467	132281574
ENSE00000732881	132283264	132283413
ENSE00000732884	132286423	132286494
ENSE00000732887	132288236	132288351
ENSE00000732890	132288550	132288651
ENSE00000732893	132295872	132296028
ENSE00000732897	132296887	132297054
ENSE00001138810	132298080	132298312
ENSE00001192932	132300630	132300803
ENSE00001192969	132311757	132311856
ENSE00001334761	132353649	132353755
ENSE00001334767	132354917	132354986
ENSE00001620965	132346261	132346471
ENSE00001668729	132331052	132331139
ENSE00001675030	132342690	132342799
ENSE00001692297	132331277	132331448
ENSE00001709422	132334608	132334727
ENSE00001754306	132336296	132336515
ENSE00001797476	132349252	132349435
ENSE00001802743	132326324	132330499
ENSE00003484958	132277060	132277152
ENSE00003496010	132271710	132271808
ENSE00003529884	132261356	132264985
ENSE00003656418	132269615	132269702

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 94.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.9826 / max 414.2160, expressed in 1812 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102891	25.7100	1807
102889	1.8255	851
102892	1.1539	727
102890	0.8932	422
205640	0.4000	185

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	94.49	gold quality
calcaneal tendon	UBERON:0003701	94.36	gold quality
left testis	UBERON:0004533	94.18	gold quality
leukocyte	CL:0000738	93.60	gold quality
monocyte	CL:0000576	93.58	gold quality
mononuclear cell	CL:0000842	93.49	gold quality
granulocyte	CL:0000094	93.38	gold quality
right lobe of thyroid gland	UBERON:0001119	93.26	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.16	gold quality
testis	UBERON:0000473	93.06	gold quality
spleen	UBERON:0002106	92.88	gold quality
left lobe of thyroid gland	UBERON:0001120	92.72	gold quality
thyroid gland	UBERON:0002046	92.54	gold quality
tendon	UBERON:0000043	92.15	gold quality
adrenal tissue	UBERON:0018303	91.96	gold quality
lymph node	UBERON:0000029	91.66	gold quality
blood	UBERON:0000178	91.19	gold quality
colonic epithelium	UBERON:0000397	90.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.44	gold quality
vermiform appendix	UBERON:0001154	90.40	gold quality
stromal cell of endometrium	CL:0002255	90.24	gold quality
upper lobe of left lung	UBERON:0008952	90.15	gold quality
right lung	UBERON:0002167	90.03	gold quality
sural nerve	UBERON:0015488	90.00	gold quality
tendon of biceps brachii	UBERON:0008188	89.96	silver quality
right ovary	UBERON:0002118	89.73	gold quality
mucosa of stomach	UBERON:0001199	89.49	gold quality
left uterine tube	UBERON:0001303	89.44	gold quality
upper lobe of lung	UBERON:0008948	89.41	gold quality
tibial nerve	UBERON:0001323	89.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

122 targeting SETX, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AB	99.95	71.31	3488

Literature-anchored findings (GeneRIF, showing 40)

• Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination. (PMID:14770181)
• Missense Mutations in senataxin is associated with juvenile amyotrophic lateral sclerosis (PMID:15106121)
• Four mutations in senataxin in the French-Canadian population including two novel missense mutations: the 5927T–>G mutation (L1976R), and the 193G–>A mutation(E65K). (PMID:15732101)
• 2 new homozygous missense mutations in SETX, M274I & R1294C, were found.The double missense mutations are responsible for autosomal recessive ataxia-ocular apraxia 2 but not autosomal dominant juvenile ALS. (PMID:16717225)
• Mother and daughter who display symptoms of cerebellar ataxia/atrophy, oculomotor defects, and tremor with mutations in syntaxin. (PMID:17096168)
• Human Senataxin, is a nuclear protein involved in the DNA damage response. It is mostly located in the nucleus and nucleoplasm with less staining in the cytoplasm. It is involved in DNA single-strand break repair. (PMID:17562789)
• defect in 2O2-induced DNA double-strand breaks repair was corrected by full-length SETX cDNA (PMID:17562789)
• A patient homozygous for a novel mutation of SETX who manifested not only ataxia but also ovarian failure. (PMID:17593543)
• Clinically this family presented with a phenotype combining typical features of AOA2 and ALS4; thus extending the phenotypic spectrum of SETX mutations. (PMID:18350359)
• study identified a novel SETX homozygous c.5308_5311delGAGA mutation that co-segregates with autosomal recessive cerebellar ataxia with cerebellar atrophy and raised alpha-fetoprotein (PMID:18405395)
• the presence of this variation in a patient with sporadic ALS, and its absence in 200 controls, supports an association between senataxin and sporadic amyotrophic lateral sclerosis (PMID:19058054)
• study analysed the phenotypic spectrum of 19 ataxia with oculo-motor apraxia type 2 patients with mutations in SETX (PMID:19141356)
• senataxin plays a role in coordinating transcriptional events, in addition to its role in DNA repair. (PMID:19515850)
• We performed molecular analyses in six patients showing clinically an AOA2 phenotype and moderate to significant elevated serum alpha-fetoprotein levels. (PMID:19569000)
• SETX mutations have a role in ataxia with oculomotor apraxia [case report] (PMID:19593598)
• large deletions, insertions, and duplications are probably an underestimated cause for ataxia with oculomotor apraxia 2 (PMID:19744353)
• The partial co-localization of SETX with telomeric DNA, demonstrated by combined immunofluorescence-Q-FISH and chromatin immunoprecipitation, suggests a possible involvement of SETX in telomere stability. (PMID:21112256)
• Senataxin mutations in amyotrophic lateral sclerosis (PMID:21190393)
• A novel nonsense truncating mutation c.6859 C > T, R2287X in SETX gene was identified in patients from one family with ataxia with oculomotor apraxia type 2. (PMID:21324166)
• results reveal a key role of senataxin in neuronal differentiation through the fibroblast growth factor 8 signalling and This study provided initial molecular bases to explain the neurodegeneration associated with loss-of-function mutations in senataxin. (PMID:21576111)
• In effect, R-loops formed over G-rich pause sites, followed by their resolution by senataxin, are key steps in the termination process. (PMID:21700224)
• This sstudy descibed that SETX gene mutation in a family diagnosed autosomal dominant proximal spinal muscular atrophy. (PMID:22088787)
• novel missense mutation c.6406C>T (p.R2136C) in a patient with inflammatory radiculoneuropathy and amyotrophic lateral sclerosis (PMID:22577233)
• Microprocessor orchestrates the recruitment of termination factors Setx and Xrn2, and the 3’-5’ exoribonuclease, Rrp6, to initiate RNAPII pausing and premature termination at the HIV-1 promoter through cleavage of the stem-loop RNA, TAR. (PMID:22980978)
• Significance of all previously reported SETX missense mutations as well as six newly identified variations in 54 patients suspected of having amyotrophic lateral sclerosis 4. (PMID:23129421)
• Senataxin plays an important cellular role at the interface of transcription and the DNA damage response and that the resolution of R-loop structures is a key event in the maintenance of genome stability. (PMID:23149945)
• Description of a new SETX gene mutation, which when combined with a recognized SETX mutation results in ataxia with oculomotor apraxia type 2. (PMID:23566282)
• This study report a Japanese SCAR1/AOA2 family with a homozygous nonsense mutation (p.Q1441X) of SETX that was identified by exome sequencing (PMID:23786967)
• SETX mutations are a frequent genetic cause of juvenile and adult onset cerebellar ataxia with neuropathy and elevated serum alpha-fetoprotein. (PMID:23941260)
• provide evidence that Rrp45, a subunit of the exosome, associates with SETX in a manner dependent on SETX sumoylation (PMID:24105744)
• Protein interaction analysis of senataxin and the ALS4 L389S mutant yields insights into senataxin post-translational modification and uncovers mutant-specific binding with a brain cytoplasmic RNA-encoded peptide. (PMID:24244371)
• genetic variations in the senataxin gene may contribute to Alzheimer’s disease pathogenesis in the Taiwanese Han population. (PMID:24694197)
• Results identify novel genes related to senataxin function in normal and disease states. (PMID:24760770)
• BRCA1/SETX complexes support a DNA repair mechanism that addresses R-loop-based DNA damage at transcriptional pause sites. (PMID:25699710)
• these data indicate a potentially causal link among inborn errors in SETX, susceptibility to infection and the development of neurologic disorders. (PMID:25822250)
• AOA2 with myoclonus associated with mutations in SETX and AFG3L2 (PMID:25927548)
• The role of senataxin in regulating gene expression on a genome-wide scale in Ataxia oculomotor apraxia 2 neurons is described. (PMID:26231220)
• The pan-neuronal expression of wild-type or mutant forms of human senataxin induced morphological plasticity at neuromuscular junction synapses. (PMID:27197982)
• Novel compound heterozygous mutations of SETX in Chinese AOA2 pedigree were identified, which broaden the mutation spectrum of SETX. (PMID:27644330)
• Expression of AOA2-causative form of SETX in Drosophila muscles resulted in an alteration of translational repression of Elav. (PMID:28245518)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	setx	ENSDARG00000022996
danio_rerio	dna2	ENSDARG00000078759
mus_musculus	Setx	ENSMUSG00000043535
rattus_norvegicus	Setx	ENSRNOG00000013491
drosophila_melanogaster	CG6701	FBGN0033889
drosophila_melanogaster	Mov10	FBGN0034187
drosophila_melanogaster	Dna2	FBGN0288690
caenorhabditis_elegans		WBGENE00001016
caenorhabditis_elegans	Y106G6D.5	WBGENE00014965
caenorhabditis_elegans	sosi-1	WBGENE00016565
caenorhabditis_elegans	eri-7	WBGENE00016566

Paralogs (10): UPF1 (ENSG00000005007), AQR (ENSG00000021776), MOV10L1 (ENSG00000073146), ZNFX1 (ENSG00000124201), HELZ2 (ENSG00000130589), IGHMBP2 (ENSG00000132740), DNA2 (ENSG00000138346), MOV10 (ENSG00000155363), CT55 (ENSG00000169551), HELZ (ENSG00000198265)

Protein

Protein identifiers

Helicase senataxin — Q7Z333 (reviewed: Q7Z333)

Alternative names: Amyotrophic lateral sclerosis 4 protein, SEN1 homolog, Senataxin

All UniProt accessions (2): Q7Z333, X6RI79

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent 5’->3’ DNA/RNA helicase that preferentially unwinds RNA substrates over DNA, playing a crucial role in resolving R-loops and promoting transcription termination. Plays a role in transcription regulation by its ability to modulate RNA Polymerase II (Pol II) binding to chromatin and through its interaction with proteins involved in transcription. Contributes to the mRNA splicing efficiency and splice site selection. Required for the resolution of R-loop RNA-DNA hybrid formation at G-rich pause sites located downstream of the poly(A) site, allowing XRN2 recruitment and XRN2-mediated degradation of the downstream cleaved RNA and hence efficient RNA polymerase II (RNAp II) transcription termination. Required for the 3’ transcriptional termination of PER1 and CRY2, thus playing an important role in the circadian rhythm regulation. Involved in DNA double-strand breaks damage response generated by oxidative stress. In association with RRP45, targets the RNA exosome complex to sites of transcription-induced DNA damage. Plays a role in the development and maturation of germ cells: essential for male meiosis, acting at the interface of transcription and meiotic recombination, and in the process of gene silencing during meiotic sex chromosome inactivation (MSCI). May be involved in telomeric stability through the regulation of telomere repeat-containing RNA (TERRA) transcription. Plays a role in neurite outgrowth in hippocampal cells through FGF8-activated signaling pathways. Inhibits retinoic acid-induced apoptosis.

Subunit / interactions. Homodimer. Interacts with PER2; the interaction inhibits termination of circadian target genes. Interacts with CHD4, POLR2A, PRKDC and TRIM28. Interacts with UBE2I. Interacts (via N-terminus domain) with EXOSC9 (via C-terminus region); the interaction enhances SETX sumoylation. Interacts with NCL (via N-terminus domain). Interacts with PABPN1, PABPC1 and SF3B1. Interacts with SMN1/SMN2 and POLR2A; SMN1/SMN2 recruits SETX to POLR2A.

Subcellular location. Nucleus. Nucleoplasm. Nucleolus. Cytoplasm. Chromosome. Telomere. Cell projection. Axon. Growth cone.

Tissue specificity. Highly expressed in skeletal muscle. Expressed in heart, fibroblast, placenta and liver. Weakly expressed in brain and lung. Expressed in the cortex of the kidney (highly expressed in tubular epithelial cells but low expression in the glomerulus).

Post-translational modifications. Ubiquitinated. Sumoylated preferentially with SUMO2 or SUMO3.

Disease relevance. Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (SCAN2) [MIM:606002] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAN2 is an autosomal recessive form associated with peripheral neuropathy and elevated serum alpha-fetoprotein, immunoglobulins and, less commonly, creatine kinase levels. Some SCAN2 patients manifest oculomotor apraxia. The disease is caused by variants affecting the gene represented in this entry. Amyotrophic lateral sclerosis 4 (ALS4) [MIM:602433] A form of amyotrophic lateral sclerosis with childhood- or adolescent-onset, and characterized by slow disease progression and the sparing of bulbar and respiratory muscles. Amyotrophic lateral sclerosis is 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.

Domain organisation. The N-terminus domain is necessary for S/G2 nuclear foci localization.

Similarity. Belongs to the DNA2/NAM7 helicase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7Z333-1	1	yes
Q7Z333-3	3
Q7Z333-4	4

RefSeq proteins (3): NP_001338456, NP_001338457, NP_055861* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041677	DNA2/NAM7_AAA_11	Domain
IPR041679	DNA2/NAM7-like_C	Domain
IPR045055	DNA2/NAM7-like	Family
IPR047187	SF1_C_Upf1	Domain

Pfam: PF13086, PF13087

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (101 total): sequence variant 34, sequence conflict 21, modified residue 15, region of interest 8, compositionally biased region 7, cross-link 7, binding site 3, splice variant 2, mutagenesis site 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z333-F1	52.93	0.11

Functional residue map

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

Ligand- & substrate-binding residues (3): 1966–1970; 2210; 2258

Post-translational modifications (22): 615, 642, 878, 911, 947, 956, 1017, 1019, 1330, 1366, 1489, 1621, 1623, 1663, 2474, 339, 894, 1056, 1063, 1340 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
65	abolishes interaction with exosc9 and ube2i and decreases sumoylation.
2181–2182	loss of enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 341 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_NEUROGENESIS, CREBP1_Q2, GOBP_MALE_GAMETE_GENERATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_HYDROGEN_PEROXIDE, GROSS_HYPOXIA_VIA_HIF1A_DN, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION

GO Biological Process (21): double-strand break repair (GO:0006302), DNA recombination (GO:0006310), DNA-templated transcription termination (GO:0006353), termination of RNA polymerase II transcription (GO:0006369), mRNA splice site recognition (GO:0006376), RNA processing (GO:0006396), DNA damage response (GO:0006974), spermatogenesis (GO:0007283), nervous system development (GO:0007399), circadian rhythm (GO:0007623), positive regulation of neuron projection development (GO:0010976), cell differentiation (GO:0030154), positive regulation of RNA splicing (GO:0033120), cellular response to oxidative stress (GO:0034599), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of termination of DNA-templated transcription (GO:0060566), cellular response to hydrogen peroxide (GO:0070301), positive regulation of DNA-templated transcription initiation (GO:2000144), positive regulation of termination of RNA polymerase II transcription, poly(A)-coupled (GO:2000806), DNA repair (GO:0006281), rhythmic process (GO:0048511)

GO Molecular Function (11): transcription termination site sequence-specific DNA binding (GO:0001147), DNA binding (GO:0003677), DNA helicase activity (GO:0003678), RNA binding (GO:0003723), ATP binding (GO:0005524), hydrolase activity (GO:0016787), DNA/RNA helicase activity (GO:0033677), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), helicase activity (GO:0004386), protein binding (GO:0005515)

GO Cellular Component (12): nuclear chromosome (GO:0000228), chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), nuclear body (GO:0016604), axon (GO:0030424), growth cone (GO:0030426), intercellular bridge (GO:0045171), chromosome (GO:0005694), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA-templated transcription termination	3
positive regulation of DNA-templated transcription	3
nuclear lumen	3
intracellular membraneless organelle	3
DNA metabolic process	2
RNA biosynthetic process	2
transcription by RNA polymerase II	2
nucleic acid binding	2
helicase activity	2
ATP-dependent activity, acting on DNA	2
DNA repair	1
DNA-templated transcription	1
spliceosomal complex assembly	1
protein-RNA complex assembly	1
gene expression	1
primary metabolic process	1
cellular response to stress	1
developmental process involved in reproduction	1
male gamete generation	1
system development	1
rhythmic process	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
cellular developmental process	1
RNA splicing	1
positive regulation of gene expression	1
regulation of RNA splicing	1
response to oxidative stress	1
cellular response to chemical stress	1
regulation of transcription by RNA polymerase II	1
regulation of termination of DNA-templated transcription	1
positive regulation of protein-containing complex disassembly	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
DNA-templated transcription initiation	1
regulation of DNA-templated transcription initiation	1
termination of RNA polymerase II transcription, poly(A)-coupled	1
positive regulation of termination of RNA polymerase II transcription	1

Protein interactions and networks

STRING

2730 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SETX	BRCA1	P38398	962
SETX	NRDC	O43847	951
SETX	APTX	Q7Z2E3	942
SETX	ALS2	Q96Q42	909
SETX	FUS	P35637	884
SETX	FXN	Q16595	863
SETX	VAPB	O95292	861
SETX	TARDBP	Q13148	845
SETX	XRN2	Q9H0D6	843
SETX	FIG4	Q92562	815
SETX	ATXN2	Q99700	786
SETX	DCTN1	Q14203	783
SETX	SOD1	P00441	777
SETX	RNASEH1	O60930	775
SETX	EXOSC10	Q01780	758

IntAct

190 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
MAPK8IP1	MAPK8	psi-mi:“MI:0914”(association)	0.770
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
HNRNPH1	TARDBP	psi-mi:“MI:0914”(association)	0.670
POLR2A	SMN1	psi-mi:“MI:0914”(association)	0.660
NEUROG3	GXYLT2	psi-mi:“MI:0914”(association)	0.640
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
SETX	POLR2A	psi-mi:“MI:0915”(physical association)	0.610
POLR2A	SETX	psi-mi:“MI:0915”(physical association)	0.610
SMN1	PRMT5	psi-mi:“MI:0914”(association)	0.600
SETX	SETX	psi-mi:“MI:0915”(physical association)	0.590
SETX	SETX	psi-mi:“MI:0407”(direct interaction)	0.590
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
POLR2A	PRMT5	psi-mi:“MI:0914”(association)	0.560
PRMT5	POLR2A	psi-mi:“MI:0914”(association)	0.560
	SETX	psi-mi:“MI:0915”(physical association)	0.560
SETX	USP2	psi-mi:“MI:0915”(physical association)	0.560
SKIC8	SETX	psi-mi:“MI:0915”(physical association)	0.560
SAMD3	SETX	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (207): BRCA1 (Two-hybrid), SETX (Affinity Capture-MS), SETX (Synthetic Growth Defect), SETX (Affinity Capture-MS), SETX (Affinity Capture-MS), SETX (Affinity Capture-MS), SETX (Affinity Capture-MS), SETX (Affinity Capture-MS), SETX (Affinity Capture-MS), SETX (Affinity Capture-MS), SETX (Affinity Capture-Western), BRCA1 (Affinity Capture-Western), SETX (Reconstituted Complex), BRCA1 (Reconstituted Complex), SETX (Reconstituted Complex)

ESM2 similar proteins: A1L2H3, A2AKX3, A5D8S0, B0S6S9, D3Z987, E1BC15, O43303, O60673, O95405, P56715, Q03188, Q2M2Z5, Q3MHH3, Q3V089, Q569L8, Q5BQN8, Q5CZC0, Q5DTT3, Q5R9I1, Q5VWN6, Q61493, Q641I1, Q6NS59, Q6NSW3, Q6ZP01, Q6ZU52, Q7TSH4, Q7Z333, Q7Z3T8, Q80U44, Q80U59, Q86UW6, Q86WS4, Q86XD8, Q8IXS0, Q8MJ03, Q8MJ04, Q8MJ06, Q8N1H7, Q8N7Z5

Diamond homologs: A0A1P8ASY1, A2AKX3, D3ZG52, E1BMP7, E9QAM5, O94387, P30771, P38859, P38935, P51530, Q5ZKG3, Q6ZQJ5, Q7Z333, Q8QHA5, Q92355, Q92900, Q98TR3, Q9EPU0, Q9HEH1, Q9URU2, F6QXW0, Q09820, Q54I89, Q86AS0, B6SFA4, F1RCY6, Q00416, Q9FJR0, Q9VYS3, O94247, Q1LXK4, Q1LXK5, Q57568, E9P860, O76512, P32644, Q0VGT4, Q6DFV5, Q6J5K9, Q86YA3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 224 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
SUMOylation of transcription factors	5	20.0×	7e-04
SUMOylation of transcription cofactors	7	11.9×	4e-04
SUMOylation of intracellular receptors	5	11.7×	5e-03
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	9	9.2×	2e-04
SUMOylation of DNA damage response and repair proteins	7	7.2×	5e-03
mRNA Polyadenylation	10	6.1×	8e-04
Processing of Capped Intron-Containing Pre-mRNA	10	5.8×	1e-03
Dengue Virus-Host Interactions	17	5.4×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

2204 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	58
Likely pathogenic	51
Uncertain significance	899
Likely benign	480
Benign	233

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027519	NM_015046.7(SETX):c.7292dup (p.Asn2431fs)	Pathogenic
1048755	NM_015046.7(SETX):c.3247T>C (p.Phe1083Leu)	Pathogenic
1299167	GRCh37/hg19 9q34.13(chr9:135209995-135210114)x1	Pathogenic
1323580	NM_015046.7(SETX):c.5008C>T (p.Gln1670Ter)	Pathogenic
1333209	NM_015046.7(SETX):c.4931_4932del (p.Ile1644fs)	Pathogenic
1359217	NM_015046.7(SETX):c.1484T>C (p.Leu495Pro)	Pathogenic
1449878	NM_015046.7(SETX):c.3681T>A (p.Cys1227Ter)	Pathogenic
1459833	NC_000009.11:g.(?135201691)(135210134_?)del	Pathogenic
1749895	NM_015046.7(SETX):c.5820del (p.Ala1941fs)	Pathogenic
2034975	NM_015046.7(SETX):c.3288_3291del (p.His1096fs)	Pathogenic
2071447	NM_015046.7(SETX):c.331C>T (p.Arg111Ter)	Pathogenic
2159109	NM_015046.7(SETX):c.4890dup (p.Ile1631fs)	Pathogenic
2284	NM_015046.7(SETX):c.4087C>T (p.Arg1363Ter)	Pathogenic
2285	NM_015046.7(SETX):c.2602C>T (p.Gln868Ter)	Pathogenic
2287	NM_015046.7(SETX):c.2967_2971del (p.Arg989fs)	Pathogenic
2289	NM_015046.7(SETX):c.1166T>C (p.Leu389Ser)	Pathogenic
2292	NM_015046.7(SETX):c.5927T>G (p.Leu1976Arg)	Pathogenic
2296	NM_015046.7(SETX):c.1027G>T (p.Glu343Ter)	Pathogenic
2326477	NM_015046.7(SETX):c.6421_6422del (p.Gln2141fs)	Pathogenic
243082	NM_015046.7(SETX):c.6322C>T (p.Gln2108Ter)	Pathogenic
280027	NM_015046.7(SETX):c.4816C>T (p.Arg1606Ter)	Pathogenic
280291	NM_015046.7(SETX):c.4936C>T (p.Gln1646Ter)	Pathogenic
2934424	NM_015046.7(SETX):c.387_388+2del	Pathogenic
2937674	NM_015046.7(SETX):c.5019del (p.Val1674fs)	Pathogenic
3245202	NC_000009.11:g.(?135171239)(135187263_?)del	Pathogenic
3245203	NC_000009.11:g.(?135201691)(135224815_?)del	Pathogenic
3376817	NM_015046.7(SETX):c.6421dup (p.Gln2141fs)	Pathogenic
3381365	NM_015046.7(SETX):c.6133C>T (p.Arg2045Ter)	Pathogenic
3571493	NM_015046.5:c.6848_6851del	Pathogenic
3571870	NM_015046.7(SETX):c.3262G>T (p.Glu1088Ter)	Pathogenic

SpliceAI

4775 predictions. Top by Δscore:

Variant	Effect	Δscore
9:132264985:CCT:C	acceptor_gain	1.0000
9:132271703:AACT:A	donor_loss	1.0000
9:132271704:ACT:A	donor_loss	1.0000
9:132271705:CT:C	donor_loss	1.0000
9:132271706:TCACC:T	donor_loss	1.0000
9:132271707:C:CC	donor_loss	1.0000
9:132271708:A:AC	donor_gain	1.0000
9:132271708:AC:A	donor_gain	1.0000
9:132271709:C:CC	donor_gain	1.0000
9:132271709:C:G	donor_loss	1.0000
9:132271709:CC:C	donor_gain	1.0000
9:132271804:CTGGT:C	acceptor_gain	1.0000
9:132271809:C:CC	acceptor_gain	1.0000
9:132271813:T:C	acceptor_gain	1.0000
9:132271813:T:TC	acceptor_gain	1.0000
9:132271831:TTTA:T	acceptor_gain	1.0000
9:132275254:A:AC	donor_gain	1.0000
9:132275254:AC:A	donor_gain	1.0000
9:132275255:C:CC	donor_gain	1.0000
9:132275255:CC:C	donor_gain	1.0000
9:132275417:TGAG:T	acceptor_gain	1.0000
9:132275420:GCTA:G	acceptor_loss	1.0000
9:132275421:C:CC	acceptor_gain	1.0000
9:132275421:CTAAA:C	acceptor_loss	1.0000
9:132275430:A:C	acceptor_gain	1.0000
9:132277056:ATACT:A	donor_loss	1.0000
9:132277057:TACTC:T	donor_loss	1.0000
9:132277058:A:AC	donor_gain	1.0000
9:132277058:A:C	donor_loss	1.0000
9:132277059:C:CC	donor_gain	1.0000

AlphaMissense

17752 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:132264973:A:G	W2434R	1.000
9:132264973:A:T	W2434R	1.000
9:132269646:A:G	L2419P	1.000
9:132269648:G:C	S2418R	1.000
9:132269648:G:T	S2418R	1.000
9:132269650:T:G	S2418R	1.000
9:132269699:G:C	F2401L	1.000
9:132269699:G:T	F2401L	1.000
9:132269701:A:G	F2401L	1.000
9:132271749:A:T	V2387D	1.000
9:132295967:A:G	L2004P	1.000
9:132296948:C:T	G1963E	1.000
9:132264951:G:T	A2441D	0.999
9:132264952:C:G	A2441P	0.999
9:132264963:A:G	L2437P	0.999
9:132269619:A:G	L2428P	0.999
9:132269634:C:T	G2423E	0.999
9:132269635:C:G	G2423R	0.999
9:132269635:C:T	G2423R	0.999
9:132269643:A:G	F2420S	0.999
9:132269658:G:T	A2415D	0.999
9:132269661:C:G	R2414P	0.999
9:132269673:A:T	V2410D	0.999
9:132269681:T:A	R2407S	0.999
9:132269681:T:G	R2407S	0.999
9:132271740:A:T	V2390D	0.999
9:132271742:A:C	C2389W	0.999
9:132271744:A:G	C2389R	0.999
9:132271752:A:T	I2386N	0.999
9:132271759:A:G	C2384R	0.999

dbSNP variants (sampled 300 via entrez): RS1000021780 (9:132297884 A>G), RS1000047176 (9:132279953 A>T), RS1000047489 (9:132337561 A>T), RS1000072826 (9:132265448 A>T), RS1000153150 (9:132307677 G>A,C), RS1000224845 (9:132323399 C>T), RS1000226364 (9:132358156 T>C), RS1000257490 (9:132323130 C>T), RS1000281115 (9:132265234 T>TG), RS1000345933 (9:132348437 T>C,G), RS1000358876 (9:132312680 G>A), RS1000379366 (9:132347638 A>G), RS1000415017 (9:132353505 T>G), RS1000420203 (9:132337888 C>T), RS1000420461 (9:132280509 T>A,C)

Disease associations

OMIM: gene MIM:608465 | disease phenotypes: MIM:602433, MIM:606002, MIM:108600, MIM:303350, MIM:118220, MIM:182960, MIM:120970, MIM:208920, MIM:272800

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 4	Definitive	Autosomal dominant
spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
distal hereditary motor neuropathy	Definitive	AD

Mondo (20): amyotrophic lateral sclerosis type 4 (MONDO:0011223), spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (MONDO:0018996), spastic ataxia (MONDO:0017845), hereditary spastic paraplegia (MONDO:0019064), Charcot-Marie-Tooth disease type 2 (MONDO:0018993), amyotrophic lateral sclerosis (MONDO:0004976), frontotemporal dementia (MONDO:0017276), Charcot-Marie-Tooth disease (MONDO:0015626), cerebellar ataxia (MONDO:0000437), pathologic nystagmus (MONDO:0004843), cerebral palsy (MONDO:0006497), distal hereditary motor neuropathy (MONDO:0018894), neuronopathy, distal hereditary motor, autosomal dominant (MONDO:0015362), cone-rod dystrophy (MONDO:0015993), dystonic disorder (MONDO:0003441)

Orphanet (17): Amyotrophic lateral sclerosis type 4 (Orphanet:357043), Spinocerebellar ataxia with axonal neuropathy type 2 (Orphanet:64753), Spastic ataxia (Orphanet:316226), Hereditary spastic paraplegia (Orphanet:685), Autosomal dominant Charcot-Marie-Tooth disease type 2 (Orphanet:64746), Amyotrophic lateral sclerosis (Orphanet:803), Frontotemporal dementia (Orphanet:282), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Rare ataxia (Orphanet:102002), Distal hereditary motor neuropathy (Orphanet:53739), Autosomal dominant distal hereditary motor neuropathy (Orphanet:140465), Cone rod dystrophy (Orphanet:1872), Ataxia-oculomotor apraxia type 1 (Orphanet:1168), Proximal spinal muscular atrophy (Orphanet:70), Genetic motor neuron disease (Orphanet:98505)

HPO phenotypes

69 total (30 of 69 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000486	Strabismus
HP:0000524	Conjunctival telangiectasia
HP:0000639	Nystagmus
HP:0000640	Gaze-evoked nystagmus
HP:0000657	Oculomotor apraxia
HP:0000764	Peripheral axonal degeneration
HP:0001152	Saccadic smooth pursuit interruptions
HP:0001251	Ataxia
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001266	Choreoathetosis
HP:0001271	Polyneuropathy
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001315	Reduced tendon reflexes
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001761	Pes cavus
HP:0002015	Dysphagia
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002072	Chorea
HP:0002141	Gait imbalance
HP:0002169	Clonus
HP:0002174	Postural tremor

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005917_1	Current cigarettes per day in chronic obstructive pulmonary disease	2.000000e-07
GCST009391_1711	Metabolite levels	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006525	cigarettes per day measurement
EFO:0010341	cholesteryl ester 16:0 measurement

MeSH disease descriptors (15)

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
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D002547	Cerebral Palsy	C10.228.140.140.254
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
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D020821	Dystonic Disorders	C10.228.662.300
D057180	Frontotemporal Dementia	C10.228.140.380.266.299; C10.574.950.300.299; C18.452.845.800.300.299; F03.615.400.380.299
D049288	Muscular Dystrophies, Limb-Girdle	C05.651.534.500.280; C10.668.491.175.500.149; C16.320.577.280
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
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
D013661	Tay-Sachs Disease	C10.228.140.163.100.435.825.300.300.500; C16.320.565.189.435.825.300.300.500; C16.320.565.398.641.803.350.300.850; C16.320.565.595.554.825.300.300.840; C18.452.132.100.435.825.300.300.500; C18.452.584.563.641.803.350.300.850; C18.452.648.189.435.825.300.300.500; C18.452.648.398.641.803.350.300.850; C18.452.648.595.554.825.300.300.840
C566550	Amyotrophic Lateral Sclerosis 4, Juvenile (supp.)
C538013	Early-onset ataxia with oculomotor apraxia and hypoalbuminemia (supp.)
C564815	Spastic Ataxia (supp.)
C537308	Spinocerebellar ataxia, autosomal recessive 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Cadmium Chloride	affects expression, increases expression	3
Cyclosporine	increases expression	2
Asbestos, Crocidolite	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	affects sumoylation	1
geldanamycin	increases expression	1
chloroacetaldehyde	decreases expression	1
triphenyl phosphate	affects expression	1
coumarin	decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
CPG-oligonucleotide	increases expression	1
torcetrapib	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Cidofovir	decreases expression	1
Atrazine	decreases expression	1
Caffeine	affects phosphorylation	1
Cannabidiol	increases expression	1
Cisplatin	affects expression	1
Clozapine	increases expression	1
Cuprizone	increases expression	1
Clodronic Acid	decreases expression	1
Doxorubicin	increases phosphorylation, affects reaction	1
Mercuric Chloride	decreases expression	1
Nickel	increases expression	1
Oxygen	decreases expression	1

Cellosaurus cell lines

14 cell lines: 5 induced pluripotent stem cell, 5 transformed cell line, 3 cancer cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0NC	Ubigene HeLa SETX KO	Cancer cell line	Female
CVCL_E7M7	KOLF2.1J SETX L1976R SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E7M8	KOLF2.1J SETX L1976R SNV/WT	Induced pluripotent stem cell	Male
CVCL_E7MA	KOLF2.1J SETX L389S SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E7MB	KOLF2.1J SETX L389S SNV/WT	Induced pluripotent stem cell	Male
CVCL_E7NM	KOLF2.1J SETX PTC PTC/PTC	Induced pluripotent stem cell	Male
CVCL_TK80	HAP1 SETX (-) 1	Cancer cell line	Male
CVCL_TK81	HAP1 SETX (-) 2	Cancer cell line	Male
CVCL_XX64	654RM	Transformed cell line	Sex unspecified
CVCL_XX65	655RM	Transformed cell line	Sex unspecified

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