OPTN

Summary

OPTN (optineurin, HGNC:17142) is a protein-coding gene on chromosome 10p13, encoding Optineurin (Q96CV9). Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8.

This gene encodes the coiled-coil containing protein optineurin. Optineurin may play a role in normal-tension glaucoma and adult-onset primary open angle glaucoma. Optineurin interacts with adenovirus E3-14.7K protein and may utilize tumor necrosis factor-alpha or Fas-ligand pathways to mediate apoptosis, inflammation or vasoconstriction. Optineurin may also function in cellular morphogenesis and membrane trafficking, vesicle trafficking, and transcription activation through its interactions with the RAB8, huntingtin, and transcription factor IIIA proteins. Alternative splicing results in multiple transcript variants encoding the same protein.

Source: NCBI Gene 10133 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis type 12 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 514 total — 35 pathogenic, 25 likely-pathogenic
• Phenotypes (HPO): 58
• MANE Select transcript: NM_001008212

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17142
Approved symbol	OPTN
Name	optineurin
Location	10p13
Locus type	gene with protein product
Status	Approved
Aliases	FIP2, HYPL, FIP-2, TFIIIA-INTP, NRP, HIP7
Ensembl gene	ENSG00000123240
Ensembl biotype	protein_coding
OMIM	602432
Entrez	10133

Gene structure

Transcript identifiers

Ensembl transcripts: 94 — 90 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000263036, ENST00000378747, ENST00000378748, ENST00000378752, ENST00000378757, ENST00000378764, ENST00000424614, ENST00000430081, ENST00000469025, ENST00000482140, ENST00000486862, ENST00000487935, ENST00000867523, ENST00000867524, ENST00000867525, ENST00000867526, ENST00000867527, ENST00000867528, ENST00000867529, ENST00000867530, ENST00000867531, ENST00000867532, ENST00000867533, ENST00000867534, ENST00000867535, ENST00000867536, ENST00000867537, ENST00000867538, ENST00000867539, ENST00000867540, ENST00000867541, ENST00000867542, ENST00000867543, ENST00000867544, ENST00000867545, ENST00000867546, ENST00000867547, ENST00000867548, ENST00000867549, ENST00000867550, ENST00000867551, ENST00000867552, ENST00000867553, ENST00000867554, ENST00000867555, ENST00000867556, ENST00000867557, ENST00000867558, ENST00000867559, ENST00000867560, ENST00000867561, ENST00000921481, ENST00000921482, ENST00000942671, ENST00000942672, ENST00000942673, ENST00000942674, ENST00000942675, ENST00000942676, ENST00000942677, ENST00000942678, ENST00000942679, ENST00000942680, ENST00000942681, ENST00000942682, ENST00000942683, ENST00000942684, ENST00000942685, ENST00000942686, ENST00000942687, ENST00000942688, ENST00000942689, ENST00000942690, ENST00000942691, ENST00000942692, ENST00000942693, ENST00000942694, ENST00000942695, ENST00000942696, ENST00000942697, ENST00000942698, ENST00000942699, ENST00000942700, ENST00000942701, ENST00000942702, ENST00000942703, ENST00000942704, ENST00000942705, ENST00000942706, ENST00000942707, ENST00000942708, ENST00000942709, ENST00000942710, ENST00000942711

RefSeq mRNA: 4 — MANE Select: NM_001008212 NM_001008211, NM_001008212, NM_001008213, NM_021980

CCDS: CCDS7094

Canonical transcript exons

ENST00000378747 — 15 exons

Exon	Start	End
ENSE00000691148	13118888	13119040
ENSE00000691219	13127745	13127903
ENSE00000837368	13110274	13110476
ENSE00000837371	13122385	13122487
ENSE00000837372	13123995	13124110
ENSE00000837373	13125418	13125567
ENSE00000837374	13125946	13126039
ENSE00000999765	13108138	13108289
ENSE00001956056	13100163	13100302
ENSE00003512825	13109112	13109288
ENSE00003550952	13133502	13133581
ENSE00003594228	13132067	13132197
ENSE00003637959	13116267	13116340
ENSE00003722976	13112453	13112635
ENSE00003738415	13136745	13138308

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.8427 / max 1157.9851, expressed in 1794 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103934	56.1908	1793
103935	1.7820	958
103937	0.7626	356
103936	0.4233	165
103932	0.3361	124
103930	0.1628	78
103931	0.1005	42
103933	0.0847	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	99.48	gold quality
gastrocnemius	UBERON:0001388	99.46	gold quality
muscle of leg	UBERON:0001383	99.39	gold quality
muscle organ	UBERON:0001630	99.25	gold quality
skeletal muscle organ	UBERON:0014892	99.25	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.24	gold quality
gluteal muscle	UBERON:0002000	99.13	gold quality
triceps brachii	UBERON:0001509	99.07	gold quality
vastus lateralis	UBERON:0001379	98.99	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.95	gold quality
skeletal muscle tissue	UBERON:0001134	98.92	gold quality
quadriceps femoris	UBERON:0001377	98.86	gold quality
tendon	UBERON:0000043	98.75	gold quality
tendon of biceps brachii	UBERON:0008188	98.75	gold quality
diaphragm	UBERON:0001103	98.74	gold quality
biceps brachii	UBERON:0001507	98.74	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.70	gold quality
calcaneal tendon	UBERON:0003701	98.63	gold quality
deltoid	UBERON:0001476	98.40	gold quality
apex of heart	UBERON:0002098	98.09	gold quality
muscle tissue	UBERON:0002385	97.91	gold quality
tibialis anterior	UBERON:0001385	97.88	gold quality
heart left ventricle	UBERON:0002084	97.50	gold quality
left testis	UBERON:0004533	97.47	gold quality
popliteal artery	UBERON:0002250	97.45	gold quality
tibial artery	UBERON:0007610	97.45	gold quality
mucosa of stomach	UBERON:0001199	97.42	gold quality
cardiac ventricle	UBERON:0002082	97.40	gold quality
sperm	CL:0000019	97.37	gold quality
artery	UBERON:0001637	97.31	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	10.66
E-GEOD-110499	no	453.17
E-CURD-112	no	3.38
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
BDNF	Activation
NEFL	Activation
NTF3	Activation
SNAP25	Activation

Upstream regulators (CollecTRI, top): IRF1, NFKB1, NFKB, NFKBIA, RELA

miRNA regulators (miRDB)

55 targeting OPTN, 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-9-5P	100.00	72.28	2361
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-2116-5P	99.32	69.34	1273

Literature-anchored findings (GeneRIF, showing 40)

• identified as an adult-onset primary open-angle glaucoma gene (PMID:11834836)
• Expression of optineurin in the trabecular meshwork is influenced by elevated intraocular pressure (PMID:12379221)
• This study suggests that alterations in OPTN gene expression are not involved in the mechanisms regulating aqueous humor outflow after an increase in intraocular eye pressure. (PMID:12646749)
• No glaucoma-specific mutations were found in the OPTN gene in Japanese glaucoma patients. However, some novel single-nucleotide polymorphisms (SNPs) in the exons and introns are reported in this paper for the first time. (PMID:12811537)
• The mutations in the optineurin gene associated with normal-tension glaucoma are not associated with adult-onset primary open-angle glaucoma (PMID:12912697)
• The association of OPTN missense mutation M98K with normal tension glaucoma but not high tension glaucoma suggests genetic heterogeneity between these two phenotypes. (PMID:12920093)
• OPTN gene is the causative gene for POAG (primary open-angle glaucoma) and suggest a different mutation pattern of OPTN in Chinese than in whites. (PMID:12939304)
• This study provides some additional evidence for the association of the Glu50Lys OPTN sequence variation with familial normal tension glaucoma. (PMID:14597044)
• The OPTN M98K amino acid substitution mutation is potentially the most important single genetic factor contributing to genetic predisposition to primary open angle glaucoma. (PMID:14627677)
• Identification of Optineurin as an adult-onset glaucoma gene and its known interaction with a group of proteins provides the first opportunity to study biochemical pathways that are thought to be involved in causation of this group of eye disorders. (PMID:14740994)
• The association of the allelic variation (Met98Lys) in the OPTN gene in Japanese patients suggest that they are involved in the pathogenesis of POAG primary open-angle glaucoma) and NTG. (PMID:15226658)
• Mutations in OPTN are not specifically associated with low-pressure glaucoma, but can play a role in juvenile open-angle glaucoma. (PMID:15326130)
• Polymorphismsin in optineurin gene is associayed with glaucoma disease progression (PMID:15370540)
• Cross-sectional analysis from baseline observations of the BMES suggested that the M98K risk-associated allele appeared at a higher prevalence in high-tension glaucoma compared with controls (PMID:15498064)
• OPTN gene is associated with primary open-angle glaucoma rather than normal-tension glaucoma in Japanese. Statistical analysis showed possible interaction between polymorphisms in OPTN and the TNF-alpha genes that would increase risk for glaucoma. (PMID:15557444)
• The findings in the current study provide further evidence that MYOC and OPTN gene variants are rare causes of NTG normal tension glaucoma). (PMID:15851979)
• In this study, subjects with glaucoma who had the OPTN E50K mutation were found to have NTG (normal tension glaucoma) that appeared to be more severe than that in a control group (PMID:16043855)
• mGLuR1a signaling is attenuated by the huntingtin-binding protein optineurin (PMID:16091361)
• Despite a putative mutation (Arg545Gln) in some patients, the present study does not suggest a significant involvement of OPTN in POAG patients of Indian origin. (PMID:16205626)
• Primary open-angle glaucoma (POAG) is genetically heterogeneous, with 6 named POAG loci GLC1A-F mapped and genes myocilin (MYOC) and optineurin (OPTN) identified at 2 of the loci. (PMID:16374045)
• In this population, mutations in the optineurin gene are not associated with adult-onset primary open-angle glaucoma. (PMID:16440206)
• The results of this study support the rare association of OPTN sequence variants with familial forms of LTG. (PMID:16988596)
• The Arg144Gln mutation in OLFM2 is a possible disease-causing mutation in Japanese patients with OAG. Common polymorphisms in OLFM2 and OPTN may interactively contribute to the development of OAG, indicating a polygenic etiology. (PMID:17122126)
• This study highlights a possible role of OPTN in vesicle trafficking and Golgi integrity. It also provides in-sights into the possible mechanisms why E50K would exhibit a propensity toward the development of glaucoma. (PMID:17148662)
• 3.59% of our primary open-angle glaucoma patients had mutations in the CYP1B1, MYOC, and OPTN genes; first report to document the involvement of the CYP1B1, MYOC, and OPTN genes in the etiology of POAG in the same set of Indian patients (PMID:17563717)
• In Spain, a minority of adult-onset ocular hypertension (OHT) primary open-angle glaucoma (POAG) patients carry heterozygous disease-causing mutations in the MYOC gene and OPTN is not involved in either OHT or POAG. (PMID:17615537)
• These results indicate that interaction exists between OPTN and MYOC genes. (PMID:17663725)
• Optineurin competitively antagonized NEMO’s binding to polyUb receptor-interacting protein, and its overexpression inhibited TNFalpha-induced NF-kappaB activation. (PMID:17702576)
• These data therefore show that (i) Rab11a regulates cell surface abundance of both GLUT4 and FAT/CD36. (PMID:17854769)
• Timolol can reduce MYOC RNA levels in HTM cultures from some individuals. Timolol does not alter OPTN or WDR36 levels or ameliorate MYOC induction by dexamethasone in vitro. (PMID:18195223)
• The OPTN[E50K] mutant associated with Primary Open Angle Glaucoma (POAG) displayed strikingly enhanced binding to TBK1, suggesting that this interaction may contribute to familial POAG caused by this mutation. (PMID:18307994)
• None of the mutations in OPTN are associated with juvenile-onset open-angle glaucoma. The variant M98K is not a risk factor and the variant c.-233+25C>G may be protective against glaucoma in Taiwanese. (PMID:18385781)
• TNF-alpha, an inflammatory cytokine, disrupts the localization of polycystin-2 to the plasma membrane and primary cilia through a scaffold protein, FIP2, which is induced by TNF-alpha (PMID:18552856)
• A novel mutation of OPTN gene with Lys322Glu change is responsible for the occurrence of primary open angle glaucoma in a Chinese family. (PMID:18683701)
• Coding variants in OPTN may not contribute to the risk for primary open-angle glaucoma in persons of West African descent. (PMID:19096531)
• Our data show no association between the five evaluated variants and POAG in the Brazilian population. (PMID:19172505)
• results suggest that there is a negative feedback loop in which TNFalpha-induced NF-kappaB activity mediates expression of optineurin, which itself functions as a negative regulator of NF-kappaB (PMID:19340308)
• A novel mutation of a Lys322Glu change in OPTN is responsible for the familial case of primary open-angle glaucoma observed in northeastern China. (PMID:19710941)
• The optineurin regulates endocytic trafficking of transferrin receptor to the juxtanuclear region. (PMID:20085643)
• Study provides new information regarding basic characteristics of optineurin that are important for future efforts in defining precisely how optineurin functions normally and how mutations may result in pathology. (PMID:20161783)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	optn	ENSDARG00000002663
mus_musculus	Optn	ENSMUSG00000026672
rattus_norvegicus	Optn	ENSRNOG00000017941

Paralogs (1): IKBKG (ENSG00000269335)

Protein

Protein identifiers

Optineurin — Q96CV9 (reviewed: Q96CV9)

Alternative names: E3-14.7K-interacting protein, Huntingtin yeast partner L, Huntingtin-interacting protein 7, Huntingtin-interacting protein L, NEMO-related protein, Optic neuropathy-inducing protein, Transcription factor IIIA-interacting protein

All UniProt accessions (5): A0A087WY28, A0A087X2G2, Q96CV9, H7C1H4, X6RKL2

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation. Plays a role in the activation of innate immune response during viral infection. Mechanistically, recruits TBK1 at the Golgi apparatus, promoting its trans-phosphorylation after RLR or TLR3 stimulation. In turn, activated TBK1 phosphorylates its downstream partner IRF3 to produce IFN-beta/IFNB1. Plays a neuroprotective role in the eye and optic nerve. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and huntingtin (HD). Mediates the interaction of Rab8 with the probable GTPase-activating protein TBC1D17 during Rab8-mediated endocytic trafficking, such as that of transferrin receptor (TFRC/TfR); regulates Rab8 recruitment to tubules emanating from the endocytic recycling compartment. Autophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family; targets ubiquitin-coated bacteria (xenophagy), such as cytoplasmic Salmonella enterica, and appears to function in the same pathway as SQSTM1 and CALCOCO2/NDP52. (Microbial infection) May constitute a cellular target for various viruses, such as adenovirus E3 14.7 or Bluetongue virus, to inhibit innate immune response. During RNA virus infection, such as that of Sendai virus, negatively regulates the induction of IFNB1.

Subunit / interactions. Self-associates. Interacts with HD. Interacts with GTF3A. Interacts with MYO6. Interacts (via UBAN) with ubiquitinated TFRC. Interacts with GTP-bound Rab8 (RAB8A and/or RAB8B). Interacts with TBC1D17. Interacts with TBK1. Interacts with TRAF3. Binds to linear ubiquitin chains. Interacts with LC3 family members MAP1LC3A, MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2; OPTN phosphorylation increases the association (at least with MAP1LC3B). Interacts with RAB12; the interaction may be indirect. Interacts with TBK1; this interaction leads to the Golgi localization of TBK1 and its subsequent activation. Interacts with palmitoyltransferase ZDHHC17/HIP14; the interaction does not lead to palmitoylation of OPTN. Interacts with CYLD. Interacts with TOM1; the interaction is indirect and is mediated by MYO6, which acts as a bridge between TOM1 and OPTN. Interacts with USP12; the interaction is independent of USP12 deubiquitinase activity and may be involved in regulation of autophagic flux. (Microbial infection) Interacts with E3 14.7 kDa protein of group C human adenovirus. Interacts with Bluetongue virus protein NS3.

Subcellular location. Cytoplasm. Perinuclear region. Golgi apparatus. trans-Golgi network. Cytoplasmic vesicle. Autophagosome. Recycling endosome.

Tissue specificity. Present in aqueous humor of the eye (at protein level). Expressed in the trabecular meshwork (at protein level). Expressed in nonpigmented ciliary epithelium (at protein level). Expressed at high levels in skeletal muscle, also detected in heart, brain, pancreas, kidney, placenta and liver. Expressed in dermal fibroblasts (at protein level).

Post-translational modifications. Phosphorylated by TBK1, leading to restrict bacterial proliferation in case of infection. Phosphorylation is induced by phorbol esters and decreases its half-time.

Disease relevance. Glaucoma 1, open angle, E (GLC1E) [MIM:137760] A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. The disease is caused by variants affecting the gene represented in this entry. Glaucoma, normal pressure (NPG) [MIM:606657] A primary glaucoma characterized by intraocular pression consistently within the statistically normal population range. Disease susceptibility is associated with variants affecting the gene represented in this entry. Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (ALS12) [MIM:613435] 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. ALS12 inheritance can be autosomal dominant or autosomal recessive. There is also sporadic occurrence. ALS12 patients may develop frontotemporal dementia. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Ubiquitin-binding motif (UBAN), also called UBD, is essential for subcellular localization to recycling endosomes and for proper trafficking of transferrin to the juxtanuclear region. It is involved in interaction with ubiquitinated TFRC. The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins.

Induction. Up-regulated by TNF. Up-regulated by IFNG. TNF and IFNG act synergistically to stimulate OPTN expression. Induced by glucocorticoids, such as dexamethasone. In an in vitro experimental setting, in which donor eyes are subjected to increased perfusion pressure (10 to 30 mm Hg) in the anterior chamber, there is no up-regulation in the trabecular meshwork at the transcript level for periods ranging between 1 and 24 hours. However, exposure to continuous elevated pressure for several days shows an induction of OPTN expression, with a 56% increase after 7 days. (Microbial infection) Up-regulated in response to Sendai virus infection or double stranded RNA treatment (at protein level); the up-regulation is direct and not mediated through a response to type I interferons; this may negatively regulate the interferon response to RNA-activated antiviral signaling pathways.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96CV9-1	1	yes
Q96CV9-2	2
Q96CV9-3	3

RefSeq proteins (4): NP_001008212, NP_001008213, NP_001008214, NP_068815 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021063	NEMO_N	Domain
IPR032419	CC2-LZ_dom	Domain
IPR034735	NEMO_ZF	Domain
IPR051301	Optineurin/NFkB_EssMod	Family

Pfam: PF11577, PF16516, PF18414

UniProt features (54 total): sequence variant 14, region of interest 7, mutagenesis site 6, binding site 4, modified residue 4, compositionally biased region 3, helix 3, coiled-coil region 2, short sequence motif 2, splice variant 2, turn 2, strand 2, chain 1, zinc finger region 1, sequence conflict 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
3VTV	X-RAY DIFFRACTION	1.7
9B0B	X-RAY DIFFRACTION	1.7
9B12	X-RAY DIFFRACTION	1.81
9M0O	X-RAY DIFFRACTION	1.83
9IKQ	X-RAY DIFFRACTION	1.93
7CZM	X-RAY DIFFRACTION	2
5EOF	X-RAY DIFFRACTION	2.05
9B0Z	X-RAY DIFFRACTION	2.41
5EOA	X-RAY DIFFRACTION	2.5
3VTW	X-RAY DIFFRACTION	2.52
5B83	X-RAY DIFFRACTION	2.69
2LO4	SOLUTION NMR
2LUE	SOLUTION NMR
5AAZ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CV9-F1	77.90	0.53

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 (4): 555; 558; 571; 575

Post-translational modifications (4): 177, 198, 342, 526

Mutagenesis-validated functional residues (6):

Position	Phenotype
50	no effect on retinal ganglion cell death, decreased interaction with tfrc, loss of localization to recycling endosomes,
178	abolishes interaction with map1lc3a and gabarapl1, no effect on binding to linear ubiquitin.
178	increases interaction with map1lc3b.
474–475	abolishes colocalization with cytosolic salmonella.
474	no effect on retinal ganglion cell death, drastically decreased interaction with tfrc, loss of localization to recycling
474	significant reduction in ubiquitin binding, decreased interaction with tbk1, loss of localization to recycling endosomes

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-5205685	PINK1-PRKN Mediated Mitophagy
R-HSA-5357786	TNFR1-induced proapoptotic signaling
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-5357956	TNFR1-induced NF-kappa-B signaling pathway
R-HSA-8854214	TBC/RABGAPs
R-HSA-9013973	TICAM1-dependent activation of IRF3/IRF7
R-HSA-936964	Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)
R-HSA-9824878	Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7
R-HSA-9828211	Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation

MSigDB gene sets: 470 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_REGULATION_OF_AUTOPHAGY, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_XENOPHAGY, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_MACROAUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (18): negative regulation of receptor recycling (GO:0001920), Golgi organization (GO:0007030), signal transduction (GO:0007165), cell death (GO:0008219), positive regulation of autophagy (GO:0010508), protein localization to Golgi apparatus (GO:0034067), cellular response to unfolded protein (GO:0034620), Golgi to plasma membrane protein transport (GO:0043001), regulation of canonical NF-kappaB signal transduction (GO:0043122), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), innate immune response (GO:0045087), defense response to Gram-negative bacterium (GO:0050829), type 2 mitophagy (GO:0061734), Golgi ribbon formation (GO:0090161), positive regulation of xenophagy (GO:1904417), immune system process (GO:0002376), autophagy (GO:0006914), intracellular protein localization (GO:0008104)

GO Molecular Function (7): zinc ion binding (GO:0008270), protein-macromolecule adaptor activity (GO:0030674), polyubiquitin modification-dependent protein binding (GO:0031593), identical protein binding (GO:0042802), K63-linked polyubiquitin modification-dependent protein binding (GO:0070530), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (13): Golgi membrane (GO:0000139), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), autophagosome (GO:0005776), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), recycling endosome membrane (GO:0055038), endosome (GO:0005768), cytoplasmic vesicle (GO:0031410), recycling endosome (GO:0055037)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
TNF signaling	3
G2/M Transition	1
Mitophagy	1
Rab regulation of trafficking	1
Toll Like Receptor 3 (TLR3) Cascade	1
TRIF (TICAM1)-mediated TLR4 signaling	1
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1
TICAM1-dependent activation of IRF3/IRF7	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	4
cellular process	2
canonical NF-kappaB signal transduction	2
protein binding	2
intracellular membrane-bounded organelle	2
endomembrane system	2
receptor recycling	1
regulation of receptor recycling	1
negative regulation of macromolecule metabolic process	1
negative regulation of signaling	1
organelle organization	1
endomembrane system organization	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
protein localization to organelle	1
response to unfolded protein	1
cellular response to topologically incorrect protein	1
Golgi to plasma membrane transport	1
protein transport	1
establishment of protein localization to plasma membrane	1
protein localization to plasma membrane	1
regulation of intracellular signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
defense response to bacterium	1
mitophagy	1
Golgi organization	1
positive regulation of macroautophagy	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
xenophagy	1
regulation of xenophagy	1

Protein interactions and networks

STRING

2045 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OPTN	TBK1	Q9UHD2	994
OPTN	SQSTM1	Q13501	991
OPTN	HTT	P42858	990
OPTN	GABARAP	O95166	988
OPTN	RAB8A	P24407	984
OPTN	CALCOCO2	Q13137	983
OPTN	RAB11A	P24410	976
OPTN	GABARAPL2	P60520	975
OPTN	F5GZY7	F5GZY7	975
OPTN	MYO5B	Q9ULV0	973
OPTN	GTF3A	Q92664	962
OPTN	TARDBP	Q13148	952
OPTN	MYOC	Q99972	951
OPTN	NBR1	Q14596	947
OPTN	TAX1BP1	Q86VP1	942

IntAct

764 interactions, top by confidence:

A	B	Type	Score
TNIP1	OPTN	psi-mi:“MI:0915”(physical association)	0.970
OPTN	TNIP1	psi-mi:“MI:0915”(physical association)	0.970
OPTN	WASHC3	psi-mi:“MI:0915”(physical association)	0.950
WASHC3	OPTN	psi-mi:“MI:0915”(physical association)	0.950
OPTN	OPTN	psi-mi:“MI:0915”(physical association)	0.930
OPTN	OPTN	psi-mi:“MI:2364”(proximity)	0.930
OPTN	TBK1	psi-mi:“MI:0915”(physical association)	0.930

BioGRID (696): PARK2 (Co-localization), OPTN (Two-hybrid), OPTN (Two-hybrid), OPTN (Two-hybrid), OPTN (Two-hybrid), TNIP1 (Two-hybrid), RAB10 (Two-hybrid), CCDC53 (Two-hybrid), ZNF398 (Two-hybrid), TBC1D15 (Two-hybrid), ZNF329 (Two-hybrid), ZNF670 (Two-hybrid), OPTN (Two-hybrid), OPTN (Affinity Capture-Western), UBC (Reconstituted Complex)

ESM2 similar proteins: A0MZ66, A0MZ67, A6PWD2, A7MD70, B3DLE8, B9EKI3, F7DP49, O35550, O35551, O45420, P82094, Q05D60, Q08DR9, Q15276, Q28IH8, Q3KR99, Q3UIJ9, Q4L180, Q4R7H3, Q4V7C8, Q53EZ4, Q5BIX7, Q5R923, Q5RA03, Q5RI56, Q5U3Z6, Q6NRC9, Q6NRW2, Q6P0R8, Q6P402, Q6P6L0, Q7YS99, Q7Z7B0, Q861Q8, Q8BT07, Q8BVC4, Q8K2Q9, Q8K3K8, Q8K4T4, Q8R5M4

Diamond homologs: A9QT41, O88522, Q5M7B7, Q5R923, Q5RI56, Q6TMG5, Q7YS99, Q861Q8, Q8R5M4, Q90Z16, Q95KA2, Q95KU9, Q96CV9, Q9Y6K9, Q8K3K8

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
PLK1	up-regulates	OPTN	phosphorylation
OPTN	“up-regulates activity”	TBK1	binding
Cullin4-RBX1-DDB1	“up-regulates activity”	OPTN	polyubiquitination
DCAF4	“up-regulates activity”	OPTN	binding
TBK1	“up-regulates activity”	OPTN	phosphorylation
HACE1	“down-regulates quantity by destabilization”	OPTN	ubiquitination
OPTN	down-regulates	Apoptosis
OPTN	up-regulates	Cell_growth
OPTN	“up-regulates quantity by expression”	BDNF	“transcriptional regulation”
OPTN	“up-regulates quantity by expression”	NTF3	“transcriptional regulation”
OPTN	“up-regulates quantity by expression”	SNAP25	“transcriptional regulation”
OPTN	“up-regulates quantity by expression”	NEFL	“transcriptional regulation”
OPTN	up-regulates	Protein_aggregates

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	35
Likely pathogenic	25
Uncertain significance	243
Likely benign	125
Benign	36

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1175766	NM_001008212.2(OPTN):c.1320del (p.Lys440fs)	Pathogenic
1297634	NM_001008212.2(OPTN):c.1242+1G>A	Pathogenic
1384838	NC_000010.11:g.13122383AG[1]	Pathogenic
1425874	NC_000010.10:g.(?13151123)(13178866_?)del	Pathogenic
1451918	NM_001008212.2(OPTN):c.986_990del (p.Arg329fs)	Pathogenic
1455344	NM_001008212.2(OPTN):c.785C>A (p.Ser262Ter)	Pathogenic
1459219	NC_000010.10:g.(?13158247)(13158360_?)del	Pathogenic
1459834	NC_000010.10:g.(?13152254)(13161060_?)del	Pathogenic
1775090	NM_001008212.2(OPTN):c.1003C>T (p.Gln335Ter)	Pathogenic
2042501	NM_001008212.2(OPTN):c.1289_1290del (p.Leu430fs)	Pathogenic
2090693	NM_001008212.2(OPTN):c.666del (p.Lys223fs)	Pathogenic
2126803	NM_001008212.2(OPTN):c.649A>T (p.Arg217Ter)	Pathogenic
2198963	NM_001008212.2(OPTN):c.1552C>T (p.Gln518Ter)	Pathogenic
2426699	NC_000010.10:g.(?13151123)(13158360_?)del	Pathogenic
2426700	NC_000010.10:g.(?13154433)(13161060_?)del	Pathogenic
2426701	NC_000010.10:g.(?13164365)(13168059_?)del	Pathogenic
2928942	NM_001008212.2(OPTN):c.1318_1334dup (p.Asp445fs)	Pathogenic
2931123	NM_001008212.2(OPTN):c.523del (p.Glu175fs)	Pathogenic
2936645	NM_001008212.2(OPTN):c.1103del (p.Met368fs)	Pathogenic
2938067	NM_001008212.2(OPTN):c.450dup (p.Gln151fs)	Pathogenic
2940980	NM_001008212.2(OPTN):c.419_420insTC (p.Lys140fs)	Pathogenic
3244820	NC_000010.10:g.(?13164365)(13164507_?)del	Pathogenic
3749506	NM_001008212.2(OPTN):c.157C>T (p.Gln53Ter)	Pathogenic
3751761	NM_001008212.2(OPTN):c.1240G>T (p.Glu414Ter)	Pathogenic
3757114	NM_001008212.2(OPTN):c.1287del (p.Lys429fs)	Pathogenic
4791885	NM_001008212.2(OPTN):c.1202dup (p.Asn401fs)	Pathogenic
576203	NM_001008212.2(OPTN):c.158_161dup (p.Lys55fs)	Pathogenic
583651	NC_000010.11:g.(?13109123)(13183100_?)del	Pathogenic
631627	NM_001008212.2(OPTN):c.403G>T (p.Glu135Ter)	Pathogenic
7096	NM_001008212.2(OPTN):c.148G>A (p.Glu50Lys)	Pathogenic

SpliceAI

2690 predictions. Top by Δscore:

Variant	Effect	Δscore
10:13109284:GAAAG:G	donor_gain	1.0000
10:13109286:AAGG:A	donor_loss	1.0000
10:13109287:AGG:A	donor_loss	1.0000
10:13109288:GGTG:G	donor_loss	1.0000
10:13109289:G:GA	donor_loss	1.0000
10:13109289:G:GG	donor_gain	1.0000
10:13109290:T:A	donor_loss	1.0000
10:13112449:CCA:C	acceptor_loss	1.0000
10:13112450:CAGG:C	acceptor_loss	1.0000
10:13112451:A:AG	acceptor_gain	1.0000
10:13112451:A:T	acceptor_loss	1.0000
10:13112452:G:C	acceptor_loss	1.0000
10:13112452:G:GG	acceptor_gain	1.0000
10:13112606:G:GT	donor_gain	1.0000
10:13112629:G:GT	donor_gain	1.0000
10:13112631:TGGCT:T	donor_gain	1.0000
10:13112632:GGCT:G	donor_gain	1.0000
10:13112632:GGCTG:G	donor_gain	1.0000
10:13112633:GCT:G	donor_gain	1.0000
10:13112633:GCTG:G	donor_gain	1.0000
10:13112634:CTGTG:C	donor_loss	1.0000
10:13112635:TG:T	donor_loss	1.0000
10:13112636:G:GG	donor_gain	1.0000
10:13112636:GTGA:G	donor_loss	1.0000
10:13112637:T:A	donor_loss	1.0000
10:13112638:GAG:G	donor_loss	1.0000
10:13112639:AGTTT:A	donor_loss	1.0000
10:13112640:G:C	donor_loss	1.0000
10:13116434:G:GT	donor_gain	1.0000
10:13119036:GAAAG:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000046414 (10:13138716 G>A), RS1000114027 (10:13099974 C>T), RS1000187816 (10:13113277 C>G,T), RS1000219415 (10:13125667 T>A), RS1000251354 (10:13132386 A>G), RS1000353324 (10:13117863 G>A), RS1000451632 (10:13112339 C>A,T), RS1000478013 (10:13132136 C>G), RS1000719830 (10:13100805 C>G,T), RS1000752897 (10:13130138 C>T), RS1000815401 (10:13130303 T>C), RS1000822357 (10:13136890 A>T), RS1000942342 (10:13106912 T>A,C,G), RS1000994845 (10:13107124 C>A,T), RS1001003971 (10:13135713 C>A,T)

Disease associations

OMIM: gene MIM:602432 | disease phenotypes: MIM:613435, MIM:137760, MIM:612069, MIM:606657

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 12	Definitive	Semidominant
glaucoma 1, open angle, E	Strong	Autosomal dominant
amyotrophic lateral sclerosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 12	Definitive	SD
glaucoma, normal tension, susceptibility to	Definitive	AD

Mondo (8): amyotrophic lateral sclerosis type 12 (MONDO:0013264), OPTN-related open angle glaucoma (MONDO:0100553), amyotrophic lateral sclerosis (MONDO:0004976), frontotemporal dementia (MONDO:0017276), amyotrophic lateral sclerosis type 10 (MONDO:0012790), motor neuron disorder (MONDO:0020128), glaucoma, normal tension, susceptibility to (MONDO:0011693), (MONDO:0007665)

Orphanet (4): Amyotrophic lateral sclerosis (Orphanet:803), Frontotemporal dementia (Orphanet:282), Frontotemporal dementia with motor neuron disease (Orphanet:275872), Motor neuron disease (Orphanet:98503)

HPO phenotypes

58 total (30 of 58 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000217	Xerostomia
HP:0000545	Myopia
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000739	Anxiety
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001308	Tongue fasciculations
HP:0001324	Muscle weakness
HP:0001347	Hyperreflexia
HP:0001618	Dysphonia
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002094	Dyspnea
HP:0002145	Frontotemporal dementia
HP:0002180	Neurodegeneration
HP:0002307	Drooling
HP:0002313	Spastic paraparesis
HP:0002360	Sleep disturbance
HP:0002380	Fasciculations
HP:0002463	Language impairment
HP:0002505	Loss of ambulation
HP:0002878	Respiratory failure
HP:0003202	Skeletal muscle atrophy
HP:0003324	Generalized muscle weakness
HP:0003376	Steppage gait
HP:0003394	Muscle spasm

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000672_2	Paget’s disease	6.000000e-13
GCST001086_1	Paget’s disease	4.000000e-38
GCST006998_5	Cerebrospinal fluid p-tau levels in mild cognitive impairment	5.000000e-08
GCST007008_4	Cerebrospinal fluid p-tau levels	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004760	t-tau measurement
EFO:0004763	p-tau measurement

MeSH disease descriptors (4)

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
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
D016472	Motor Neuron Disease	C10.574.562; C10.668.467
C567429	Amyotrophic Lateral Sclerosis 10 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	6
sodium arsenite	affects expression, increases expression	3
Benzo(a)pyrene	decreases methylation, increases expression, affects methylation	3
Cisplatin	affects reaction, decreases expression, affects response to substance, affects expression	3
Fluorouracil	increases expression, affects response to substance	3
Tetrachlorodibenzodioxin	increases expression	3
cobaltous chloride	increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Tretinoin	increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	increases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
nickel chloride	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
ciglitazone	affects binding, increases expression	1
entinostat	increases expression	1
monomethylarsonous acid	decreases expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
NSC 689534	affects binding, increases expression	1

Cellosaurus cell lines

16 cell lines: 12 cancer cell line, 2 induced pluripotent stem cell, 1 transformed cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1VD	ICC13-7	Cancer cell line	Female
CVCL_A6LN	U2OS OPTN KO	Cancer cell line	Female
CVCL_C0KI	AIW002-02/OPTN-KO	Induced pluripotent stem cell	Male
CVCL_C2VN	HeLa S3 penta KO	Cancer cell line	Female
CVCL_C2VP	HeLa S3 penta KO-ATG13 KO	Cancer cell line	Female
CVCL_C2VQ	HeLa S3 penta KO-ATG14 KO	Cancer cell line	Female
CVCL_C2VR	HeLa S3 penta KO-TBK1 KO	Cancer cell line	Female
CVCL_C2VS	HeLa S3 penta KO-ULK1/ULK2 DKO	Cancer cell line	Female
CVCL_C2VT	HeLa S3 penta KO-TBK1/ULK1/ULK2 TKO	Cancer cell line	Female
CVCL_C8QB	HeLa S3 penta KO-AZI2/TBKBP1 DKO clone 20	Cancer cell line	Female

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