DCTN1

Summary

DCTN1 (dynactin subunit 1, HGNC:2711) is a protein-coding gene on chromosome 2p13.1, encoding Dynactin subunit 1 (Q14203). Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. It is a selective cancer dependency (DepMap: 34.3% of cell lines).

This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 10 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. Dynactin is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit interacts with dynein intermediate chain by its domains directly binding to dynein and binds to microtubules via a highly conserved glycine-rich cytoskeleton-associated protein (CAP-Gly) domain in its N-terminus. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. Mutations in this gene cause distal hereditary motor neuronopathy type VIIB (HMN7B) which is also known as distal spinal and bulbar muscular atrophy (dSBMA).

Source: NCBI Gene 1639 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis type 1 (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,601 total — 6 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 88
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 34.3% of screened cell lines
• MANE Select transcript: NM_004082

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2711
Approved symbol	DCTN1
Name	dynactin subunit 1
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204843
Ensembl biotype	protein_coding
OMIM	601143
Entrez	1639

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 28 protein_coding, 7 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000361874, ENST00000394003, ENST00000409240, ENST00000409438, ENST00000409567, ENST00000409868, ENST00000413111, ENST00000417090, ENST00000421392, ENST00000434055, ENST00000437375, ENST00000440727, ENST00000449655, ENST00000454119, ENST00000458655, ENST00000462813, ENST00000463583, ENST00000466110, ENST00000470351, ENST00000477966, ENST00000491465, ENST00000492717, ENST00000495643, ENST00000495895, ENST00000497666, ENST00000628224, ENST00000633691, ENST00000680606, ENST00000898641, ENST00000898642, ENST00000971125, ENST00000971126, ENST00000971127, ENST00000971128, ENST00000971129, ENST00000971130, ENST00000971131, ENST00000971132, ENST00000971133

RefSeq mRNA: 8 — MANE Select: NM_004082 NM_001135040, NM_001135041, NM_001190836, NM_001190837, NM_001378991, NM_001378992, NM_004082, NM_023019

CCDS: CCDS1939, CCDS46341, CCDS46342, CCDS46343, CCDS54368, CCDS54369, CCDS92781

Canonical transcript exons

ENST00000628224 — 32 exons

Exon	Start	End
ENSE00000762527	74368728	74368880
ENSE00000762538	74377648	74377726
ENSE00001199788	74366459	74366620
ENSE00001261323	74367971	74368131
ENSE00001408363	74376742	74376762
ENSE00002453672	74374323	74374340
ENSE00002484288	74363614	74363628
ENSE00003468565	74365075	74365241
ENSE00003486002	74369965	74370069
ENSE00003488537	74362994	74363177
ENSE00003490713	74362650	74362729
ENSE00003498466	74363294	74363427
ENSE00003503948	74367045	74367107
ENSE00003507126	74366783	74366932
ENSE00003509714	74371537	74371728
ENSE00003543635	74369098	74369214
ENSE00003562831	74365893	74366018
ENSE00003581273	74370466	74370544
ENSE00003589987	74370979	74371176
ENSE00003598271	74366244	74366375
ENSE00003625068	74367352	74367420
ENSE00003625419	74365515	74365657
ENSE00003632144	74378000	74378245
ENSE00003655193	74370621	74370825
ENSE00003658047	74369300	74369491
ENSE00003666120	74367696	74367864
ENSE00003673000	74370186	74370345
ENSE00003683337	74362052	74362141
ENSE00003693700	74372928	74372948
ENSE00003766163	74380005	74380311
ENSE00003786741	74377432	74377466
ENSE00003911922	74361155	74361636

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.9942 / max 645.9126, expressed in 1818 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29187	46.7390	1814
29184	9.6559	466
29185	8.5117	880
29189	6.3175	1716
29186	2.4835	1392
29188	0.7825	354
29183	0.2779	77
202241	0.1229	61
202242	0.0885	56
29181	0.0112	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	99.12	gold quality
prefrontal cortex	UBERON:0000451	99.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.94	gold quality
apex of heart	UBERON:0002098	98.89	gold quality
anterior cingulate cortex	UBERON:0009835	98.87	gold quality
cingulate cortex	UBERON:0003027	98.86	gold quality
cerebellar cortex	UBERON:0002129	98.84	gold quality
cerebellar hemisphere	UBERON:0002245	98.84	gold quality
nucleus accumbens	UBERON:0001882	98.63	gold quality
amygdala	UBERON:0001876	98.61	gold quality
putamen	UBERON:0001874	98.56	gold quality
caudate nucleus	UBERON:0001873	98.48	gold quality
adenohypophysis	UBERON:0002196	98.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.42	gold quality
frontal cortex	UBERON:0001870	98.26	gold quality
left testis	UBERON:0004533	98.22	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.21	gold quality
cerebellum	UBERON:0002037	98.20	gold quality
hypothalamus	UBERON:0001898	98.19	gold quality
right testis	UBERON:0004534	98.12	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.09	gold quality
neocortex	UBERON:0001950	98.04	gold quality
pituitary gland	UBERON:0000007	98.02	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.89	gold quality
spinal cord	UBERON:0002240	97.84	gold quality
forebrain	UBERON:0001890	97.69	gold quality
telencephalon	UBERON:0001893	97.67	gold quality
sural nerve	UBERON:0015488	97.64	gold quality
brain	UBERON:0000955	97.61	gold quality
cerebral cortex	UBERON:0000956	97.40	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

Upstream regulators (CollecTRI, top): JUN

miRNA regulators (miRDB)

26 targeting DCTN1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-495-5P	97.62	68.28	682
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-662	90.64	62.72	148

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Genomic organization of the DCTN1-SLC4A5 locus encoding both NBC4 and p150(Glued). (PMID:12063394)
• dysfunction of dynactin-mediated transport can lead to human motor neuron disease (PMID:12627231)
• neither APC nor p150glued binding domain is necessary for EB1 or EBF3 to induce microtubule bundling (PMID:14514668)
• role in extension and assembly of adherens junctions in photoreceptor development (PMID:15067220)
• Heterozygous missense mutations of DCTN1 were found in a sporadic case of ALS (T1249I), 1 pt with familial ALS (M571T), two pts with familial ALS, & two unaffected relatives (R785W). Alleleic variants of DCTN1 may be a genomic risk factor for ALS. (PMID:15326253)
• a specific requirement for p150(Glued)/dynein/functional microtubules in activation of MKK3/6 and p38 MAPKs in vivo. (PMID:15375157)
• The R1101K sequence alteration of the DCTN1 gene may predispose subjects to ALS and FTD. (PMID:16240349)
• The Gly59Ser mutation disrupts folding of the cytoskeleton-associated protein glycine-rich (CAP-Gly) domain, resulting in aggregation of p150Glued protein in vitro and in vivo, accompanied by an increase in cell death in a motor neuron cell line. (PMID:16505168)
• The function of p150(Glued) in membrane trafficking is not associated with plus-end localization. (PMID:16772339)
• Dynactin p150(Glued) plays an important role in the functional integrity of the keratinocyte microparasol. (PMID:17344930)
• Our findings provide a potential mechanism by which p150(Glued) protein function is regulated by SCFs. (PMID:17532294)
• The results indicate that the DCTN1 gene is probably not influencing susceptibility to neurodegeneration in MS. (PMID:17824900)
• Data use the complex formed between the CAP-Gly domain of p150(glued) and the C-terminal zinc knuckle of CLIP170 as a model system to explore the structure-function relationship of CAP-Gly-mediated protein interactions. (PMID:17828277)
• the N-terminal projection domain of tau binds to the C-terminus of the p150 subunit of the dynactin complex (PMID:17932487)
• p150Glued may activate and thereby facilitate the recruitment of EB1 to the tips of microtubules to regulate their dynamics. (PMID:18081319)
• The glycine59serine missense mutation in p150(glued) knock-in mice abrogates the normal function of the protein and accelerates motor neuron degeneration. (PMID:18094236)
• Motor neuron disease occurring in a mutant dynactin mouse model is characterized by defects in vesicular trafficking. (PMID:18305234)
• p150(Glued) transgenic mice exhibit late-onset, slowly progressive muscle weakness but do not have a shortened lifespan, consistent with the human phenotype. (PMID:18364389)
• Regulation of dynactin through the differential expression of p150Glued isoforms. (PMID:18812314)
• REST/NRSF, dynactin p150(Glued), huntingtin, HAP1, and RILP form a complex involved in the translocation of REST/NRSF into the nucleus and HAP1 controls REST/NRSF cellular localization in neurons (PMID:18922795)
• DCTN1 mutations, previously associated with motor neuron disease, can underlie the selective vulnerability of other neuronal populations in distinct neurodegenerative disorders. (PMID:19136952)
• the CAP-Gly domain has a critical role in the initiation and persistence of dynein-dependent movement of the mitotic spindle and nucleus, but it is otherwise dispensable for dynein-based movement. (PMID:19279216)
• This study suggests that pathogenic mutations in DCTN1 are rare and do not play a common role in the development of Parkinson disease, frontotemporal lobar degeneration, or amyotrophic lateral sclerosis. (PMID:19506225)
• Results describe how ORP1L contacts VAP to control Rab7-RILP-p150 Glued and late endosome positioning. (PMID:19564404)
• DCTN1 subunit p150Glued isoforms notable for differential interaction with microtubules. (PMID:19778315)
• Disruption of the SNX6-p150(Glued) interaction causes failure in formation and detachment of the tubulovesicular sorting structures from endosomes and results in block of CI-MPR retrieval from endosomes to the TGN. (PMID:19935774)
• study describes a new family carrying a G71R mutation in the DCTN1 gene; the proband displayed a series of distinctive features not previously described in Perry syndrome (PMID:20437543)
• demonstrate that the domains harboring mutated CAP-gly domains bind to microtubules but fail to bind to EB1 (PMID:20518521)
• Data show that polo-like kinase 1 phosphorylation of p150(Glued) might be one major pathway of NEBD regulation. (PMID:20679239)
• DCTN1 mutation in patients with with early stage of Perry syndrome presented with marked autonomic dysfunction including orthostatic hypotension and decreased cardiac uptake with [123]I-metaiodobenzylguanidine scintigram features (PMID:20702129)
• Par6alpha controls centrosome organization through its association with the dynactin subunit p150(Glued). (PMID:20719959)
• Endosome movement requires an intact dynactin complex to allow p150(Glued) to activate dynein, since p50 over-expression, which disrupts the dynactin complex, inhibits inward movement even though dynein and p150(Glued) remain membrane-bound. (PMID:21915335)
• End-binding proteins interact with the CAP-Gly domains of CLIP-170 and p150(glued). (PMID:22119847)
• Data suggest that TRAPPC9 serves to uncouple p150(Glued) from the COPII coat, and to relay the vesicle-dynactin interaction at the target membrane. (PMID:22279557)
• The tubule formations were dependent on microtubule interactions, and specifically controlled by Kif16b and dynein 1. (PMID:22357949)
• Studies indicate that binding of dynactin, LIS1 and NudEL regulate cytoplasmic dynein motor activity. (PMID:22373868)
• The p150(Glued) CAP-Gly domain regulates dynein-mediated retrograde transport at synaptic termini, and this function of dynactin is disrupted by a mutation that causes motor neuron disease. (PMID:22542187)
• Overexpression of TBCB leads to the decreased localization of p150 to the microtubule network that might result in a functional modulation of this protein complex. (PMID:22777741)
• LIS1 is required for dynein-mediated transport induced by membrane tethering of BICD2-N and LIS1 contributes to dynein accumulation at microtubule plus ends and BICD2-positive cellular structures. (PMID:22956769)
• mTORC1 activation requires dynein-dependent transport to a position in the cell where it can be activated (PMID:22987636)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	dctn1a	ENSDARG00000019743
danio_rerio	dctn1b	ENSDARG00000056753
mus_musculus	Dctn1	ENSMUSG00000031865
rattus_norvegicus	C4h2orf81	ENSRNOG00000010048
drosophila_melanogaster	DCTN1-p150	FBGN0001108
drosophila_melanogaster	Dred	FBGN0036882
caenorhabditis_elegans		WBGENE00001017

Paralogs (4): CLIP3 (ENSG00000105270), CLIP2 (ENSG00000106665), CLIP4 (ENSG00000115295), CLIP1 (ENSG00000130779)

Protein

Protein identifiers

Dynactin subunit 1 — Q14203 (reviewed: Q14203)

Alternative names: 150 kDa dynein-associated polypeptide, DAP-150, p135, p150-glued

All UniProt accessions (13): A0A7P0Z4C3, A0A804CDA6, C9J1B7, C9JJD0, C9JJN7, C9JKG6, C9JTE5, C9JUI8, C9JZA4, E7EX90, E9PCY0, Q14203, Q6AWB1

UniProt curated annotations — full annotation on UniProt →

Function. Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. Plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting and tethering dynein to microtubules. Binds to both dynein and microtubules providing a link between specific cargos, microtubules and dynein. Essential for targeting dynein to microtubule plus ends, recruiting dynein to membranous cargos and enhancing dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Can also act as a brake to slow the dynein motor during motility along the microtubule. Can regulate microtubule stability by promoting microtubule formation, nucleation and polymerization and by inhibiting microtubule catastrophe in neurons. Inhibits microtubule catastrophe by binding both to microtubules and to tubulin, leading to enhanced microtubule stability along the axon. Plays a role in metaphase spindle orientation. Plays a role in centriole cohesion and subdistal appendage organization and function. Its recruitment to the centriole in a KIF3A-dependent manner is essential for the maintenance of centriole cohesion and the formation of subdistal appendage. Also required for microtubule anchoring at the mother centriole. Plays a role in primary cilia formation.

Subunit / interactions. Monomer and homodimer. Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. DCTN1/p150(glued) binds directly to microtubules and to cytoplasmic dynein. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin. Interacts with the C-terminus of MAPRE1, MAPRE2 and MAPRE3. Interacts (via C-terminus) with SNX6. Interacts with CLN3, DYNAP, ECPAS and FBXL5. Interacts with MISP; this interaction regulates its distribution at the cell cortex. Interacts with CEP131. Interacts with CEP126. Interacts with CLIP1. Interacts with dynein intermediate chain and dynein heavy chain. Interacts with PLK1 (via POLO-box domain). Interacts with TBCB. Binds preferentially to tyrosinated microtubules than to detyrosinated microtubules. Interacts with PARD6A. Interacts with HPS6. Interacts with KIF3A. Interacts with BICD2. Interacts with DST (isoform 9). Interacts with DST (isoform 1). Identified in a complex with MREG and RILP. Interacts with BCCIP (isoform 2/alpha). Interacts with DCDC1. Interacts with AKNA. Interacts with DYNC1I2. Interacts with RUFY3 and RUFY4.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Spindle. Nucleus envelope. Cell cortex.

Tissue specificity. Brain.

Post-translational modifications. Ubiquitinated by a SCF complex containing FBXL5, leading to its degradation by the proteasome. Phosphorylation by SLK at Thr-145, Thr-146 and Thr-147 targets DCTN1 to the centrosome. It is uncertain if SLK phosphorylates all three threonines or one or two of them. PLK1-mediated phosphorylation at Ser-179 is essential for its localization in the nuclear envelope, promotes its dissociation from microtubules during early mitosis and positively regulates nuclear envelope breakdown during prophase.

Disease relevance. Neuronopathy, distal hereditary motor, autosomal dominant 14 (HMND14) [MIM:607641] A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. The disease is caused by variants affecting the gene represented in this entry. Amyotrophic lateral sclerosis (ALS) [MIM:105400] 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. Disease susceptibility is associated with variants affecting the gene represented in this entry. Perry syndrome (PERRYS) [MIM:168605] A neuropsychiatric disorder characterized by mental depression not responsive to antidepressant drugs or electroconvulsive therapy, sleep disturbances, exhaustion and marked weight loss. Parkinsonism develops later and respiratory failure occurred terminally. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The CAP-Gly domain is essential for interactions with microtubules and its binding partners and for its motion along the microtubules. Essential for its preferential binding to tyrosinated microtubules and for promoting the sustained interaction of the dynein motor with microtubules.

Similarity. Belongs to the dynactin 150 kDa subunit family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q14203-1	p150	yes
Q14203-2	p135
Q14203-3	3
Q14203-4	4
Q14203-5	5
Q14203-6	6

RefSeq proteins (8): NP_001128512, NP_001128513, NP_001177765, NP_001177766, NP_001365920, NP_001365921, NP_004073, NP_075408 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000938	CAP-Gly_domain	Domain
IPR022157	Dynactin	Domain
IPR036859	CAP-Gly_dom_sf	Homologous_superfamily

Pfam: PF01302, PF12455

UniProt features (70 total): sequence variant 17, sequence conflict 10, strand 9, mutagenesis site 8, modified residue 6, splice variant 5, compositionally biased region 4, region of interest 3, coiled-coil region 3, turn 2, chain 1, domain 1, helix 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
1TXQ	X-RAY DIFFRACTION	1.8
2HQH	X-RAY DIFFRACTION	1.8
2HKQ	X-RAY DIFFRACTION	1.86
2HKN	X-RAY DIFFRACTION	1.87
2HL5	X-RAY DIFFRACTION	1.93
2HL3	X-RAY DIFFRACTION	2.03
3TQ7	X-RAY DIFFRACTION	2.3
3E2U	X-RAY DIFFRACTION	2.6
9B7J	ELECTRON MICROSCOPY	3.49
9YND	ELECTRON MICROSCOPY	4.26
9YNH	ELECTRON MICROSCOPY	5.5
9YNE	ELECTRON MICROSCOPY	8.46
2COY	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14203-F1	77.43	0.28

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 (6): 108, 145, 146, 147, 179, 212

Mutagenesis-validated functional residues (8):

Position	Phenotype
68	abolishes interaction with clip1.
90	abolishes interaction with clip1.
145	affects centrosomal localization; when associated with a-146 and a-147.
146	affects centrosomal localization; when associated with a-145 and a-147.
147	affects centrosomal localization; when associated with a-145 and a-146.
179	non-phosphorylatable by plk1. decreased nuclear envelope localization. no loss of microtubule-binding. no effect on its
179	no loss of localization to nuclear envelope. decrease in microtubule-binding. no effect on its interaction with clip1.
212	no effect on its interaction with clip1 and plk1.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-8854518	AURKA Activation by TPX2

MSigDB gene sets: 481 (showing top): ATF_B, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, RNGTGGGC_UNKNOWN, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_PIGMENT_GRANULE_LOCALIZATION, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_BEHAVIOR, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_VESICLE_LOCALIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_MICROTUBULE_ANCHORING

GO Biological Process (23): establishment of mitotic spindle orientation (GO:0000132), mitotic cell cycle (GO:0000278), mitotic nuclear membrane disassembly (GO:0007077), nuclear migration (GO:0007097), nervous system development (GO:0007399), neuromuscular junction development (GO:0007528), centriole-centriole cohesion (GO:0010457), ventral spinal cord development (GO:0021517), positive regulation of microtubule polymerization (GO:0031116), melanosome transport (GO:0032402), microtubule anchoring at centrosome (GO:0034454), retrograde transport, endosome to Golgi (GO:0042147), neuromuscular process (GO:0050905), cell division (GO:0051301), regulation of mitotic spindle organization (GO:0060236), motor behavior (GO:0061744), neuron cellular homeostasis (GO:0070050), positive regulation of microtubule nucleation (GO:0090063), maintenance of synapse structure (GO:0099558), positive regulation of neuromuscular junction development (GO:1904398), non-motile cilium assembly (GO:1905515), neuron projection maintenance (GO:1990535), nuclear membrane disassembly (GO:0051081)

GO Molecular Function (5): microtubule binding (GO:0008017), tubulin binding (GO:0015631), protein kinase binding (GO:0019901), tau protein binding (GO:0048156), protein binding (GO:0005515)

GO Cellular Component (31): kinetochore (GO:0000776), spindle pole (GO:0000922), acrosomal vesicle (GO:0001669), nuclear envelope (GO:0005635), cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), spindle (GO:0005819), cytosol (GO:0005829), microtubule (GO:0005874), microtubule associated complex (GO:0005875), cilium (GO:0005929), cell cortex (GO:0005938), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), dynein complex (GO:0030286), axon (GO:0030424), cell leading edge (GO:0031252), perinuclear theca (GO:0033011), microtubule plus-end (GO:0035371), ciliary basal body (GO:0036064), neuron projection (GO:0043005), neuronal cell body (GO:0043025), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686), cell cortex region (GO:0099738), centriolar subdistal appendage (GO:0120103), nucleus (GO:0005634), cytoskeleton (GO:0005856), retromer complex (GO:0030904), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
G2/M Transition	2
Centrosome maturation	2
Adaptive Immune System	1
Cellular responses to stress	1
IRE1alpha activates chaperones	1
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1
Signaling by ALK in cancer	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membraneless organelle	3
microtubule cytoskeleton	3
mitotic cell cycle	2
synapse organization	2
cytoskeletal protein binding	2
microtubule organizing center	2
cytoplasm	2
cytoskeleton	2
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
cell cycle	1
mitotic nuclear division	1
nuclear membrane disassembly	1
mitotic cell cycle process	1
intracellular transport	1
nucleus localization	1
establishment of organelle localization	1
system development	1
centrosome cycle	1
cell cycle process	1
spinal cord development	1
anatomical structure development	1
positive regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
positive regulation of protein polymerization	1
microtubule polymerization	1
positive regulation of supramolecular fiber organization	1
melanosome localization	1
establishment of melanosome localization	1
pigment granule transport	1
microtubule anchoring at microtubule organizing center	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
nervous system process	1
cellular process	1
mitotic spindle organization	1
regulation of spindle organization	1
behavior	1

Protein interactions and networks

STRING

2680 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCTN1	DCTN2	Q13561	999
DCTN1	HAP1	P54257	979
DCTN1	TPPP	O94811	958
DCTN1	CLIP1	P30622	955
DCTN1	DCTN3	O75935	938
DCTN1	SNX5	Q9Y5X3	932
DCTN1	SNX6	Q9UNH7	908
DCTN1	ACTR10	Q9NZ32	907
DCTN1	ACTR1A	P42024	906
DCTN1	VCP	P55072	895
DCTN1	DYNC1H1	Q14204	892
DCTN1	MAPRE1	Q15691	882
DCTN1	HTT	P42858	879
DCTN1	MAPK8IP3	Q9UPT6	875
DCTN1	DCTN5	Q9BTE1	822

IntAct

243 interactions, top by confidence:

A	B	Type	Score
DCTN1	MAPRE1	psi-mi:“MI:0407”(direct interaction)	0.900
MAPRE1	DCTN1	psi-mi:“MI:0407”(direct interaction)	0.900
SNX6	SNX1	psi-mi:“MI:0914”(association)	0.880
MAPRE1	CLASP2	psi-mi:“MI:0914”(association)	0.850
ACTR1A	DCTN2	psi-mi:“MI:0914”(association)	0.790
DCTN1	DCTN6	psi-mi:“MI:0914”(association)	0.780
CLIP1	DCTN1	psi-mi:“MI:0407”(direct interaction)	0.760
DCTN1	CLIP1	psi-mi:“MI:0407”(direct interaction)	0.760
DCTN2	DCTN6	psi-mi:“MI:0914”(association)	0.730
DCTN2	DCTN3	psi-mi:“MI:0914”(association)	0.730
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DCTN1	DCTN3	psi-mi:“MI:0914”(association)	0.710
DYNC1I2	DYNC1LI2	psi-mi:“MI:0914”(association)	0.680
CEP170	KIF2A	psi-mi:“MI:2364”(proximity)	0.650
ACTR1B	DCTN1	psi-mi:“MI:0915”(physical association)	0.650
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640

BioGRID (731): DCTN1 (Two-hybrid), MAPT (Two-hybrid), DCTN1 (Reconstituted Complex), MAPT (Co-purification), DCTN1 (Affinity Capture-Western), DCTN1 (Affinity Capture-RNA), DCTN1 (Affinity Capture-RNA), DCTN1 (Two-hybrid), DCTN1 (Affinity Capture-MS), DCTN1 (Affinity Capture-MS), DCTN1 (Affinity Capture-MS), BZW1 (Co-fractionation), CYFIP1 (Co-fractionation), DCTN1 (Co-fractionation), DCTN1 (Co-fractionation)

ESM2 similar proteins: A0A0D1E2P6, A0A0D2XVZ5, A0A0P0VG31, A0A0P1AAU8, A0A287B8J2, A2WYG9, A4QP73, B9EHT4, B9F2Y7, D0NCC1, J9VKM5, O08788, O59739, P0C7L7, P0CP26, P0CP27, P14725, P28023, P39742, P82874, P92792, Q10MW6, Q13217, Q14203, Q149L6, Q27968, Q28I38, Q54M21, Q54NS3, Q58DR2, Q5JJI4, Q5JNB5, Q5R686, Q5R6H3, Q5ZI13, Q6PCJ1, Q6YUL8, Q7ZXQ8, Q8TBM8, Q91YW3

Diamond homologs: A0A287B8J2, B9EHT4, O08788, O42184, O42667, O55156, P28023, P30622, P33420, P35458, Q10235, Q14203, Q20728, Q54Z01, Q5E951, Q5R686, Q5U243, Q66HD5, Q6PCJ1, Q8CI96, Q8N3C7, Q922J3, Q96DZ5, Q99426, Q9D1E6, Q9JK25, Q9NQT8, Q9UDT6, Q9VJE5, Q9Z0H8, E9Q309, P13496, P34531, Q01397, Q15813, Q32KS0, Q55CN0, Q5FVQ9, Q5RBD9, Q5U378

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PLK1	up-regulates	DCTN1	phosphorylation
CLIP1	“up-regulates activity”	DCTN1	binding
FBXL5	“down-regulates quantity by destabilization”	DCTN1	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	DCTN1	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 170 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
COPI-independent Golgi-to-ER retrograde traffic	20	37.1×	3e-24
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	19	32.8×	5e-22
Aggrephagy	12	26.6×	8e-13
RHO GTPases activate IQGAPs	7	21.6×	6e-07
Gap junction trafficking and regulation	5	21.2×	4e-05
Gap junction trafficking	5	21.2×	4e-05
Loss of Nlp from mitotic centrosomes	14	19.8×	5e-13
Loss of proteins required for interphase microtubule organization from the centrosome	14	19.8×	5e-13

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of microtubule polymerization	6	28.7×	2e-05
microtubule bundle formation	5	18.1×	2e-03
cellular response to reactive oxygen species	5	14.6×	3e-03
substantia nigra development	5	13.0×	4e-03
microtubule cytoskeleton organization	14	12.0×	1e-08
mitotic spindle organization	6	11.6×	2e-03
intracellular protein localization	10	7.4×	3e-04
neuron migration	7	6.6×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1601 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	5
Uncertain significance	808
Likely benign	579
Benign	49

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1458171	NM_004082.5(DCTN1):c.175G>C (p.Gly59Arg)	Pathogenic
1929273	NM_004082.5(DCTN1):c.626dup (p.Leu210fs)	Pathogenic
21390	NM_004082.5(DCTN1):c.212G>A (p.Gly71Glu)	Pathogenic
2499593	NM_004082.5(DCTN1):c.279+2T>C	Pathogenic
8401	NM_004082.5(DCTN1):c.175G>A (p.Gly59Ser)	Pathogenic
8407	NM_004082.5(DCTN1):c.221A>C (p.Gln74Pro)	Pathogenic
1474510	NM_004082.5(DCTN1):c.3823C>T (p.Arg1275Cys)	Likely pathogenic
1699560	NM_004082.5(DCTN1):c.156T>G (p.Phe52Leu)	Likely pathogenic
3899837	NM_004082.5(DCTN1):c.3532_3609+7del	Likely pathogenic
582950	NM_004082.5(DCTN1):c.232T>C (p.Tyr78His)	Likely pathogenic
976655	NM_004082.5(DCTN1):c.1864A>T (p.Ile622Phe)	Likely pathogenic

SpliceAI

4324 predictions. Top by Δscore:

Variant	Effect	Δscore
2:74361502:G:C	donor_gain	1.0000
2:74361644:T:C	acceptor_gain	1.0000
2:74361644:T:TC	acceptor_gain	1.0000
2:74361647:A:AC	acceptor_gain	1.0000
2:74361647:A:C	acceptor_gain	1.0000
2:74362050:AC:A	donor_gain	1.0000
2:74362051:CC:C	donor_gain	1.0000
2:74362644:GCTGA:G	donor_loss	1.0000
2:74362645:CTGAC:C	donor_loss	1.0000
2:74362646:TGA:T	donor_loss	1.0000
2:74362647:GACCT:G	donor_loss	1.0000
2:74362648:A:AT	donor_loss	1.0000
2:74362649:C:A	donor_loss	1.0000
2:74362727:CAG:C	acceptor_gain	1.0000
2:74362729:GC:G	acceptor_loss	1.0000
2:74362730:C:CA	acceptor_loss	1.0000
2:74362730:C:CC	acceptor_gain	1.0000
2:74362988:ACAT:A	donor_loss	1.0000
2:74362990:ATAC:A	donor_loss	1.0000
2:74362990:ATACC:A	donor_loss	1.0000
2:74362991:TA:T	donor_loss	1.0000
2:74362991:TACCA:T	donor_loss	1.0000
2:74362992:A:AC	donor_gain	1.0000
2:74362992:ACCA:A	donor_loss	1.0000
2:74362993:C:CA	donor_loss	1.0000
2:74362993:C:CC	donor_gain	1.0000
2:74362993:CCA:C	donor_gain	1.0000
2:74363018:C:CT	donor_gain	1.0000
2:74363019:T:TT	donor_gain	1.0000
2:74363173:GCTCC:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000109598 (2:74368272 T>C,G), RS1000218255 (2:74361269 G>A), RS1000270471 (2:74360786 T>A), RS1000356314 (2:74362264 A>G), RS1000402202 (2:74389770 G>A), RS1000456717 (2:74374809 G>C), RS1000625652 (2:74372270 C>A), RS1000734190 (2:74378858 C>T), RS1000844851 (2:74381162 CTA>C), RS1000874173 (2:74381422 A>G), RS1001356757 (2:74374388 G>A,C), RS1001380792 (2:74362374 G>A,C), RS1001405757 (2:74387133 G>C), RS1001412011 (2:74362646 T>C), RS1001479294 (2:74390989 T>C)

Disease associations

OMIM: gene MIM:601143 | disease phenotypes: MIM:105400, MIM:168605, MIM:607641, MIM:118220

GenCC curated gene-disease

Disease	Classification	Inheritance
Perry syndrome	Strong	Autosomal dominant
neuronopathy, distal hereditary motor, type 7B	Strong	Autosomal dominant
amyotrophic lateral sclerosis type 1	Strong	Autosomal dominant
distal hereditary motor neuropathy type 7	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Moderate	AD

Mondo (13): amyotrophic lateral sclerosis type 1 (MONDO:0007103), Perry syndrome (MONDO:0008201), neuronopathy, distal hereditary motor, type 7B (MONDO:0011879), amyotrophic lateral sclerosis (MONDO:0004976), peripheral neuropathy (MONDO:0005244), generalized dystonia (MONDO:0000476), dystonic disorder (MONDO:0003441), parkinsonian disorder (MONDO:0021095), Charcot-Marie-Tooth disease (MONDO:0015626), hereditary motor neuron disease (MONDO:0024257), frontotemporal dementia (MONDO:0017276), Charcot-Marie-Tooth disease type 2 (MONDO:0018993), distal hereditary motor neuropathy type 7 (MONDO:0015355)

Orphanet (8): Distal hereditary motor neuropathy type 7 (Orphanet:139589), Perry syndrome (Orphanet:178509), Amyotrophic lateral sclerosis (Orphanet:803), Generalized isolated dystonia (Orphanet:376724), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Genetic motor neuron disease (Orphanet:98505), Frontotemporal dementia (Orphanet:282), Autosomal dominant Charcot-Marie-Tooth disease type 2 (Orphanet:64746)

HPO phenotypes

88 total (30 of 88 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000217	Xerostomia
HP:0000298	Mask-like facies
HP:0000511	Vertical supranuclear gaze palsy
HP:0000708	Atypical behavior
HP:0000710	Hyperorality
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000719	Inappropriate behavior
HP:0000726	Dementia
HP:0000734	Disinhibition
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000751	Personality changes
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001300	Parkinsonism
HP:0001308	Tongue fasciculations
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001605	Vocal cord paralysis
HP:0001618	Dysphonia
HP:0001621	Weak voice
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002063	Rigidity
HP:0002067	Bradykinesia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004250_20	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	2.000000e-06
GCST010002_394	Refractive error	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007965	response to combination chemotherapy

MeSH disease descriptors (9)

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
D004422	Dystonia Musculorum Deformans	C10.228.140.079.357; C10.228.662.300.200; C10.574.500.393; C16.320.400.330
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
D020734	Parkinsonian Disorders	C10.228.140.079.862; C10.228.662.600
C531617	Amyotrophic lateral sclerosis 1 (supp.)
C564362	Neuronopathy, Distal Hereditary Motor, Type Viib (supp.)
C566822	Perry Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067281 (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
7.63	Kd	23.48	nM	CHEMBL5653589
7.63	ED50	23.48	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	2148203: Binding affinity to human DCTN1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0235	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression, increases expression	3
bisphenol A	increases expression	2
bisphenol S	increases expression, increases methylation	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Amiodarone	increases expression	1
Vehicle Emissions	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Furaldehyde	affects cotreatment, decreases expression, affects localization, increases expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	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
CHEMBL5651245	Binding	Binding affinity to human DCTN1 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

6 cell lines: 3 induced pluripotent stem cell, 3 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E7KA	KOLF2.1J DCTN1 G59S SNV/WT	Induced pluripotent stem cell	Male
CVCL_E7KC	KOLF2.1J DCTN1 R785W SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E7KD	KOLF2.1J DCTN1 R785W SNV/WT	Induced pluripotent stem cell	Male
CVCL_EY81	ND32946	Finite cell line	Female
CVCL_EZ55	ND40079	Finite cell line	Female
CVCL_EZ56	ND40080	Finite cell line	Female

Clinical trials (associated diseases)

299 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
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