EWSR1

Summary

EWSR1 (EWS RNA binding protein 1, HGNC:3508) is a protein-coding gene on chromosome 22q12.2, encoding RNA-binding protein EWS (Q01844). Binds to ssRNA containing the consensus sequence 5’-AGGUAA-3’. It is a common-essential gene (DepMap: required in 98.7% of cancer cell lines).

This gene encodes a multifunctional protein that is involved in various cellular processes, including gene expression, cell signaling, and RNA processing and transport. The protein includes an N-terminal transcriptional activation domain and a C-terminal RNA-binding domain. Chromosomal translocations between this gene and various genes encoding transcription factors result in the production of chimeric proteins that are involved in tumorigenesis. These chimeric proteins usually consist of the N-terminal transcriptional activation domain of this protein fused to the C-terminal DNA-binding domain of the transcription factor protein. Mutations in this gene, specifically a t(11;22)(q24;q12) translocation, are known to cause Ewing sarcoma as well as neuroectodermal and various other tumors. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1 and 14.

Source: NCBI Gene 2130 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis (Moderate, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 123 total
• Phenotypes (HPO): 20
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• Cancer dependency (DepMap): dependent in 98.7% of screened cell lines (common-essential)
• Transcription factor: yes — 62 downstream targets (CollecTRI)
• MANE Select transcript: NM_005243

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3508
Approved symbol	EWSR1
Name	EWS RNA binding protein 1
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	EWS
Ensembl gene	ENSG00000182944
Ensembl biotype	protein_coding
OMIM	133450
Entrez	2130

Gene structure

Transcript identifiers

Ensembl transcripts: 94 — 87 protein_coding, 7 retained_intron

ENST00000331029, ENST00000332035, ENST00000332050, ENST00000333395, ENST00000360091, ENST00000397938, ENST00000406548, ENST00000414183, ENST00000415761, ENST00000436425, ENST00000437155, ENST00000444626, ENST00000447973, ENST00000455726, ENST00000469669, ENST00000479135, ENST00000483415, ENST00000483629, ENST00000485037, ENST00000493426, ENST00000610553, ENST00000629659, ENST00000889471, ENST00000889472, ENST00000889473, ENST00000889474, ENST00000889475, ENST00000889476, ENST00000889477, ENST00000889478, ENST00000889479, ENST00000889480, ENST00000889481, ENST00000889482, ENST00000889483, ENST00000889484, ENST00000889485, ENST00000889486, ENST00000889487, ENST00000889488, ENST00000889489, ENST00000889490, ENST00000889491, ENST00000889492, ENST00000889494, ENST00000889495, ENST00000889497, ENST00000889499, ENST00000889500, ENST00000889502, ENST00000889504, ENST00000889505, ENST00000889506, ENST00000889507, ENST00000889508, ENST00000889509, ENST00000889510, ENST00000889511, ENST00000889512, ENST00000889513, ENST00000889514, ENST00000925319, ENST00000925320, ENST00000925321, ENST00000925322, ENST00000925323, ENST00000925324, ENST00000925325, ENST00000925326, ENST00000925327, ENST00000925328, ENST00000925329, ENST00000925330, ENST00000925331, ENST00000925332, ENST00000925333, ENST00000925334, ENST00000959975, ENST00000959976, ENST00000959977, ENST00000959978, ENST00000959979, ENST00000959980, ENST00000959981, ENST00000959982, ENST00000959983, ENST00000959984, ENST00000959985, ENST00000959986, ENST00000959987, ENST00000959988, ENST00000959989, ENST00000959990, ENST00000959991

RefSeq mRNA: 5 — MANE Select: NM_005243 NM_001163285, NM_001163286, NM_001163287, NM_005243, NM_013986

CCDS: CCDS13851, CCDS13852, CCDS54512, CCDS54513, CCDS54514

Canonical transcript exons

ENST00000397938 — 17 exons

Exon	Start	End
ENSE00001300293	29291562	29291599
ENSE00001787873	29288606	29288786
ENSE00001941182	29268268	29268349
ENSE00003470269	29292488	29292606
ENSE00003495391	29278030	29278216
ENSE00003513248	29299599	29299851
ENSE00003523502	29282390	29282557
ENSE00003524528	29296239	29296368
ENSE00003531289	29272380	29272431
ENSE00003534354	29297827	29297949
ENSE00003554408	29292137	29292169
ENSE00003570564	29286923	29287134
ENSE00003584318	29273741	29273864
ENSE00003589287	29298733	29298895
ENSE00003671623	29272216	29272252
ENSE00003684056	29299234	29299331
ENSE00003901472	29300122	29300521

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.8416 / max 569.3175, expressed in 1816 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191598	45.4480	1815
191599	2.1794	1119
191597	1.2142	836

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.13	gold quality
left testis	UBERON:0004533	99.05	gold quality
right testis	UBERON:0004534	99.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.96	gold quality
cerebellar hemisphere	UBERON:0002245	98.95	gold quality
right lobe of thyroid gland	UBERON:0001119	98.90	gold quality
right adrenal gland cortex	UBERON:0035827	98.90	gold quality
right adrenal gland	UBERON:0001233	98.85	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.84	gold quality
metanephros cortex	UBERON:0010533	98.84	gold quality
left adrenal gland cortex	UBERON:0035825	98.84	gold quality
left adrenal gland	UBERON:0001234	98.83	gold quality
ganglionic eminence	UBERON:0004023	98.81	gold quality
cortical plate	UBERON:0005343	98.81	gold quality
body of uterus	UBERON:0009853	98.80	gold quality
left lobe of thyroid gland	UBERON:0001120	98.79	gold quality
body of pancreas	UBERON:0001150	98.78	gold quality
right ovary	UBERON:0002118	98.78	gold quality
adrenal cortex	UBERON:0001235	98.77	gold quality
cerebellar cortex	UBERON:0002129	98.76	gold quality
ventricular zone	UBERON:0003053	98.76	gold quality
adenohypophysis	UBERON:0002196	98.74	gold quality
left ovary	UBERON:0002119	98.73	gold quality
mucosa of stomach	UBERON:0001199	98.67	gold quality
left uterine tube	UBERON:0001303	98.67	gold quality
endocervix	UBERON:0000458	98.64	gold quality
lymph node	UBERON:0000029	98.59	gold quality
adrenal gland	UBERON:0002369	98.59	gold quality
transverse colon	UBERON:0001157	98.58	gold quality
granulocyte	CL:0000094	98.56	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: yes

Downstream targets (CollecTRI)

62 targets.

Target	Regulation
ABCC3
AKT1S1
ATF1	Unknown
AURKA	Activation
AURKB	Activation
BCL2L1
CASP3
CAV1
CCK	Unknown
CCND1	Activation
CCNE1	Unknown
CD99
CDKN1A	Unknown
CDKN1B
CDKN1C	Unknown
CEL
CFL1
COL11A2
CREBBP
CSF1R
DKK1
DKK2
EGR2	Unknown
EWSR1
EYA3
EZH2
FGF10	Unknown
FLI1
GJA1
GLI1	Unknown

Upstream regulators (CollecTRI, top): ATF1, EWSR1, FLI1, NR0B1, PAX1

miRNA regulators (miRDB)

23 targeting EWSR1, 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-340-5P	100.00	72.50	4437
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-1178-3P	98.57	67.09	890
HSA-MIR-6837-3P	98.42	66.71	1149
HSA-MIR-597-3P	96.46	68.03	1035
HSA-MIR-7108-5P	96.42	66.17	598

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Induction of the interleukin-2/15 receptor beta-chain by the EWS-WT1 translocation product. (PMID:11960373)
• Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses. (PMID:11992546)
• The AF2 domain of the orphan nuclear receptor TEC is essential for the transcriptional activity of the oncogenic fusion protein EWS (PMID:12049818)
• The transcription factor gene CIZ/NMP4 is recurrently involved in acute leukemia through fusion with either EWSR1 or TAF15. (PMID:12359745)
• EWS may function as a co-activator of CBP-dependent transcription factors (PMID:12459554)
• role in upregulation of Id2 in Ewing sarcoma (PMID:12527902)
• identification of its target genes as a chimeric protein with ATF-1 (PMID:12527906)
• present findings indicate that expression of EWS protein in the various subcellular compartments is affected by the methylation process, in particular by the availability of intracellular S-adenosyl-L-methionine (PMID:12915128)
• EWS interacts with FLI1 and their oncogenic fusion protein. (PMID:14534527)
• oncogenic rearrangement of EWS to produce EWS/Fli-1 may enhance the antiapoptotic effect of Brn-3a and inhibit its ability to promote neuronal differentiation. (PMID:15021903)
• First time 2 different EWS fusion transcripts found in same patient. It may be EWS translocations are not first step in Ewing’s sarcoma (PMID:15044653)
• These findings identify the repression of insulin-like growth factor binding protein 3 gene by EWS/FLI-1 as a key event in the development of Ewing’s sarcoma. (PMID:15282325)
• Simultaneous expression of the EWSR1-ATF1 and MITF-M transcripts in clear cell carcinoma has led to the proposal that the MITF-M promoter is transactivated by EWSR1-ATF1. (PMID:15884099)
• Oct-4-mediated transactivation is stimulated by EWS (PMID:15917470)
• EWS-Fli1 may play a role in the regulation of PDGF-induced tumor proliferation-signaling enzymes via PLD2 expression in Ewing sarcoma cells (PMID:15919668)
• There was evidence of EWS oncogene protein fusion in this sarcoma. (PMID:16327442)
• Regions in the N-terminal transcriptional activation domain guide the subnuclear partition of EWS protein and contain another but different nuclear localization/retention signal that allows nucleocytoplasmic shuttling of the N-terminal domain. (PMID:16965792)
• The gene that was most reproducibly up-regulated by EWS/FLI was NR0B1. (PMID:17114343)
• variation in overall gene expression patterns downstream of EWS-FLIl was observed, but also differential regulation of directly EWS-FLI1-bound genes (PMID:17163154)
• EWS/FLI1 has a role in regulating tumor angiogenesis in Ewing’s sarcoma via suppression of thrombospondins TSP1 and TSP2 (PMID:17638877)
• A single tumor carrying a t(12;22) translocation expressed a hitherto unknown EWSR1-DDIT3 fusion transcript (13-3) linking the complete RNA-binding domain of EWSR1 with a short piece of the 5’-UTR (PMID:17647282)
• report for the first time the presence of EWSR1-CREB1 in angiomatoid fibrous histiocytoma, which now appears to be the most frequent gene fusion in this tumor (PMID:17724745)
• In mesenchymal stem cells EWS/FLI1 changed morphology from a mesenchymal spindle shape to a small round-to-polygonal cell, downregulated mesenchyme-positive markers CD10 & CD13 and the upregulated Ewing’s family tumor markers CD54, CD99, CD117, & CD271. (PMID:18212050)
• None of the 12 uterine tumors with neuroectodermal differentiation had a detectable rearrangement in the EWSR1 gene. (PMID:18223324)
• role of EWS/LI1 as an inhibitor of cellular senescence implicating the retinoblastoma family of proteins as key mediators of this inhibition (PMID:18271016)
• EWSR1-PBX1 fusion gene resulting from a t(1;22)(q23;q12) translocation is associated with myoepithelioma.(\ (PMID:18383210)
• EWS-FLI1 directly stimulates cyclin D1 gene transcription. (PMID:18413612)
• EWS/FLI mediates transcriptional repression via NKX2.2 during oncogenic transformation in Ewing’s sarcoma (PMID:18414662)
• EWS contributes to start site recognition in TATA-less mammalian promoters. (PMID:18453593)
• Analyzed the status of SMARCB1 protein expression in sarcomas associated with chromosomal translocation involving EWS. (PMID:18580682)
• In this study, the vast majority of extraskeletal myxoid chondrosarcomas are associated with a rearrangement at the EWSR1 locus (22q12). (PMID:18587326)
• FUS, EWS and TAF15 proto-oncoproteins were targeted to stress granules induced by heat shock and oxidative stress (PMID:18620564)
• IGF1 is a common target gene of Ewing’s sarcoma fusion proteins EWS-FLI-1, EWS-ERG and FUS-ERG in mesenchymal progenitor cells (PMID:18648544)
• data obtained from this screen helped to identify IMR-90 cells, a human fetal fibroblast, that upon further manipulation can maintain stable EWS/FLI1 expression without the reported toxicity (PMID:18838963)
• results suggest that EWS-FLI1 inhibits normal limb development and accelerates the formation of poorly differentiated sarcomas (PMID:18974141)
• the mitotic kinases Aurora A and Aurora B are regulated by EWS-Fli1 fusion protein in Ewing sarcoma cells (PMID:19074838)
• temporally and spatially regulated functions of the EWS protein and, particularly, into its role in the regulation of the cell cycle and possibly cell differentiation. (PMID:19133275)
• In three Ewings sarcoma samples, copy number imbalances were detected in chromosomes 11 and 22 affecting the FLI1 and EWSR1 loci. (PMID:19144156)
• found that EWS-Oct-4-mediated transcriptional activation was inhibited by EWS-Oct-4 (V351P) protein in vivo. Thus, this mutation in the POU DNA-binding domain results in a dominant negative protein (PMID:19170206)
• indicated GLI1 as a direct transcriptional target of EWS-FLI1 (PMID:19189974)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ewsr1a	ENSDARG00000020258
danio_rerio	ewsr1b	ENSDARG00000020465
danio_rerio		ENSDARG00000117011
mus_musculus	Ewsr1	ENSMUSG00000009079
rattus_norvegicus	Ewsr1	ENSRNOG00000009437
drosophila_melanogaster	caz	FBGN0285954
caenorhabditis_elegans		WBGENE00016173

Paralogs (2): FUS (ENSG00000089280), TAF15 (ENSG00000270647)

Protein

Protein identifiers

RNA-binding protein EWS — Q01844 (reviewed: Q01844)

Alternative names: EWS oncogene, Ewing sarcoma breakpoint region 1 protein

All UniProt accessions (11): Q01844, A0A0D9SFL3, B0QYJ3, B0QYJ4, B0QYJ5, B0QYJ6, B0QYJ7, B0QYK0, C9JGE3, F8WC90, H7BY36

UniProt curated annotations — full annotation on UniProt →

Function. Binds to ssRNA containing the consensus sequence 5’-AGGUAA-3’. Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

Subunit / interactions. Binds POLR2C, SF1, calmodulin and RNA. Interacts with PTK2B/FAK2 and TDRD3. Binds calmodulin in the presence, but not in the absence, of calcium ion. Forms a complex with REC8, PRDM9, SYCP3 and SYCP1; complex formation is dependent of phosphorylated form of REC8 and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8.

Subcellular location. Nucleus. Cytoplasm. Cell membrane.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated; calmodulin-binding inhibits phosphorylation of Ser-266. Highly methylated on arginine residues. Methylation is mediated by PRMT1 and, at lower level by PRMT8.

Disease relevance. Ewing sarcoma (ES) [MIM:612219] A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. The protein represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving EWSR1 are found in patients with Ewing sarcoma. Translocation t(11;22)(q24;q12) with FLI1. Translocation t(7;22)(p22;q12) with ETV1. Translocation t(21;22)(q22;q21) with ERG. Translocation t(2;21;22)(q23;q22;q12) that forms a EWSR1-FEV fusion protein with potential oncogenic activity. A chromosomal aberration involving EWSR1 has been found in extraskeletal myxoid chondrosarcoma. Translocation t(9;22)(q22-31;q11-12) with NR4A3. A chromosomal aberration involving EWSR1 is associated with desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with WT1. A chromosomal aberration involving EWSR1 is associated with malignant melanoma of soft parts (MMSP). Translocation t(12;22)(q13;q12) with ATF1. Malignant melanoma of soft parts, also known as soft tissue clear cell sarcoma, is a rare tumor developing in tendons and aponeuroses. A chromosomal aberration involving EWSR1 is associated with small round cell sarcoma. Translocation t(11;22)(p36.1;q12) with PATZ1. Angiomatoid fibrous histiocytoma (AFH) [MIM:612160] A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving EWSR1 are found in patients with angiomatoid fibrous histiocytoma. Translocation t(12;22)(q13;q12) with ATF1 generates a chimeric EWSR1/ATF1 protein. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type. EFPS arise due to chromosomal translocations in which EWSR1 is fused to a variety of cellular transcription factors. EFPS are very potent transcriptional activators dependent on the EAD and a C-terminal DNA-binding domain contributed by the fusion partner. The spectrum of malignancies associated with EFPS are thought to arise via EFP-induced transcriptional deregulation, with the tumor phenotype specified by the EWSR1 fusion partner and cell type. Transcriptional repression of the transforming growth factor beta type II receptor (TGF beta RII) is an important target of the EWS-FLI1, EWS-ERG, or EWS-ETV1 oncogene.

Domain organisation. EWS activation domain (EAD) functions as a potent activation domain in EFPS. EWSR1 binds POLR2C but not POLR2E or POLR2G, whereas the isolated EAD binds POLR2E and POLR2G but not POLR2C. Cis-linked RNA-binding domain (RBD) can strongly and specifically repress trans-activation by the EAD.

Similarity. Belongs to the RRM TET family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q01844-1	EWS	yes
Q01844-2	EWS-B
Q01844-3	3
Q01844-4	4
Q01844-5	5
Q01844-6	6

RefSeq proteins (5): NP_001156757, NP_001156758, NP_001156759, NP_005234, NP_053733 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR001876	Znf_RanBP2	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034869	EWS_RRM	Domain
IPR034870	TET_fam	Family
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036443	Znf_RanBP2_sf	Homologous_superfamily

Pfam: PF00076, PF00641

UniProt features (117 total): modified residue 38, repeat 31, compositionally biased region 11, mutagenesis site 9, splice variant 6, strand 5, region of interest 5, helix 2, turn 2, domain 2, site 2, chain 1, sequence conflict 1, zinc finger region 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CPE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01844-F1	50.88	0.03

Functional residue map

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

Catalytic / active sites (2): 265 (breakpoint for translocation to form chimeric ewsr1/atf1 protein); 348–349 (breakpoint for insertion to form ewsr1-fev fusion protein)

Post-translational modifications (38): 266, 300, 302, 304, 309, 314, 317, 321, 439, 455, 464, 471, 471, 486, 490, 494, 500, 503, 506, 506 …

Mutagenesis-validated functional residues (9):

Position	Phenotype
651	no effect on nuclear targeting.
652	cytoplasmic localization.
652	no effect on nuclear targeting.
653	no effect on nuclear targeting.
654	no effect on nuclear targeting.
655	cytoplasmic localization.
656	cytoplasmic localization.
648	cytoplasmic localization.
648	no effect on nuclear targeting.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 230 (showing top): RNGTGGGC_UNKNOWN, AP1_01, TGCGCANK_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MYLLYKANGAS_AMPLIFICATION_HOT_SPOT_22, PUJANA_CHEK2_PCC_NETWORK, MUELLER_PLURINET, MYCMAX_01, BLALOCK_ALZHEIMERS_DISEASE_UP, TGCTGAY_UNKNOWN, MODULE_123, MODULE_98, FISCHER_DREAM_TARGETS, ZHANG_BREAST_CANCER_PROGENITORS_UP

GO Biological Process (1): regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): transcription coregulator activity (GO:0003712), RNA binding (GO:0003723), calmodulin binding (GO:0005516), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), plasma membrane (GO:0005886), Cajal body (GO:0015030), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein binding	2
binding	2
nuclear lumen	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription regulator activity	1
nucleic acid binding	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

3788 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EWSR1	DHX9	Q08211	991
EWSR1	CD99	P14209	943
EWSR1	SNRPC	P09234	925
EWSR1	YBX1	P16990	920
EWSR1	NR4A3	Q92570	900
EWSR1	FLII	Q13045	896
EWSR1	WT1	P19544	888
EWSR1	ETV1	P50549	883
EWSR1	PATZ1	Q9HBE1	880
EWSR1	FLI1	Q01543	879
EWSR1	ATF1	P18846	874
EWSR1	DROSHA	Q9NRR4	853
EWSR1	MAZ	P56270	845
EWSR1	CUX1	P39880	832
EWSR1	CD99L2	Q8TCZ2	825

IntAct

378 interactions, top by confidence:

A	B	Type	Score
EWSR1	ATPAF2	psi-mi:“MI:0915”(physical association)	0.780
ATPAF2	EWSR1	psi-mi:“MI:0915”(physical association)	0.780
MAPK1IP1L	EWSR1	psi-mi:“MI:0915”(physical association)	0.740
EWSR1	MAPK1IP1L	psi-mi:“MI:0915”(physical association)	0.740
EWSR1	PLSCR1	psi-mi:“MI:0915”(physical association)	0.670
PLSCR1	EWSR1	psi-mi:“MI:0915”(physical association)	0.670
EWSR1	SMAD4	psi-mi:“MI:0915”(physical association)	0.670
ATXN3	EWSR1	psi-mi:“MI:0915”(physical association)	0.670
EP300	EWSR1	psi-mi:“MI:0915”(physical association)	0.570
EWSR1	RASSF1	psi-mi:“MI:0915”(physical association)	0.570
RASSF1	EWSR1	psi-mi:“MI:0914”(association)	0.570
EWSR1	EP300	psi-mi:“MI:0915”(physical association)	0.570
EWSR1	SEC24D	psi-mi:“MI:0915”(physical association)	0.560
EWSR1	SEC24A	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	EWSR1	psi-mi:“MI:0915”(physical association)	0.560
TRAF1	EWSR1	psi-mi:“MI:0915”(physical association)	0.560
EWSR1	TFG	psi-mi:“MI:0915”(physical association)	0.560
SSBP3	EWSR1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1016): PLSCR1 (Two-hybrid), TRAF1 (Two-hybrid), TRAF2 (Two-hybrid), SEC24D (Two-hybrid), TFG (Two-hybrid), SEC24A (Two-hybrid), SSBP3 (Two-hybrid), PRR13 (Two-hybrid), ATPAF2 (Two-hybrid), MAPK1IP1L (Two-hybrid), PEF1 (Two-hybrid), EWSR1 (Reconstituted Complex), EWSR1 (Affinity Capture-MS), EWSR1 (Affinity Capture-MS), EWSR1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D1C8Z4, A5A6H4, A7VJC2, O88569, P04256, P07909, P09651, P09867, P17130, P19198, P21522, P22626, P35637, P48810, P49312, P51968, P51989, P51990, P51991, P51992, P56959, Q01844, Q08473, Q13151, Q22037, Q28009, Q28521, Q2HJ60, Q32P51, Q43472, Q5PQ53, Q5RBU8, Q61545, Q640A2, Q641Z8, Q6DC93, Q6URK4, Q7ZX83, Q8BG05, Q8EA81

Diamond homologs: O43120, P35637, P56959, Q01844, Q28009, Q61545, Q92804, Q94KD0, B5DGI7, O75526, P07909, P08199, P13383, P15771, P19338, P33240, P40561, P41891, P49310, Q03251, Q03878, Q05966, Q14498, Q27294, Q27W01, Q28BZ1, Q28IQ9, Q29RT0, Q3ZCE8, Q44554, Q44556, Q4R4J7, Q4R813, Q57014, Q5D018, Q5RC80, Q5RDA3, Q5RF26, Q6IRQ4, Q6PH90

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
MAPK1	unknown	EWSR1	phosphorylation
MAPK11	unknown	EWSR1	phosphorylation
MAPK14	unknown	EWSR1	phosphorylation
MAPK3	unknown	EWSR1	phosphorylation
Gbeta	unknown	EWSR1	phosphorylation
ERK1/2	unknown	EWSR1	phosphorylation
PRKCA	“down-regulates activity”	EWSR1	phosphorylation
PRKCB	“down-regulates activity”	EWSR1	phosphorylation
SF1	down-regulates	EWSR1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 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
DNA Double Strand Break Response	5	21.1×	9e-04
Homology Directed Repair	5	13.7×	2e-03
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	5	13.7×	2e-03
DNA Double-Strand Break Repair	6	13.2×	1e-03
GSK3B-mediated proteasomal degradation of PD-L1(CD274)	6	12.6×	1e-03
DNA Damage Recognition in GG-NER	5	12.6×	2e-03
GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	5	11.0×	3e-03
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	8	10.4×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	7	14.9×	1e-04
intrinsic apoptotic signaling pathway	6	14.4×	7e-04
autophagosome maturation	6	14.1×	7e-04
positive regulation of type I interferon production	5	14.1×	3e-03
cellular response to UV	5	9.9×	8e-03
G1/S transition of mitotic cell cycle	7	9.4×	1e-03
autophagosome assembly	6	9.1×	4e-03
positive regulation of protein ubiquitination	6	8.6×	5e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

Fusions between EWSR1 and multiple 3` partners are regularly identified in soft tissue sarcomas and can aid in differential diagnosis. The fusion product usually contains the N-terminal transcription-activating domain of EWSR1 and the C-terminal DNA-binding domain of the fusion partner, generating a novel transcription factor.

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — ES, GBM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	12
Benign	20

Top pathogenic / likely-pathogenic (0)

SpliceAI

2607 predictions. Top by Δscore:

Variant	Effect	Δscore
22:29268348:GG:G	donor_gain	1.0000
22:29268349:GG:G	donor_gain	1.0000
22:29268349:GGT:G	donor_loss	1.0000
22:29272250:GGG:G	donor_gain	1.0000
22:29272251:GG:G	donor_gain	1.0000
22:29272251:GGG:G	donor_gain	1.0000
22:29272252:GG:G	donor_gain	1.0000
22:29272252:GGT:G	donor_loss	1.0000
22:29272253:G:GG	donor_gain	1.0000
22:29272254:T:G	donor_loss	1.0000
22:29272375:TGCA:T	acceptor_loss	1.0000
22:29272376:GCAGC:G	acceptor_loss	1.0000
22:29272378:A:AG	acceptor_gain	1.0000
22:29272379:G:GA	acceptor_gain	1.0000
22:29272379:GCT:G	acceptor_gain	1.0000
22:29273733:T:A	acceptor_gain	1.0000
22:29273740:GGC:G	acceptor_gain	1.0000
22:29273740:GGCAT:G	acceptor_gain	1.0000
22:29273865:G:A	donor_loss	1.0000
22:29273865:G:GG	donor_gain	1.0000
22:29273866:TAA:T	donor_loss	1.0000
22:29278026:CTAG:C	acceptor_loss	1.0000
22:29278027:TAG:T	acceptor_loss	1.0000
22:29278029:GGTT:G	acceptor_gain	1.0000
22:29278217:G:C	donor_loss	1.0000
22:29278218:T:A	donor_loss	1.0000
22:29286921:A:AG	acceptor_gain	1.0000
22:29286921:A:AT	acceptor_loss	1.0000
22:29286922:G:GT	acceptor_gain	1.0000
22:29286922:GC:G	acceptor_gain	1.0000

AlphaMissense

4227 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:29292545:T:C	L368S	1.000
22:29296311:G:C	A413P	1.000
22:29296312:C:A	A413D	1.000
22:29296318:T:A	V415E	1.000
22:29296351:C:A	A426D	1.000
22:29298876:G:C	D521H	1.000
22:29298876:G:T	D521Y	1.000
22:29298877:A:C	D521A	1.000
22:29298877:A:G	D521G	1.000
22:29298877:A:T	D521V	1.000
22:29298878:C:A	D521E	1.000
22:29298878:C:G	D521E	1.000
22:29298879:T:A	W522R	1.000
22:29298879:T:C	W522R	1.000
22:29298880:G:C	W522S	1.000
22:29298880:G:T	W522L	1.000
22:29298881:G:C	W522C	1.000
22:29298881:G:T	W522C	1.000
22:29298885:T:A	C524S	1.000
22:29298885:T:C	C524R	1.000
22:29298886:G:A	C524Y	1.000
22:29298886:G:C	C524S	1.000
22:29298886:G:T	C524F	1.000
22:29298887:T:G	C524W	1.000
22:29299238:T:A	C529S	1.000
22:29299238:T:C	C529R	1.000
22:29299239:G:A	C529Y	1.000
22:29299239:G:C	C529S	1.000
22:29299239:G:T	C529F	1.000
22:29299240:T:G	C529W	1.000

dbSNP variants (sampled 300 via entrez): RS1000110207 (22:29280325 C>G,T), RS1000187053 (22:29266814 T>G), RS1000197310 (22:29295986 C>T), RS1000218198 (22:29267045 A>G), RS1000233730 (22:29268585 C>G,T), RS1000394967 (22:29297200 G>A), RS1000452916 (22:29274582 T>C), RS1000559842 (22:29300669 C>G,T), RS1000610237 (22:29284451 A>G), RS1000619244 (22:29290070 C>T), RS1000753651 (22:29289799 A>G), RS1000820868 (22:29289819 CTT>C,CT), RS1000913017 (22:29284759 C>A), RS1000923106 (22:29274735 A>G,T), RS1001013799 (22:29300869 C>G)

Disease associations

OMIM: gene MIM:133450 | disease phenotypes: MIM:612219

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Disputed	UD

Mondo (2): amyotrophic lateral sclerosis (MONDO:0004976), Ewing sarcoma (MONDO:0012817)

Orphanet (3): Amyotrophic lateral sclerosis (Orphanet:803), OBSOLETE: Neuroepithelioma (Orphanet:2677), Skeletal Ewing sarcoma (Orphanet:319)

HPO phenotypes

20 total (21 of 20 shown, HPO-id order):

HPO	Term
HP:0001442	Typified by somatic mosaicism
HP:0001541	Ascites
HP:0001824	Weight loss
HP:0001903	Anemia
HP:0002017	Nausea and vomiting
HP:0002027	Abdominal pain
HP:0002240	Hepatomegaly
HP:0002585	Abnormal peritoneum morphology
HP:0002595	Ileus
HP:0002716	Lymphadenopathy
HP:0002894	Neoplasm of the pancreas
HP:0003270	Abdominal distention
HP:0004326	Cachexia
HP:0010788	Testicular neoplasm
HP:0012254	Ewing sarcoma
HP:0100006	Neoplasm of the central nervous system
HP:0100242	Sarcoma
HP:0100526	Neoplasm of the lung
HP:0100615	Ovarian neoplasm
HP:0100721	Mediastinal lymphadenopathy
HP:0007354	Amyotrophic lateral sclerosis

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001937_28	Breast cancer	3.000000e-09
GCST002553_2	Pancreatic cancer	1.000000e-08
GCST004603_150	Platelet count	3.000000e-10
GCST90002401_271	Platelet distribution width	1.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007984	platelet component distribution width

MeSH disease descriptors (2)

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
D012512	Sarcoma, Ewing	C04.557.450.565.575.650.800; C04.557.450.795.620.800

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3351202 (SINGLE PROTEIN), CHEMBL3885568 (CHIMERIC PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

7 potent at pChembl≥5 of 11 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.82	IC50	150	nM	CHEMBL3360409
6.75	IC50	180	nM	CHEMBL3360408
6.48	IC50	330	nM	CHEMBL3360406
6.46	IC50	350	nM	CHEMBL2011500
6.11	IC50	770	nM	CHEMBL3360384
5.32	Kd	4800	nM	CHEMBL3360410
5.24	IC50	5810	nM	MOLIBRESIB

PubChem BioAssay actives

7 with measured affinity, of 35 total; 7 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
4,7-dichloro-3-[2-[4-(dimethylamino)phenyl]-2-oxoethyl]-3-hydroxy-1H-indol-2-one	1171938: Inhibition of transcriptional activity of full-length EWS-FLI1 (unknown origin) expressed in COS7 cells by NR0B1-luciferase reporter gene assay	ic50	0.1500	uM
4,7-dichloro-3-hydroxy-3-[2-[4-(methylamino)phenyl]-2-oxoethyl]-1H-indol-2-one	1171938: Inhibition of transcriptional activity of full-length EWS-FLI1 (unknown origin) expressed in COS7 cells by NR0B1-luciferase reporter gene assay	ic50	0.1800	uM
4,7-dichloro-3-hydroxy-3-[2-(4-methylsulfanylphenyl)-2-oxoethyl]-1H-indol-2-one	1171938: Inhibition of transcriptional activity of full-length EWS-FLI1 (unknown origin) expressed in COS7 cells by NR0B1-luciferase reporter gene assay	ic50	0.3300	uM
4,7-dichloro-3-hydroxy-3-[2-(4-methoxyphenyl)-2-oxoethyl]-1H-indol-2-one	1171938: Inhibition of transcriptional activity of full-length EWS-FLI1 (unknown origin) expressed in COS7 cells by NR0B1-luciferase reporter gene assay	ic50	0.3500	uM
3-hydroxy-4,7-dimethoxy-3-[2-(4-methoxyphenyl)-2-oxoethyl]-1H-indol-2-one	1171938: Inhibition of transcriptional activity of full-length EWS-FLI1 (unknown origin) expressed in COS7 cells by NR0B1-luciferase reporter gene assay	ic50	0.7700	uM
N-[4-[2-(4,7-dichloro-3-hydroxy-2-oxo-1H-indol-3-yl)acetyl]phenyl]-N-methyl-6-[5-[(4R)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanamide	1171939: Binding affinity to purified recombinant EWS-FLI1 (unknown origin) after 1 hr by colorimetric phosphatase assay	kd	4.8000	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178885: Inhibition of EWSR1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	5.8100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, affects expression	3
Valproic Acid	affects expression, decreases expression	3
bisphenol A	decreases expression, increases expression	2
(+)-JQ1 compound	increases response to substance, affects binding, decreases reaction, decreases expression	2
Air Pollutants	increases expression, affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
quinomethionate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
geraniol	decreases expression	1
glycidyl methacrylate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
phosphatidylbutanol	affects reaction, increases abundance, increases reaction	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
romidepsin	decreases activity, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Sevoflurane	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4155322	Binding	Binding affinity to RNA-binding protein EWS isoform 6 in human A549 cells at 0.15 mM after 4 hrs by HPLC-MS based pull down assay relative to control	Synthesis, cytotoxic evaluation and target identification of thieno[2,3-d]pyrimidine derivatives with a dithiocarbamate side chain at C2 position. — Eur J Med Chem

Cellosaurus cell lines

152 cell lines: 151 cancer cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_0080	A-673	Cancer cell line	Female
CVCL_0530	SK-N-MC	Cancer cell line	Female
CVCL_0627	SK-ES-1	Cancer cell line	Male
CVCL_0631	SK-NEP-1	Cancer cell line	Female
CVCL_0J30	CCS292	Cancer cell line	Sex unspecified
CVCL_0J31	DTC1	Cancer cell line	Sex unspecified
CVCL_0J32	Hewga-CCS	Cancer cell line	Female
CVCL_0J33	MP-CCS-SY	Cancer cell line	Female
CVCL_0J34	MST-1	Cancer cell line	Female
CVCL_0J35	MST-2	Cancer cell line	Male

Clinical trials (associated diseases)

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

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