FUS

Summary

FUS (FUS RNA binding protein, HGNC:4010) is a protein-coding gene on chromosome 16p11.2, encoding RNA-binding protein FUS (P35637). DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response.

This gene encodes a multifunctional protein component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex. The hnRNP complex is involved in pre-mRNA splicing and the export of fully processed mRNA to the cytoplasm. This protein belongs to the FET family of RNA-binding proteins which have been implicated in cellular processes that include regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. Alternative splicing results in multiple transcript variants. Defects in this gene result in amyotrophic lateral sclerosis type 6.

Source: NCBI Gene 2521 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis type 6 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 688 total — 32 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 118
• Druggable target: yes
• Cancer driver (intOGen): ambiguous (mixed evidence) across 1 cancer types
• MANE Select transcript: NM_004960

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4010
Approved symbol	FUS
Name	FUS RNA binding protein
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	TLS, FUS1, hnRNP-P2, HNRNPP2
Ensembl gene	ENSG00000089280
Ensembl biotype	protein_coding
OMIM	137070
Entrez	2521

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 36 protein_coding, 8 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000254108, ENST00000380244, ENST00000474990, ENST00000483853, ENST00000487045, ENST00000487509, ENST00000487974, ENST00000564766, ENST00000566605, ENST00000568685, ENST00000568901, ENST00000569760, ENST00000570090, ENST00000715541, ENST00000715542, ENST00000875021, ENST00000875022, ENST00000875023, ENST00000875024, ENST00000875025, ENST00000875026, ENST00000875027, ENST00000875028, ENST00000875029, ENST00000875030, ENST00000875031, ENST00000875032, ENST00000875033, ENST00000925795, ENST00000925796, ENST00000925797, ENST00000925798, ENST00000925799, ENST00000925800, ENST00000925801, ENST00000925802, ENST00000925803, ENST00000925805, ENST00000925806, ENST00000925807, ENST00000925808, ENST00000948616, ENST00000948617, ENST00000948618, ENST00000948619, ENST00000948620, ENST00000948621

RefSeq mRNA: 3 — MANE Select: NM_004960 NM_001170634, NM_001170937, NM_004960

CCDS: CCDS10707, CCDS58454

Canonical transcript exons

ENST00000254108 — 15 exons

Exon	Start	End
ENSE00001791812	31184939	31185179
ENSE00003475065	31182398	31182422
ENSE00003494295	31190742	31190842
ENSE00003524436	31189123	31189226
ENSE00003534484	31189665	31189794
ENSE00003537617	31184209	31184396
ENSE00003599547	31183858	31184002
ENSE00003604625	31190275	31190398
ENSE00003630677	31182513	31182664
ENSE00003637572	31190963	31191110
ENSE00003653971	31190040	31190141
ENSE00003903481	31180139	31180227
ENSE00004027046	31188325	31188357
ENSE00004027047	31191399	31191605
ENSE00004027052	31186802	31186836

Expression profiles

Bgee: expression breadth ubiquitous, 304 present calls, max score 99.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 264.7030 / max 2181.2839, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153775	261.6294	1827
153785	1.9866	1044
153779	1.0870	640

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	99.63	gold quality
ventricular zone	UBERON:0003053	99.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.61	gold quality
cerebellar hemisphere	UBERON:0002245	99.60	gold quality
left testis	UBERON:0004533	99.60	gold quality
ganglionic eminence	UBERON:0004023	99.57	gold quality
right uterine tube	UBERON:0001302	99.49	gold quality
embryo	UBERON:0000922	99.47	gold quality
right ovary	UBERON:0002118	99.45	gold quality
left ovary	UBERON:0002119	99.45	gold quality
cerebellar cortex	UBERON:0002129	99.45	gold quality
right lobe of thyroid gland	UBERON:0001119	99.42	gold quality
cortical plate	UBERON:0005343	99.41	gold quality
adenohypophysis	UBERON:0002196	99.36	gold quality
body of uterus	UBERON:0009853	99.36	gold quality
metanephros cortex	UBERON:0010533	99.34	gold quality
left lobe of thyroid gland	UBERON:0001120	99.33	gold quality
left uterine tube	UBERON:0001303	99.32	gold quality
endocervix	UBERON:0000458	99.31	gold quality
granulocyte	CL:0000094	99.30	gold quality
nerve	UBERON:0001021	99.30	gold quality
tibial nerve	UBERON:0001323	99.30	gold quality
tendon of biceps brachii	UBERON:0008188	99.30	gold quality
cerebellum	UBERON:0002037	99.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.23	gold quality
mucosa of stomach	UBERON:0001199	99.20	gold quality
thyroid gland	UBERON:0002046	99.17	gold quality
ectocervix	UBERON:0012249	99.17	gold quality
skin of abdomen	UBERON:0001416	99.14	gold quality
endometrium epithelium	UBERON:0004811	99.11	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-76312	yes	467.03
E-CURD-122	yes	35.57
E-GEOD-134144	yes	29.62
E-MTAB-10042	yes	4.39
E-MTAB-6819	no	274.48
E-HCAD-4	no	37.84
E-GEOD-93593	no	6.61
E-GEOD-125970	no	3.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
AR	Unknown
DDIT3	Activation
KLK3	Unknown
MDM2	Repression

Upstream regulators (CollecTRI, top): AR, DDIT3, GTF3A, NFKB, SP1, TBP, TP53

miRNA regulators (miRDB)

127 targeting FUS, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107

Literature-anchored findings (GeneRIF, showing 40)

• Temperature-dependent localization of TLS-CHOP to splicing factor compartments and association with Cajal bodies. A region within the N-terminal sequence required for colocalization with the splicing factor SC-35 is identified. (PMID:12169268)
• Proto-oncoprotein TLS/FUS is associated to the nuclear matrix and complexed with splicing factors PTB, SRm160, and SR proteins and plays a role in spliceosome assembly (PMID:12581738)
• FUS was fused with BBF2H7 in a low grade myxoid liposarcoma. (PMID:12915480)
• data suggest that different FUS/CHOP variants cause transformation of mesenchymal cells via the same pathways with comparable efficacy (PMID:15286712)
• the zinc finger domain plays a more predominant role in RNA recognition than the RRM domain in TLS (PMID:15299008)
• Effect of FUS-DDIT3 fusion on IL6 expression is C/EBP beta dependent in myxoid lipoxarcoma. (PMID:15688424)
• The oncogenic TLS-ERG fusion protein activates two different sets of genes sharing little similarity when transforms hematopoietic cells and fibroblasts. (PMID:15988032)
• Patients with immunophenotype of Pre-B-acute lymphoblastic leukemia were found to carry: TLS/ERG. (PMID:16215946)
• Interaction of beta-catenin with FUS/TLS and other RNA-binding proteins involved in the regulation of pre-mRNA splicing in colorectal cancer (PMID:16230076)
• Development of lipoblasts and the typical MLS/RCLS capillary network could be an effect of the DDIT3 transcription factor partner of the fusion oncogene. (PMID:16651630)
• FUS-DDIT3 is a chimeric oncogene generated by the most common chromosomal translocation t(12;16)(q13;p11) associated to liposarcomas. (PMID:17468515)
• Presence of FUS/CREB3L2 and FUS/CREB3L1 in low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma suggests these neoplasms may be related. (PMID:17721195)
• the sequestration of TLS to polyQ aggregates may play a role in diverse pathological changes in the brains of patients with polyQ diseases. (PMID:18167354)
• TLS serves as a key transcriptional regulatory sensor of DNA damage signals that, on the basis of its allosteric modulation by RNA, specifically binds to and inhibits CBP and p300 HAT activities on a repressed gene target, cyclin D1 (PMID:18509338)
• 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)
• The FUS-DDIT3 protein induces increased expression of the CAAT/enhancer-binding protein (C/EBP) and nuclear factor-kappaB (NF-kappaB)-controlled gene IL8, and the N-terminal FUS part is required for this activation. (PMID:18850010)
• All cases of pleomorphic liposarcoma (PLS) showed a varied distribution of extra signals with polyploidy and amplification in each histological area. No CHOP fusion transcript was found in any case of PLS by nested RT-PCR. (PMID:19037998)
• study reports 13 mutations in FUS/TLS gene on chromosome 16 that were specific for familial amyotrophic lateral sclerosis; mutant forms of FUS/TLS accumulated in the cytoplasm of neurons (PMID:19251627)
• identification of missense mutations in FUS in familial amyotrophic lateral sclerosis type 6; expression studies revealed aberrant localization of mutant FUS protein (PMID:19251628)
• TDP-43 and FUS/TLS have striking structural and functional similarities, implicating alterations in RNA processing as a key event in amyotrophic lateral sclerosis pathogenesis. (PMID:19303844)
• study presents genetic analysis data on FUS/TLS in a cohort of 52 index cases from 7 Italian regions with non-SOD1 & non-TARDBP familial amyotrophic lateral sclerosis to further define spectrum & frequency of FUS/TLS mutations (PMID:19450904)
• The results of this study suggested that FUS may play an important role in the pathogenesis of neuronal intermediate filament inclusion disease. (PMID:19669651)
• Results suggest that FUS is the pathological protein in a significant subgroup of sporadic frontotemporal dementia and reinforce the concept that FTD and amyotrophic lateral sclerosis are closely related conditions. (PMID:19674978)
• TLS regulates both RNAPs II and III and supports the possibility that cross-regulation between RNA polymerases is important in maintaining normal cell growth. (PMID:19841068)
• FUS missense mutations are present in 0.7% of Italian SALS cases. (PMID:19861302)
• Mutations in FUS are a significant cause of familial amyotrophic lateral sclerosis in Belgium. (PMID:19922450)
• FUS gene mutations are involved in ALS. (PMID:19965854)
• The FUS mutation in this Japanese family caused familial amyotrophic lateral sclerosis with pathological features of multiple system degeneration and neuronal basophilic inclusions (PMID:19967541)
• FUS-DDIT3 and the normal DDIT3 bind CDK2. (PMID:20017906)
• This study indicated that mutations in FUS/TLS are not a major cause of sporadic ALS in the German population. (PMID:20018407)
• FUS/TLS protein genetic variability in sporadic frontetemporal lobar degeneration. (PMID:20061612)
• In a first analysis of FUS in patients with frontotemporal lobar degeneration (FTLD), we identified a novel FUS missense mutation, M254V, in 1 patient with pure FTLD (PMID:20124201)
• The data of this study suggested that understanding how mutations disrupt the RNA binding domain encoded by exon 15 may be key to unraveling the role of FUS in motor neuron degeneration. (PMID:20138404)
• This study discovered FUS mutations in Dutch patients with familial amyotrophic lateral sclerosis and the occurrence of benign variation in the gene. (PMID:20142531)
• Data identified 4 mutations (S513P, K510E, R514S, H517P) in exon 14 and 15 of FUS in screened 40 FALS families. (PMID:20224596)
• Findings extend the mutation spectrum in FUS leading to sporadic amyotrophic lateral sclerosis and describe the first de novo mutation in FUS. (PMID:20232451)
• Caudate atrophy seen in magnetic resonance imaging is a feature that can distinguish frontotemporal lobar degeneration-fused in sarcoma protein (FTLD-FUS) from FTLD-TAR DNA-binding protein-43 (TDP) protein, and FTLD-TAU protein. (PMID:20236174)
• FUS/TLS mutations represented approximately 5% of FALS cases screened. A FUS/TLS mutation was also identified in a single SALS case. (PMID:20385912)
• We present 2 cases of SEF with cytogenetic analysis for FUS rearrangement (PMID:20499220)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fus	ENSDARG00000037968
mus_musculus	Fus	ENSMUSG00000030795
rattus_norvegicus	Fus	ENSRNOG00000023360
rattus_norvegicus		ENSRNOG00000077981
drosophila_melanogaster	caz	FBGN0285954
caenorhabditis_elegans		WBGENE00016173

Paralogs (2): EWSR1 (ENSG00000182944), TAF15 (ENSG00000270647)

Protein

Protein identifiers

RNA-binding protein FUS — P35637 (reviewed: P35637)

Alternative names: 75 kDa DNA-pairing protein, Oncogene FUS, Oncogene TLS, POMp75, Translocated in liposarcoma protein

All UniProt accessions (6): P35637, A0AAQ5BIG2, A0AAQ5BIK3, H3BNZ4, H3BPE7, Q6IBQ5

UniProt curated annotations — full annotation on UniProt →

Function. DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response. Binds to ssRNA containing the consensus sequence 5’-AGGUAA-3’. Binds to nascent pre-mRNAs and acts as a molecular mediator between RNA polymerase II and U1 small nuclear ribonucleoprotein thereby coupling transcription and splicing. Also binds its own pre-mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay. Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair. In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis.

Subunit / interactions. Self-oligomerizes (via N-terminal region). Oligomerization is essential for chromatin binding. Component of nuclear riboprotein complexes. Interacts with ILF3, TDRD3 and SF1. Interacts through its C-terminus with SFRS13A. Interacts with OTUB1 and SARNP. Interacts with LRSAM1. Interacts with SAFB1 in a DNA-dependent manner; this interaction tethers FUS to chromatin. Interacts with MATR3. Interacts with SNRNP70 and POLR2A; these interactions couple RNA transcription and splicing. Interacts (through its RNA-binding domain) with RALY (through its RNA-binding domain); both are components of the same RNPs.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Arg-216 and Arg-218 are dimethylated, probably to asymmetric dimethylarginine. Phosphorylated in its N-terminal serine residues upon induced DNA damage. ATM and DNA-PK are able to phosphorylate FUS N-terminal region.

Disease relevance. A chromosomal aberration involving FUS is found in a patient with malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with DDIT3. A chromosomal aberration involving FUS is a cause of acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with ERG. 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. A chromosomal aberration involving FUS is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(12;16)(q13;p11.2) with ATF1 generates a chimeric FUS/ATF1 protein. Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia (ALS6) [MIM:608030] A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. The disease is caused by variants affecting the gene represented in this entry. Tremor, hereditary essential 4 (ETM4) [MIM:614782] A common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles may also be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the RRM TET family.

Isoforms (2)

UniProt ID	Names	Canonical?
P35637-1	Long	yes
P35637-2	Short

RefSeq proteins (3): NP_001164105, NP_001164408, NP_004951* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00076, PF00641

UniProt features (109 total): modified residue 33, sequence variant 23, strand 17, compositionally biased region 12, turn 7, helix 6, region of interest 3, site 2, chain 1, domain 1, zinc finger region 1, cross-link 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
6KJ3	ELECTRON CRYSTALLOGRAPHY	0.6
6KJ1	ELECTRON CRYSTALLOGRAPHY	0.65
6KJ4	ELECTRON CRYSTALLOGRAPHY	0.65
6KJ2	ELECTRON CRYSTALLOGRAPHY	0.67
5XSG	ELECTRON CRYSTALLOGRAPHY	0.73
6BWZ	X-RAY DIFFRACTION	1.1
6BXV	X-RAY DIFFRACTION	1.1
6BZP	ELECTRON CRYSTALLOGRAPHY	1.1
5XRR	X-RAY DIFFRACTION	1.5
4FDD	X-RAY DIFFRACTION	2.3
6XFM	ELECTRON MICROSCOPY	2.62
7CYL	X-RAY DIFFRACTION	2.7
5YVI	X-RAY DIFFRACTION	2.9
7VQQ	ELECTRON MICROSCOPY	2.9
4FQ3	X-RAY DIFFRACTION	3
5YVH	X-RAY DIFFRACTION	3.15
5YVG	X-RAY DIFFRACTION	4.05
2LA6	SOLUTION NMR
2LCW	SOLUTION NMR
5W3N	SOLID-STATE NMR
6G99	SOLUTION NMR
6GBM	SOLUTION NMR
6SNJ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35637-F1	54.96	0.09

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): 175 (breakpoint for translocation to form chimeric fus/atf1 protein); 266–267 (breakpoint for translocation to form fus/tls-chop oncogene)

Post-translational modifications (34): 26, 30, 42, 216, 216, 218, 218, 221, 242, 244, 248, 251, 259, 277, 286, 340, 377, 383, 386, 388 …

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 531 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GGGACCA_MIR133A_MIR133B, MORF_DNMT1, ELVIDGE_HYPOXIA_DN, GOBP_REGULATION_OF_DNA_RECOMBINATION, MORF_ESPL1, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_UBE2I, MORF_HDAC1, MORF_UBE2N, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MORF_CDK2, HSIAO_HOUSEKEEPING_GENES

GO Biological Process (11): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), RNA splicing (GO:0008380), regulation of RNA splicing (GO:0043484), mRNA stabilization (GO:0048255), protein homooligomerization (GO:0051260), membraneless organelle assembly (GO:0140694), positive regulation of double-strand break repair via homologous recombination (GO:1905168), amyloid fibril formation (GO:1990000), gene expression (GO:0010467), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (12): DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), molecular condensate scaffold activity (GO:0140693), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), presynaptic cytosol (GO:0099523), postsynaptic cytosol (GO:0099524), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
mRNA Splicing	1
Metabolism of RNA	1
mRNA 3’-end processing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
DNA-templated transcription	2
regulation of gene expression	2
regulation of DNA-templated transcription	2
nucleic acid binding	2
cellular anatomical structure	2
synapse	2
cytosol	2
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
RNA processing	1
RNA splicing	1
regulation of primary metabolic process	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
protein complex oligomerization	1
organelle assembly	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of DNA recombination	1
positive regulation of double-strand break repair	1
protein metabolic process	1
supramolecular fiber organization	1
macromolecule biosynthetic process	1
positive regulation of RNA biosynthetic process	1
transcription regulator activity	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
mRNA binding	1
transition metal ion binding	1
protein binding	1
protein-macromolecule adaptor activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
presynapse	1
postsynapse	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3788 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FUS	TARDBP	Q13148	999
FUS	SOD1	P00441	992
FUS	DROSHA	Q9NRR4	988
FUS	A0A087WTZ4	A0A087WTZ4	986
FUS	SRSF10	O75494	951
FUS	HNRNPA2B1	P22626	943
FUS	OPTN	Q96CV9	939
FUS	UBQLN2	Q9UHD9	934
FUS	SFPQ	P23246	933
FUS	ILF3	Q12906	927
FUS	C9orf72	Q96LT7	919
FUS	ATXN2	Q99700	918
FUS	SRSF2	Q01130	899
FUS	NONO	P30807	893
FUS	MAPT	P10636	889

IntAct

373 interactions, top by confidence:

A	B	Type	Score
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
FUS	FUS	psi-mi:“MI:0915”(physical association)	0.830
FUS	FUS	psi-mi:“MI:0407”(direct interaction)	0.830
FUS	TARDBP	psi-mi:“MI:0914”(association)	0.750
FUS	TARDBP	psi-mi:“MI:0403”(colocalization)	0.750
FUS	TARDBP	psi-mi:“MI:0915”(physical association)	0.750
FUS	SAFB	psi-mi:“MI:0915”(physical association)	0.730
FUS	SAFB	psi-mi:“MI:0403”(colocalization)	0.730
FUS	MATR3	psi-mi:“MI:0914”(association)	0.730
FUS	MATR3	psi-mi:“MI:0403”(colocalization)	0.730
MAGEB2	FUS	psi-mi:“MI:0915”(physical association)	0.680
EIF1B	FUS	psi-mi:“MI:0915”(physical association)	0.680
BCAR3	FUS	psi-mi:“MI:0915”(physical association)	0.680

BioGRID (1089): VCP (Affinity Capture-MS), SFPQ (Affinity Capture-MS), YWHAZ (Affinity Capture-MS), YWHAQ (Affinity Capture-MS), PFN1 (Affinity Capture-MS), FASN (Affinity Capture-MS), PGK1 (Affinity Capture-MS), CKB (Affinity Capture-MS), ENO1 (Affinity Capture-MS), LDHB (Affinity Capture-MS), PAICS (Affinity Capture-MS), PHGDH (Affinity Capture-MS), LDHA (Affinity Capture-MS), GAPDH (Affinity Capture-MS), PKM (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: A4FV72, B0BN49, B3LYP1, B3P0D7, B4GLK8, B4IBA4, B4JUT1, B4KCD5, B4LZ88, B4M205, B4NB54, B4PL68, B4QV17, B5DGI7, B7FAL5, C0HFE5, F4I9J7, O14102, O42847, P04147, P08199, P08621, P09405, P13383, P19338, P32588, P33240, P35637, P40561, P49311, P52299, P56959, Q03878, Q10B98, Q14498, Q15427, Q177H0, Q1DXH0, Q1RMR2, Q21832

SIGNOR signaling

33 interactions.

A	Effect	B	Mechanism
FUS	“up-regulates activity”	PA2G4	sumoylation
FUS	“up-regulates activity”	GEMIN4	relocalization
FUS	“up-regulates activity”	GEMIN6	relocalization
FUS	“up-regulates activity”	SMN1	relocalization
FUS	“up-regulates quantity by stabilization”	CSDE1	“post transcriptional regulation”
PRMT1	“down-regulates activity”	FUS	methylation
FUS	“up-regulates quantity”	Protein_aggregates
FUS	“down-regulates activity”	DHX9	relocalization
FUS	“down-regulates activity”	DDX3X	relocalization
Exosome_Complex	“up-regulates activity”	FUS	relocalization
D-glucitol	“down-regulates activity”	FUS	relocalization
Osmotic_stress	“down-regulates activity”	FUS	relocalization
mTORC2	“down-regulates activity”	FUS
FUS	down-regulates	Protein_synthesis
SAFB	“up-regulates activity”	FUS	relocalization
FUS	“up-regulates activity”	MATR3	relocalization
FUS	“up-regulates activity”	SNRNP70	binding
EGFR	“up-regulates activity”	FUS	phosphorylation
ABL1	“down-regulates activity”	FUS	phosphorylation
SF1	down-regulates	FUS	binding
FUS	“up-regulates quantity”	DLG4	“post transcriptional regulation”
FUS	“up-regulates quantity”	SHANK1	“post transcriptional regulation”
FUS	“down-regulates quantity by repression”	HNRNPA2B1	“post transcriptional regulation”
FUS	“down-regulates quantity by repression”	DUSP22	“post transcriptional regulation”
FUS	“down-regulates quantity by repression”	MPHOSPH9	“post transcriptional regulation”
FUS	“down-regulates quantity by repression”	ADARB1	“post transcriptional regulation”
FUS	“down-regulates quantity by repression”	GRIA4	“post transcriptional regulation”
FUS	“down-regulates quantity by repression”	AGRN	“post transcriptional regulation”
FUS	“down-regulates quantity by repression”	VPS16	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 122 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	30.9×	2e-04
Homology Directed Repair	5	20.0×	6e-04
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	5	20.0×	6e-04
DNA Double-Strand Break Repair	6	19.4×	2e-04
GSK3B-mediated proteasomal degradation of PD-L1(CD274)	5	15.4×	1e-03
SUMO E3 ligases SUMOylate target proteins	6	13.9×	6e-04
Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A	5	13.2×	2e-03
SUMOylation	6	12.7×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	6	20.7×	2e-04
cellular response to UV	6	17.1×	3e-04
epidermal growth factor receptor signaling pathway	5	11.9×	4e-03
G1/S transition of mitotic cell cycle	6	11.6×	2e-03
regulation of autophagy	5	11.6×	5e-03
positive regulation of translation	5	10.9×	6e-03
DNA damage response	15	7.7×	1e-06
mRNA splicing, via spliceosome	8	7.0×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: ambiguous (mixed evidence) across 1 cancer types — HCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	14
Uncertain significance	285
Likely benign	184
Benign	47

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1073222	NM_004960.4(FUS):c.1554_1557del (p.Gln519fs)	Pathogenic
1423819	NM_004960.4(FUS):c.1500dup (p.Gly501fs)	Pathogenic
1458206	NM_004960.4(FUS):c.1509_1510del (p.Gly504fs)	Pathogenic
1485282	NM_004960.4(FUS):c.1391_1392dup (p.Gly465fs)	Pathogenic
16221	NM_004960.4(FUS):c.1551C>G (p.His517Gln)	Pathogenic
16222	NM_004960.4(FUS):c.1561C>G (p.Arg521Gly)	Pathogenic
16223	NM_004960.4(FUS):c.1553G>A (p.Arg518Lys)	Pathogenic
16224	NM_004960.4(FUS):c.1561C>T (p.Arg521Cys)	Pathogenic
16225	NM_004960.4(FUS):c.1562G>A (p.Arg521His)	Pathogenic
1918103	NM_004960.4(FUS):c.253C>T (p.Gln85Ter)	Pathogenic
2046744	NM_004960.4(FUS):c.1573C>A (p.Pro525Thr)	Pathogenic
2419096	NM_004960.4(FUS):c.1449_1488del (p.Tyr484fs)	Pathogenic
280109	NM_004960.4(FUS):c.1572G>C (p.Arg524Ser)	Pathogenic
280110	NM_004960.4(FUS):c.1574C>T (p.Pro525Leu)	Pathogenic
280356	NM_004960.4(FUS):c.1504_1505del (p.Asp502fs)	Pathogenic
280602	NM_004960.4(FUS):c.1510_1514dup (p.Phe506fs)	Pathogenic
2925592	NM_004960.4(FUS):c.1540A>G (p.Arg514Gly)	Pathogenic
2945054	NM_004960.4(FUS):c.1531dup (p.Met511fs)	Pathogenic
29707	NM_004960.4(FUS):c.1483C>T (p.Arg495Ter)	Pathogenic
29708	NM_004960.4(FUS):c.616G>A (p.Gly206Ser)	Pathogenic
37070	NM_004960.4(FUS):c.868C>T (p.Gln290Ter)	Pathogenic
3759352	NM_004960.4(FUS):c.1542G>T (p.Arg514Ser)	Pathogenic
3760171	NM_004960.4(FUS):c.1496del (p.Gly499fs)	Pathogenic
4783811	NM_004960.4(FUS):c.1561C>A (p.Arg521Ser)	Pathogenic
4792377	NM_004960.4(FUS):c.1441C>T (p.Arg481Ter)	Pathogenic
665141	NM_004960.4(FUS):c.1509_1510dup (p.Gly504fs)	Pathogenic
817574	NM_004960.4(FUS):c.1022_1023del (p.Ser340_Phe341insTer)	Pathogenic
847302	NM_004960.4(FUS):c.1541+1G>A	Pathogenic
873230	NM_004960.4(FUS):c.1394-1G>T	Pathogenic
873231	NM_004960.4(FUS):c.1555C>T (p.Gln519Ter)	Pathogenic

SpliceAI

1976 predictions. Top by Δscore:

Variant	Effect	Δscore
16:31180225:ACGG:A	donor_loss	1.0000
16:31180226:CGG:C	donor_loss	1.0000
16:31180228:G:GG	donor_gain	1.0000
16:31180229:T:A	donor_loss	1.0000
16:31182660:GAACA:G	donor_gain	1.0000
16:31182665:G:GG	donor_gain	1.0000
16:31183849:T:G	acceptor_gain	1.0000
16:31183852:T:A	acceptor_gain	1.0000
16:31183856:AGCAG:A	acceptor_gain	1.0000
16:31183857:GCAGG:G	acceptor_gain	1.0000
16:31184000:A:T	donor_gain	1.0000
16:31184002:GGTAC:G	donor_loss	1.0000
16:31184004:T:G	donor_loss	1.0000
16:31184207:A:AG	acceptor_gain	1.0000
16:31184208:G:GA	acceptor_gain	1.0000
16:31184208:GTT:G	acceptor_gain	1.0000
16:31184208:GTTAC:G	acceptor_gain	1.0000
16:31184935:A:AG	acceptor_gain	1.0000
16:31184935:ACAG:A	acceptor_gain	1.0000
16:31184936:C:G	acceptor_gain	1.0000
16:31184937:A:AG	acceptor_gain	1.0000
16:31184937:AG:A	acceptor_gain	1.0000
16:31184938:G:GA	acceptor_gain	1.0000
16:31184938:GG:G	acceptor_gain	1.0000
16:31184938:GGT:G	acceptor_gain	1.0000
16:31184938:GGTA:G	acceptor_gain	1.0000
16:31184938:GGTAA:G	acceptor_gain	1.0000
16:31185177:GGG:G	donor_gain	1.0000
16:31185178:GG:G	donor_gain	1.0000
16:31185178:GGG:G	donor_gain	1.0000

AlphaMissense

3410 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:31189128:G:C	D280H	1.000
16:31189133:T:A	N281K	1.000
16:31189133:T:G	N281K	1.000
16:31189137:G:C	D283H	1.000
16:31189140:A:G	N284D	1.000
16:31189141:A:T	N284I	1.000
16:31189142:C:A	N284K	1.000
16:31189142:C:G	N284K	1.000
16:31189144:A:T	N285I	1.000
16:31189145:C:A	N285K	1.000
16:31189145:C:G	N285K	1.000
16:31189146:A:C	T286P	1.000
16:31189147:C:A	T286N	1.000
16:31189147:C:T	T286I	1.000
16:31189149:A:T	I287F	1.000
16:31189150:T:A	I287N	1.000
16:31189150:T:C	I287T	1.000
16:31189150:T:G	I287S	1.000
16:31189151:C:G	I287M	1.000
16:31189152:T:A	F288I	1.000
16:31189152:T:C	F288L	1.000
16:31189152:T:G	F288V	1.000
16:31189153:T:C	F288S	1.000
16:31189153:T:G	F288C	1.000
16:31189154:T:A	F288L	1.000
16:31189154:T:G	F288L	1.000
16:31189155:G:A	V289M	1.000
16:31189156:T:A	V289E	1.000
16:31189156:T:C	V289A	1.000
16:31189156:T:G	V289G	1.000

dbSNP variants (sampled 300 via entrez): RS1000102185 (16:31183364 C>G,T), RS1000620035 (16:31194746 C>T), RS1000688424 (16:31193641 G>C), RS1000810417 (16:31194098 C>T), RS1000898225 (16:31194957 T>A), RS1000961494 (16:31184795 A>G), RS1000980236 (16:31180417 G>T), RS1001142727 (16:31184662 T>C), RS1001328650 (16:31185019 G>A), RS1001507280 (16:31184545 G>A,C,T), RS1001645052 (16:31178155 C>T), RS1001777832 (16:31193862 C>A), RS1001858774 (16:31187967 G>T), RS1001909530 (16:31187781 C>A,T), RS1001944936 (16:31190600 C>G)

Disease associations

OMIM: gene MIM:137070 | disease phenotypes: MIM:608030, MIM:614782, MIM:615972

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Definitive	Autosomal dominant
amyotrophic lateral sclerosis type 6	Strong	Autosomal dominant
juvenile amyotrophic lateral sclerosis	Supportive	Autosomal recessive
tremor, hereditary essential, 4	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 6	Definitive	AD

Mondo (8): amyotrophic lateral sclerosis type 6 (MONDO:0011951), tremor, hereditary essential, 4 (MONDO:0013888), juvenile amyotrophic lateral sclerosis (MONDO:0017593), amyotrophic lateral sclerosis (MONDO:0004976), frontotemporal dementia (MONDO:0017276), dystonic disorder (MONDO:0003441), nanophthalmos 4 (MONDO:0014426), distal hereditary motor neuropathy (MONDO:0018894)

Orphanet (6): Frontotemporal dementia with motor neuron disease (Orphanet:275872), Amyotrophic lateral sclerosis (Orphanet:803), Juvenile amyotrophic lateral sclerosis (Orphanet:300605), Frontotemporal dementia (Orphanet:282), Nanophthalmos (Orphanet:35612), Distal hereditary motor neuropathy (Orphanet:53739)

HPO phenotypes

118 total (30 of 118 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000217	Xerostomia
HP:0000252	Microcephaly
HP:0000508	Ptosis
HP:0000605	Supranuclear gaze palsy
HP:0000639	Nystagmus
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000734	Disinhibition
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001264	Spastic diplegia
HP:0001265	Hyporeflexia
HP:0001276	Hypertonia
HP:0001283	Bulbar palsy
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001308	Tongue fasciculations
HP:0001317	Abnormal cerebellum morphology
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008103_175	Bipolar disorder	8.000000e-06
GCST008115_45	Bipolar I disorder	5.000000e-07
GCST010242_215	HDL cholesterol levels	7.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009963	bipolar I disorder
EFO:0004612	high density lipoprotein cholesterol 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
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
C567699	Amyotrophic Lateral Sclerosis 6, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724679 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.76	Kd	17.47	nM	CHEMBL3752910
7.76	ED50	17.47	nM	CHEMBL3752910
7.44	Kd	36.62	nM	CHEMBL5653589
7.44	ED50	36.62	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 10 total; 2 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148404: Binding affinity to human FUS incubated for 45 mins by Kinobead based pull down assay	kd	0.0175	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148404: Binding affinity to human FUS incubated for 45 mins by Kinobead based pull down assay	kd	0.0366	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects splicing, decreases expression	3
methylparaben	affects splicing, increases expression	3
sodium arsenite	affects expression, affects splicing, increases abundance, affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
deoxynivalenol	increases expression	2
perfluorooctanoic acid	decreases expression	2
perfluoro-n-nonanoic acid	decreases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	2
bisphenol S	affects expression, increases expression	2
Copper	affects binding, decreases expression, increases expression	2
Curcumin	decreases expression, increases expression	2
Silicon Dioxide	increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
graphene oxide	decreases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
trichostatin A	affects cotreatment, increases expression	1
tetrabromobisphenol A	decreases expression	1
butylidenephthalide	increases expression	1
ferrous chloride	decreases expression	1
cupric chloride	increases expression	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651446	Binding	Binding affinity to human FUS 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

76 cell lines: 47 induced pluripotent stem cell, 15 cancer cell line, 9 transformed cell line, 4 finite cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_1927	YNH-1	Cancer cell line	Male
CVCL_A0TJ	HEK293 FUS KO	Transformed cell line	Female
CVCL_A1VS	NCC-MLPS1-C1	Cancer cell line	Male
CVCL_A454	JIH-4	Cancer cell line	Male
CVCL_A455	TSU-1621MT	Cancer cell line	Female
CVCL_A5CF	TEX	Transformed cell line	Sex unspecified
CVCL_A5QY	KCLi008-A	Induced pluripotent stem cell	Male
CVCL_A5QZ	KCLi009-A	Induced pluripotent stem cell	Female
CVCL_A5RA	KCLi010-A	Induced pluripotent stem cell	Male
CVCL_A7NL	IRTA17	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
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