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): 704 total — 31 pathogenic, 17 likely-pathogenic (top 5% of genes corpus-wide)
• Regional missense constraint (gnomAD): 2 of 6 regions constrained (≈18% of expected missense variation)
• GTEx eGene: eQTL in 7 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 118
• Cancer driver (intOGen): ambiguous (mixed evidence) across 1 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.10 (highly constrained)
• MANE Select transcript: NM_004960
• Interaction hub: 3,838 STRING partners (top 1% of genes corpus-wide)

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: 60 — 41 protein_coding, 10 nonsense_mediated_decay, 8 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000254108

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 8, TSL 3: 1, TSL 5: 1

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, ENST00000982089, ENST00001034632, ENST00001034634, ENST00001087674, ENST00001087676, ENST00001087677, ENST00001087680, ENST00001094132, ENST00001094133, ENST00001107790, ENST00001129828, ENST00001129829, ENST00001140773

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.

Highest expression (Bgee): testis, ventricular zone, hemisphere of cerebellum, cerebellar hemisphere, ganglionic eminence.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FUS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 7 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

9 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	1.1e-03	-0.12	16:31248691:C:A
Cells EBV-transformed lymphocytes	eqtl	1.4e-03	+0.78	16:31005687:G:T
Brain Cerebellum	eqtl	4.2e-03	+0.86	16:31460537:A:C
Skin Sun Exposed Lower leg	eqtl	1.4e-02	+0.33	16:31941041:T:C
Skin Sun Exposed Lower leg	sqtl	1.7e-02	-0.17	16:31244463:C:G
Pituitary	eqtl	3.0e-02	+0.20	16:31966429:G:A
Cells Cultured fibroblasts	eqtl	3.3e-02	-0.27	16:30581429:C:T
Vagina	eqtl	3.7e-02	-2.40	16:31895514:C:T
Cells Cultured fibroblasts	sqtl	4.5e-02	-0.60	16:30877645:T:C

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

showing 100 of 304 tissues 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
spleen	UBERON:0002106	99.10	gold quality
upper lobe of left lung	UBERON:0008952	99.09	gold quality
colonic epithelium	UBERON:0000397	99.04	gold quality
skin of leg	UBERON:0001511	99.04	gold quality
right frontal lobe	UBERON:0002810	99.04	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.04	gold quality
minor salivary gland	UBERON:0001830	99.03	gold quality
peritoneum	UBERON:0002358	99.03	gold quality
omental fat pad	UBERON:0010414	99.03	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.02	gold quality
mucosa of transverse colon	UBERON:0004991	99.00	gold quality
body of pancreas	UBERON:0001150	98.99	gold quality
transverse colon	UBERON:0001157	98.99	gold quality
body of stomach	UBERON:0001161	98.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.95	gold quality
pituitary gland	UBERON:0000007	98.94	gold quality
lymph node	UBERON:0000029	98.94	gold quality
right lung	UBERON:0002167	98.94	gold quality
right adrenal gland cortex	UBERON:0035827	98.89	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.89	gold quality
ovary	UBERON:0000992	98.88	gold quality
lower esophagus	UBERON:0013473	98.88	gold quality
monocyte	CL:0000576	98.86	gold quality
right adrenal gland	UBERON:0001233	98.81	gold quality
right coronary artery	UBERON:0001625	98.80	gold quality
left adrenal gland cortex	UBERON:0035825	98.79	gold quality
nucleus accumbens	UBERON:0001882	98.78	gold quality
upper lobe of lung	UBERON:0008948	98.78	gold quality
left adrenal gland	UBERON:0001234	98.77	gold quality
lower esophagus mucosa	UBERON:0035834	98.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.74	gold quality
thoracic aorta	UBERON:0001515	98.73	gold quality
ascending aorta	UBERON:0001496	98.72	gold quality
apex of heart	UBERON:0002098	98.72	gold quality
descending thoracic aorta	UBERON:0002345	98.72	gold quality
leukocyte	CL:0000738	98.71	gold quality
mononuclear cell	CL:0000842	98.71	gold quality
left coronary artery	UBERON:0001626	98.71	gold quality
vagina	UBERON:0000996	98.69	gold quality
esophagus	UBERON:0001043	98.69	gold quality
stromal cell of endometrium	CL:0002255	98.68	gold quality
paraflocculus	UBERON:0005351	98.68	gold quality
amygdala	UBERON:0001876	98.66	gold quality
smooth muscle tissue	UBERON:0001135	98.65	gold quality
putamen	UBERON:0001874	98.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.63	gold quality
coronary artery	UBERON:0001621	98.61	gold quality
right atrium auricular region	UBERON:0006631	98.61	gold quality
aorta	UBERON:0000947	98.60	gold quality
vermiform appendix	UBERON:0001154	98.60	gold quality
adrenal cortex	UBERON:0001235	98.59	gold quality
small intestine	UBERON:0002108	98.58	gold quality
esophagus mucosa	UBERON:0002469	98.57	gold quality
prefrontal cortex	UBERON:0000451	98.55	gold quality
tibial artery	UBERON:0007610	98.54	gold quality
popliteal artery	UBERON:0002250	98.53	gold quality
rectum	UBERON:0001052	98.51	gold quality
fundus of stomach	UBERON:0001160	98.51	gold quality
gall bladder	UBERON:0002110	98.48	gold quality
caudate nucleus	UBERON:0001873	98.46	gold quality
saliva-secreting gland	UBERON:0001044	98.45	gold quality
caecum	UBERON:0001153	98.42	gold quality
mouth mucosa	UBERON:0003729	98.42	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.42	gold quality
sigmoid colon	UBERON:0001159	98.41	gold quality
olfactory bulb	UBERON:0002264	98.38	gold quality
cingulate cortex	UBERON:0003027	98.37	gold quality
stomach	UBERON:0000945	98.35	gold quality
anterior cingulate cortex	UBERON:0009835	98.32	gold quality
zone of skin	UBERON:0000014	98.29	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	203.2
Thymus	tissue	162.4
Frontal cortex	tissue	161.9
Ovary	tissue	148.1	high
Tonsil	tissue	106.1	high
Appendix	tissue	97.2	high
Bone marrow	tissue	93.4	high
Fallopian tube	tissue	93.3	high
Skeletal muscle	tissue	92.4	high
Smooth muscle	tissue	91.7	high
Lymph node	tissue	91.5	high
Endometrium 1	tissue	90.4	high
Corpus callosum	tissue	86.9
Adipose tissue	tissue	83.0	high
Spinal cord	tissue	83.0
Urinary bladder	tissue	81.6	high
Tongue	tissue	80.3
Thalamus	tissue	80.1
Parathyroid gland	tissue	79.9	high
Midbrain	tissue	79.1
Medulla oblongata	tissue	77.4
Nucleus accumbens	tissue	77.2
Periaqueductal gray	tissue	75.6
Hypothalamus	tissue	75.1
Pons	tissue	74.5
Putamen	tissue	72.8
Superior colliculi	tissue	72.1
Hippocampal formation	tissue	71.7
Substantia nigra	tissue	71.0
Cerebellum	tissue	69.7	high
Ventral forebrain	tissue	69.6
Hippocampus	tissue	68.6	high
Colon	tissue	67.9	high
Seminal vesicle	tissue	66.4	high
Olfactory bulb	tissue	66.1
Heart muscle	tissue	66.0	high
Vagina	tissue	65.9	high
Basal ganglia	tissue	65.9	high
Septum	tissue	65.9
Spleen	tissue	65.4	high
Cerebral cortex	tissue	65.2	high
Somatosensory cortex	tissue	65.2
Postcentral gyrus	tissue	65.1
Cervix	tissue	63.4	high
Amygdala	tissue	62.7
Prefrontal cortex	tissue	62.5
Motor cortex	tissue	62.1
Locus coeruleus	tissue	61.5
Lung	tissue	61.1	high
Breast	tissue	61.0	high
Temporal cortex	tissue	60.1
Entorhinal cortex	tissue	59.4
Occipital cortex	tissue	59.3
Rectum	tissue	59.0	high
Retrosplenial cortex	tissue	58.4
Retrosplenial and cingulate cortex	tissue	57.6
Kidney	tissue	57.1	high
Salivary gland	tissue	56.6	high
Duodenum	tissue	56.1	high
Stomach 1	tissue	56.0	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Orbitofrontal gyrus, anterior (92.6), White matter (86.9), Area parastriata, superior (83.0), Dorsal spinal cord (83.0), Cerebellar nuclei (82.2).

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)

Targeting FUS by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 127 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.104, missense Z 2.83 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000254108 splits into 6 regions with different missense tolerance; 2 are missense-constrained (≈18% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
16:31,180,215–31,185,121	276 / 303.3	0.91	no
16:31,185,122–31,189,144	51 / 72.2	0.71	no
16:31,189,145–31,190,094	26 / 109.3	0.24	yes (p 1.6e-15)
16:31,190,095–31,190,742	63 / 83.0	0.76	no
16:31,190,743–31,190,790	0 / 19.2	0.00	yes (p 1.2e-05)
16:31,190,791–31,191,435	96 / 120.7	0.80	no

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	Fusl1	ENSRNOG00000077981
drosophila_melanogaster	caz	FBGN0285954
caenorhabditis_elegans		WBGENE00016173

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1353633) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 21 distinct phenotype terms.

Mouse phenotype (MP)	Records
neonatal lethality, complete penetrance	2
small thymus	1
motor neuron degeneration	1
decreased motor neuron number	1
abnormal neuromuscular synapse morphology	1
abnormal gait	1
abnormal suckling behavior	1
impaired limb coordination	1
abnormal embryo size	1
premature death	1
lymphoid hypoplasia	1
abnormal immunoglobulin level	1
abnormal chromosome morphology	1
aneuploidy	1
chromosome breakage	1
decreased lymphocyte cell number	1
decreased B cell number	1
increased prepulse inhibition	1
abnormal hippocampus pyramidal cell morphology	1
increased respiratory quotient	1
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q3ZCE8	100.0%	Diamond
Xenopus tropicalis	Q28BZ1	98.9%	Diamond
Salmo salar	B5DGI7	92.6%	Diamond
Arabidopsis thaliana	Q94KD0	73.1%	Diamond
Gallus gallus	P15771	68.5%	Diamond
Schizosaccharomyces pombe 972h-	O43120	39.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PYDC1	protein-coding	260434
PYCARD	protein-coding	29108
ITGAM	protein-coding	3684
TRIM72	protein-coding	493829
PYCARD-AS1	ncRNA	100652740
PRSS36	protein-coding	146547
PRSS8	protein-coding	5652
KAT8	protein-coding	84148
ITGAX	protein-coding	3687

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): A0AAQ5BIG2, A0AAQ5BIK3, P35637, 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 by resolution:

PDB	Title	Method	Resolution (Å)
6KJ3	120kV MicroED structure of FUS (37-42) SYSGYS solved from merged datasets at 0.60 A	ELECTRON CRYSTALLOGRAPHY	0.6
6KJ1	200kV MicroED structure of FUS (37-42) SYSGYS solved from merged datasets at 0.65 A	ELECTRON CRYSTALLOGRAPHY	0.65
6KJ4	120kV MicroED structure of FUS (37-42) SYSGYS solved from single crystal at 0.65 A	ELECTRON CRYSTALLOGRAPHY	0.65
6KJ2	200kV MicroED structure of FUS (37-42) SYSGYS solved from single crystal at 0.67 A	ELECTRON CRYSTALLOGRAPHY	0.67
5XSG	Ultrahigh resolution structure of FUS (37-42) SYSGYS determined by MicroED	ELECTRON CRYSTALLOGRAPHY	0.73
6BWZ	SYSGYS from low-complexity domain of FUS, residues 37-42	X-RAY DIFFRACTION	1.1
6BXV	SYSSYGQS from low-complexity domain of FUS, residues 54-61	X-RAY DIFFRACTION	1.1
6BZP	STGGYG from low-complexity domain of FUS, residues 77-82	ELECTRON CRYSTALLOGRAPHY	1.1
5XRR	Crystal structure of FUS (54-59) SYSSYG	X-RAY DIFFRACTION	1.5
4FDD	Crystal structure of KAP beta2-PY-NLS	X-RAY DIFFRACTION	2.3
6XFM	Molecular structure of the core of amyloid-like fibrils formed by residues 111-214 of FUS	ELECTRON MICROSCOPY	2.62
7CYL	Crystal structure of Karyopherin-beta2 in complex with FUS PY-NLS(P525L)	X-RAY DIFFRACTION	2.7
5YVI	Crystal structure of Karyopherin beta2 in complex with FUS(456-526)	X-RAY DIFFRACTION	2.9
7VQQ	Cryo-EM structure of amyloid fibril formed by FUS low complexity domain	ELECTRON MICROSCOPY	2.9
4FQ3	Crystal structure of transportin/FUS-NLS	X-RAY DIFFRACTION	3
5YVH	Crystal structure of Karyopherin beta2 in complex with FUS(371-526)	X-RAY DIFFRACTION	3.15
5YVG	Crystal structure of Karyopherin beta2 in complex with FUS(full length)	X-RAY DIFFRACTION	4.05
2LA6	Solution NMR Structure of RRM domain of RNA-binding protein FUS from homo sapiens …	SOLUTION NMR
2LCW	solution structure of FUS/TLS RRM domain	SOLUTION NMR
5W3N	Molecular structure of FUS low sequence complexity domain protein fibrils	SOLID-STATE NMR
6G99	Solution structure of FUS-ZnF bound to UGGUG	SOLUTION NMR
6GBM	Solution structure of FUS-RRM bound to stem-loop RNA	SOLUTION NMR
6SNJ	Solution structure of the FUS/TLS RNA recognition motif in complex with U1 snRNA stem …	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH supported · IF supported

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)

Position	Role
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)

Type	Positions
Phosphoserine	26, 30, 42, 221, 277, 340
Asymmetric dimethylarginine	216, 218, 242, 244, 248, 251, 259, 377, 383, 386, 388, 394, 407, 473, 476, 481, 485, 487, 491, 495, 498, 503
Omega-n-methylarginine	216, 218, 407, 503
Phosphothreonine	286
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	334

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 6; 1 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-9918481	Dengue Virus-Host Interactions ⚕	curated
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA	curated
R-HSA-9770562	mRNA Polyadenylation	curated
R-HSA-72163	mRNA Splicing - Major Pathway	curated
R-HSA-8953854	Metabolism of RNA	—
R-HSA-72172	mRNA Splicing	—

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 (10): 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), 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

5 top-level categories:

Category	Pathways
mRNA Splicing	1
Metabolism of RNA	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
Processing of Capped Intron-Containing Pre-mRNA	1

GO top-level categories

38 GO namespaces:

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
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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 16 of 29 annotations. The rest are phylogenetic / computational / electronic (IEA).

16 experimentally-supported GO terms:

GO term	NS	Evidence
RNA splicing	BP	direct assay
amyloid fibril formation	BP	direct assay
mRNA stabilization	BP	direct assay
membraneless organelle assembly	BP	direct assay
positive regulation of double-strand break repair via homologous recombination	BP	direct assay
protein homooligomerization	BP	direct assay
regulation of DNA-templated transcription	BP	direct assay
regulation of RNA splicing	BP	direct assay
regulation of transcription by RNA polymerase II	BP	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	direct assay
chromatin binding	MF	direct assay
identical protein binding	MF	physical interaction
molecular condensate scaffold activity	MF	direct assay
transcription coactivator activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,838 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FUS	TARDBP	Q13148	970
FUS	A0A087WTZ4	A0A087WTZ4	966
FUS	SOD1	P00441	929
FUS	C9orf72	Q96LT7	892
FUS	VAPB	O95292	832
FUS	CREB3L2	Q70SY1	824
FUS	ATF1	P18846	820
FUS	SETX	Q7Z333	818
FUS	ALS2	Q96Q42	810
FUS	OPTN	Q96CV9	800
FUS	UBQLN2	Q9UHD9	799
FUS	SRSF10	O75494	795
FUS	VCP	P55072	772
FUS	ATXN2	Q99700	766
FUS	NR4A3	Q92570	762

IntAct

Human interaction partners of FUS in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 69 partners by confidence:

Partner	Interaction type	MIscore	Records
TARDBP	association	0.750	8
TAF15	physical association	0.740	3
SAFB	physical association	0.730	6
MATR3	association	0.730	3
BCAR3	physical association	0.680	4
EIF1B	physical association	0.680	4
MAGEB2	physical association	0.680	4
RYBP	physical association	0.670	3
HNRNPA1	association	0.670	1
PRMT1	physical association	0.660	8
RBMX	physical association	0.660	1
RALY	proximity	0.640	5
DHX9	colocalization	0.630	1
EP300	physical association	0.590	4
TNPO1	direct interaction	0.590	3
SMN1	direct interaction	0.590	1
GSK3B	physical association	0.560	4
BAG6	physical association	0.560	3
CBLB	physical association	0.560	3
CSNK1D	physical association	0.560	3
GRIN1	physical association	0.560	3
OTUB1	physical association	0.560	3
PBX4	physical association	0.560	3
PTBP2	physical association	0.560	3
RELA	physical association	0.560	3
RPP25	physical association	0.560	3
RXRA	physical association	0.560	3
SEM1	physical association	0.560	3
SPATA22	physical association	0.560	3
VCL	physical association	0.560	3

BioGRID (1,107 interactions; top human partners by supporting records in a sample of 600 records): SMARCA4 (Affinity Capture-Western; 5 records), HNRNPD (Affinity Capture-MS; 4 records), PRMT1 (Affinity Capture-MS; 4 records), SFPQ (Affinity Capture-MS; 4 records), AKT1 (Affinity Capture-Western; 3 records), ARID1A (Affinity Capture-Western; 3 records), CDC5L (Affinity Capture-MS; 3 records), CTDSPL2 (Affinity Capture-MS; 3 records), HNRNPL (Affinity Capture-MS; 3 records), MATR3 (Affinity Capture-MS; 3 records), SNRPC (Affinity Capture-MS; 3 records), UBQLN2 (Affinity Capture-MS; 3 records), AGR2 (Proximity Label-MS; 2 records), BRCA1 (Affinity Capture-MS; 2 records), CDK9 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 32 of 33 signaling 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”
FUS	“down-regulates quantity by repression”	ATXN2	“post transcriptional regulation”
FUS	“down-regulates quantity by repression”	AMPA	“post transcriptional regulation”
TNPO1	“up-regulates activity”	FUS	relocalization

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
Spliceosome, E complex	129	RBM17, DDX39A, GEMIN2, NCBP2, PRPF31, SART3, SF3A2, SNRPA, SRSF7, DDX39B, DHX15, GEMIN5, SCAF4, SMARCB1, SNRPD3, SYNCRIP, U2AF2, HNRNPC, SF3B2, SMARCC2, SFSWAP, USP39, GEMIN6, HNRNPK, RBM42, SF3B1, SF3B4, SNRPG, SRSF6, BCAS2, SMN1, CPSF7, SMARCE1, SRSF8, ARID1A, LSM4, SNRPC, CHD8, FUS, SNRNP70, SRSF11, NUDT21, PBRM1, SNRPB2, SNRPD1, YBX1, SF1, SNRPD2, SRSF2, SRSF5, PPIH, SRSF3, DDX20, SART1, SRSF1, SRSF4, PRPF19, RBM39, RBMXL2, SREK1, PRPF3, SMARCA2, U2AF1, SF3B6, SMARCA1, CPSF1, DDX23, DHX9, RUVBL1, SNRPF, SRRM2, ALYREF, HNRNPA0, HNRNPH1, PCBP2, RBM10, SF3B3, STRAP, HNRNPR, RBM25, ACTBL2, CHERP, SNRPA1, ACTL6A, DDX46, HNRNPL, RBM7, CPSF6, ARID2, DNAJC8, EFTUD2, KHSRP, RUVBL2, SMARCA4, PCBP1, SNRNP40, SNRPE, PRPF4, PRPF8, SF3A1, SF3A3, SNRNP200, ZCCHC8, DDX5, LUC7L3, SMARCC1, HNRNPA2B1, HNRNPD, HTATSF1, LUC7L2, PHF5A, PRPF6, SMARCD1, SNRPB, GEMIN8, U2SURP, NCBP1, GEMIN4, HNRNPU, MTREX, ARID1B, CHD4, HNRNPM, PRPF40A, HNRNPF, SRRT, DDX17, HNRNPA1, PUF60
Spliceosome, A complex	112	RBM39, SAP30BP, CDK11A, CHERP, HNRNPA1, HNRNPK, HNRNPR, HNRNPU, RBM25, SF3A1, DDX46, HNRNPA3, RNPS1, SART1, SF1, SF3A2, SF3B4, SNRPB, ACIN1, CCAR2, DHX9, ELAVL1, ILF2, SF3B3, SRSF5, HNRNPA2B1, CD2BP2, DDX5, PUF60, RBM17, SNRPA1, TCERG1, ZC3H18, SNRPD1, SRSF2, SYNCRIP, ZNF207, CTNNBL1, HSPA8, NCBP2, SF3B2, TRA2B, YBX1, RBM10, SF3A3, SRRM1, SRSF6, SRSF7, SUGP1, DDX42, DNAJC8, EFTUD2, PRCC, SF3B5, SMNDC1, SNRNP200, WBP11, CDC5L, PPP1R8, PRPF6, BCAS2, NCBP1, PRPF19, PRPF3, SNRPD3, SRSF4, U2AF2, HNRNPUL1, NRIP2, PHF5A, RBM5, RBMX, SNRPA, SRRM2, U2AF1, CCAR1, CFAP20, CIRBP, DDX23, SF3B1, SF3B6, SNRPB2, SNRPE, BUB3, DHX15, PCBP1, PPP1CA, PQBP1, SNRNP70, SRSF1, U2SURP, DDX17, SNRPC, SNRPD2, SNRPF, SNRPG, SRRT, SRSF3, SRSF9, AGGF1, FUS, HNRNPC, HTATSF1, ILF3, PLRG1, SEC31B, TRIR, CWC15, HNRNPAB, PNN, PRPF40A, PRPF8
Large Drosha complex	20	DDX1, FUS, RALY, TARDBP, DDX17, DHX15, HNRNPH1, HNRNPM, DDX3X, DROSHA, HNRNPU, HNRNPUL1, ILF2, TAF15, DDX5, DGCR8, EWSR1, HNRNPDL, ILF3, SRPK1
DGCR8 multiprotein complex	11	DDX17, FUS, HNRNPH1, HNRNPR, HSPA5, NCL, DDX5, DGCR8, DHX9, HNRNPU, ILF3

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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
mRNA Polyadenylation	6	10.8×	3e-03
mRNA Splicing - Major Pathway	7	7.8×	3e-03
Metabolism of RNA	9	7.7×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	5	18.5×	2e-03
mRNA splicing, via spliceosome	6	8.3×	7e-03

Disease & clinical

Cancer significance

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

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for FUS: 704 ClinVar records (48 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	31
Likely pathogenic	17
Uncertain significance	293
Likely benign	190
Benign	47

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 48 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
280110	NM_004960.4(FUS):c.1574C>T (p.Pro525Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
16224	NM_004960.4(FUS):c.1561C>T (p.Arg521Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
16222	NM_004960.4(FUS):c.1561C>G (p.Arg521Gly)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
16225	NM_004960.4(FUS):c.1562G>A (p.Arg521His)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
29707	NM_004960.4(FUS):c.1483C>T (p.Arg495Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
1458206	NM_004960.4(FUS):c.1509_1510del (p.Gly504fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
1073222	NM_004960.4(FUS):c.1554_1557del (p.Gln519fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
2925592	NM_004960.4(FUS):c.1540A>G (p.Arg514Gly)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
16223	NM_004960.4(FUS):c.1553G>A (p.Arg518Lys)	Pathogenic	criteria provided, single submitter	2
280109	NM_004960.4(FUS):c.1572G>C (p.Arg524Ser)	Pathogenic	criteria provided, single submitter	1
280356	NM_004960.4(FUS):c.1504_1505del (p.Asp502fs)	Pathogenic	criteria provided, single submitter	1
280602	NM_004960.4(FUS):c.1510_1514dup (p.Phe506fs)	Pathogenic	criteria provided, single submitter	1
665141	NM_004960.4(FUS):c.1509_1510dup (p.Gly504fs)	Pathogenic	criteria provided, single submitter	1
817574	NM_004960.4(FUS):c.1022_1023del (p.Ser340_Phe341insTer)	Pathogenic	criteria provided, single submitter	1
847302	NM_004960.4(FUS):c.1541+1G>A	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore FUS’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 882):

Position(s)	Effect	Δscore	Sites
16:31180228–31180229	donor_loss	1.0000	5
16:31183849	acceptor_gain	1.0000
16:31183852	acceptor_gain	1.0000
16:31184000	donor_gain	1.0000
16:31184003–31184004	donor_loss	1.0000	3
16:31184936	acceptor_gain	1.0000
16:31184937–31184938	acceptor_loss	1.0000	5
16:31185180–31185181	donor_loss	1.0000	4
16:31188314	acceptor_gain	1.0000
16:31189118	acceptor_gain	1.0000

AlphaMissense

1,564 missense substitutions predicted likely pathogenic (of 3,410 scored), across 400 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M321	9	0.992	1.000
M511	9	0.871	0.975
F305	8	1.000	1.000
D343	8	1.000	1.000
D425	8	1.000	1.000
N435	8	1.000	1.000
N437	8	1.000	1.000
F288	8	0.999	1.000
F354	8	0.999	1.000
F438	8	0.999	1.000
N284	8	0.998	1.000
N445	8	0.998	1.000
F368	8	0.996	1.000
D280	8	0.994	1.000
F359	8	0.993	1.000
D327	8	0.992	1.000
N285	8	0.990	1.000
D283	8	0.989	1.000
F341	8	0.988	1.000
D342	8	0.988	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	4.03e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000737

Disease associations

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

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
amyotrophic lateral sclerosis	Definitive	Autosomal dominant	2
amyotrophic lateral sclerosis type 6	Strong	Autosomal dominant	2
juvenile amyotrophic lateral sclerosis	Supportive	Autosomal recessive
tremor, hereditary essential, 4	Limited	Autosomal dominant	2

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 6	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
Adult-onset neurological disorders	green
Amyotrophic lateral sclerosis/motor neuron disease	green
Neurodegenerative disorders, adult onset	green

Mondo (5): amyotrophic lateral sclerosis type 6 (MONDO:0011951), tremor, hereditary essential, 4 (MONDO:0013888), juvenile amyotrophic lateral sclerosis (MONDO:0017593), nanophthalmos 4 (MONDO:0014426), amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (4): Frontotemporal dementia with motor neuron disease (Orphanet:275872), Amyotrophic lateral sclerosis (Orphanet:803), Juvenile amyotrophic lateral sclerosis (Orphanet:300605), Nanophthalmos (Orphanet:35612)

HPO phenotypes

showing 60 of 118 phenotypes (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
HP:0001482	Subcutaneous nodule
HP:0001618	Dysphonia
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002027	Abdominal pain
HP:0002061	Lower limb spasticity
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002072	Chorea
HP:0002073	Progressive cerebellar ataxia
HP:0002094	Dyspnea
HP:0002127	Abnormal upper motor neuron morphology
HP:0002145	Frontotemporal dementia
HP:0002167	Abnormal speech pattern
HP:0002169	Clonus
HP:0002171	Gliosis
HP:0002174	Postural tremor
HP:0002179	Opisthotonus
HP:0002180	Neurodegeneration
HP:0002186	Apraxia
HP:0002273	Tetraparesis
HP:0002283	Global brain atrophy
HP:0002300	Mutism
HP:0002307	Drooling
HP:0002313	Spastic paraparesis
HP:0002314	Degeneration of the lateral corticospinal tracts
HP:0002345	Action tremor
HP:0002360	Sleep disturbance
HP:0002366	Abnormal lower motor neuron morphology
HP:0002380	Fasciculations
HP:0002385	Paraparesis

GWAS associations

3 associations:

Study	Trait	p-value
GCST010242_414	HDL cholesterol levels	7e-9
GCST008115_45	Bipolar I disorder	5e-7
GCST008103_26	Bipolar disorder	8e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0009963	bipolar I disorder
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors

2 disease descriptors:

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
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 (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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	decreases expression, affects expression, affects splicing	3
methylparaben	affects splicing, increases expression	3
sodium arsenite	affects expression, affects splicing, increases abundance, affects cotreatment, increases expression	3
Benzo(a)pyrene	increases methylation, decreases expression	3
deoxynivalenol	increases expression	2
perfluorooctanoic acid	decreases expression	2
perfluoro-n-nonanoic acid	decreases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	increases expression, decreases expression	2
bisphenol S	increases expression, affects expression	2
Copper	decreases expression, increases expression, affects binding	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	affects cotreatment, decreases expression, increases abundance	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

77 cell lines: 47 induced pluripotent stem cell, 15 cancer cell line, 10 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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00542412	Phase 4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	Phase 4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	Phase 4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	Phase 4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	Phase 4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	Phase 4	ACTIVE_NOT_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	Phase 3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	Phase 3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	Phase 3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	Phase 3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	Phase 3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	Phase 3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	Phase 3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	Phase 3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	Phase 3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	Phase 3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	Phase 3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	Phase 3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	Phase 3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	Phase 3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	Phase 3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	Phase 3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	Phase 3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	Phase 3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	Phase 3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	Phase 3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	Phase 3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	Phase 3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	Phase 3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	Phase 3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	Phase 3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	Phase 3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	Phase 3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	Phase 3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	Phase 3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	Phase 3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	Phase 3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	Phase 3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	Phase 3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	Phase 3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04577404	Phase 3	COMPLETED	Safety Extension Study of Oral Edaravone Administered in Subjects With Amyotrophic Lateral Sclerosis (ALS)
NCT04745299	Phase 3	COMPLETED	Evaluation the Efficacy and Safety of Mutiple Lenzumestrocel (Neuronata-R® Inj.) Treatment in Patients With ALS
NCT04768972	Phase 3	ACTIVE_NOT_RECRUITING	FUSION: A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)
NCT04944784	Phase 3	TERMINATED	A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT05021536	Phase 3	UNKNOWN	Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment
NCT05151471	Phase 3	TERMINATED	Efficacy and Safety Extension Study of Oral Edaravone Administered in Subjects With ALS
NCT05178810	Phase 3	COMPLETED	Study to Investigate the Efficacy and Safety of FAB122 (Daily Oral Edaravone) in Patients With Amyotrophic Lateral Sclerosis
NCT05193994	Phase 3	TERMINATED	Triumeq in Amyotrophic Lateral Sclerosis
NCT05442775	Phase 3	TERMINATED	A Phase 3, Open-Label Extension of COURAGE-ALS (CY 5031)
NCT05568615	Phase 3	COMPLETED	Extension Study Following the Studies MT-1186-A03 or A04 to Evaluate the Safety of Oral Edaravone in Subjects With ALS
NCT05619783	Phase 3	COMPLETED	Extension Study Evaluating The Safety And Tolerability of AMX0035
NCT05753852	Phase 3	UNKNOWN	Open Label Extension of TUDCA-ALS Study
NCT05866926	Phase 3	TERMINATED	Study to Investigate the Long-term Safety of FAB122 in Patients With Amyotrophic Lateral Sclerosis
NCT06008249	Phase 3	TERMINATED	Platform Trial to Assess the Efficacy of Multiple Drugs in Amyotrophic Lateral Sclerosis (ALS)
NCT06658977	Phase 3	TERMINATED	RolloverTreatment With Triumeq for People With ALS Following the Lighthouse II Trial
NCT06973629	Phase 3	NOT_YET_RECRUITING	Efficacy and Safety of MSC-NTF (NurOwn) in Participants With Early Symptomatic ALS and Moderate Disease Presentation in ALS (ENDURANCE STUDY)
NCT07174492	Phase 3	NOT_YET_RECRUITING	Efficacy and Safety of Masitinib in Combination With SoC Versus Placebo in the Treatment of ALS Patients
NCT07322003	Phase 3	RECRUITING	Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS
NCT00004771	Phase 2	COMPLETED	Phase II Study of Leuprolide and Testosterone for Men With Kennedy’s Disease or Other Motor Neuron Disease
NCT00005674	Phase 2	COMPLETED	Clinical Trial of Creatine in Amyotrophic Lateral Sclerosis [ALS]

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FUS across ~30M SureChEMBL compounds — explore on Sugi Predict.