FUS

Chr 16ADAR

FUS RNA binding protein

ENSG00000089280UniProt: P35637OMIM: 137070

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 (PubMed:27731383). Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). 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 (PubMed:26124092). Also binds its own pre-mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay (PubMed:24204307). Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair (PubMed:10567410). In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis (By similarity)

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Amyotrophic lateral sclerosis 6, with or without frontotemporal dementiaMIM #608030
ADAR
Essential tremor, hereditary, 4MIM #614782
AD
UniProtAngiomatoid fibrous histiocytoma

Clinical highlights

Gene-disease validity (ClinGen)
amyotrophic lateral sclerosis type 6 · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
6
Active trials
918
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.24
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.24LOEUF
pLI 0.999
Z-score 5.16
OE 0.10 (0.05–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.21Z-score
OE missense 0.66 (0.59–0.74)
217 obs / 329.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.10 (0.05–0.24)
0≤0.351.4
Missense OE?0.66 (0.59–0.74)
0≤0.61.4
Synonymous OE?1.25
0≤1.21.6
LoF obs/exp: 4 / 38.6Missense obs/exp: 217 / 329.7Syn Z: -2.13

ClinVar

No ClinVar data available.

Protein Context — Lollipop Plot

FUS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Brain NeoplasmsLiquid Biopsy

BRAINFUL (BRAIN Tumor Focused Ultrasound-enabled Liquid Biopsy) Trial

ACTIVE NOT RECRUITING
NCT04940507Phase NAUniversity Health Network, TorontoStarted 2021-06-10
Magnetic Resonance Guided Focused Ultrasound Tumor Ablation and Liquid Biopsy AcquisitionMagnetic Resonance Guided Focused Ultrasound Thalamotomy
Amyotrophic Lateral Sclerosis

Longitudinal Assessment of Autonomic and Sensory Nervous System in ALS

RECRUITING
NCT05747937Phase NAIstituti Clinici Scientifici Maugeri SpAStarted 2021-05-15
Skin biopsyCardiovascular Reflexes testingAdministration of clinical scales evaluating autonomic symptoms, pain small fiber neuropathy symptoms
Neurodegenerative DiseaseBehavioral Variant Frontotemporal Dementia (bvFTD)Primary Progressive Aphasia(PPA)

Tracking and Predicting How Brain Damage Spreads in Neurodegenerative Diseases

ENROLLING BY INVITATION
NCT07567664Phase NAIRCCS San RaffaeleStarted 2017-06-01
3 Tesla MRI without contrast mediumBlood sample for genetic analysisCerebrospinal fluid sampling (CSF)
Amyotrophic Lateral Sclerosis (ALS)

Study on the Safety and Efficacy of RAG-21 in the Treatment of Amyotrophic Lateral Sclerosis Patients With FUS Gene Mutations

NOT YET RECRUITING
NCT07080801Phase EARLY_PHASE1Beijing Tiantan HospitalStarted 2025-08
RAG-21
Amyotrophic Lateral Sclerosis

Development of Targeted RNA-Seq for Amyotrophic Lateral Sclerosis Diagnosis

RECRUITING
NCT06083584Centre Hospitalier Universitaire de NīmesStarted 2023-11-22
RNA sequencing
ALS

Amyotrophic Lateral Sclerosis (ALS) Families Project

RECRUITING
NCT03865420Columbia UniversityStarted 2018-09-11

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients