FUS
Chr 16ADFUS RNA binding protein
Also known as: ALS6, ETM4, FUS1, HNRNPP2, POMP75, TLS, altFUS
The protein is a component of the heterogeneous nuclear ribonucleoprotein complex that regulates pre-mRNA splicing and export of processed mRNA to the cytoplasm, and belongs to the FET family of RNA-binding proteins involved in gene expression regulation and genomic integrity maintenance. Mutations cause autosomal dominant amyotrophic lateral sclerosis type 6 with or without frontotemporal dementia, and hereditary essential tremor type 4. The pathogenic mechanism involves loss of function, with the gene showing extreme intolerance to loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
FUS · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Development of Targeted RNA-Seq for Amyotrophic Lateral Sclerosis Diagnosis
RECRUITINGStudy on the Safety and Efficacy of RAG-21 in the Treatment of Amyotrophic Lateral Sclerosis Patients With FUS Gene Mutations
NOT YET RECRUITINGAmyotrophic Lateral Sclerosis (ALS) Families Project
RECRUITINGBRAINFUL (BRAIN Tumor Focused Ultrasound-enabled Liquid Biopsy) Trial
ACTIVE NOT RECRUITINGLongitudinal Assessment of Autonomic and Sensory Nervous System in ALS
RECRUITINGTracking and Predicting How Brain Damage Spreads in Neurodegenerative Diseases
ENROLLING BY INVITATIONExternal Resources
Links to major genomics databases and tools