FUS Gene (FUS RNA Binding Protein)
Comprehensive genomic and functional overview of the FUS gene, its role in ALS, frontotemporal dementia, and cancer.
Gene Information Card
| Symbol | FUS |
|---|---|
| Full Name | FUS RNA binding protein |
| Gene Type | Protein coding |
| Chromosomal Location | 16p11.2 |
| NCBI Gene ID | 2521 ncbi.nlm.nih.gov/gene/2521 |
| Ensembl ID | ENSG00000089280 |
| UniProt ID | P35637 |
| OMIM ID | 137070 |
| HGNC ID | 4010 |
| Aliases | ALS6, FUS1, HNRNPP2, POMP75, TLS |
Description
The FUS gene encodes a multifunctional RNA-binding protein involved in transcription regulation, RNA splicing, DNA repair, and stress granule formation. Mutations in FUS are a major cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The protein shuttles between nucleus and cytoplasm; pathological cytoplasmic aggregation is a hallmark of FUS-related neurodegeneration. FUS is also implicated in certain cancers through chromosomal translocations.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic lateral sclerosis 6 (ALS6) | Dominant mutations cause cytoplasmic mislocalization and aggregation of FUS protein, leading to motor neuron degeneration. | OMIM #608030; ClinVar |
| Frontotemporal dementia (FTD) | Similar mechanism as ALS: FUS aggregates in neurons of frontal and temporal lobes. | OMIM #137070; ClinVar |
| Myxoid liposarcoma | Chromosomal translocation t(12;16)(q13;p11) fuses FUS with DDIT3, producing oncogenic fusion protein. | COSMIC; NCBI |
| Acute myeloid leukemia | FUS-ERG fusion from t(16;21)(p11;q22) translocation. | COSMIC; NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 38.2 | High |
| Spinal cord | 32.1 | High |
| Testis | 25.4 | Medium |
| Heart | 18.7 | Medium |
| Liver | 12.3 | Medium |
| Lung | 10.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 42.1 | Neuronal model |
| HeLa (cervical carcinoma) | 35.6 | High expression |
| HEK293 (embryonic kidney) | 30.2 | Common model |
| A549 (lung carcinoma) | 28.4 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg521Cys (R521C) | Missense | ~5% of familial ALS | Cytoplasmic mislocalization, aggregation |
| p.Arg521Gly (R521G) | Missense | Rare | Similar to R521C |
| p.Pro525Leu (P525L) | Missense | Rare, severe juvenile ALS | Aggregation, impaired nuclear import |
| p.Gly156Glu (G156E) | Missense | Rare | Altered RNA binding |
| FUS-DDIT3 fusion | Translocation | Sporadic in myxoid liposarcoma | Oncogenic fusion protein |
Mutation functional classification
Loss of Function (LOF)
Not clearly established; most ALS mutations are gain-of-toxic-function.
Gain of Function (GOF)
Dominant mutations cause aberrant cytoplasmic aggregation and toxicity, consistent with gain-of-function.
Dominant Negative (DN)
Some evidence that mutant FUS interferes with wild-type FUS function in RNA processing.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • DNA binding (GO:0003677) |
| • mRNA splicing | • via spliceosome (GO:0000398) |
| • Stress granule assembly (GO:0034063) | • Nucleus (GO:0005634) |
| • Cytoplasm (GO:0005737) |
Pathways
• RNA splicing (Reactome: R-HSA-72163)
• Processing of Capped Intron-Containing Pre-mRNA (Reactome: R-HSA-72203)
• Amyotrophic lateral sclerosis (KEGG: hsa05014)
Protein Summary
FUS is a 526-amino acid RNA-binding protein with an N-terminal QGSY-rich domain, a glycine-rich region, an RRM domain, a zinc finger domain, and a C-terminal nuclear localization signal (NLS). It participates in transcription, pre-mRNA splicing, DNA repair, and stress granule dynamics. Pathogenic mutations cluster in the C-terminal NLS, impairing nuclear import and promoting cytoplasmic aggregation. The protein is ubiquitously expressed, with highest levels in brain and spinal cord.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FUS Knockout HEK293 Cell Line | EDC07631 | Human | 2521 | Details Get a Quote |
| GFUS Knockout HEK293 Cell Line | EDJ-KQ5972 | Human | 7264 | Details Get a Quote |
| FUS Knockout A-549 Cell Line | EDJ-KQ20011 | Human | 2521 | Details Get a Quote |
| FUS Knockout HCT 116 Cell Line | EDJ-KQ20012 | Human | 2521 | Details Get a Quote |
| FUS Knockout HeLa Cell Line | EDJ-KQ20013 | Human | 2521 | Details Get a Quote |
| GFUS Knockout A-549 Cell Line | EDJ-KQ29542 | Human | 7264 | Details Get a Quote |
| GFUS Knockout HCT 116 Cell Line | EDJ-KQ29543 | Human | 7264 | Details Get a Quote |
| GFUS Knockout HeLa Cell Line | EDJ-KQ29544 | Human | 7264 | Details Get a Quote |
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