EWSR1 Gene (EWS RNA Binding Protein 1)
A key player in Ewing sarcoma and related neoplasms, encoding an RNA-binding protein involved in transcription and splicing.
Gene Information Card
| Symbol | EWSR1 |
|---|---|
| Full Name | EWS RNA Binding Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q12.2 |
| NCBI Gene ID | 2130 ncbi.nlm.nih.gov/gene/2130 |
| Ensembl ID | ENSG00000182944 |
| UniProt ID | Q01844 |
| OMIM ID | 133450 |
| HGNC ID | 3508 |
| Aliases | EWS, EWS-FLI1, bK984G1.4 |
Description
EWSR1 encodes a multifunctional RNA-binding protein that participates in transcription, RNA splicing, and DNA damage response. It is ubiquitously expressed and frequently involved in chromosomal translocations that generate oncogenic fusion proteins, most notably EWSR1-FLI1 in Ewing sarcoma. These fusions drive tumorigenesis by altering gene expression programs.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ewing sarcoma | EWSR1-FLI1 fusion (t(11;22)(q24;q12)) acts as an aberrant transcription factor driving oncogenesis. | ClinVar, COSMIC, OMIM |
| Desmoplastic small round cell tumor | EWSR1-WT1 fusion (t(11;22)(p13;q12)) leads to chimeric transcription factor. | ClinVar, COSMIC, OMIM |
| Clear cell sarcoma | EWSR1-ATF1 fusion (t(12;22)(q13;q12)) activates oncogenic pathways. | ClinVar, COSMIC, OMIM |
| Myxoid liposarcoma | EWSR1-DDIT3 fusion (t(12;22)(q13;q12)) disrupts adipocyte differentiation. | ClinVar, COSMIC, OMIM |
| Angiomatoid fibrous histiocytoma | EWSR1-CREB1 fusion (t(2;22)(q33;q12)) drives tumor formation. | ClinVar, COSMIC, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Kidney | 10.1 | Medium |
| Liver | 6.7 | Low |
| Lung | 9.4 | Medium |
| Muscle | 7.8 | Low |
| Pancreas | 11.2 | Medium |
| Skin | 14.0 | Medium |
| Testis | 18.5 | High |
| Thyroid | 13.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A-673 (Ewing sarcoma) | 22.3 | High expression; EWSR1-FLI1 fusion positive |
| SK-N-MC (Ewing sarcoma) | 19.8 | High expression; EWSR1-FLI1 fusion positive |
| HeLa (cervical carcinoma) | 15.4 | Moderate expression |
| HEK293 (embryonic kidney) | 12.1 | Moderate expression |
| K562 (leukemia) | 9.7 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| EWSR1-FLI1 fusion | Chromosomal translocation | ~85% in Ewing sarcoma | Oncogenic fusion protein; aberrant transcription factor |
| EWSR1-ERG fusion | Chromosomal translocation | ~10% in Ewing sarcoma | Alternative fusion; similar oncogenic mechanism |
| EWSR1-WT1 fusion | Chromosomal translocation | >90% in desmoplastic small round cell tumor | Chimeric transcription factor |
| EWSR1-ATF1 fusion | Chromosomal translocation | >90% in clear cell sarcoma | Activation of CREB pathway |
| EWSR1-DDIT3 fusion | Chromosomal translocation | >90% in myxoid liposarcoma | Blocks adipogenesis |
Mutation functional classification
Loss of Function (LOF)
Not commonly described; wild-type EWSR1 loss may contribute to genomic instability but is not a primary driver.
Gain of Function (GOF)
EWSR1 fusions (e.g., EWSR1-FLI1) acquire novel transcriptional activation properties, driving oncogenic gene expression.
Dominant Negative (DN)
EWSR1 fusions may interfere with wild-type EWSR1 function in RNA processing, contributing to tumorigenesis.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ewing sarcoma pathway (KEGG: hsa05212)
• RNA splicing (Reactome: R-HSA-72163)
• Transcriptional regulation by TP53 (Reactome: R-HSA-3700989)
• Processing of Capped Intron-Containing Pre-mRNA (Reactome: R-HSA-72203)
Protein Summary
The EWSR1 protein (656 amino acids) contains an N-terminal transcriptional activation domain (TAD) rich in glutamine, serine, and tyrosine, and a C-terminal RNA recognition motif (RRM) and zinc finger domain. It shuttles between nucleus and cytoplasm, participating in transcription, pre-mRNA splicing, and DNA damage response. In cancer, the N-terminal TAD of EWSR1 fuses with various transcription factor partners (e.g., FLI1, ERG, WT1), creating potent oncoproteins that misregulate gene expression.
Related Services
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| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EWSR1 (c.13+85G>A )Point Mutation in HAP1 Cell Line | EDC03474 | Human | 2130 | Details Get a Quote |
