RBFOX2
RNA Binding Fox-1 Homolog 2: A Master Regulator of Alternative Splicing in Development and Disease
Gene Information Card
| Symbol | RBFOX2 |
|---|---|
| Full Name | RNA Binding Fox-1 Homolog 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.1 |
| NCBI Gene ID | 23543 ncbi.nlm.nih.gov/gene/23543 |
| Ensembl ID | ENSG00000100320 |
| UniProt ID | O43251 |
| OMIM ID | 612149 |
| HGNC ID | 18222 |
| Aliases | RBM9, FOX-2, HRNBP2, FXH2 |
Description
RBFOX2 (RNA Binding Fox-1 Homolog 2) encodes a member of the Fox-1 family of RNA-binding proteins that regulate alternative splicing. The protein contains an N-terminal RNA recognition motif (RRM) that binds to (U)GCAUG elements in pre-mRNA introns. RBFOX2 controls tissue-specific splicing events critical for neuronal, muscle, and cardiac development. It also modulates splicing in cancer, influencing cell proliferation, migration, and apoptosis. RBFOX2 is widely expressed, with highest levels in brain, heart, and skeletal muscle.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | RBFOX2 mis-splicing of NUMB, BIN1, and other targets promotes oncogenic pathways | PMID: 23431136; COSMIC |
| Colorectal cancer | Altered RBFOX2 expression correlates with splicing changes in EMT-related genes | PMID: 27149846; COSMIC |
| Pancreatic cancer | RBFOX2 loss drives splicing of MAP2K7 and enhances metastasis | PMID: 29429982 |
| Cardiac hypertrophy | RBFOX2 regulates splicing of CAMK2D and other cardiac transcripts | PMID: 26951611 |
| Autism spectrum disorder | RBFOX2 variants affect splicing of synaptic genes | ClinVar; PMID: 22542183 |
| Myotonic dystrophy type 2 | RBFOX2 sequestration by expanded CCTG repeats disrupts splicing | PMID: 16794022 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 38.5 | High |
| Heart | 32.1 | High |
| Skeletal muscle | 28.7 | High |
| Liver | 6.2 | Low |
| Kidney | 12.4 | Medium |
| Lung | 10.8 | Medium |
| Pancreas | 8.5 | Low |
| Testis | 15.3 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 22.1 | Embryonic kidney; high RBFOX2 expression |
| SH-SY5Y | 35.6 | Neuroblastoma; neuronal model |
| MCF7 | 18.4 | Breast cancer; moderate expression |
| HepG2 | 9.2 | Hepatocellular carcinoma; low expression |
| A549 | 14.7 | Lung cancer; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.01% | Altered RNA-binding affinity; associated with neurodevelopmental delay (ClinVar) |
| c.1246G>A (p.Gly416Arg) | Missense | <0.01% | Impaired splicing regulation; reported in autism (ClinVar) |
| c.1450_1451del (p.Lys484Glufs*3) | Frameshift | <0.01% | Loss of function; linked to intellectual disability (ClinVar) |
| Amplification | Copy number gain | ~2% in breast cancer | Overexpression; may drive oncogenic splicing (COSMIC) |
| Deletion | Copy number loss | ~1% in pancreatic cancer | Reduced expression; promotes metastasis (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Lys484Glufs*3) lead to truncated protein lacking the C-terminal domain, reducing splicing activity.
Gain of Function (GOF)
Amplification or overexpression in some cancers may enhance splicing of pro-proliferative transcripts, acting as an oncogenic driver.
Dominant Negative (DN)
Missense mutations in the RRM domain (e.g., p.Arg339Trp) can disrupt RNA binding and interfere with wild-type RBFOX2 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Alternative splicing regulation (Reactome: R-HSA-72172)
• mRNA processing (Reactome: R-HSA-72163)
• Gene expression (Reactome: R-HSA-74160)
• RBFOX2-mediated splicing of neuronal transcripts (PMID: 22542183)
Protein Summary
RBFOX2 is a 397-amino acid RNA-binding protein with a single RRM domain that recognizes (U)GCAUG motifs. It shuttles between nucleus and cytoplasm, regulating alternative splicing of hundreds of pre-mRNAs. Key targets include NUMB, BIN1, CAMK2D, and MAP2K7. RBFOX2 is essential for neuronal differentiation, muscle development, and cardiac function. Dysregulation contributes to cancer, neurodevelopmental disorders, and myotonic dystrophy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RBFOX2 Knockout HEK293 Cell Line | EDJ-KQ8054 | Human | 23543 | Details Get a Quote |
| RBFOX2 Knockout A-549 Cell Line | EDJ-KQ33871 | Human | 23543 | Details Get a Quote |
| RBFOX2 Knockout HCT 116 Cell Line | EDJ-KQ33872 | Human | 23543 | Details Get a Quote |
| RBFOX2 Knockout HeLa Cell Line | EDJ-KQ33873 | Human | 23543 | Details Get a Quote |
