FBXO9: F-Box Protein 9 – A Substrate Recognition Component of the SCF Ubiquitin Ligase Complex
Comprehensive genomic and proteomic analysis of FBXO9, including expression, mutations, and disease associations.
Gene Information Card
| Symbol | FBXO9 |
|---|---|
| Full Name | F-box protein 9 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p12.3-p12.1 |
| NCBI Gene ID | 26268 ncbi.nlm.nih.gov/gene/26268 |
| Ensembl ID | ENSG00000112182 |
| UniProt ID | Q9UK97 |
| OMIM ID | 609094 |
| HGNC ID | 13591 |
| Aliases | FBX9, FBG2, F-box only protein 9 |
Description
FBXO9 encodes a member of the F-box protein family, characterized by an F-box domain. F-box proteins constitute one of the four subunits of the SCF (SKP1-cullin-F-box) ubiquitin ligase complex, which mediates ubiquitination and subsequent proteasomal degradation of target proteins. FBXO9 functions as the substrate recognition component, binding specific substrates for ubiquitination. It plays roles in cell cycle regulation, signal transduction, and development. Dysregulation of FBXO9 has been implicated in various cancers and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | FBXO9 overexpression may promote degradation of tumor suppressors, enhancing cell proliferation. | COSMIC, ClinVar |
| Colorectal cancer | Altered FBXO9 expression correlates with poor prognosis; potential role in Wnt/β-catenin pathway regulation. | COSMIC, NCBI Gene |
| Neurodevelopmental disorders | De novo missense variants in FBXO9 associated with intellectual disability and developmental delay. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain (cerebellum) | 8.2 | Low |
| Lung | 6.1 | Low |
| Liver | 4.8 | Low |
| Kidney | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney cells; moderate expression |
| HeLa | 7.8 | Cervical cancer cells; low expression |
| MCF7 | 9.4 | Breast cancer cells; moderate expression |
| A549 | 6.5 | Lung cancer cells; low 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% | Alters substrate binding; associated with neurodevelopmental delay |
| c.1246G>A (p.Gly416Arg) | Missense | <0.01% | Potential loss of function; reported in breast cancer |
| c.1480_1481insA (p.Thr494Asnfs*12) | Frameshift | <0.01% | Truncation; likely loss of function in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein, impairing SCF complex assembly and substrate ubiquitination.
Gain of Function (GOF)
Missense mutations that enhance substrate affinity or alter specificity, potentially leading to oncogenic degradation of tumor suppressors.
Dominant Negative (DN)
Mutations that produce a stable but non-functional F-box protein, competing with wild-type FBXO9 and disrupting normal ubiquitination.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • protein ubiquitination (GO:0016567) | • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146) |
| • proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161) |
Pathways
• SCF ubiquitin ligase complex pathway
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
• Cell cycle regulation via degradation of cyclins and CDK inhibitors
Protein Summary
FBXO9 is a 538-amino acid protein containing an N-terminal F-box domain (residues 42–87) and a C-terminal substrate-binding domain. It interacts with SKP1 and CUL1 to form the SCF ubiquitin ligase complex. The protein is localized in the nucleus and cytoplasm. Post-translational modifications include phosphorylation, which may regulate substrate specificity. Structural studies reveal that the F-box domain mediates SKP1 binding, while the C-terminal region recognizes specific degron motifs in target proteins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FBXO9 Knockout HEK293 Cell Line | EDJ-KQ8502 | Human | 26268 | Details Get a Quote |
| FBXO9 Knockout A-549 Cell Line | EDJ-KQ33316 | Human | 26268 | Details Get a Quote |
| FBXO9 Knockout HCT 116 Cell Line | EDJ-KQ34628 | Human | 26268 | Details Get a Quote |
| FBXO9 Knockout HeLa Cell Line | EDJ-KQ34629 | Human | 26268 | Details Get a Quote |
