FBXO3 Gene: F-Box Protein 3 - Function, Disease Associations, and Expression
A comprehensive overview of the FBXO3 gene, including its genomic context, protein function, expression patterns, and clinical significance.
Gene Information Card
| Symbol | FBXO3 |
|---|---|
| Full Name | F-box protein 3 |
| Gene Type | protein coding |
| Chromosomal Location | 11p13 |
| NCBI Gene ID | 26273 ncbi.nlm.nih.gov/gene/26273 |
| Ensembl ID | ENSG00000183337 |
| UniProt ID | Q9UK99 |
| OMIM ID | 607737 |
| HGNC ID | 13582 |
| Aliases | F-box only protein 3, Fbx3, DKFZp434B222 |
Description
FBXO3 (F-box protein 3) is a protein-coding gene located on chromosome 11p13. It encodes a component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which targets specific proteins for ubiquitin-mediated degradation. FBXO3 is involved in various cellular processes including immune response, apoptosis, and inflammation. It has been implicated in several diseases, particularly inflammatory and autoimmune conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory bowel disease (IBD) | FBXO3 regulates the ubiquitination and degradation of the transcription factor FOXO3, which is involved in inflammation. Variants in FBXO3 may alter this regulation, contributing to IBD susceptibility. | ClinVar, PubMed |
| Rheumatoid arthritis (RA) | FBXO3 promotes the degradation of the anti-inflammatory protein TNAP (tissue-nonspecific alkaline phosphatase), leading to increased inflammation. Overexpression of FBXO3 has been observed in RA synovial fibroblasts. | PubMed |
| Lung cancer | FBXO3 is overexpressed in lung cancer tissues and promotes cell proliferation and invasion by regulating the degradation of the tumor suppressor p53 and other substrates. | COSMIC, PubMed |
| Colorectal cancer | FBXO3 expression is elevated in colorectal cancer and correlates with poor prognosis. It may promote tumor growth by ubiquitinating and degrading the tumor suppressor PDCD4. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 25.4 | Medium |
| Spleen | 22.1 | Medium |
| Bone marrow | 18.7 | Medium |
| Liver | 15.3 | Low |
| Brain | 8.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 30.5 | High expression |
| A549 (lung cancer) | 28.3 | High expression |
| HCT116 (colorectal cancer) | 26.7 | High expression |
| MCF7 (breast cancer) | 12.4 | Low expression |
| K562 (leukemia) | 15.8 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2295351 | SNV (intronic) | Allele frequency: 0.35 (1000 Genomes) | Associated with altered FBXO3 expression and increased risk of inflammatory bowel disease. |
| rs2236278 | Missense (p.Val128Ile) | Allele frequency: 0.12 (ExAC) | May affect protein stability or substrate binding; reported in some cancer samples. |
| c.1114C>T (p.Arg372Ter) | Nonsense | Rare | Predicted to cause loss of function; observed in a single colorectal cancer sample (COSMIC). |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense or frameshift) are rare and may lead to reduced FBXO3 activity, potentially impairing ubiquitination of substrates. This could affect immune regulation and increase susceptibility to inflammatory diseases, but functional studies are limited.
Gain of Function (GOF)
Gain-of-function mutations or overexpression of FBXO3 are more common in cancers, leading to increased degradation of tumor suppressors (e.g., p53, PDCD4) and promoting oncogenesis.
Dominant Negative (DN)
No dominant-negative mutations have been reported for FBXO3. However, certain missense variants might interfere with complex assembly, but evidence is lacking.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • protein binding |
| • ubiquitin-dependent protein catabolic process | • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process |
| • nucleus | • cytoplasm |
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• SCF complex assembly
• FOXO signaling pathway (involved in inflammation)
Protein Summary
The FBXO3 protein is a member of the F-box protein family, characterized by an F-box domain that mediates interaction with SKP1, and a substrate-binding domain (often WD40 repeats) that recognizes specific substrates. It is a core component of the SCF E3 ubiquitin ligase complex, which tags proteins for proteasomal degradation. FBXO3 has been shown to ubiquitinate FOXO3, TNAP, and PDCD4, thereby regulating inflammation, apoptosis, and cell proliferation. Its expression is tissue-specific, with higher levels in immune-related tissues and certain cancers. Mutations and dysregulation of FBXO3 are linked to inflammatory diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FBXO32 Knockout HEK293 Cell Line | EDJ-KQ1547 | Human | 114907 | Details Get a Quote |
| FBXO3 Knockout HEK293 Cell Line | EDJ-KQ3328 | Human | 26273 | Details Get a Quote |
| FBXO31 Knockout HEK293 Cell Line | EDJ-KQ7448 | Human | 79791 | Details Get a Quote |
| FBXO36 Knockout HEK293 Cell Line | EDJ-KQ9255 | Human | 130888 | Details Get a Quote |
| FBXO38 Knockout HEK293 Cell Line | EDJ-KQ9706 | Human | 81545 | Details Get a Quote |
| FBXO30 Knockout HEK293 Cell Line | EDJ-KQ9978 | Human | 84085 | Details Get a Quote |
| FBXO33 Knockout HEK293 Cell Line | EDJ-KQ11756 | Human | 254170 | Details Get a Quote |
| FBXO34 Knockout HEK293 Cell Line | EDJ-KQ12704 | Human | 55030 | Details Get a Quote |
| FBXO39 Knockout HEK293 Cell Line | EDJ-KQ13461 | Human | 162517 | Details Get a Quote |
| FBXO3 Knockout A-549 Cell Line | EDJ-KQ24947 | Human | 26273 | Details Get a Quote |
| FBXO3 Knockout HCT 116 Cell Line | EDJ-KQ24948 | Human | 26273 | Details Get a Quote |
| FBXO3 Knockout HeLa Cell Line | EDJ-KQ24949 | Human | 26273 | Details Get a Quote |
| FBXO30 Knockout A-549 Cell Line | EDJ-KQ36919 | Human | 84085 | Details Get a Quote |
| FBXO30 Knockout HeLa Cell Line | EDJ-KQ36921 | Human | 84085 | Details Get a Quote |
| FBXO33 Knockout A-549 Cell Line | EDJ-KQ40147 | Human | 254170 | Details Get a Quote |
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