FBXO7 Gene: F-box Only Protein 7 - Genetics, Function, and Clinical Significance
A comprehensive biomedical overview of FBXO7, including genomic context, protein function, associated diseases, expression patterns, and mutation landscape.
Gene Information Card
| Symbol | FBXO7 |
|---|---|
| Full Name | F-box only protein 7 |
| Gene Type | protein coding |
| Chromosomal Location | 22q12.3 |
| NCBI Gene ID | 25793 ncbi.nlm.nih.gov/gene/25793 |
| Ensembl ID | ENSG00000100225 |
| UniProt ID | Q9Y3I1 |
| OMIM ID | 605648 |
| HGNC ID | 13586 |
| Aliases | FBX7, PARK15, DKFZp686K09120 |
Description
FBXO7 encodes the F-box only protein 7, a component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. This protein plays a critical role in ubiquitin-mediated protein degradation and has been implicated in mitophagy, mitochondrial homeostasis, and cell cycle regulation. Mutations in FBXO7 are associated with autosomal recessive early-onset Parkinson disease 15 (PARK15), characterized by pyramidal tract signs and cognitive impairment. The protein is widely expressed, with notable levels in the brain, and its dysfunction contributes to neurodegeneration.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Parkinson disease 15 (PARK15) | Loss-of-function mutations impair mitophagy and mitochondrial quality control, leading to dopaminergic neuron degeneration. | ClinVar, OMIM (605648) |
| Parkinson disease, early-onset (general) | Compound heterozygous or homozygous mutations disrupt protein function, contributing to disease pathogenesis. | ClinVar, literature |
| Cancer (potential) | Altered expression may affect cell cycle and apoptosis, but direct causal evidence is limited. | COSMIC (somatic mutations observed) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | ~10 | Medium |
| Testis | ~8 | Medium |
| Heart | ~6 | Low |
| Liver | ~5 | Low |
| Kidney | ~4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | ~12 | Neuronal model |
| HeLa (cervical carcinoma) | ~9 | Common cell line |
| HEK293 (embryonic kidney) | ~8 | Widely used |
| A549 (lung carcinoma) | ~7 | Epithelial |
| MCF7 (breast carcinoma) | ~6 | Hormone-responsive |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.122G>C (p.Arg41Pro) | Missense | Rare (found in PARK15 families) | Impairs protein stability and mitophagy |
| c.155A>G (p.Lys52Arg) | Missense | Rare | Reduced E3 ligase activity |
| c.859G>A (p.Gly287Arg) | Missense | Rare | Disrupts protein-protein interactions |
| c.1142delC (p.Pro381LeufsTer?) | Frameshift | Rare | Truncated protein, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations lead to loss of function, impairing mitophagy and ubiquitin ligase activity, contributing to Parkinson disease.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some variants may exert dominant-negative effects but not classical gain-of-function.
Dominant Negative (DN)
Certain missense mutations (e.g., p.Arg41Pro) may act in a dominant-negative manner by interfering with complex assembly, though inheritance is typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • protein binding |
| • zinc ion binding | • mitochondrion |
| • cytoplasm | • nucleus |
| • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process | • mitophagy |
| • regulation of mitotic cell cycle |
Pathways
• Ubiquitin-Proteasome System (UPS)
• Mitophagy (PINK1/Parkin pathway)
• Cell Cycle Regulation
Protein Summary
FBXO7 is a 522-amino acid protein containing an F-box domain, which mediates interaction with SKP1, and a C-terminal domain involved in substrate recognition. It functions as part of the SCF E3 ubiquitin ligase complex, targeting proteins for proteasomal degradation. Additionally, FBXO7 participates in mitophagy by interacting with PINK1 and Parkin, facilitating mitochondrial clearance. Its role in cell cycle regulation and apoptosis underscores its broader cellular significance. Mutations causing loss of function lead to mitochondrial dysfunction and neurodegeneration, particularly in dopaminergic neurons.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FBXO7 Knockout HEK293 Cell Line | EDJ-KQ8230 | Human | 25793 | Details Get a Quote |
| FBXO7 Knockout A-549 Cell Line | EDJ-KQ34130 | Human | 25793 | Details Get a Quote |
| FBXO7 Knockout HCT 116 Cell Line | EDJ-KQ34131 | Human | 25793 | Details Get a Quote |
| FBXO7 Knockout HeLa Cell Line | EDJ-KQ34132 | Human | 25793 | Details Get a Quote |
