| FBXO45 — F-Box Protein 45 | |
|---|---|
| Symbol | FBXO45 |
| Full Name | F-Box Protein 45 |
| Chromosome | 3q29 |
| NCBI Gene | 200185 |
| Ensembl | ENSG00000157542 |
| UniProt | Q9C0B1 |
| Diseases | [Amyotrophic Lateral Sclerosis (ALS)](/diseases/amyotrophic-lateral-sclerosis), [Frontotemporal Dementia](/diseases/frontotemporal-dementia), Intellectual disability |
| Expression | Brain, Spinal cord, Muscle |
FBXO45 (F-Box Protein 45) is a member of the F-box protein family, which are substrate recognition components of the SCF (Skp1-Cullin1-F-box) ubiquitin ligase complex. Located on chromosome 3q29, FBXO45 plays critical roles in protein quality control, synaptic function, and has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)[1].
FBXO45 contains an F-box domain that recruits the protein to the SCF ubiquitin ligase complex. Its primary functions include:
As an F-box protein, FBXO45 targets specific substrates for ubiquitination and subsequent degradation by the proteasome. This process is essential for:
FBXO45 is highly expressed in neurons and plays important roles at the synapse:
FBXO45 has been implicated in mitophagy (mitochondrial autophagy), helping to remove dysfunctional mitochondria that accumulate in neurodegeneration.
FBXO45 has been linked to ALS through several mechanisms[1:1][2]:
FBXO45 is implicated in FTD pathogenesis:
FBXO45 variants have been associated with neurodevelopmental disorders, reflecting its critical role in brain development and synaptic function.
FBXO45 is enriched in:
FBXO45 targets several neuronal proteins for degradation:
Targeting FBXO45 therapeutically presents significant challenges:
| Model | Description | Key Findings |
|---|---|---|
| FBXO45 KO mice | Complete knockout | Synaptic deficits, learning impairment |
| FBXO45 knockdown zebrafish | Partial loss | Motor axon guidance defects |
| ALS-FBXO45 transgenic | Mutant overexpression | Protein aggregate formation |
Current research is focused on: