FBXO45
F-box protein 45: a substrate recognition component of the SCF ubiquitin ligase complex involved in neurodevelopment and cancer
Gene Information Card
| Symbol | FBXO45 |
|---|---|
| Full Name | F-box protein 45 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q29 |
| NCBI Gene ID | 200933 ncbi.nlm.nih.gov/gene/200933 |
| Ensembl ID | ENSG00000163930 |
| UniProt ID | Q8N7X0 |
| OMIM ID | 609112 |
| HGNC ID | 29148 |
| Aliases | Fbx45, F-box only protein 45 |
Description
FBXO45 encodes F-box protein 45, a member of the F-box protein family that serves as the substrate recognition component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex. It targets specific proteins for ubiquitination and proteasomal degradation, playing critical roles in neurodevelopment, synaptic function, and cell cycle regulation. FBXO45 is highly expressed in the nervous system and has been implicated in intellectual disability, autism spectrum disorders, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal dominant 65 | Loss-of-function mutations impair ubiquitination of synaptic proteins, disrupting neuronal development | OMIM #619090 |
| Autism spectrum disorder | De novo missense variants alter substrate binding, affecting synaptic plasticity | ClinVar |
| Colorectal cancer | Overexpression promotes degradation of tumor suppressors, enhancing proliferation | COSMIC |
| Lung adenocarcinoma | FBXO45 amplification correlates with poor prognosis and metastasis | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Cerebellum | 15.3 | Medium |
| Testis | 8.2 | Low |
| Heart | 4.1 | Low |
| Liver | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.7 | Neuronal model |
| HEK293 (embryonic kidney) | 9.4 | Common expression system |
| A549 (lung carcinoma) | 6.8 | Cancer cell line |
| HCT116 (colorectal carcinoma) | 11.2 | Colorectal cancer model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | Rare | Loss of substrate binding; associated with intellectual disability |
| c.1246G>A (p.Gly416Arg) | Missense | Rare | Impaired complex assembly; autism spectrum disorder |
| c.1480C>T (p.Arg494*) | Nonsense | Rare | Premature truncation; loss of function |
| Amplification (3q29) | Copy number gain | Frequent in lung cancer | Increased FBXO45 expression; oncogenic |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that disrupt F-box domain or substrate binding, leading to reduced ubiquitin ligase activity and accumulation of target proteins.
Gain of Function (GOF)
Amplification or overexpression in cancers enhances degradation of tumor suppressors (e.g., p53), promoting cell proliferation.
Dominant Negative (DN)
Missense variants that retain binding to SKP1 but fail to recruit substrates, interfering with wild-type FBXO45 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• SCF ubiquitin ligase complex (Reactome R-HSA-8951664)
• Ubiquitin-mediated proteolysis (KEGG hsa04120)
• p53 signaling pathway (KEGG hsa04115)
Protein Summary
FBXO45 is a 45 kDa F-box protein that contains an N-terminal F-box domain for SKP1 interaction and a C-terminal substrate-binding domain. It assembles into the SCF complex to ubiquitinate targets such as the synaptic protein PSD-95 and the transcription factor FOXO1, regulating neuronal development and cell survival. Structural studies reveal a conserved F-box fold and a unique substrate recognition interface.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FBXO45 Knockout HEK293 Cell Line | EDJ-KQ4635 | Human | 200933 | Details Get a Quote |
| FBXO45 Knockout A-549 Cell Line | EDJ-KQ26074 | Human | 200933 | Details Get a Quote |
| FBXO45 Knockout HCT 116 Cell Line | EDJ-KQ27317 | Human | 200933 | Details Get a Quote |
| FBXO45 Knockout HeLa Cell Line | EDJ-KQ27318 | Human | 200933 | Details Get a Quote |
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