FBXO44: F-Box Protein 44 – A Substrate Recognition Component of the SCF Ubiquitin Ligase Complex
Comprehensive genomic and proteomic analysis of FBXO44, including expression, mutations, and disease associations.
Gene Information Card
| Symbol | FBXO44 |
|---|---|
| Full Name | F-box protein 44 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.22 |
| NCBI Gene ID | 93611 ncbi.nlm.nih.gov/gene/93611 |
| Ensembl ID | ENSG00000117525 |
| UniProt ID | Q9H4M3 |
| OMIM ID | 609101 |
| HGNC ID | 18583 |
| Aliases | FBX44, F-box only protein 44, MGC13170 |
Description
FBXO44 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. FBXO44 functions as the substrate recognition component, binding specific substrates for ubiquitination. It is involved in cell cycle regulation, apoptosis, and neurodevelopment. Alternative splicing results in multiple transcript variants.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | FBXO44 overexpression may promote degradation of tumor suppressors, contributing to oncogenesis. | COSMIC; PMID: 25691885 |
| Neurodevelopmental disorders | Variants in FBXO44 have been associated with intellectual disability and autism spectrum disorder. | ClinVar; PMID: 28135719 |
| Epilepsy | Rare missense variants reported in patients with epilepsy, possibly affecting neuronal protein turnover. | ClinVar; PMID: 30311386 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 4.7 | Low |
| Kidney | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | Embryonic kidney; high expression |
| SH-SY5Y | 11.8 | Neuroblastoma; moderate expression |
| HeLa | 9.5 | Cervical cancer; moderate expression |
| MCF7 | 7.3 | Breast cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | 0.001% (gnomAD) | Unknown; predicted damaging by SIFT |
| c.287G>A (p.Arg96Gln) | Missense | 0.002% (gnomAD) | Unknown; predicted benign |
| c.502_503insA (p.Thr168Asnfs*5) | Frameshift | <0.001% | Loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants that truncate the F-box domain or substrate-binding region are classified as loss-of-function, impairing ubiquitin ligase activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for FBXO44.
Dominant Negative (DN)
Missense variants in the F-box domain may act as dominant-negative by competing with wild-type FBXO44 for SKP1 binding, but evidence is limited.
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 (Reactome: R-HSA-8951664)
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
Protein Summary
FBXO44 is a 385-amino acid protein containing an N-terminal F-box domain (residues 30–74) that mediates interaction with SKP1, and a C-terminal substrate-binding region. It is localized to the nucleus and cytoplasm. The protein is involved in the ubiquitination of substrates such as cyclin D1 and other cell cycle regulators. Post-translational modifications include phosphorylation at Ser/Thr residues, which may regulate substrate specificity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FBXO44 Knockout HEK293 Cell Line | EDJ-KQ11244 | Human | 93611 | Details Get a Quote |
| FBXO44 Knockout A-549 Cell Line | EDJ-KQ38011 | Human | 93611 | Details Get a Quote |
| FBXO44 Knockout HCT 116 Cell Line | EDJ-KQ39336 | Human | 93611 | Details Get a Quote |
| FBXO44 Knockout HeLa Cell Line | EDJ-KQ39337 | Human | 93611 | Details Get a Quote |
