FBXL4: A Key Regulator of Mitochondrial Dynamics and Cellular Energy Metabolism
Comprehensive genomic and clinical overview of the FBXL4 gene, its role in mitochondrial disease, and associated phenotypes.
Gene Information Card
| Symbol | FBXL4 |
|---|---|
| Full Name | F-box and leucine-rich repeat protein 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q16.1 |
| NCBI Gene ID | 26235 ncbi.nlm.nih.gov/gene/26235 |
| Ensembl ID | ENSG00000112294 |
| UniProt ID | Q9UKA2 |
| OMIM ID | 605654 |
| HGNC ID | 13610 |
| Aliases | FBL4, F-box/LRR-repeat protein 4, FLJ13149 |
Description
FBXL4 (F-box and leucine-rich repeat protein 4) encodes a component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex. It is involved in mitochondrial quality control, mitophagy, and regulation of mitochondrial dynamics. Loss-of-function mutations cause mitochondrial DNA depletion syndrome 13 (MTDPS13), an autosomal recessive disorder characterized by encephalopathy, hypotonia, and lactic acidosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial DNA depletion syndrome 13 (MTDPS13) | Loss-of-function mutations impair mitophagy and mitochondrial turnover, leading to mtDNA depletion and respiratory chain deficiency. | ClinVar, OMIM |
| Encephalopathy, acute, with lactic acidosis | FBXL4 deficiency disrupts mitochondrial homeostasis, causing energy failure in neural tissues. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | Medium |
| Heart | 10.8 | Medium |
| Brain | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 9.2 | Cervical carcinoma |
| HEK293 | 11.0 | Embryonic kidney |
| SH-SY5Y | 7.8 | Neuroblastoma |
| HepG2 | 6.5 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335*) | Nonsense | Rare | Loss of function; premature truncation |
| c.1210C>T (p.Arg404Trp) | Missense | Rare | Loss of function; impaired protein stability |
| c.1462C>T (p.Arg488*) | Nonsense | Rare | Loss of function; nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Majority of reported FBXL4 mutations are loss-of-function (nonsense, frameshift, splice-site), leading to reduced or absent protein activity and mitochondrial dysfunction.
Gain of Function (GOF)
No gain-of-function mutations have been reported for FBXL4.
Dominant Negative (DN)
No dominant-negative mutations have been characterized; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• SCF ubiquitin ligase complex pathway
• Mitophagy (mitochondrial autophagy)
• Ubiquitin-proteasome system
Protein Summary
FBXL4 is a 621-amino acid protein containing an F-box domain and multiple leucine-rich repeats. It serves as a substrate recognition subunit of the SCF ubiquitin ligase complex, targeting proteins for proteasomal degradation. It localizes to mitochondria and regulates mitophagy, mitochondrial fission/fusion, and mtDNA maintenance. Loss of FBXL4 leads to mitochondrial fragmentation, reduced ATP production, and accumulation of damaged mitochondria.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FBXL4 Knockout HEK293 Cell Line | EDJ-KQ8469 | Human | 26235 | Details Get a Quote |
| FBXL4 Knockout A-549 Cell Line | EDJ-KQ34584 | Human | 26235 | Details Get a Quote |
| FBXL4 Knockout HCT 116 Cell Line | EDJ-KQ34585 | Human | 26235 | Details Get a Quote |
| FBXL4 Knockout HeLa Cell Line | EDJ-KQ34586 | Human | 26235 | Details Get a Quote |
