FBXL4
Chr 6ARF-box and leucine rich repeat protein 4
Also known as: FBL4, FBL5, MTDPS13
The protein functions as part of an E3 ubiquitin ligase complex that regulates protein degradation, including control of lysine-specific demethylase 4A levels in cell-cycle regulation. Biallelic mutations cause mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), inherited in an autosomal recessive pattern. The pathogenic mechanism involves disrupted mitochondrial DNA maintenance leading to mitochondrial dysfunction and subsequent encephalomyopathy.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
ClinVar Variant Classifications
73 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 15 | 0 | 4 | 1 | 20 |
Likely Pathogenic | 4 | 18 | 1 | 0 | 23 |
VUS | 0 | 6 | 3 | 2 | 11 |
Likely Benign | 0 | 0 | 1 | 2 | 3 |
Benign | 0 | 1 | 1 | 3 | 5 |
Conflicting | — | 11 | |||
| Total | 19 | 25 | 10 | 8 | 73 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FBXL4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools