FBXO45
Chr 3F-box protein 45
Also known as: Fbx45
FBXO45 encodes a component of E3 ubiquitin ligase complexes that targets specific proteins for degradation and is required for normal neuromuscular synaptogenesis, axon pathfinding, and neuronal migration during brain development. Mutations cause autosomal recessive developmental and epileptic encephalopathy with severe intellectual disability and early-onset seizures. This neurodevelopmental disorder primarily affects the central nervous system with onset in infancy or early childhood.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
125 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 | 0 | 0 | 84 | 0 | 84 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 17 | 14 | 0 | 31 |
Likely Benign | 0 | 0 | 1 | 0 | 1 |
Benign | 0 | 0 | 0 | 3 | 3 |
Conflicting | — | 1 | |||
| Total | 0 | 17 | 102 | 3 | 123 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FBXO45 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools