FBXO45

Chr 3

F-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.

Summary from RefSeq, UniProt
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0
Active trials
10
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.27
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryFBXO45
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.27LOEUF
pLI 0.971
Z-score 3.06
OE 0.00 (0.000.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.34Z-score
OE missense 0.44 (0.360.55)
62 obs / 139.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.27)
00.351.4
Missense OE0.44 (0.360.55)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 0 / 10.9Missense obs/exp: 62 / 139.9Syn Z: 0.68
DN
0.18100th %ile
GOF
0.3788th %ile
LOF
0.78top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.27

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

0 submitted variants 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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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