FBXW5

Chr 9

F-box and WD repeat domain containing 5

Also known as: Fbw5

This gene encodes an F-box protein that serves as a substrate recognition component of SCF and DCX E3 ubiquitin ligase complexes, targeting specific proteins including SASS6, EPS8, and TSC2 for degradation to regulate centriole duplication, cell cycle progression, and mTOR signaling. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and developmental regression. The gene shows very low constraint against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.53
Clinical SummaryFBXW5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.53LOEUF
pLI 0.000
Z-score -0.35
OE 1.08 (0.781.53)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.90Z-score
OE missense 1.27 (1.181.36)
506 obs / 399.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.08 (0.781.53)
00.351.4
Missense OE1.27 (1.181.36)
00.61.4
Synonymous OE1.44
01.21.6
LoF obs/exp: 23 / 21.3Missense obs/exp: 506 / 399.1Syn Z: -4.72

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FBXW5 · 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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