FBXW11

Chr 5AD

F-box and WD repeat domain containing 11

Also known as: BTRC2, BTRCP2, FBW1B, FBXW1B, Fbw11, Hos, NEDJED

NCBI Gene: 23291ENSG00000072803UniProt: Q9UKB1

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbws class and, in addition to an F-box, contains multiple WD40 repeats. This gene contains at least 14 exons, and its alternative splicing generates 3 transcript variants diverging at the presence/absence of two alternate exons. [provided by RefSeq, Jul 2008]

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Primary Disease Associations & Inheritance

Neurodevelopmental, jaw, eye, and digital syndromeMIM #618914
AD
0
Active trials
15
Pubs (1 yr)
29
P/LP submissions
36%
P/LP missense
0.31
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— FBXW11
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 110 VUS of 157 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.31LOEUF
pLI 0.976
Z-score 4.56
OE 0.15 (0.08–0.31)
Highly constrained

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

Missense Constraint
3.96Z-score
OE missense 0.37 (0.32–0.43)
115 obs / 311.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.15 (0.08–0.31)
0≤0.351.4
Missense OE0.37 (0.32–0.43)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 5 / 33.5Missense obs/exp: 115 / 311.5Syn Z: 0.39
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongFBXW11-related syndromic intellectual disabilityOTHERAD
DN
0.3694th %ile
GOF
0.4776th %ile
LOF
0.70top 10%

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

LOFprediction above median · LOEUF 0.31

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

157 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic8
VUS110
Likely Benign9
Conflicting3
14
Pathogenic
8
Likely Pathogenic
110
VUS
9
Likely Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
8
0
0
8
VUS
11
83
16
0
110
Likely Benign
0
0
2
7
9
Benign
0
0
0
0
0
Conflicting
—3
Total1191327144

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FBXW11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients