FBXW2

Chr 9

F-box and WD repeat domain containing 2

Also known as: FBW2, Fwd2, Md6

NCBI Gene: 26190ENSG00000119402UniProt: Q9UKT8OMIM: 609071

This gene encodes a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes that target specific proteins for ubiquitin-mediated degradation. Mutations cause disease through loss of function, as indicated by the extremely high pLI score (0.999) and very low LOEUF score (0.153) suggesting severe intolerance to protein-truncating variants. However, the specific neurological phenotype and inheritance pattern associated with FBXW2 mutations are not established in the provided data.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
LOFmechanismLOEUF 0.15
Clinical Summary— FBXW2
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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 38 VUS of 73 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.15LOEUF
pLI 0.999
Z-score 4.09
OE 0.00 (0.00–0.15)
Highly constrained

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

Missense Constraint
2.44Z-score
OE missense 0.56 (0.49–0.65)
137 obs / 244.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.15)
0≤0.351.4
Missense OE0.56 (0.49–0.65)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 0 / 19.5Missense obs/exp: 137 / 244.1Syn Z: -0.17
DN
0.2598th %ile
GOF
0.3986th %ile
LOF
0.70top 10%

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

LOFprediction above median · LOEUF 0.15

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

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS38
Likely Benign1
21
Pathogenic
1
Likely Pathogenic
38
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
0
37
1
0
38
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total03823061

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

View in ClinVar →

Protein Context — Lollipop Plot

FBXW2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 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