FBXO11

Chr 2AD

F-box protein 11

Also known as: FBX11, IDDFBA, UBR6, UG063H01, VIT1

NCBI Gene: 80204ENSG00000138081UniProt: Q86XK2

This gene encodes an F-box protein that serves as a substrate recognition component of SCF E3 ubiquitin ligase complexes, targeting specific proteins like BCL6, DTL, and SNAI1 for ubiquitination and proteasomal degradation. Mutations cause intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variation (pLI >0.99), indicating that such variants are likely pathogenic when they occur.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Intellectual developmental disorder with dysmorphic facies and behavioral abnormalitiesMIM #618089
AD
0
Active trials
14
Pubs (1 yr)
36
P/LP submissions
34%
P/LP missense
0.10
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical Summary— FBXO11
⚡
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.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 164 VUS of 400 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.10LOEUF
pLI 1.000
Z-score 6.35
OE 0.02 (0.01–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
4.38Z-score
OE missense 0.44 (0.39–0.49)
208 obs / 477.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.01–0.10)
0≤0.351.4
Missense OE0.44 (0.39–0.49)
0≤0.61.4
Synonymous OE1.25
0≤1.21.6
LoF obs/exp: 1 / 48.9Missense obs/exp: 208 / 477.2Syn Z: -2.44
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFBXO11-related variable neurodevelopmental disorderLOFAD
DN
0.2599th %ile
GOF
0.3987th %ile
LOF
0.83top 5%

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

LOFprediction above median · 1 literature citation · 44% of P/LP variants are LoF · LOEUF 0.10

Literature Evidence

LOFThe authors stated that deletions/mutations found in DLBCLs are largely monoallelic, indicating that FBXO11 is a haploinsufficient tumor suppressor gene.PMID:22113614

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

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic21
VUS164
Likely Benign159
Benign9
Conflicting7
11
Pathogenic
21
Likely Pathogenic
164
VUS
159
Likely Benign
9
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
1
4
0
11
Likely Pathogenic
8
10
3
0
21
VUS
0
129
32
3
164
Likely Benign
0
10
74
75
159
Benign
0
2
7
0
9
Conflicting
—7
Total1415212078371

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

View in ClinVar →

Protein Context — Lollipop Plot

FBXO11 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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
De novo variants in FBXO11 cause a syndromic form of intellectual disability with behavioral problems and dysmorphisms.
Jansen S et al.·Eur J Hum Genet
2019
FBXO11 variants are associated with intellectual disability and variable clinical manifestation in Chinese affected individuals.
Pan X et al.·J Hum Genet
2024
De novo missense variants in FBXO11 alter its protein expression and subcellular localization.
Gregor A et al.·Hum Mol Genet
2022
Cullin-associated and neddylation-dissociated 1 regulate reprogramming of lipid metabolism through SKP1-Cullin-1-F-box(FBXO11) -mediated heterogeneous nuclear ribonucleoprotein A2/B1 ubiquitination and promote hepatocellular carcinoma.
Zhang H et al.·Clin Transl Med
2023
How many phenotypes for the FBXO11 related disease? Report on a new patient with a tricho-rhino-phalangeal like phenotype.
Mégarbané A et al.·Eur J Med Genet
2024Case report
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
FBXO11 suppression rewires an NPM1-centered interactome influencing the progression of myelodysplastic syndrome.
Niederkorn M et al.·J Clin Invest
2026Open Access
Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1.
Kincross H et al.·J Clin Invest
2026Open Access
[Clinical and genetic analysis of a child with Intellectual developmental disorder with dysmorphic features and behavioral abnormalities due to a de novo variant of FBXO11 gene].
Zhang Q et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025
Regulatory polymorphisms of MSH6, MSH2, FBXO11, and PPP1R21 genes affect survival of patients with immunotherapy-treated lung cancer.
Esposito M et al.·J Immunother Cancer
2025Open AccessCohort
Tumor suppressor FBXO11 drives ubiquitin proteasomal degradation of KIF2C to limit ovarian cancer progression and is transcriptionally repressed by ZNF217.
Chen Q et al.·Cell Signal
2025
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