FBXO11

Chr 2AD

F-box protein 11

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

NCBI Gene: 80204 ENSG00000138081 UniProt: Q86XK2 OMIM: 607871

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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 Fbxs class. It can function as an arginine methyltransferase that symmetrically dimethylates arginine residues, and it acts as an adaptor protein to mediate the neddylation of p53, which leads to the suppression of p53 function. This gene is known to be down-regulated in melanocytes from patients with vitiligo, a skin disorder that results in depigmentation. Polymorphisms in this gene are associated with chronic otitis media with effusion and recurrent otitis media (COME/ROM), a hearing loss disorder, and the knockout of the homologous mouse gene results in the deaf mouse mutant Jeff (Jf), a single gene model of otitis media. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder with dysmorphic facies and behavioral abnormalitiesMIM #618089

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.10

LOEUF· LoF intol.

LOF

Mechanism· G2P