FBXW7

Chr 4AD

F-box and WD repeat domain containing 7

Also known as: AGO, CDC4, DEDHIL, FBW6, FBW7, FBX30, FBXW6, SEL-10

NCBI Gene: 55294 ENSG00000109670 UniProt: Q969H0 OMIM: 606278

This gene encodes an F-box protein that serves as the substrate recognition component of an SCF ubiquitin ligase complex, targeting phosphorylated proteins including cyclin E, MYC, NOTCH, and JUN for proteasomal degradation. Mutations cause autosomal dominant developmental delay, hypotonia, and impaired language with early childhood onset. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.23), reflecting its essential cellular role in protein degradation pathways.

GeneReviews 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 was previously referred to as FBX30, and belongs to the Fbws class; in addition to an F-box, this protein contains 7 tandem WD40 repeats. This protein binds directly to cyclin E and probably targets cyclin E for ubiquitin-mediated degradation. Mutations in this gene are detected in ovarian and breast cancer cell lines, implicating the gene's potential role in the pathogenesis of human cancers. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental delay, hypotonia, and impaired languageMIM #620012

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

243

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.23

LOEUF· LoF intol.

LOF

Mechanism· predicted

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