FBXO32

Chr 8

F-box protein 32

Also known as: Fbx32, MAFbx

NCBI Gene: 114907 ENSG00000156804 UniProt: Q969P5

The encoded protein functions as a substrate recognition component of the SCF E3 ubiquitin-protein ligase complex, mediating ubiquitination and proteasomal degradation of target proteins involved in skeletal muscle atrophy, macrophage function, and cell cycle regulation. Mutations in this gene cause autosomal dominant or recessive neurodevelopmental disorders with variable features including intellectual disability, developmental delay, and potentially muscle-related phenotypes. This gene is highly constrained against loss-of-function variants (pLI 0.997, LOEUF 0.222), indicating that complete loss of protein function is likely incompatible with normal development.

ResearchSummary from RefSeq, 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 the 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 and contains an F-box domain. This protein is highly expressed during muscle atrophy, whereas mice deficient in this gene were found to be resistant to atrophy. This protein is thus a potential drug target for the treatment of muscle atrophy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

dilated cardiomyopathy · ARLimitednot for standalone diagnostic reporting

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.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.22

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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