FBXL3

Chr 13

F-box and leucine rich repeat protein 3

Also known as: FBL3, FBL3A, FBXL3A, IDDSFAS

NCBI Gene: 26224 ENSG00000005812 UniProt: Q9UKT7

The protein functions as a substrate-recognition component of the SCF(FBXL3) E3 ubiquitin ligase complex that regulates circadian rhythm by mediating ubiquitination and degradation of CRY1 and CRY2 proteins in the nucleus. Mutations cause sleep-wake cycle disorders with disrupted circadian rhythms, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.29), 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 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 Fbls class and, in addition to an F-box, contains several tandem leucine-rich repeats and is localized in the nucleus. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder with short stature, facial anomalies, and speech defects

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429