FBXL5

Chr 4

F-box and leucine rich repeat protein 5

Also known as: CC2D2A-AS1, FBL4, FBL5, FLR1

NCBI Gene: 26234 ENSG00000118564 UniProt: Q9UKA1 OMIM: 605655

The protein functions as a component of SCF ubiquitin ligase complexes that regulate iron homeostasis by promoting degradation of iron regulatory proteins, particularly under conditions of iron sufficiency and oxidative stress. Mutations in this highly constrained gene cause autosomal recessive neurodevelopmental disorders characterized by intellectual disability, developmental delay, and seizures. The gene shows extreme intolerance to loss-of-function variants, indicating that even partial loss of protein function can have significant clinical consequences.

OMIM 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. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Aug 2010]

OMIM ResearchGenerating clinical summary…

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)

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P/LP submissions

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P/LP missense

0.24

LOEUF· LoF intol.

LOF

Mechanism· predicted