FBXL4

Chr 6AR

F-box and leucine rich repeat protein 4

Also known as: FBL4, FBL5, MTDPS13

NCBI Gene: 26235 ENSG00000112234 UniProt: Q9UKA2 OMIM: 605654

The protein functions as part of an E3 ubiquitin ligase complex that regulates protein degradation, including control of lysine-specific demethylase 4A levels in cell-cycle regulation. Biallelic mutations cause mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), inherited in an autosomal recessive pattern. The pathogenic mechanism involves disrupted mitochondrial DNA maintenance leading to mitochondrial dysfunction and subsequent encephalomyopathy.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the F-box protein family, which are characterized by an approximately 40 amino acid motif, the F-box. F-box proteins constitute one subunit of modular E3 ubiquitin ligase complexes, called SCF complexes, which function in phosphorylation-dependent ubiquitination. The F-box domain mediates protein-protein interactions and binds directly to S-phase kinase-associated protein 1. In addition to an F-box domain, the encoded protein contains at least 9 tandem leucine-rich repeats. The ubiquitin ligase complex containing the encoded protein may function in cell-cycle control by regulating levels of lysine-specific demethylase 4A. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type)MIM #615471

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.92

LOEUF

LOF

Mechanism· G2P

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GeneReview available — FBXL4