FBXO38

Chr 5

F-box protein 38

Also known as: Fbx38, HMN2D, HMND6, MOKA, SP329

NCBI Gene: 81545 ENSG00000145868 UniProt: Q6PIJ6

This gene encodes a substrate recognition component of an E3 ubiquitin ligase complex that mediates proteasomal degradation of target proteins and acts as a transcriptional co-activator of KLF7, a regulator of neuronal differentiation. Heterozygous mutations cause autosomal dominant distal hereditary motor neuronopathy type IID, which affects peripheral motor neurons. The gene is highly constrained against loss-of-function variants (pLI=1.0, LOEUF=0.27), indicating that biallelic loss-of-function mutations are likely incompatible with life.

ResearchSummary from RefSeq, UniProt

This gene encodes a large protein that contains an F-box domain and may participate in protein ubiquitination. The encoded protein is a transcriptional co-activator of Krueppel-like factor 7 (Klf7). A heterozygous mutation in this gene was found in individuals with autosomal dominant distal hereditary motor neuronopathy type IID. There is a pseudogene for this gene on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeuronopathy, distal hereditary motor, autosomal dominant 6

Clinical highlights

Gene-disease validity (ClinGen)

distal hereditary motor neuropathy · ADModerateconsider for supplementary testing

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

0.27

LOEUF· LoF intol.

LOF

Mechanism· predicted

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