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…

LOFmechanismLOEUF 0.22

Clinical Summary— FBXO32

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Gene-Disease Validity (ClinGen)

dilated cardiomyopathy · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 33 VUS of 64 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.22LOEUF

pLI 0.997

Z-score 4.09

OE 0.05 (0.02–0.22)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.57Z-score

OE missense 0.68 (0.59–0.79)

135 obs / 197.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.22)

0≤0.351.4

Missense OE?0.68 (0.59–0.79)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 1 / 21.4Missense obs/exp: 135 / 197.2Syn Z: 0.79

This gene — mechanism propensity

0.3792th %ile

GOF

0.5169th %ile

LOF

0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.22

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

64 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS33

Likely Benign1

Benign17

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	1	0	0	1
VUS	33	0	0	33
Likely Benign	0	0	1	1
Benign	1	11	5	17
Total	35	11	6	52

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

50 pathogenic / likely-pathogenic (of 54) ClinVar copy-number / structural variants overlap FBXO32 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →