FBXO7

Chr 22AR

F-box protein 7

Also known as: FBX, FBX07, FBX7, PARK15, PKPS

NCBI Gene: 25793 ENSG00000100225 UniProt: Q9Y3I1 OMIM: 605648

This protein functions as a substrate recognition component of SCF E3 ubiquitin ligase complexes, mediating the ubiquitination and degradation of target proteins involved in cell cycle regulation, mitochondrial quality control, and proteasome assembly. Mutations cause Parkinson disease 15, an autosomal recessive early-onset parkinsonian syndrome. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, 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 it may play a role in regulation of hematopoiesis. Alternatively spliced transcript variants of this gene have been identified with the full-length natures of only some variants being determined. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.881 OMIM phenotype

Clinical Summary— FBXO7

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

49 unique Pathogenic / Likely Pathogenic· 149 VUS of 492 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — FBXO7

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.88LOEUF

pLI 0.000

Z-score 2.03

OE 0.56 (0.37–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.44Z-score

OE missense 1.07 (0.98–1.18)

305 obs / 284.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.56 (0.37–0.88)

0≤0.351.4

Missense OE?1.07 (0.98–1.18)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 14 / 25.0Missense obs/exp: 305 / 284.1Syn Z: 0.63

This gene — mechanism propensity

0.6842th %ile

GOF

0.3590th %ile

LOF

0.3165th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

492 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31

Likely Pathogenic18

VUS149

Likely Benign221

Benign35

Conflicting11

Pathogenic

Likely Pathogenic

149

VUS

221

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	24	5	2	0	31
Likely Pathogenic	17	1	0	0	18
VUS	4	123	20	2	149
Likely Benign	0	14	84	123	221
Benign	0	4	29	2	35
Conflicting	—				11
Total	45	147	135	127	465

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap FBXO7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →