FBXO7

Chr 22AR

F-box protein 7

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

NCBI Gene: 25793ENSG00000100225UniProt: Q9Y3I1

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]

Primary Disease Associations & Inheritance

Parkinson disease 15, autosomal recessiveMIM #260300
AR
512
ClinVar variants
41
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— FBXO7
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 108 VUS of 512 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.88LOEUF
pLI 0.000
Z-score 2.03
OE 0.56 (0.37–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.44Z-score
OE missense 1.07 (0.98–1.18)
305 obs / 284.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.37–0.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.98–1.18)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 14 / 25.0Missense obs/exp: 305 / 284.1Syn Z: 0.63

ClinVar Variant Classifications

512 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic14
VUS108
Likely Benign196
Benign27
Conflicting1
27
Pathogenic
14
Likely Pathogenic
108
VUS
196
Likely Benign
27
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
4
10
0
27
Likely Pathogenic
6
0
8
0
14
VUS
1
100
6
1
108
Likely Benign
0
10
78
108
196
Benign
0
1
26
0
27
Conflicting
—1
Total20115128109373

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

View in ClinVar →

Protein Context — Lollipop Plot

FBXO7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Parkinson disease 15, autosomal recessive

MIM #260300

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Monogenic Parkinson's Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing.
Jia F et al.·Genes (Basel)
2022Review
FBXO7 Confers Mesenchymal Properties and Chemoresistance in Glioblastoma by Controlling Rbfox2-Mediated Alternative Splicing.
Li S et al.·Adv Sci (Weinh)
2023
The role of genetics in Parkinson's disease: a large cohort study in Chinese mainland population.
Zhao Y et al.·Brain
2020Cohort
The characteristics of FBXO7 and its role in human diseases.
Zhong Y et al.·Gene
2023Review
Pathophysiological mechanisms linking F-box only protein 7 (FBXO7) and Parkinson's disease (PD).
Zhou ZD et al.·Mutat Res Rev Mutat Res
2018Review
Genotype-Phenotype Relations for the Atypical Parkinsonism Genes: MDSGene Systematic Review.
Wittke C et al.·Mov Disord
2021Review
FBXO7 Pathogenic Variants in Early-Onset Parkinsonism: Insights from a Neuroimaging Perspective and Review of the Literature.
Şahin E et al.·Mov Disord Clin Pract
2025Review
Mechanistic contributions of FBXO7 to Parkinson disease.
Joseph S et al.·J Neurochem
2018Review
FBXO7 mutations in Parkinson's disease and multiple system atrophy.
Conedera S et al.·Neurobiol Aging
2016Review
Autophagy and Parkinson's Disease.
Lu J et al.·Adv Exp Med Biol
2020Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Parkinson Disease

Aquaporin-4 Single Nucleotide Polymorphisms in Patients With Idiopathic and Familial Parkinson's Disease

ACTIVE NOT RECRUITING
NCT04553185University of ExeterStarted 2018-11-28
Study procedure

External Resources

Links to major genomics databases and tools