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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.881 OMIM phenotype
Clinical SummaryFBXO7
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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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

Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.000
Z-score 2.03
OE 0.56 (0.370.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.44Z-score
OE missense 1.07 (0.981.18)
305 obs / 284.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.56 (0.370.88)
00.351.4
Missense OE1.07 (0.981.18)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 14 / 25.0Missense obs/exp: 305 / 284.1Syn Z: 0.63
DN
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

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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