FBXO10

Chr 9

F-box protein 10

Also known as: FBX10, PRMT11

NCBI Gene: 26267ENSG00000147912UniProt: Q9UK96

Members of the F-box protein family, such as FBXO10, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

197
ClinVar variants
71
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FBXO10
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
71 Pathogenic / Likely Pathogenic· 96 VUS of 197 total submissions

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.
0.65LOEUF
pLI 0.000
Z-score 3.25
OE 0.43 (0.29–0.65)
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.
1.89Z-score
OE missense 0.78 (0.72–0.84)
466 obs / 595.9 exp
Tolerant

Mild missense constraint

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.0.43 (0.29–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.72–0.84)
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.0.85
0≤1.21.6
LoF obs/exp: 16 / 37.5Missense obs/exp: 466 / 595.9Syn Z: 1.85

ClinVar Variant Classifications

197 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic9
VUS96
Likely Benign5
Benign5
62
Pathogenic
9
Likely Pathogenic
96
VUS
5
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
62
0
62
Likely Pathogenic
0
0
9
0
9
VUS
0
92
4
0
96
Likely Benign
0
3
0
2
5
Benign
0
1
0
4
5
Total096756177

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

View in ClinVar →

Protein Context — Lollipop Plot

FBXO10 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer.
Song H et al.·J Med Genet
2021
Receptor for advanced glycation end products is targeted by FBXO10 for ubiquitination and degradation.
Evankovich J et al.·FASEB J
2017
Differential 12-O-Tetradecanoylphorbol-13-acetate-induced activation of rat mammary carcinoma susceptibility Fbxo10 variant promoters via a PKC-AP1 pathway.
Xu X et al.·Mol Carcinog
2015
Rat Mcs5a is a compound quantitative trait locus with orthologous human loci that associate with breast cancer risk.
Samuelson DJ et al.·Proc Natl Acad Sci U S A
2007
An insulator loop resides between the synthetically interacting elements of the human/rat conserved breast cancer susceptibility locus MCS5A/Mcs5a.
Smits BM et al.·Nucleic Acids Res
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
FBXO10 inhibits ferroptosis and promotes the progression of esophageal squamous cell carcinoma by post-translational mediation of ACSL4 degradation.
Feng S et al.·J Mol Histol
2025
FBXO10 Drives Hepatocellular Carcinoma Proliferation via K63-Linked Ubiquitination and Stabilization of FRMPD1.
Liu W et al.·Curr Issues Mol Biol
2025🔓 Open Access
Geranylgeranylated SCFFBXO10 regulates selective outer mitochondrial membrane proteostasis and function.
Bhat SA et al.·Cell Rep
2024🔓 Open Access
FBXO10 prevents chronic unpredictable stress-induced behavioral despair and cognitive impairment through promoting RAGE degradation.
Li J et al.·CNS Neurosci Ther
2021🔓 Open Access
Loss-of-function of Fbxo10, encoding a post-translational regulator of BCL2 in lymphomas, has no discernible effect on BCL2 or B lymphocyte accumulation in mice.
Masle-Farquhar E et al.·PLoS One
2021🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools