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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FBXO9
F-box protein 9
Chromosome 6 · 6p12.1
NCBI Gene: 26268Ensembl: ENSG00000112146.17HGNC: HGNC:13588UniProt: Q9UK97
39PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingubiquitin-like ligase-substrate adaptor activitySCF ubiquitin ligase complexprotein ubiquitinationsmoking initiationplacenta praeviaacute myeloid leukemianeoplasm
✦AI Summary

FBXO9 (F-box protein 9) functions as a substrate recognition component of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes, mediating K48-linked polyubiquitination and subsequent proteasomal degradation of target proteins 1. The protein plays critical roles in regulating cellular homeostasis through multiple pathways. FBXO9 controls mTOR signaling by targeting TTI1 and TELO2 for degradation when bound to mTORC1, leading to growth restraint, while sparing mTORC2 components 2. In epithelial cells, FBXO9 maintains survival by regulating chr6 modulator PRMT4 turnover through ubiquitination at K228, with endotoxin-mediated reduction of FBXO9 levels contributing to epithelial cell death in lung injury 1. Additionally, FBXO9 regulates the Hippo pathway effector YAP through GSK-3β-dependent recognition and K48-linked ubiquitination at K76, with this axis being modulated by Akt signaling 3. Clinically, FBXO9 expression patterns are associated with cancer prognosis, showing downregulation in ovarian cancer where it correlates with DNA damage repair pathways 4. The protein is also implicated in acute lymphoblastic leukemia risk assessment 5 and psychological stress responses 6, highlighting its broader physiological significance.

Sources cited
1
FBXO9 functions as substrate recognition component of SCF E3 ubiquitin ligase and regulates PRMT4 degradation
PMID: 34480022
2
FBXO9 controls mTOR signaling pathways and plays roles in cancer
PMID: 35025031
3
FBXO9 mediates YAP ubiquitination and degradation in GSK-3β-dependent manner
PMID: 40902979
4
FBXO9 is downregulated in ovarian cancer and correlates with DNA damage repair pathways
PMID: 38136595
5
FBXO9 is involved in acute lymphoblastic leukemia risk assessment
PMID: 39453390
6
FBXO9 is implicated in psychological stress responses
PMID: 35648061
Disease Associationsⓘ20
smoking initiationOpen Targets
0.36Weak
placenta praeviaOpen Targets
0.12Weak
acute myeloid leukemiaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.08Suggestive
lung cancerOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
cancerOpen Targets
0.06Suggestive
thyroid hormone metabolism, abnormal, 2Open Targets
0.04Suggestive
hypertriglyceridemia 2Open Targets
0.04Suggestive
hypothyroidism, congenital, nongoitrous, 8Open Targets
0.03Suggestive
Combined hyperlipidemiaOpen Targets
0.03Suggestive
immunodeficiency 88Open Targets
0.03Suggestive
neutropenia, severe congenital, 1, autosomal dominantOpen Targets
0.03Suggestive
chronic myeloproliferative disorderOpen Targets
0.03Suggestive
lung adenocarcinomaOpen Targets
0.02Suggestive
SepsisOpen Targets
0.01Suggestive
ovarian carcinomaOpen Targets
0.01Suggestive
dry eye syndromeOpen Targets
0.01Suggestive
Parkinson diseaseOpen Targets
0.01Suggestive
Chédiak-Higashi syndromeOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CUL1Protein interaction68%SKP1Protein interaction68%FBXL22Shared pathway50%ZNRF2Shared pathway50%FBXL19Shared pathway40%KBTBD6Shared pathway40%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
72%
Heart
58%
Lung
48%
Ovary
48%
Brain
43%
Gene Interaction Network
Click a node to explore
FBXO9CUL1SKP1FBXL22ZNRF2FBXL19KBTBD6
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9UK97
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.65LoF Tolerant
pLIⓘ
0.25Tolerant
Observed/Expected LoF0.42 [0.27–0.65]
RankingsWhere FBXO9 stands among ~20K protein-coding genes
  • #10,322of 20,598
    Most Researched39
  • #4,732of 17,882
    Most Constrained (LOEUF)0.65
Genes detectedFBXO9
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
F-box only protein 9 and its role in cancer.
PMID: 35025031
Mol Biol Rep · 2022
1.00
2
FBXO9 mediated the ubiquitination and degradation of YAP in a GSK-3β-dependent manner.
PMID: 40902979
J Biol Chem · 2025
0.90
3
Ubiquitin-related gene markers predict immunotherapy response and prognosis in patients with epithelial ovarian carcinoma.
PMID: 39448713
Sci Rep · 2024
0.80
4
Identification of a Prognostic Signature for Ovarian Cancer Based on Ubiquitin-Related Genes Suggesting a Potential Role for FBXO9.
PMID: 38136595
Biomolecules · 2023
0.70
5
Endotoxin stabilizes protein arginine methyltransferase 4 (PRMT4) protein triggering death of lung epithelia.
PMID: 34480022
Cell Death Dis · 2021
0.60