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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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FBXL17
F-box and leucine rich repeat protein 17
Chromosome 5 · 5q21.3
NCBI Gene: 64839Ensembl: ENSG00000145743.18HGNC: HGNC:13615UniProt: Q9UF56
38PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingprotein polyubiquitinationprotein quality control for misfolded or incompletely synthesized proteinsnucleoplasmIrritabilityAbnormality of the skeletal systempost-traumatic stress disordersmoking initiation
✦AI Summary

FBXL17 encodes a substrate-recognition component of the SCF(FBXL17) E3 ubiquitin ligase complex that plays a critical role in dimerization quality control (DQC), a cellular pathway that ensures proper protein complex formation 1. The protein specifically recognizes and targets aberrant BTB (Broad-complex, tramtrack, and bric-à-brac) domain dimers for ubiquitination and proteasomal degradation by binding to conserved degrons at dimer interfaces 21. FBXL17 regulates multiple important cellular processes through targeted protein degradation. It controls the oxidative stress response by ubiquitinating BACH1, working complementarily with FBXO22 to recognize different structural states of BACH1 BTB dimers 34. In Hedgehog signaling, SCF(FBXL17) mediates degradation of SUFU, enabling GLI1 release for proper signal transduction 5. The complex also targets PRMT1 through an acetylation-dependent degron mechanism 6. This quality control function is essential for neural development, as FBXL17 is required for differentiation and survival of neural crest and neuronal cells 1. Disruption of FBXL17 has clinical implications, with genomic rearrangements observed in breast cancer affecting its ubiquitin ligase activity 7, and mutations in its pathway components linked to medulloblastoma development 5.

Sources cited
1
FBXL17 is a component of dimerization quality control pathway and required for neural cell differentiation and survival
PMID: 30190310
2
SCF-FBXL17 disrupts aberrant BTB dimers and wraps around single BTB domains for ubiquitination
PMID: 32814905
3
FBXL17 recognizes BACH1 as a monomer through a ligase switch mechanism with FBXO22
PMID: 39657677
4
FBXL17 recognizes destabilized BACH1 BTB dimers as complementary E3 ligase to FBXO22
PMID: 39504958
5
SCF(FBXL17) ubiquitinates SUFU to regulate Hedgehog signaling and affects medulloblastoma development
PMID: 27234298
6
SCF(FBXL17) mediates PRMT1 degradation through acetylation-dependent degron recognition
PMID: 28883095
7
FBXL17 is rearranged in breast cancer, disrupting its ubiquitin ligase activity
PMID: 31560077
Disease Associationsⓘ20
IrritabilityOpen Targets
0.47Moderate
Abnormality of the skeletal systemOpen Targets
0.42Moderate
post-traumatic stress disorderOpen Targets
0.40Weak
smoking initiationOpen Targets
0.40Weak
neurotic disorderOpen Targets
0.39Weak
obesityOpen Targets
0.36Weak
coronary artery diseaseOpen Targets
0.35Weak
hypertensionOpen Targets
0.35Weak
placenta praeviaOpen Targets
0.32Weak
Abruptio PlacentaeOpen Targets
0.31Weak
essential hypertensionOpen Targets
0.31Weak
connective tissue diseaseOpen Targets
0.31Weak
aortic stenosisOpen Targets
0.30Weak
thyroiditisOpen Targets
0.30Weak
overnutritionOpen Targets
0.28Weak
attention deficit hyperactivity disorderOpen Targets
0.28Weak
substance abuseOpen Targets
0.28Weak
major depressive disorderOpen Targets
0.26Weak
smoking behaviorOpen Targets
0.26Weak
coronary atherosclerosisOpen Targets
0.25Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
BACH1Protein interaction98%SKP1Protein interaction90%CUL1Protein interaction90%KEAP1Protein interaction90%KLHL12Protein interaction90%SUFUProtein interaction78%
Tissue Expression6 tissues
Brain
100%
Heart
98%
Bone Marrow
27%
Liver
24%
Lung
18%
Ovary
17%
Gene Interaction Network
Click a node to explore
FBXL17BACH1SKP1CUL1KEAP1KLHL12SUFU
PROTEIN STRUCTURE
Preparing viewer…
PDB8UBT · 3.10 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.68LoF Tolerant
pLIⓘ
0.08Tolerant
Observed/Expected LoF0.45 [0.30–0.68]
RankingsWhere FBXL17 stands among ~20K protein-coding genes
  • #10,472of 20,598
    Most Researched38
  • #5,036of 17,882
    Most Constrained (LOEUF)0.68
Genes detectedFBXL17
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Dual BACH1 regulation by complementary SCF-type E3 ligases.
PMID: 39657677
Cell · 2024
1.00
2
Recognition of BACH1 quaternary structure degrons by two F-box proteins under oxidative stress.
PMID: 39504958
Cell · 2024
0.90
3
Structural basis for dimerization quality control.
PMID: 32814905
Nature · 2020
0.80
4
Analysis of genetic mutation characteristics in 40 Chinese patients with hepatocellular carcinoma.
PMID: 41661474
Genes Genomics · 2026
0.70
5
SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signaling and medulloblastoma development.
PMID: 27234298
EMBO J · 2016
0.60