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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
FBXW7
F-box and WD repeat domain containing 7
Chromosome 4 Β· 4q31.3
NCBI Gene: 55294Ensembl: ENSG00000109670.17HGNC: HGNC:16712UniProt: G0Z2K0
616PubMed Papers
21Diseases
0Drugs
31Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairHighly ConstrainedHub Gene
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
ubiquitin-like ligase-substrate adaptor activityprotein ubiquitinationprotein bindingcyclin bindingdevelopmental delay, hypotonia, and impaired languagecolorectal adenocarcinomacervical squamous cell carcinomaendometrial cancer
✦AI Summary

FBXW7 is a substrate recognition component of SCF E3 ubiquitin-ligase complexes that mediates ubiquitination and proteasomal degradation of phosphorylated target proteins 123. Key substrates include oncoproteins (MYC, CCNE1/2, NOTCH1/2, JUN) and metabolic regulators (NR1D1, FASN, EZH2), positioning FBXW7 as a critical tumor suppressor 456. In T-ALL, Aurora B kinase phosphorylation of MYC at serine 67 prevents FBXW7-mediated degradation, promoting leukemogenesis; AURKB inhibition restores MYC degradation 7. FBXW7 loss in colorectal cancer promotes FASN-mediated lipogenesis and tumor growth, particularly when stabilized by CSN6 5. In the tumor microenvironment, FBXW7 depletion in cancer-associated fibroblasts activates KMT2 methyltransferase activity and IL-17 signaling, creating paracrine effects that enhance tumor growth 8. Mechanically overloaded chondrocytes downregulate FBXW7, leading to MKK7 stabilization, JNK activation, and accelerated senescence in osteoarthritis 9. In IBD, elevated FBXW7 in intestinal macrophages promotes CCL2/7 expression via EZH2 degradation, increasing inflammatory cell recruitment 6. FBXW7 mutations appear under positive selection in IBD-affected colon 10, while miR-92a-3p suppresses FBXW7 to promote CRC metastasis and chemotherapy resistance 11. The Trim21-FBXW7 axis regulates intestinal Th17 differentiation through JunB and Rorc modulation 12.

Sources cited
1
In T-ALL, Aurora B kinase phosphorylation of MYC at serine 67 prevents FBXW7-mediated degradation, promoting leukemogenesis; AURKB inhibition restores MYC degradation .
PMID: 32049046
2
Key substrates include oncoproteins (MYC, CCNE1/2, NOTCH1/2, JUN) and metabolic regulators (NR1D1, FASN, EZH2), positioning FBXW7 as a critical tumor suppressor , , .
PMID: 37202390
3
In the tumor microenvironment, FBXW7 depletion in cancer-associated fibroblasts activates KMT2 methyltransferase activity and IL-17 signaling, creating paracrine effects that enhance tumor growth .
PMID: 40127278
4
Mechanically overloaded chondrocytes downregulate FBXW7, leading to MKK7 stabilization, JNK activation, and accelerated senescence in osteoarthritis .
PMID: 35058228
5
Key substrates include oncoproteins (MYC, CCNE1/2, NOTCH1/2, JUN) and metabolic regulators (NR1D1, FASN, EZH2), positioning FBXW7 as a critical tumor suppressor , , .
PMID: 31246581
6
FBXW7 mutations appear under positive selection in IBD-affected colon , while miR-92a-3p suppresses FBXW7 to promote CRC metastasis and chemotherapy resistance .
PMID: 32697969
7
FBXW7 mutations appear under positive selection in IBD-affected colon , while miR-92a-3p suppresses FBXW7 to promote CRC metastasis and chemotherapy resistance .
PMID: 31064356
8
The Trim21-FBXW7 axis regulates intestinal Th17 differentiation through JunB and Rorc modulation .
PMID: 40215968
Disease Associationsβ“˜21
developmental delay, hypotonia, and impaired languageOpen Targets
0.73Strong
colorectal adenocarcinomaOpen Targets
0.65Moderate
cervical squamous cell carcinomaOpen Targets
0.55Moderate
endometrial cancerOpen Targets
0.51Moderate
colon adenocarcinomaOpen Targets
0.49Moderate
type 2 diabetes mellitusOpen Targets
0.48Moderate
esophageal cancerOpen Targets
0.47Moderate
Uterine CarcinosarcomaOpen Targets
0.46Moderate
urinary bladder cancerOpen Targets
0.46Moderate
head and neck squamous cell carcinomaOpen Targets
0.44Moderate
cancerOpen Targets
0.44Moderate
Anal Squamous Cell CarcinomaOpen Targets
0.43Moderate
gastric adenocarcinomaOpen Targets
0.42Moderate
squamous cell lung carcinomaOpen Targets
0.38Weak
chronic lymphocytic leukemiaOpen Targets
0.38Weak
T-cell acute lymphoblastic leukemiaOpen Targets
0.37Weak
rectal adenocarcinomaOpen Targets
0.37Weak
Endometrial Serous AdenocarcinomaOpen Targets
0.37Weak
endometrium adenocarcinomaOpen Targets
0.37Weak
esophageal adenocarcinomaOpen Targets
0.37Weak
Developmental delay, hypotonia, and impaired languageUniProt
Pathogenic Variants31
NM_001349798.2(FBXW7):c.2065C>T (p.Arg689Trp)Pathogenic
Developmental delay, hypotonia, and impaired language|Embryonal rhabdomyosarcoma|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 689
NM_001349798.2(FBXW7):c.2020C>T (p.Arg674Trp)Pathogenic
Developmental delay, hypotonia, and impaired language|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 674
NM_001349798.2(FBXW7):c.1944_1945del (p.Trp649fs)Likely pathogenic
not provided|FBXW7-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 649
NM_001349798.2(FBXW7):c.1177C>T (p.Arg393Ter)Pathogenic
not provided|Medulloblastoma WNT activated
β˜…β˜†β˜†β˜†2025β†’ Residue 393
NM_001349798.2(FBXW7):c.1149_1152dup (p.Thr385fs)Likely pathogenic
Developmental delay, hypotonia, and impaired language
β˜…β˜†β˜†β˜†2025β†’ Residue 385
NM_001349798.2(FBXW7):c.502-2450C>TLikely pathogenic
Developmental delay, hypotonia, and impaired language
β˜…β˜†β˜†β˜†2025
NM_001349798.2(FBXW7):c.802_803del (p.Met268fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 268
NM_001349798.2(FBXW7):c.1331_1332del (p.Lys444fs)Pathogenic
Developmental delay, hypotonia, and impaired language
β˜…β˜†β˜†β˜†2024β†’ Residue 444
NM_001349798.2(FBXW7):c.1989_1990del (p.Ser665fs)Likely pathogenic
Developmental delay
β˜…β˜†β˜†β˜†2024β†’ Residue 665
NM_001349798.2(FBXW7):c.981_985del (p.Glu328fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 328
NM_001349798.2(FBXW7):c.471_472insCTCC (p.Ser158fs)Likely pathogenic
Developmental delay, hypotonia, and impaired language
β˜…β˜†β˜†β˜†2024β†’ Residue 158
NM_001349798.2(FBXW7):c.915_918dup (p.Thr307fs)Likely pathogenic
Developmental delay, hypotonia, and impaired language
β˜…β˜†β˜†β˜†2024β†’ Residue 307
NM_001349798.2(FBXW7):c.670C>T (p.Arg224Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 224
NM_001349798.2(FBXW7):c.1433C>T (p.Ser478Phe)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2023β†’ Residue 478
NM_001349798.2(FBXW7):c.1919del (p.Ser640fs)Likely pathogenic
Developmental delay, hypotonia, and impaired language
β˜…β˜†β˜†β˜†2023β†’ Residue 640
NM_001349798.2(FBXW7):c.1315A>G (p.Thr439Ala)Likely pathogenic
Developmental delay, hypotonia, and impaired language
β˜…β˜†β˜†β˜†2023β†’ Residue 439
NM_001349798.2(FBXW7):c.1793A>T (p.Asn598Ile)Likely pathogenic
FBXW7-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 598
NM_001349798.2(FBXW7):c.1393C>T (p.Arg465Cys)Pathogenic
not provided|Neoplasm|Colorectal cancer
β˜…β˜†β˜†β˜†2022β†’ Residue 465
NM_001349798.2(FBXW7):c.1439A>G (p.Asp480Gly)Likely pathogenic
Developmental delay, hypotonia, and impaired language|Pervasive developmental disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 480
NM_001349798.2(FBXW7):c.1259A>T (p.His420Leu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 420
View on ClinVar β†—
Related Genes
ACVR1Protein interaction100%CCNE1Protein interaction100%NFKB2Protein interaction100%SKP2Protein interaction100%CCNE2Protein interaction100%MYCBP2Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
62%
Heart
45%
Lung
22%
Liver
21%
Ovary
17%
Gene Interaction Network
Click a node to explore
FBXW7ACVR1CCNE1NFKB2SKP2CCNE2MYCBP2
PROTEIN STRUCTURE
Preparing viewer…
PDB2OVR Β· 2.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.18Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.10 [0.05–0.18]
RankingsWhere FBXW7 stands among ~20K protein-coding genes
  • #377of 20,598
    Most Researched616 Β· top 5%
  • #1,772of 5,498
    Most Pathogenic Variants31
  • #344of 17,882
    Most Constrained (LOEUF)0.18 Β· top 5%
Genes detectedFBXW7
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
Somatic Evolution in Non-neoplastic IBD-Affected Colon.
PMID: 32697969
Cell Β· 2020
1.00
2
FBXW7 Gene Mutation and Expression in Colorectal Cancer (CRC): A Systematic Review from Molecular Mechanisms to Clinical Translation.
PMID: 41373479
Int J Mol Sci Β· 2025
0.92
3
Mechanical overloading promotes chondrocyte senescence and osteoarthritis development through downregulating FBXW7.
PMID: 35058228
Ann Rheum Dis Β· 2022
0.90
4
Fbxw7 Tumor Suppressor: A Vital Regulator Contributes to Human Tumorigenesis.
PMID: 26886596
Medicine (Baltimore) Β· 2016
0.88
5
Epigenetic status of FBXW7 gene and its role in Ovarian cancer pathogenesis.
PMID: 37247277
Asian Pac J Cancer Prev Β· 2023
0.84