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FBXW7 (F-box/WD repeat-containing protein 7) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Non-Hodgkin lymphoma, Endometrial cancer and 5 more.
Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognises and binds phosphorylated sites/phosphodegrons within target proteins and thereafter brings them to the SCF complex for ubiquitination. Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, MLST8, RICTOR, and probably PSEN1.
CIViC holds 14 clinical evidence items and 0 assertions across 12 variants, naming Regorafenib Anhydrous, Cetuximab, Panitumumab and Everolimus and others. Open Targets scores its association with cancer at 0.83 (direct and indirect evidence; datatypes genetic literature 0.41, affected pathway 0.75, literature 0.99, genetic association 0.55, somatic mutation 0.98, animal model 0.45). IntOGen calls it a driver in 42 cohorts (11 activating, 30 loss-of-function), covering Anal Squamous Cell Carcinoma, Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Cervical Adenocarcinoma, Cervical Squamous Cell Carcinoma, Cholangiocarcinoma and others.
In plain words · FBXW7 (F-box/WD repeat-containing protein 7) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Non-Hodgkin lymphoma, Endometrial cancer and 5 more.
FBXW7 (F-box/WD repeat-containing protein 7) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Non-Hodgkin lymphoma, Endometrial cancer and 5 more.
Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
No product in this corpus aims at FBXW7 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA FBXW7: RNA tissue enhanced (brain 58 nTPM, skin 1 58 nTPM); high antibody staining in 33 normal tissues; highest cancer staining prostate cancer (9 of 11 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Lymphoma, Endometrial cancer, Breast cancer (all types), Leukaemia, Cervical cancer, Oesophageal cancer and more); Open Targets associates it with 3 specific cancer types at or above 0.5 (colorectal adenocarcinoma, cervical squamous cell carcinoma, endometrial cancer). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt Q969H0; CIViC gene FBXW7; IntOGen FBXW7; Human Protein Atlas FBXW7 tissue; Open Targets ENSG00000109670 associations
First described 1999. Earliest sequence paper UniProt cites for the protein: Winston J.T. et al, Curr. Biol, 1999, "A family of mammalian F-box proteins". Source.
Sources: HGNC HGNC:16712 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q969H0 (protein name, function text, keywords and locations (REST API)); CIViC gene FBXW7 (14 evidence items, 0 assertions, 12 variants; diseases: Colorectal Cancer, Cancer, Renal Cell Carcinoma, T-cell Acute Lymphoblastic Leukaemia (GraphQL API, CC0)); Open Targets ENSG00000109670 (association with cancer (MONDO_0004992) 0.83; per-cancer scores at or above 0.5: colorectal cancer 0.76, gastric cancer 0.51, oesophageal cancer 0.61, urinary bladder cancer 0.57, ovarian cancer 0.54, endometrial cancer 0.67 (GraphQL API, CC0)); IntOGen FBXW7 (driver in 42 cohorts (Act 11, LoF 30); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognises and binds phosphorylated sites/phosphodegrons within target proteins and thereafter brings them to the SCF complex for ubiquitination. Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, MLST8, RICTOR, and probably PSEN1. Acts as a negative regulator of JNK signalling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation. Involved in bone homeostasis and negative regulation of osteoclast differentiation. Regulates the amplitude of the cyclic expression of hepatic core clock genes and genes involved in lipid and glucose metabolism via ubiquitination and proteasomal degradation of their transcriptional repressor NR1D1; CDK1-dependent phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination. Location: Nucleus, nucleoplasm; Chromosome; Cytoplasm; Nucleus, nucleolus (UniProt). Locus 4q31.3 (HGNC).
RNA: tissue enhanced (brain 58 nTPM, skin 1 58 nTPM), detected in all normal tissues.
Medium: Cerebellum, Cervix, Endometrium, Epididymis, Fallopian tube, Hippocampus, Liver, Oral mucosa.
Medium only: carcinoid, lung cancer, stomach cancer, testis cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Colorectal cancer | 13-17% | Inactivating mutation | cBioPortal: 1,127 of 7,237, 15.6%, in crc_msk_2026; 145 of 1,134, 12.8%, in crc_msk_2017; 205 of 1,516, 13.5%, in crc_eo_2020; 90 of 534, 16.9%, in coadread_tcga_pan_can_atlas_2018; 37 of 224, 16.5%, in coadread_tcga_pub; 86 of 619, 13.9%, in coadread_dfci_2016. | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"FBXW7" OR ABSTRACT:"FBXW7" OR TITLE:"F-box and WD repeat domain containing 7" OR ABSTRACT:"F-box and WD repeat domain containing 7" OR TITLE:"F-box/WD repeat-containing protein 7" OR ABSTRACT:"F-box/WD repeat-containing protein 7" OR TITLE:"FLJ11071" OR ABSTRACT:"FLJ11071" OR TITLE:"SEL-10" OR ABSTRACT:"SEL-10" OR TITLE:"SEL10" OR ABSTRACT:"SEL10") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about FBXW7, not a curated reading list.
Shares Leukaemia (all types), Endometrial cancer, CIViC, IntOGen.
Shares Leukaemia (all types), Cervical cancer, IntOGen, Breast cancer (all types).
Shares Leukaemia (all types), Endometrial cancer, Oesophageal cancer, Cervical cancer.
Shares Leukaemia (all types), Endometrial cancer, CIViC, IntOGen.
Shares Leukaemia (all types), Endometrial cancer, CIViC, IntOGen.
Shares Leukaemia (all types), CIViC, IntOGen, Breast cancer (all types).
Shares Leukaemia (all types), CIViC, IntOGen, Breast cancer (all types).
Shares Leukaemia (all types), Endometrial cancer, Breast cancer (all types), Non-Hodgkin lymphoma (all types).