FBXW7
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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).
External identifiers
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)
Biology
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).
- Colorectal cancer: Open Targets association 0.76 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease
- Non-Hodgkin lymphoma: Open Targets association 0.68 with non-Hodgkin lymphoma (MONDO_0018908)
- Endometrial cancer: Open Targets association 0.67 with endometrial cancer (MONDO_0011962); IntOGen driver in 4 cohorts (UCEC)
- Breast cancer: Open Targets association 0.51 with breast cancer (MONDO_0007254); IntOGen driver in 4 cohorts (BRCA)
- Leukaemia: Open Targets association 0.63 with leukaemia (MONDO_0005059)
- Cervical cancer: Open Targets association 0.62 with cervical cancer (MONDO_0002974); IntOGen driver in 3 cohorts (CEAD, CESC)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 6 therapies; IntOGen calls it an activating (Act) driver in 11 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 30 cohorts; CIViC holds 14 clinical evidence items on its variants; UniProt keyword "DNA repair". Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: T-cell Acute Lymphoblastic Leukaemia.
Latest papers
topQuery 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.
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