{"entity":{"id":"fbxw7","kind":"target","name":"FBXW7","aka":["F-box and WD repeat domain containing 7","F-box/WD repeat-containing protein 7","FLJ11071","SEL-10","SEL10","FBW7","FBX30","CDC4","FBXW6"],"tldr":"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.","summary":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:16712","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16712"},{"label":"UniProt Q969H0","url":"https://www.uniprot.org/uniprotkb/Q969H0/entry"},{"label":"NCBI Gene 55294","url":"https://www.ncbi.nlm.nih.gov/gene/55294"},{"label":"Ensembl ENSG00000109670","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000109670"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["colorectal","non-hodgkin-lymphoma","endometrial","breast-cancer","leukaemia","cervical","esophageal","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-tcga-colorectal-comprehensive-characterization-nature-2012"],"journals":[],"dependsOn":[],"notes":["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.","Colorectal cancer: inactivating mutation in 13 to 17%, leaning hypermutated (39.9% of MSI-high against 12.6% of microsatellite-stable samples in crc_msk_2026). Its substrates, MYC, cyclin E and NOTCH1, connect it to the MYC-directed transcriptional programme the TCGA analysis identified as the common output of the disease (Cancer Genome Atlas Network 2012)."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"FBXW7","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker","dna-repair"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:16712","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16712","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q969H0","url":"https://www.uniprot.org/uniprotkb/Q969H0/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene FBXW7","url":"https://civicdb.org/features/12903","note":"14 evidence items, 0 assertions, 12 variants; diseases: Colorectal Cancer, Cancer, Renal Cell Carcinoma, T-cell Acute Lymphoblastic Leukaemia (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000109670","url":"https://platform.opentargets.org/target/ENSG00000109670/associations","note":"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)"},{"label":"IntOGen FBXW7","url":"https://www.intogen.org/search?gene=FBXW7","note":"driver in 42 cohorts (Act 11, LoF 30); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"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.)","specificitySources":[{"label":"UniProt Q969H0","url":"https://www.uniprot.org/uniprotkb/Q969H0/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene FBXW7","url":"https://civicdb.org/features/12903","note":"14 evidence items, 0 assertions, 12 variants; diseases: Colorectal Cancer, Cancer, Renal Cell Carcinoma, T-cell Acute Lymphoblastic Leukaemia (GraphQL API, CC0)"},{"label":"IntOGen FBXW7","url":"https://www.intogen.org/search?gene=FBXW7","note":"driver in 42 cohorts (Act 11, LoF 30); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas FBXW7 tissue","url":"https://www.proteinatlas.org/ENSG00000109670-FBXW7/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000109670 associations","url":"https://platform.opentargets.org/target/ENSG00000109670/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:16712","ensembl":"ENSG00000109670","uniprot":"Q969H0","entrez":"55294","firstDescribed":1999,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Winston J.T. et al, Curr. Biol, 1999, \"A family of mammalian F-box proteins\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/10531037/","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).","whereFound":["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)","Colorectal cancer: inactivating mutation 13-17%"],"targetClass":"tumor-suppressor","prevalence":[{"cancerId":"colorectal","pct":"13-17","measure":"Inactivating mutation","source":"https://www.cbioportal.org/study/summary?id=crc_msk_2026","note":"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."}]},"route":"/targets/fbxw7/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"paper":[{"id":"paper-tcga-colorectal-comprehensive-characterization-nature-2012","kind":"paper","name":"Comprehensive molecular characterization of human colon and rectal cancer","route":"/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/"}]}}