{"entity":{"id":"cul3","kind":"target","name":"CUL3","aka":["cullin 3","Cullin-3"],"tldr":"CUL3 (Cullin-3) 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 and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Renal cell carcinoma, Non-small-cell lung cancer and Papillary renal cell carcinoma.","summary":"Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant, naming Platinum Doublet. Open Targets scores its association with cancer at 0.55 (direct and indirect evidence; datatypes literature 0.95, animal model 0.56, genetic association 0.03, somatic mutation 0.71). IntOGen calls it a driver in 4 cohorts (1 activating, 3 loss-of-function), covering Lung Squamous Cell Carcinoma, Papillary Renal Cell Carcinoma, Renal Cell Carcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:2553","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2553"},{"label":"UniProt Q13618","url":"https://www.uniprot.org/uniprotkb/Q13618/entry"},{"label":"NCBI Gene 8452","url":"https://www.ncbi.nlm.nih.gov/gene/8452"},{"label":"Ensembl ENSG00000036257","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000036257"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["rcc","nsclc","papillary-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"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 1 therapies; IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 3 cohorts; CIViC holds 1 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"CUL3","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:2553","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2553","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q13618","url":"https://www.uniprot.org/uniprotkb/Q13618/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CUL3","url":"https://civicdb.org/features/6688","note":"1 evidence items, 0 assertions, 1 variants; diseases: Lung Non-small Cell Carcinoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000036257","url":"https://platform.opentargets.org/target/ENSG00000036257/associations","note":"association with cancer (MONDO_0004992) 0.55;  (GraphQL API, CC0)"},{"label":"IntOGen CUL3","url":"https://www.intogen.org/search?gene=CUL3","note":"driver in 4 cohorts (Act 1, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:2553","ensembl":"ENSG00000036257","uniprot":"Q13618","entrez":"8452","biology":"Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. Location: Nucleus; Golgi apparatus; Cell projection, cilium, flagellum; Cytoplasm, cytoskeleton, spindle (UniProt). Locus 2q36.2 (HGNC).","whereFound":["Renal cell carcinoma: IntOGen driver in 2 cohorts (PRCC, RCC)","Non-small-cell lung cancer: CIViC evidence names this disease; IntOGen driver in 2 cohorts (LUSC)","Papillary renal cell carcinoma: IntOGen driver in 1 cohort (PRCC)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/cul3/","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":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"papillary-rcc","kind":"cancer","name":"Papillary renal cell carcinoma","route":"/cancers/papillary-rcc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}]}}