{"entity":{"id":"cyld","kind":"target","name":"CYLD","aka":["CYLD lysine 63 deubiquitinase","Ubiquitin carboxyl-terminal hydrolase CYLD","KIAA0849","USPL2","CYLD1"],"tldr":"CYLD (Ubiquitin carboxyl-terminal hydrolase CYLD) is an enzyme. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Bladder & urothelial cancer, Breast cancer, Colorectal cancer and 5 more.","summary":"Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-induced necroptosis. Negatively regulates NF-kappa-B activation by deubiquitinating upstream signalling factors. Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation.\n\nOpen Targets scores its association with cancer at 0.73 (direct and indirect evidence; datatypes literature 0.98, animal model 0.44, genetic association 0.02, somatic mutation 0.94). IntOGen calls it a driver in 11 cohorts (2 activating, 7 loss-of-function), covering Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Colorectal Adenocarcinoma, Head and Neck Squamous Cell Carcinoma, Nasopharyngeal Carcinoma, Non-Small Cell Lung Cancer and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:2584","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2584"},{"label":"UniProt Q9NQC7","url":"https://www.uniprot.org/uniprotkb/Q9NQC7/entry"},{"label":"NCBI Gene 1540","url":"https://www.ncbi.nlm.nih.gov/gene/1540"},{"label":"Ensembl ENSG00000083799","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000083799"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["urothelial","breast-cancer","colorectal","head-and-neck","nasopharyngeal","multiple-myeloma","prostate","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: IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 7 cohorts. Evidence tier \"cohort-driver\" 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":"CYLD","role":["oncogene-driver","tumour-suppressor"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:2584","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2584","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9NQC7","url":"https://www.uniprot.org/uniprotkb/Q9NQC7/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000083799","url":"https://platform.opentargets.org/target/ENSG00000083799/associations","note":"association with cancer (MONDO_0004992) 0.73; per-cancer scores at or above 0.5: melanoma 0.58, skin cancer 0.57, thymic carcinoma 0.51 (GraphQL API, CC0)"},{"label":"IntOGen CYLD","url":"https://www.intogen.org/search?gene=CYLD","note":"driver in 11 cohorts (Act 2, LoF 7); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:2584","ensembl":"ENSG00000083799","uniprot":"Q9NQC7","entrez":"1540","biology":"Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-induced necroptosis. Negatively regulates NF-kappa-B activation by deubiquitinating upstream signalling factors. Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation. Negative regulator of Wnt signalling. Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilisation of microtubules. Plays a role in the regulation of microtubule dynamics, and thereby contributes to the regulation of cell proliferation, cell polarisation, cell migration, and angiogenesis. Location: Cytoplasm; Cytoplasm, perinuclear region; Cytoplasm, cytoskeleton; Cell membrane (UniProt). Locus 16q12.1 (HGNC).","whereFound":["Bladder & urothelial cancer: IntOGen driver in 1 cohort (BLCA)","Breast cancer: IntOGen driver in 1 cohort (BRCA)","Colorectal cancer: IntOGen driver in 1 cohort (COADREAD)","Head and neck squamous cell carcinoma: IntOGen driver in 1 cohort (HNSC)","Nasopharyngeal carcinoma: IntOGen driver in 1 cohort (NPC)","Multiple myeloma: IntOGen driver in 1 cohort (PCM)"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/cyld/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"nasopharyngeal","kind":"cancer","name":"Nasopharyngeal carcinoma","route":"/cancers/nasopharyngeal/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}]}}