{"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"}],"specificitySources":[],"hgnc":"HGNC:2584","ensembl":"ENSG00000083799","uniprot":"Q9NQC7","entrez":"1540","firstDescribed":1998,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Nagase et al, DNA Res, 1998, \"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/10048485/","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/"}]}}