# CYLD

Source: https://onco.cc/targets/cyld/  
OnCo record `cyld` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Open 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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: CYLD lysine 63 deubiquitinase; Ubiquitin carboxyl-terminal hydrolase CYLD; KIAA0849; USPL2; CYLD1
- Tags: cancer-genes-wave
- Symbol: CYLD
- Class: enzyme
- 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).
- Where found: 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)

## 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.

## Sources

- HGNC HGNC:2584: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2584
- UniProt Q9NQC7: https://www.uniprot.org/uniprotkb/Q9NQC7/entry
- NCBI Gene 1540: https://www.ncbi.nlm.nih.gov/gene/1540
- Ensembl ENSG00000083799: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000083799

## Connected records

- collections: [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Nasopharyngeal carcinoma](https://onco.cc/cancers/nasopharyngeal/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/)

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JSON: https://onco.cc/api/v1/entities/cyld.json