# USP6

Source: https://onco.cc/targets/usp6/  
OnCo record `usp6` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

USP6 (Ubiquitin carboxyl-terminal hydrolase 6) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Colorectal cancer, Breast cancer, Hepatocellular carcinoma and 5 more.

## Summary

Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyses its own deubiquitination. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity.

Open Targets scores its association with cancer at 0.74 (direct and indirect evidence; datatypes literature 0.78, animal model 0.53, genetic association 0.00, somatic mutation 0.96). IntOGen calls it a driver in 8 cohorts (5 activating, 0 loss-of-function), covering Acute Myeloid Leukaemia, Basal Cell Carcinoma, Invasive Breast Carcinoma, Colorectal Adenocarcinoma, Hepatocellular Carcinoma, Lung Squamous Cell Carcinoma and others.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: ubiquitin specific peptidase 6; Ubiquitin carboxyl-terminal hydrolase 6; Tre-2; TRE17; Tre2; HRP1; TRESMCR
- Tags: cancer-genes-wave
- Symbol: USP6
- Class: oncogene
- Biology: Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyses its own deubiquitination. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity. Promotes plasma membrane localisation of ARF6 and selectively regulates ARF6-dependent endocytic protein trafficking. Is able to initiate tumorigenesis by inducing the production of matrix metalloproteinases following NF-kappa-B activation. May act as a GTPase-activating protein for RAB3A. Location: Cell membrane; Cytoplasm; Endosome (UniProt). Locus 17p13.2 (HGNC).
- Where found: Colorectal cancer: Open Targets association 0.59 with colorectal cancer (MONDO_0005575); IntOGen driver in 1 cohort (COADREAD); Breast cancer: Open Targets association 0.51 with breast cancer (MONDO_0007254); IntOGen driver in 1 cohort (BRCA); Hepatocellular carcinoma: IntOGen driver in 1 cohort (HCC); Prostate cancer: IntOGen driver in 1 cohort (PRAD); Skin cancer: Open Targets association 0.57 with skin cancer (MONDO_0002898); Lung cancer: Open Targets association 0.54 with lung cancer (MONDO_0008903)

## 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 5 cohorts; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.

## Sources

- HGNC HGNC:12629: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12629
- UniProt P35125: https://www.uniprot.org/uniprotkb/P35125/entry
- NCBI Gene 9098: https://www.ncbi.nlm.nih.gov/gene/9098
- Ensembl ENSG00000129204: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000129204

## Connected records

- collections: [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)

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JSON: https://onco.cc/api/v1/entities/usp6.json