# UBR5

Source: https://onco.cc/targets/ubr5/  
OnCo record `ubr5` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

UBR5 (E3 ubiquitin-protein ligase UBR5) is an enzyme. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Gastric & gastro-oesophageal junction cancer, Breast cancer, Renal cell carcinoma and 5 more.

## Summary

E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus. Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates. Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilising according to the N-end rule, leading to their degradation.

CIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.70 (direct and indirect evidence; datatypes literature 0.98, genetic association 0.27, somatic mutation 0.88). IntOGen calls it a driver in 7 cohorts (2 activating, 5 loss-of-function), covering Acute Myeloid Leukaemia, Invasive Breast Carcinoma, Chromophobe Renal Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, Melanoma, Stomach Adenocarcinoma.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: ubiquitin protein ligase E3 component n-recognin 5; E3 ubiquitin-protein ligase UBR5; DD5; KIAA0896; EDD1
- Tags: cancer-genes-wave
- Symbol: UBR5
- Class: enzyme
- Biology: E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus. Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates. Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilising according to the N-end rule, leading to their degradation. Recognises type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalysing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4. Together with ITCH, catalyses 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH. Location: Nucleus; Cytoplasm (UniProt). Locus 8q22.3 (HGNC).
- Where found: Gastric & gastro-oesophageal junction cancer: Open Targets association 0.57 with gastric cancer (MONDO_0001056); IntOGen driver in 2 cohorts (STAD); Breast cancer: Open Targets association 0.57 with breast cancer (MONDO_0007254); IntOGen driver in 1 cohort (BRCA); Renal cell carcinoma: IntOGen driver in 1 cohort (CHRCC); Skin cancer: Open Targets association 0.57 with skin cancer (MONDO_0002898); Colorectal cancer: Open Targets association 0.55 with colorectal cancer (MONDO_0005575); Non-Hodgkin lymphoma: Open Targets association 0.52 with non-Hodgkin lymphoma (MONDO_0018908)

## 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 5 cohorts; CIViC holds 1 clinical evidence items on its variants; UniProt keyword "DNA repair". Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.

## Sources

- HGNC HGNC:16806: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16806
- UniProt O95071: https://www.uniprot.org/uniprotkb/O95071/entry
- NCBI Gene 51366: https://www.ncbi.nlm.nih.gov/gene/51366
- Ensembl ENSG00000104517: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000104517

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)

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JSON: https://onco.cc/api/v1/entities/ubr5.json