# PARG

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

## TL;DR

PARG clears away the poly(ADP-ribose) chains that PARP enzymes lay down at damaged DNA. Blocking it is meant to deepen the replication stress some cancers already live with, as a partner or alternative to PARP inhibitors; two PARG inhibitors are in trials.

## Summary

PARG (chromosome 10q11.23) is the enzyme that degrades poly(ADP-ribose) by cutting the bonds between its ribose units; the poly(ADP-ribose) made after DNA damage lasts only briefly because PARG removes it rapidly (UniProt Q86W56). A 2020 review in Genes & Development describes PARG inhibitors as exploiting and exacerbating the replication deficiencies of cancer cells and as possible complements to PARP inhibitors, which act through synthetic lethality with mutations in DNA repair genes (Slade, doi:10.1101/gad.334516.119). In OnCo, DAT-2645 is an oral PARG inhibitor for tumours with BRCA1/2 loss of function or other DNA repair defects, and ETX-19477 an oral PARG inhibitor aimed at replication stress and fork-protection defects.

## Fields

- Kind: Target
- Last checked: 2026-11-03
- Also known as: poly(ADP-ribose) glycohydrolase
- Tags: pipeline-gap-target
- Symbol: PARG
- Class: enzyme
- Biology: Mainly an exo-glycohydrolase that releases ADP-ribose from poly(ADP-ribose) chains; it cannot remove the last ADP-ribose attached to a protein (UniProt Q86W56). It reverses what PARP1 and PARP2 build at DNA lesions.
- Where found: Tumours with BRCA1/2 loss of function or other DNA repair defects (DAT-2645); Tumours with replication stress or fork-protection defects (ETX-19477)

## Notes

- Prevalence not recorded: HGNC, UniProt and the paper cited give no positivity rate.

## Sources

- HGNC HGNC:8605: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:8605
- UniProt Q86W56: https://www.uniprot.org/uniprotkb/Q86W56/entry
- NCBI Gene 8505: https://www.ncbi.nlm.nih.gov/gene/8505
- PARP and PARG inhibitors in cancer treatment (Genes Dev 2020): https://doi.org/10.1101/gad.334516.119

## Connected records

- targets: [PARP](https://onco.cc/targets/parp/)
- cancers: [Metastatic cancer (cancer that has spread)](https://onco.cc/cancers/metastatic-cancer/)
- drugs: [DAT-2645](https://onco.cc/drugs/dat-2645/), [ETX-19477](https://onco.cc/drugs/etx-19477/)

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