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Endonuclease domain-containing 1 protein (ENDOD1)
- Target
- ENDOD1
- Molecular classification
- Enzyme (specifically, DNA/RNA non-specific endonuclease family), Other (multi-pass transmembrane protein with roles connecting to immunity and DNA repair)
01
Overview
Endonuclease domain-containing 1 protein (ENDOD1) is a multi-pass transmembrane enzyme, part of the DNA/RNA non-specific endonuclease family, encoded by the ENDOD1 gene. It is predicted to function as a DNase and RNase and is involved in DNA single-strand break repair. ENDOD1 modulates the innate immune response via the cGAS-STING pathway, interacting with RNF26, and can localize to both the cytoplasm and, under stress conditions, the nucleus. Loss of ENDOD1 causes synthetic lethality in tumors with TP53 mutations and in homologous recombination-defective backgrounds, making it an emerging candidate for cancer therapies designed on synthetic lethality principles[1][2][3][5][10][11].
- Other names
- ENDOD1KIAA0830Endonuclease domain containing 1Endonuclease domain-containing 1 protein
02
Mechanism of action
Synthetic lethality (hypothetical strategy: inhibition of ENDOD1 in cancers harboring TP53 mutations causes lethal DNA repair defects and cell death) Potential modulation of DNA repair by influencing PARP association and cGAS-STING pathway
03
Biological functions
DNA single-strand break repairInnate immune response modulation (via cGAS-STING pathway, by interaction with RNF26)DNase and RNase activityNucleic acid bindingCell cycle regulation (including cell proliferation control)
04
Disease associations
Cancer (ENDOD1 deficiency is synthetic lethal with TP53 mutations, suggesting potential in targeting cancers with TP53 loss)Other (potential modulation in immune responses, given role in cGAS-STING pathway)
05
Safety considerations
DNA repair inhibition overlap (systemic inhibition may theoretically impact normal tissues with high DNA repair demands)Potential immunological effects (given its role in innate immune signaling, modulation may have immune-related safety concerns, though these are not well described to date)
06
Interacting drugs
None identified to date (as of current knowledge, there are no marketed drugs or clinical-stage compounds that directly target ENDOD1)
07
Biomarkers
TP53 mutational status (tumors with TP53 mutations are especially sensitive to ENDOD1 loss and could serve as an efficacy biomarker for ENDOD1-targeted approaches)
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