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Zinc finger protein 451 (ZNF451)
- Target
- ZNF451
- Molecular classification
- Transcription factor, E3 SUMO-protein ligase, Zinc finger protein (C2H2-type), Chromatin modifier, Protein coding gene/protein family: zinc finger superfamily
01
Overview
Zinc finger protein 451 is a nuclear protein characterized by C2H2-type zinc finger domains, and functions principally as an E3 SUMO-protein ligase. It enables sumoylation of Top2 DNA-protein crosslinks, recruits DNA repair proteins (such as Tdp2), and remodels enzymes involved in genome integrity. ZNF451 serves as a transcription corepressor and regulator, modulates chromatin structure, and can interact with pathways such as TGF-beta signaling and AR targets. Its misregulation or mutation may contribute to neurodevelopmental disorders, cancer, and other human diseases via impaired DNA repair and transcriptional control. The protein is a candidate therapeutic target in oncology and genome stability contexts, though no drugs currently target it directly.
- Other names
- COASTERDJ417I1.1KIAA0576KIAA1702ZATT
02
Mechanism of action
SUMOylation inhibition/activation (future drugs may block or enhance ZNF451 ligase activity); Transcription modulation (potential indirect action); DNA damage response modulation (potential for DDR-inhibition therapies)
03
Biological functions
Transcription regulation (corepressor and regulator inhibitor)Protein modification (sumoylation)DNA repair (reversal of DNA-protein crosslinks)Negative regulation of transforming growth factor beta receptor signalingChromatin remodelingRegulation of AR targetsInhibition of histone acetylation
04
Disease associations
Cancer (associated via DNA repair, SUMO pathway, chromatin dynamics)Autism spectrum disorderRuijs-Aalfs syndromeOther neurodevelopmental diseases (inferred from general ZNF roles)
05
Safety considerations
Possible risks include genomic instability or off-target effects if transcription regulation or DNA-protein crosslink repair is perturbed; targeting E3 ligases in therapy poses challenges of specificity and potential toxicity
06
Interacting drugs
No explicit drugs directly interact or are approved for ZNF451; regulatory function is studied, but drugs targeting SUMOylation or DNA repair (PARP inhibitors, proteasome inhibitors) may intersect mechanistically
07
Biomarkers
No established biomarkers directly linked to ZNF451 for patient selection or monitoring as of current reports
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