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7 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ZNF593
zinc finger protein 593
Chromosome 1 · 1p36.11
NCBI Gene: 51042Ensembl: ENSG00000142684.9HGNC: HGNC:30943UniProt: O00488
46PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTranscription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
zinc ion bindingnucleoplasmnucleolusprotein bindingneurodegenerative diseasebreast cancerRare familial disorder with hypertrophic cardiomyopathyhypertrophic cardiomyopathy
✦AI Summary

ZNF593 is a zinc finger protein with multiple regulatory functions spanning nuclear and cytoplasmic compartments. Structurally, it comprises a classic C(2)H(2) zinc finger domain flanked by disordered regions 1. Nuclearly, ZNF593 negatively modulates Oct-2 transcriptional activity by inhibiting its DNA binding 2, and interacts with ZFX to facilitate histone H4 acetylation and transcriptional elongation 3. Additionally, ZNF593 promotes pre-60S ribosomal particle nuclear export during ribosomal maturation. In the cytoplasm, ZNF593 functions as a critical immune checkpoint. Following viral infection, ZNF593 translocates from the nucleus to the cytoplasm where it directly binds cGAS and suppresses its DNA-binding capacity, thereby attenuating the cGAS-mediated antiviral interferon-β response 4. ZNF593 deficiency enhances antiviral immunity and improves survival against HSV-1 infection. Clinically, ZNF593 dysregulation is implicated in systemic lupus erythematosus pathogenesis; restoring ZNF593 expression reduces pathogenic interferon production in SLE patients and animal models 4. Beyond immunity, ZNF593-AS (an antisense transcript) protects against cardiac hypertrophy by upregulating mitofusin-2 and improving mitochondrial function 5. These findings establish ZNF593 as a multifunctional regulator bridging transcription, ribosomal biogenesis, and innate immunity.

Sources cited
1
ZNF593 translocates to cytoplasm after viral infection and suppresses cGAS-DNA binding to attenuate IFN-β production; ZNF593 deficiency improves antiviral responses and survival against HSV-1; elevated ZNF593 reduces IFN production in SLE
PMID: 40210981
2
ZNF593 interacts with ZFX transcriptional activator and is part of chromatin-associated protein complexes that enhance histone H4 acetylation and reduce RNA polymerase II pausing
PMID: 38726870
3
ZNF593 structure contains a C(2)H(2) zinc finger domain with a beta-hairpin and kinked alpha-helix within a predominantly disordered protein
PMID: 18287285
4
ZNF593 (hT86) dominantly inhibits Oct-2 DNA-binding activity and transcriptional function through protein-protein interaction
PMID: 9115366
5
lncRNA ZNF593-AS upregulates mitofusin-2 expression and improves mitochondrial function to protect against cardiac hypertrophy and remodeling
PMID: 38743133
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.37Weak
breast cancerOpen Targets
0.07Suggestive
hypertrophic cardiomyopathyOpen Targets
0.05Suggestive
Rare familial disorder with hypertrophic cardiomyopathyOpen Targets
0.05Suggestive
diabetic cardiomyopathyOpen Targets
0.05Suggestive
diabetes mellitusOpen Targets
0.05Suggestive
Arrhythmogenic right ventricular dysplasiaOpen Targets
0.04Suggestive
Familial dilated cardiomyopathy with conduction defect due to LMNA mutationOpen Targets
0.04Suggestive
catecholaminergic polymorphic ventricular tachycardiaOpen Targets
0.04Suggestive
Atrial stand stillOpen Targets
0.04Suggestive
smoking initiationOpen Targets
0.04Suggestive
sick sinus syndrome 2, autosomal dominantOpen Targets
0.04Suggestive
hypertrophic cardiomyopathy 6Open Targets
0.04Suggestive
atrial conduction diseaseOpen Targets
0.03Suggestive
dilated cardiomyopathy 1EOpen Targets
0.03Suggestive
long QT syndrome 15Open Targets
0.03Suggestive
Romano-Ward syndromeOpen Targets
0.03Suggestive
catecholaminergic polymorphic ventricular tachycardia 1Open Targets
0.03Suggestive
neoplasmOpen Targets
0.03Suggestive
Brugada syndromeOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RPL39Protein interaction100%RPL13AProtein interaction100%RPL38Protein interaction100%RPL27Protein interaction100%RPL29Protein interaction100%RPL32Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Liver
83%
Ovary
55%
Lung
40%
Bone Marrow
0%
Heart
0%
Gene Interaction Network
Click a node to explore
ZNF593RPL39RPL13ARPL38RPL27RPL29RPL32
PROTEIN STRUCTURE
Preparing viewer…
PDB8FLE · 2.48 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.91LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.45 [0.99–1.91]
RankingsWhere ZNF593 stands among ~20K protein-coding genes
  • #9,404of 20,598
    Most Researched46
  • #17,293of 17,882
    Most Constrained (LOEUF)1.91
Genes detectedZNF593
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
ZNF593 regulates the cGAS-mediated innate immune response by attenuating cGAS-DNA binding.
PMID: 40210981
Cell Death Differ · 2025
1.00
2
Reduction of ZFX levels decreases histone H4 acetylation and increases Pol2 pausing at target promoters.
PMID: 38726870
Nucleic Acids Res · 2024
0.86
3
Multiple stressors produce differential transcriptomic patterns in a stream-dwelling salamander.
PMID: 31185901
BMC Genomics · 2019
0.71
4
LncRNA ZNF593-AS Alleviates Contractile Dysfunction in Dilated Cardiomyopathy.
PMID: 33550812
Circ Res · 2021
0.57
5
The solution structure of ZNF593 from Homo sapiens reveals a zinc finger in a predominantly unstructured protein.
PMID: 18287285
Protein Sci · 2008
0.43