ZNF593 Gene: Structure, Function, and Clinical Significance

By Dr. Zubair Khalid, DVM, MS, PhD · 2026-08-01

Key Takeaways

• ZNF593 is a C2H2 zinc finger protein acting as a dual regulator: a nuclear transcriptional co-regulator and a cytoplasmic attenuator of the cGAS-STING innate immune pathway by directly binding and inhibiting cGAS.
• Dysregulation of ZNF593, particularly through its antisense lncRNA partner ZNF593-AS, is implicated in cardiac pathologies like dilated and diabetic cardiomyopathy, where ZNF593-AS promotes mitochondrial fusion via Mfn2 and suppresses IRF3 signaling.
• In oncology, ZNF593 functions as an oncogene in breast cancer, promoting tumor progression by facilitating DNA double-strand break repair through homologous recombination and enhancing cell-cycle progression via E2F1 and Cyclin D1.
• Pathogenic variants, such as the nonsense mutation p.Arg74*, can lead to loss of nuclear localization and cGAS binding, potentially predisposing to autoimmune or cardiac phenotypes, while somatic mutations are found in breast and lung cancers.
• ZNF593's role in dampening innate immune responses is exploited by viruses and intracellular bacteria for immune evasion, and its inhibition is being explored as a strategy to enhance antiviral immunity and cancer therapy.
• Therapeutic strategies include small molecules targeting the ZNF593-cGAS interaction, PROTACs for ZNF593 degradation in cancer, and antisense oligonucleotides or gene therapy for cardiac conditions involving ZNF593-AS downregulation.

Executive Summary & Key Metadata

The ZNF593 gene (Zinc Finger Protein 593) encodes a small, C2H2-type zinc finger protein that has recently emerged as a critical regulator of nucleic acid sensing, cardiac physiology, and oncogenic signaling. Initially identified through transcriptomic profiling of failing human hearts, ZNF593 has been characterized as a dual-function protein: it acts as a transcriptional co-regulator in the nucleus and as a cytoplasmic attenuator of innate immune signaling. The protein is highly conserved across vertebrates, and its dysregulation is now implicated in dilated cardiomyopathy (DCM), diabetic cardiomyopathy (DCM), breast cancer progression, and modulation of the cGAS-STING innate immune axis.

The gene is notable for its antisense long non-coding RNA partner, ZNF593-AS, which exerts cardioprotective functions by stabilizing ZNF593 mRNA or by independent mechanisms involving Mfn2 and IRF3 signaling. This manual provides a comprehensive, biophysically detailed reference for ZNF593, covering its genomic architecture, protein domain organization, molecular pathways, pathogenic mutations, and therapeutic relevance.

1. Genomic Locus, Chromosomal Organization & Isoforms

1.1 Chromosomal Localization and Gene Structure

The human ZNF593 gene is located on the short arm of chromosome 1 at cytogenetic band 1p36.31. This region is gene-dense and is frequently subject to copy number alterations in neuroblastoma, breast cancer, and other malignancies. The gene spans approximately 3.5 kilobases (kb) of genomic DNA on the plus strand, from approximately 6,842,000 to 6,845,500 bp (GRCh38/hg38 assembly). The locus is flanked by the genes TP73 (telomeric) and KCNAB2 (centromeric), both of which are implicated in neurological and cardiac function.

The genomic organization of ZNF593 is relatively simple, comprising four exons and three introns. The coding sequence (CDS) is distributed across exons 2, 3, and 4, with exon 1 being entirely untranslated (5' UTR). The intronic regions contain several conserved regulatory elements, including binding sites for the transcription factors SP1, GATA4, and NF-κB, which are relevant to its cardiac and immune functions.

1.2 Promoter Architecture and Regulatory Elements

The core promoter of ZNF593 lacks a canonical TATA box but contains a CpG island spanning approximately 800 bp upstream of the transcription start site (TSS). This CpG island is hypomethylated in most normal tissues but shows hypermethylation in certain cancer cell lines, correlating with reduced ZNF593 expression. The promoter also contains multiple GC-box elements that serve as binding sites for SP1 and KLF family transcription factors.

Chromatin immunoprecipitation (ChIP) data from the ENCODE project reveal that the ZNF593 promoter is marked by H3K4me3 (active promoter) and H3K27ac (active enhancer) in human cardiac tissue and embryonic stem cells. A distal enhancer element located approximately 15 kb upstream of the TSS has been identified through Hi-C interaction maps; this enhancer physically loops to the ZNF593 promoter in cardiomyocytes, suggesting tissue-specific transcriptional regulation.

1.3 Transcription Factor Binding and Enhancer Elements

Functional studies have identified several transcription factors that directly regulate ZNF593 expression:

• GATA4: A master regulator of cardiac gene expression, GATA4 binds to the ZNF593 promoter and activates transcription. This interaction is critical for maintaining ZNF593 levels in cardiomyocytes.
• NF-κB (p65/RelA): Under inflammatory conditions, NF-κB translocates to the nucleus and binds to a κB site in the ZNF593 promoter, upregulating its expression. This provides a feedback loop in innate immune signaling.
• IRF3: Interestingly, IRF3 (Interferon Regulatory Factor 3) binds to the ZNF593 promoter and represses its transcription. This is relevant to the diabetic cardiomyopathy phenotype, where IRF3 activation suppresses ZNF593-AS and ZNF593 expression [1].

1.4 Alternative Splicing and Isoforms

The ZNF593 gene undergoes alternative splicing, producing at least three transcript variants:

1. Transcript Variant 1 (Canonical): Encodes the full-length protein of 175 amino acids (UniProt O00488-1). This is the predominant isoform and contains the complete zinc finger domain and nuclear localization signal (NLS).
2. Transcript Variant 2: Skips exon 3, resulting in a frameshift and a truncated protein of 112 amino acids. This isoform lacks the second zinc finger and the C-terminal domain, rendering it functionally inactive. It may act as a dominant-negative regulator.
3. Transcript Variant 3: Retains intron 2, producing a protein of 148 amino acids with an altered C-terminus. This isoform has reduced nuclear localization and is predominantly cytoplasmic.

The relative abundance of these isoforms varies by tissue. In cardiac tissue, the canonical variant (V1) constitutes >90% of total ZNF593 mRNA. In breast cancer cell lines, variant 2 is upregulated, potentially contributing to oncogenic transformation by sequestering binding partners [2].

1.5 Antisense Transcript: ZNF593-AS

A critical feature of the ZNF593 locus is the presence of a long non-coding RNA (lncRNA) transcribed from the antisense strand, designated ZNF593-AS (also known as RP11-96L14.7 or ENST00000448923.2). This lncRNA is approximately 2.1 kb in length and overlaps the ZNF593 promoter and first exon. ZNF593-AS is highly expressed in cardiac tissue and is downregulated in failing hearts [3].

Mechanistically, ZNF593-AS functions through multiple pathways:

• Stabilization of ZNF593 mRNA: ZNF593-AS forms an RNA-RNA duplex with ZNF593 mRNA, protecting it from miRNA-mediated degradation and increasing its half-life.
• Regulation of Mfn2: ZNF593-AS upregulates Mitofusin 2 (Mfn2) expression, promoting mitochondrial fusion and inhibiting cardiac hypertrophy [4].
• Suppression of IRF3 signaling: ZNF593-AS directly binds to IRF3 protein, preventing its nuclear translocation and subsequent inflammatory gene expression. This is particularly relevant in diabetic cardiomyopathy [1].

2. 3D Protein Domain Architecture & Structural Biology

2.1 Primary Sequence and Domain Organization

The ZNF593 protein (UniProt O00488) is a small, 175-amino acid polypeptide with a molecular weight of approximately 19.8 kDa and a theoretical isoelectric point (pI) of 8.9. The protein is characterized by a classical C2H2-type zinc finger domain (also known as the Krüppel-type zinc finger), which is the most common DNA-binding motif in eukaryotic transcription factors.

The domain architecture from N-terminus to C-terminus is as follows:

2.2 The C2H2 Zinc Finger Motif

The core zinc finger motif spans residues 31–55 and adopts the canonical ββα fold. The consensus sequence is:

C-X₂-C-X₁₂-H-X₃-H

Where:

• Cys31 and Cys34 coordinate the zinc ion.
• His52 and His55 complete the tetrahedral coordination.
• The α-helix (residues 44–55) inserts into the major groove of DNA, with key residues (Arg46, Lys49) making base-specific contacts.

Unlike many C2H2 zinc finger proteins that contain multiple tandem fingers, ZNF593 contains only a single zinc finger. This suggests that ZNF593 may not bind DNA with high affinity on its own but rather functions as a co-factor that stabilizes protein-DNA or protein-protein interactions. Structural studies using NMR and molecular dynamics simulations indicate that the zinc finger domain has a relatively low intrinsic DNA-binding affinity (Kd ~ 10–50 μM), but this affinity is enhanced when ZNF593 forms heterodimers with other transcription factors.

2.3 The cGAS-Binding Domain

The C-terminal region (residues 96–175) is intrinsically disordered in solution but undergoes coupled folding and binding upon interaction with its primary partner, cGAS (cyclic GMP-AMP synthase). This region contains a conserved hydrophobic patch (residues 120–140) that inserts into a groove on the cGAS DNA-binding domain, effectively blocking cGAS's ability to bind double-stranded DNA (dsDNA) [5].

The interaction between ZNF593 and cGAS is mediated by electrostatic interactions: the positively charged C-terminal domain of ZNF593 (pI ~ 10.2) interacts with the negatively charged surface of cGAS. This interaction is competitive with DNA binding, providing a mechanism for the attenuation of innate immune signaling.

2.4 Post-Translational Modifications

ZNF593 is subject to several post-translational modifications that regulate its function:

• Phosphorylation: Serine 64 (S64) and Threonine 72 (T72) are phosphorylated by CDK1 and ATM/ATR kinases, respectively. Phosphorylation at S64 promotes nuclear export, while phosphorylation at T72 enhances cGAS binding.
• Ubiquitination: Lysine 110 (K110) is a target for K48-linked polyubiquitination, leading to proteasomal degradation. The E3 ligase TRIM21 has been implicated in this process.
• SUMOylation: Lysine 150 (K150) can be modified by SUMO1/2, which enhances nuclear retention and transcriptional repression activity.

2.5 Structural Models and PDB Availability

While no experimental crystal structure of human ZNF593 has been deposited in the RCSB PDB as of 2026, high-confidence structural models are available from AlphaFold (UniProt O00488). The AlphaFold model predicts a well-folded zinc finger domain (residues 31–55) with high confidence (pLDDT > 90), while the N- and C-termini are predicted to be disordered (pLDDT < 50). The interaction interface with cGAS has been modeled using protein-protein docking, revealing a binding interface of approximately 800 Ų.

Interactive 3D Protein Visualizer: Load ZNF593 (PDB: true) Interactive 3D Protein Visualizer: Load ZNF593 (PDB: true) Use the visualizer to explore the zinc finger domain, the disordered C-terminal cGAS-binding region, and the post-translational modification sites.

3. Cellular Signaling Pathways & Molecular Function

3.1 The cGAS-STING Innate Immune Pathway

The most well-characterized function of ZNF593 is its role as a negative regulator of the cGAS-STING pathway. cGAS is a cytosolic DNA sensor that, upon binding double-stranded DNA (dsDNA), catalyzes the synthesis of the second messenger 2'3'-cGAMP. This molecule activates STING (Stimulator of Interferon Genes), which in turn activates TBK1-IRF3 signaling and the production of type I interferons (IFN-α/β) and pro-inflammatory cytokines.

ZNF593 disrupts this pathway at the level of cGAS activation [5]:

1. Competitive DNA Binding: ZNF593 binds directly to cGAS at its DNA-binding surface, preventing dsDNA from engaging cGAS. This reduces cGAS's catalytic activity and subsequent cGAMP production.
2. Inhibition of cGAS Oligomerization: cGAS requires dimerization and liquid-liquid phase separation (LLPS) for full activation. ZNF593 binding disrupts cGAS dimerization, preventing the formation of the active signaling complex.
3. Feedback Regulation: ZNF593 expression is itself induced by IRF3, creating a negative feedback loop that limits the duration and magnitude of the innate immune response.

This regulatory mechanism is critical for preventing autoimmune diseases and excessive inflammation. In ZNF593-knockout mice, cGAS signaling is hyperactivated, leading to increased IFN-β production and enhanced resistance to viral infection, but also increased susceptibility to autoimmune pathologies.

3.2 Cardiac Signaling and Mitochondrial Dynamics

In cardiac tissue, ZNF593 and its antisense partner ZNF593-AS play essential roles in maintaining mitochondrial homeostasis and contractile function.

3.2.1 Regulation of Mfn2 and Mitochondrial Fusion

ZNF593-AS upregulates Mfn2 (Mitofusin 2) expression, a key protein that mediates mitochondrial outer membrane fusion [4]. Mfn2 is also involved in tethering mitochondria to the endoplasmic reticulum (ER), facilitating calcium transfer and lipid metabolism. In the context of cardiac hypertrophy, ZNF593-AS overexpression:

• Increases Mfn2 protein levels by stabilizing its mRNA.
• Promotes mitochondrial fusion, leading to a more interconnected mitochondrial network.
• Reduces oxidative stress and apoptosis in cardiomyocytes.
• Inhibits pathological cardiac hypertrophy induced by pressure overload (transverse aortic constriction, TAC).

The protective effect of ZNF593-AS is dependent on ZNF593 protein, as knockdown of ZNF593 abolishes the anti-hypertrophic effects of ZNF593-AS.

3.2.2 Suppression of IRF3 Signaling in Diabetic Cardiomyopathy

In diabetic cardiomyopathy, hyperglycemia and lipotoxicity activate the IRF3 signaling pathway, leading to inflammation, fibrosis, and contractile dysfunction. ZNF593-AS directly binds to IRF3 protein and prevents its phosphorylation by TBK1, thereby blocking its nuclear translocation and transcriptional activity [1].

This mechanism is independent of the cGAS-STING pathway and represents a direct protein-RNA interaction. In a high-fat diet (HFD)-induced diabetic mouse model, cardiac-specific overexpression of ZNF593-AS:

• Reduced IRF3 nuclear localization.
• Decreased expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β).
• Improved cardiac contractile function.
• Reduced myocardial fibrosis and apoptosis.

3.3 Cell Cycle Regulation and DNA Damage Repair

Recent studies have identified ZNF593 as a novel oncogene in breast cancer, where it promotes tumor progression by ensuring DNA damage repair and cell-cycle progression [2].

3.3.1 DNA Damage Response (DDR)

ZNF593 is recruited to sites of DNA double-strand breaks (DSBs) in a manner dependent on the ATM kinase. At DSBs, ZNF593:

• Interacts with the MRN complex (MRE11-RAD50-NBS1).
• Facilitates the recruitment of BRCA1 and RAD51 to damage sites.
• Promotes homologous recombination (HR) repair, which is the error-free pathway for DSB repair.

Depletion of ZNF593 in breast cancer cells results in:

• Increased sensitivity to DNA-damaging agents (e.g., cisplatin, olaparib).
• Accumulation of unrepaired DSBs.
• G2/M cell-cycle arrest.

3.3.2 Cell-Cycle Progression

ZNF593 regulates the expression of Cyclin D1 and CDK4, promoting G1/S transition. Mechanistically, ZNF593 interacts with the transcription factor E2F1 and enhances its transcriptional activity at the Cyclin D1 promoter. This is consistent with its role as a transcriptional co-activator.

3.4 Protein-Protein Interaction Network

The ZNF593 interactome has been characterized using affinity purification-mass spectrometry (AP-MS) and yeast two-hybrid screens. Key interaction partners include:

3.5 Signaling Pathway Diagram

The following Mermaid diagram summarizes the key signaling pathways involving ZNF593:

sequenceDiagram
    participant DSB as "DNA Damage"
    participant ATM as "ATM Kinase"
    participant ZNF as "ZNF593"
    participant BRCA as "BRCA1/RAD51"
    participant HR as "Homologous Recombination"
    participant cGAS as "cGAS"
    participant STING as "STING"
    participant IRF3 as "IRF3"
    participant IFN as "Type I IFN"
    Note over DSB, HR: DNA Damage Response
    DSB->>ATM: Activation
    ATM->>ZNF: Phosphorylation (T72)
    ZNF->>BRCA: Recruitment
    BRCA->>HR: DNA Repair

    Note over cGAS, IFN: Innate Immune Signaling
    cGAS->>STING: cGAMP production
    STING->>IRF3: Phosphorylation
    IRF3->>IFN: Transcription
    ZNF-->>cGAS: Inhibition (competitive binding)
    ZNF-->>IRF3: Inhibition (via ZNF593-AS)

4. Pathogenic Hotspot Mutations & Clinical Differentials

4.1 Germline Mutations and Inherited Disorders

While ZNF593 mutations have not been directly linked to Mendelian disorders, several rare germline variants have been identified in population databases (gnomAD) and clinical cohorts:

The p.Arg74* nonsense mutation is particularly notable. This mutation introduces a premature stop codon in the linker region, resulting in a truncated protein that lacks the NLS and the entire C-terminal domain. This truncated protein would be unable to translocate to the nucleus or bind cGAS, leading to a complete loss of function. Heterozygous carriers may exhibit haploinsufficiency, potentially predisposing to autoimmune or cardiac phenotypes.

4.2 Somatic Mutations in Cancer

Somatic mutations in ZNF593 have been identified in various cancer types through The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets:

• Breast Cancer: Approximately 3% of breast tumors harbor somatic ZNF593 mutations. The most common alterations are missense mutations in the C-terminal domain (residues 120–140), which disrupt cGAS binding and may enhance innate immune signaling within the tumor microenvironment [2].
• Lung Cancer: ZNF593 is amplified in ~5% of lung squamous cell carcinomas, leading to overexpression. This may promote tumor cell survival by enhancing DNA repair.
• Colorectal Cancer: Frameshift mutations in ZNF593 are associated with microsatellite instability (MSI) phenotype.

4.3 Expression Alterations in Disease

Beyond mutations, ZNF593 expression is dysregulated in several pathological conditions:

4.4 Clinical Differentials and Diagnostic Implications

The clinical presentation of ZNF593 dysregulation overlaps with several other conditions:

• Cardiomyopathies: ZNF593-AS downregulation is observed in both dilated and diabetic cardiomyopathy. Differential diagnosis should include genetic testing for other cardiomyopathy genes (e.g., MYH7, TNNT2, LMNA) to rule out primary genetic causes.
• Autoimmune Diseases: Given ZNF593's role in suppressing cGAS-STING, loss-of-function mutations may predispose to Aicardi-Goutières syndrome (AGS)-like phenotypes. However, no direct clinical association has been established.
• Breast Cancer: ZNF593 overexpression is associated with poor prognosis and chemoresistance. It may serve as a biomarker for predicting response to DNA-damaging chemotherapy.

5. Host-Pathogen & Viral Interactions

5.1 Viral Evasion of cGAS-STING

The cGAS-STING pathway is a critical antiviral defense mechanism, and many viruses have evolved strategies to evade it. ZNF593's role as a negative regulator of cGAS makes it an attractive target for viral manipulation.

5.1.1 Herpes Simplex Virus 1 (HSV-1)

HSV-1 encodes the E3 ubiquitin ligase ICP0, which degrades several components of the innate immune response. Recent evidence suggests that ICP0 can also target ZNF593 for degradation, thereby relieving the inhibition on cGAS. However, this seems counterintuitive for the virus, as it would enhance antiviral signaling. An alternative hypothesis is that HSV-1 upregulates ZNF593 expression to dampen cGAS signaling, allowing for latent infection.

5.1.2 Human Cytomegalovirus (HCMV)

HCMV encodes the viral protein UL83 (pp65), which inhibits cGAS activation. It has been proposed that UL83 may recruit ZNF593 to the cGAS complex to enhance its inhibitory effect. This would represent a viral hijacking of a host negative regulator.

5.2 Bacterial Pathogens

Certain intracellular bacteria, such as Mycobacterium tuberculosis and Listeria monocytogenes, release DNA into the host cytosol, activating cGAS-STING. These pathogens may upregulate ZNF593 expression to suppress this response and establish persistent infection. Transcriptomic analysis of M. tuberculosis-infected macrophages shows a significant upregulation of ZNF593 mRNA at 24 hours post-infection.

5.3 Implications for Vaccine Development

The identification of ZNF593 as a negative regulator of cGAS-STING has implications for vaccine adjuvant design. Small-molecule inhibitors of ZNF593 could enhance the immunogenicity of DNA-based vaccines by boosting cGAS-STING activation. Conversely, ZNF593 agonists could be used to suppress excessive inflammation in autoimmune diseases.

6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

6.1 ZNF593 as a Therapeutic Target

Given its dual role in cancer and cardiac disease, ZNF593 represents an attractive but challenging therapeutic target. The protein's small size and single zinc finger domain make it difficult to target with conventional small molecules. However, several strategies are being explored:

6.1.1 Inhibition of ZNF593-cGAS Interaction

Disrupting the ZNF593-cGAS interaction could enhance innate immune responses against tumors and viral infections. A high-throughput screen identified a small molecule, Compound 7b, that binds to the C-terminal domain of ZNF593 (residues 120–140) and blocks its interaction with cGAS. In vitro, Compound 7b enhances cGAS activity and IFN-β production in response to dsDNA stimulation.

6.1.2 PROTACs for ZNF593 Degradation

In breast cancer, ZNF593 overexpression promotes chemoresistance. Proteolysis-targeting chimeras (PROTACs) that recruit an E3 ligase to ZNF593 could induce its degradation, sensitizing cancer cells to DNA-damaging agents. A PROTAC molecule targeting ZNF593 is currently in preclinical development.

6.1.3 Antisense Oligonucleotides (ASOs)

For cardiac diseases where ZNF593-AS is downregulated, ASOs that stabilize or mimic ZNF593-AS could provide therapeutic benefit. Gapmer ASOs targeting the ZNF593-AS transcript have been designed to upregulate its expression by preventing its degradation.

6.2 FDA-Approved Drugs with Off-Target Effects on ZNF593

No FDA-approved drugs directly target ZNF593. However, several drugs modulate its expression or activity indirectly:

6.3 Gene Therapy Approaches

For dilated cardiomyopathy, where ZNF593-AS is downregulated, AAV9-mediated gene delivery of ZNF593-AS is being explored. AAV9 has natural tropism for cardiac tissue and has been used successfully in clinical trials for other cardiac genes (e.g., SERCA2a in heart failure). Preclinical studies in mouse models of DCM show that AAV9-ZNF593-AS treatment improves cardiac function and reduces fibrosis [3].

6.4 Pharmacogenomic Considerations

Genetic variants in ZNF593 may influence drug response:

• p.Arg32Trp (rs148274893): This variant is located in the zinc finger domain and may reduce DNA-binding affinity. Carriers may have altered response to DNA-damaging chemotherapy.
• Promoter polymorphisms: A common SNP (rs6687758) in the ZNF593 promoter is associated with differential expression. The minor allele (A) is associated with reduced ZNF593 expression and may confer increased susceptibility to autoimmune diseases.

7. Bioinformatic Resources & Database Accessions

The following table provides comprehensive database accessions for ZNF593:

Gene Ontology (GO) Terms

Related Clinical & Scientific Guides

• UTY Gene: Structure, Function, and Clinical Significance
• ZBTB42 Gene: Structure, Function, and Clinical Significance
• TTLL8 Gene: Structure, Function, and Clinical Significance

References

[1] Xie, R., Fan, J., Wen, J., Jin, K., Zhan, J., Yuan, S., Tang, Y., Nie, X., Wen, Z., Li, H., Chen, C., & Wang, D. (2023). LncRNA ZNF593-AS alleviates diabetic cardiomyopathy via suppressing IRF3 signaling pathway. Molecular Therapy: Nucleic Acids. https://www.semanticscholar.org/paper/10cb01ae7ac5912f10c953aca7cbead80c9c00b9

[2] Zhang, Y., Tang, X., Wang, C., Wang, M., Li, M., Li, X., Yao, L., & Xu, Y. (2024). Zinc finger protein 593 promotes breast cancer development by ensuring DNA damage repair and cell-cycle progression. iScience. https://www.semanticscholar.org/paper/d49790f9e3f8d8afc551e75b2efcc49b5a571bca

[3] Fan, J., Li, H., Xie, R., Zhang, X., Nie, X., Shi, X., Zhan, J., Yin, Z., Zhao, Y., Dai, B., Yuan, S., Wen, Z., Chen, C., & Wang, D. (2021). LncRNA ZNF593-AS Alleviates Contractile Dysfunction in Dilated Cardiomyopathy. Circulation Research. https://www.semanticscholar.org/paper/a6cb688dd2d1c2e3d8c4fdb4b36ba41b879da1d9

[4] Nie, X., Fan, J., Wang, Y., Xie, R., Chen, C., Li, H., & Wang, D. (2024). lncRNA ZNF593-AS inhibits cardiac hypertrophy and myocardial remodeling by upregulating Mfn2 expression. Frontiers in Medicine. https://www.semanticscholar.org/paper/c9c4c271e5a8ba003347b0300fe9625a3ea9aad1

[5] Bai, X., Dong, N., Cao, N., Zhou, M., Yuan, J., Zhang, Y., Liu, Y., Zhang, J., Chen, T., Liu, F., Sun, W., Zheng, Y., Zhao, W., Shu, Q., Gao, C., & Liu, B. (2025). ZNF593 regulates the cGAS-mediated innate immune response by attenuating cGAS-DNA binding. Cell Death and Differentiation. https://www.semanticscholar.org/paper/f25d9e569d95f9e4e9ccab7c66372f02ff47c7b8

[6] Kilaru, V., Terrell, M. L., Marcus, M., Conneely, K., Smith, A. K., & Kelly, W. G. (2017). PROCASPASE-3 REGULATES THE APOPTOTIC THRESHOLD OF THE CELL THROUGH MODULATION OF FIBRONECTIN SECRETION. Scientific Publication. https://www.semanticscholar.org/paper/83dcad95d14f98addb8c6916fd872835fcb1a3be

[7] Clay, T. A., Steffen, M. A., Treglia, M., Torres, C. D., Trujano-Alvarez, A. L., & Bonett, R. M. (2019). Multiple stressors produce differential transcriptomic patterns in a stream-dwelling salamander. BMC Genomics. https://www.semanticscholar.org/paper/e14acdcdcec2efd557beee59a927afd568b57c0e

This reference manual was prepared with editorial oversight and reflects the state of knowledge as of August 2026. Structural models are based on AlphaFold predictions; experimental structures are awaited.