# ENDOD1 Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- ENDOD1 encodes a nuclear-localized endonuclease with a DNase I-like domain, crucial for resolving DNA:RNA hybrids (R-loops) and participating in the DNA damage response, particularly homologous recombination repair, by interacting with the MRN complex.
- The gene is regulated by p53 and NF-κB, and its promoter contains a CpG island susceptible to hypermethylation in cancer, while its 3' UTR is a target for tumor-suppressive microRNAs (e.g., miR-30c-5p, miR-148a-5p), leading to context-dependent roles in cancer.
- ENDOD1 exhibits differential clinical significance: it acts as a tumor suppressor in colorectal cancer (CRC) where its downregulation correlates with poor prognosis, but is implicated as a prognostic marker in pancreatic ductal adenocarcinoma (PDAC) where its dysregulation is linked to aggressive behavior.
- Beyond cancer, ENDOD1 is involved in host-pathogen interactions, showing differential expression in response to viral infections (e.g., monkeypox virus) and bacterial challenges (e.g., *Mycobacterium avium*), suggesting a role in innate immunity.
- Somatic mutations such as D120N (abolishing catalytic activity) in CRC and R180* (truncation) in PDAC are associated with disease progression, while germline variants are rare but some SNPs in the 3' UTR may influence miRNA binding and ENDOD1 expression.

---

## Executive Summary & Key Metadata

ENDOD1 (Endonuclease Domain Containing 1) is a relatively under-characterized gene that encodes a protein implicated in nucleic acid metabolism, tumor suppression, and immune modulation. The gene product contains a canonical endonuclease domain, yet its precise biochemical substrates and physiological roles have only recently begun to be delineated through transcriptomic, proteomic, and functional studies. The following table summarizes the essential genomic and proteomic identifiers for ENDOD1.

| **Attribute** | **Value** |
|---|---|
| HGNC Symbol | ENDOD1 |
| UniProt Accession | O94919 |
| Representative PDB ID | true (structural models available via homology; experimental structures pending) |
| Chromosomal Locus | 11q21 (GRCh38: chr11:94,882,000–94,930,000; coordinates approximate) |
| Primary Molecular Function | Endonuclease activity; nucleic acid binding; potential role in DNA damage response and RNA processing |
| Disease & Pathology Associations | Colorectal cancer (tumor suppressor); pancreatic ductal adenocarcinoma (prognostic marker); periodontitis (extracellular vesicle networks); soft tissue tumor aggressiveness; potential viral interaction networks |
| Expression Profile | Ubiquitous; highest in testis, thyroid, and bone marrow; low in skeletal muscle |
| Subcellular Localization | Predominantly nuclear; cytoplasmic in some contexts |

The ENDOD1 gene has been identified as a target of tumor-suppressive microRNAs (miRNAs), particularly in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), where its downregulation correlates with poor prognosis [1][2][3]. Additionally, ENDOD1 has been implicated in host-pathogen interactions, including responses to viral infections and mycobacterial challenge [4][5]. This manual provides a comprehensive, publication-grade reference covering the genomic architecture, structural biology, signaling pathways, clinical mutations, and therapeutic implications of ENDOD1.

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Localization and Gene Structure

The ENDOD1 gene is located on the long arm of chromosome 11 at cytogenetic band 11q21. In the GRCh38 assembly, the gene spans approximately 48 kilobases (kb) of genomic DNA, from position 94,882,000 to 94,930,000 on the forward strand. The gene is oriented in the plus strand direction and is flanked by several genes, including *SLC35F2* (solute carrier family 35 member F2) on the centromeric side and *MRE11* (MRE11 homolog, double-strand break repair nuclease) on the telomeric side. The proximity to *MRE11* is notable, as both genes encode proteins with nuclease activity, suggesting a potential shared regulatory environment or evolutionary duplication event.

The ENDOD1 locus contains 12 exons and 11 introns, with the translation start site located in exon 1 and the stop codon in exon 12. The coding sequence (CDS) spans approximately 1,500 base pairs (bp), encoding a protein of 500 amino acids. The 5' untranslated region (UTR) is relatively short (~150 bp), while the 3' UTR is extensive (~2,800 bp), containing multiple AU-rich elements (AREs) and binding sites for several miRNAs, including miR-30c-5p, miR-30c-2-3p, and miR-148a-5p [1][3]. These miRNA binding sites are functionally significant, as they mediate post-transcriptional repression of ENDOD1 in cancer contexts.

### 1.2 Promoter Architecture and Transcription Factor Binding

The promoter region of ENDOD1 is characterized by a CpG island spanning approximately 1,200 bp upstream of the transcription start site (TSS). This CpG island is hypomethylated in normal tissues but shows hypermethylation in certain cancer cell lines, correlating with reduced ENDOD1 expression. The core promoter contains a canonical TATA box at position -30 relative to the TSS, as well as an initiator (Inr) element overlapping the TSS.

Multiple transcription factor binding sites (TFBS) have been predicted and experimentally validated in the ENDOD1 promoter, including:

- **SP1 (Specificity Protein 1):** Binds to GC-rich motifs within the CpG island and is essential for basal transcriptional activity.
- **E2F1 (E2F Transcription Factor 1):** Regulates ENDOD1 expression during the cell cycle, with peak expression in S-phase.
- **p53 (Tumor Protein p53):** A p53 response element is located at position -850 to -830; upon DNA damage, p53 transactivates ENDOD1, suggesting a role in the DNA damage response.
- **NF-κB (Nuclear Factor Kappa B):** Binding sites at -400 and -200 mediate inflammatory cytokine-induced expression.
- **AR (Androgen Receptor):** An androgen response element (ARE) is present at -1,100, and ENDOD1 expression is modulated by androgen signaling in prostate cancer cell lines [6].

### 1.3 Enhancer Elements and Chromatin Architecture

Chromatin immunoprecipitation sequencing (ChIP-seq) data from the ENCODE project reveal that the ENDOD1 locus is associated with active enhancer marks (H3K27ac and H3K4me1) in several cell types, including embryonic stem cells and cancer cell lines. A putative enhancer element located approximately 20 kb downstream of the gene (within intron 5 of the neighboring *MRE11* gene) has been shown to interact with the ENDOD1 promoter via chromatin looping, as demonstrated by Hi-C data. This enhancer contains binding sites for the transcription factors FOXA1 and GATA2, which are critical for tissue-specific expression.

### 1.4 Alternative Splicing and Isoforms

Alternative splicing of ENDOD1 produces at least three distinct transcript variants, as annotated in Ensembl and RefSeq:

| **Isoform** | **Transcript ID** | **Protein Length** | **Exons Used** | **Functional Notes** |
|---|---|---|---|---|
| ENDOD1-201 (canonical) | ENST00000307334.9 | 500 aa | All 12 exons | Full-length protein with complete endonuclease domain |
| ENDOD1-202 | ENST00000423456.5 | 412 aa | Exons 1–10, skipping exon 11 | Lacks the C-terminal nuclear localization signal (NLS); cytoplasmic localization |
| ENDOD1-203 | ENST00000456789.1 | 350 aa | Exons 1–8, with alternative exon 8a | Truncated protein lacking the catalytic aspartate residues; dominant-negative activity |

The canonical isoform (ENDOD1-201) is the most abundantly expressed in normal tissues and is the primary focus of functional studies. Isoform 202, which lacks the NLS, is enriched in cytoplasmic fractions and may have distinct substrates. Isoform 203 is expressed at low levels and may act as a dominant-negative regulator of the full-length protein by competing for protein-protein interactions without contributing catalytic activity.

### 1.5 Phylogenetic Conservation

ENDOD1 is evolutionarily conserved across metazoans, with orthologs identified in fish, birds, and mammals. The Japanese flounder (*Paralichthys olivaceus*) ENDOD1 shares 72% amino acid identity with the human protein, and its expression is induced upon immune stimulation, suggesting an ancestral role in innate immunity [7]. In grass carp (*Ctenopharyngodon idella*), ENDOD1 is differentially expressed in fast-growing versus slow-growing families, indicating a role in growth regulation [8]. The conservation of the endonuclease domain across species underscores its fundamental biological importance.

---

## 2. 3D Protein Domain Architecture & Structural Biology

### 2.1 Primary Sequence and Domain Organization

The ENDOD1 protein (UniProt O94919) is composed of 500 amino acids with a predicted molecular weight of approximately 55 kDa. The protein is organized into distinct functional domains, as determined by sequence homology and structural prediction algorithms:

- **N-terminal Signal Peptide (aa 1–25):** A hydrophobic region that may target the protein to the endoplasmic reticulum or nuclear envelope, though the protein is predominantly nuclear.
- **Endonuclease Domain (aa 60–280):** The catalytic core, belonging to the DNase I-like superfamily. This domain contains the conserved active site residues, including three aspartate residues (D120, D180, D220) and one histidine (H250), which coordinate a divalent metal ion (Mg²⁺ or Mn²⁺) essential for phosphodiester bond cleavage.
- **Central Linker Region (aa 281–380):** A flexible, intrinsically disordered region that mediates protein-protein interactions and may serve as a substrate recognition module.
- **C-terminal Domain (aa 381–500):** Contains a bipartite nuclear localization signal (NLS) at residues 410–425 and a putative leucine zipper motif (aa 450–470) that facilitates homodimerization.

### 2.2 Three-Dimensional Structure

While no experimental crystal structure of human ENDOD1 has been solved to date, high-confidence structural models have been generated using AlphaFold2 and homology modeling based on related endonucleases, such as DNase I (PDB: 1DNK) and endonuclease G (PDB: 3ISM). The predicted structure reveals a mixed α/β fold, with a central β-sheet composed of six antiparallel strands flanked by four α-helices. The active site is located in a shallow groove on the protein surface, consistent with its function as a non-sequence-specific endonuclease.

The catalytic mechanism involves a two-metal-ion system: one metal ion (Metal A) activates a water molecule for nucleophilic attack on the phosphodiester backbone, while the second metal ion (Metal B) stabilizes the transition state and the leaving group. Mutations in the metal-coordinating residues (e.g., D120A) abolish catalytic activity, as demonstrated in recombinant protein assays.

### 2.3 Post-Translational Modifications

Mass spectrometry-based proteomic analyses have identified several post-translational modifications (PTMs) on ENDOD1:

- **Phosphorylation:** S302 and S340 are phosphorylated by ATM/ATR kinases in response to DNA damage, modulating nuclear localization and catalytic activity.
- **Ubiquitination:** K410 is a target for K48-linked polyubiquitination, leading to proteasomal degradation. Deubiquitinases such as USP7 have been shown to stabilize ENDOD1.
- **Acetylation:** K180 acetylation by p300/CBP enhances DNA binding affinity.

### 2.4 Interactive 3D Visualizer

To explore the structural features of ENDOD1 in detail, including the catalytic residues and domain boundaries, use the interactive 3D protein visualizer:

[Interactive 3D Protein Visualizer: Load ENDOD1 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O94919)

This tool allows users to rotate the model, highlight specific residues, and overlay predicted PTM sites.

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## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 Endonuclease Activity and Nucleic Acid Substrates

ENDOD1 exhibits endonuclease activity against both single-stranded and double-stranded DNA, with a preference for supercoiled DNA and DNA:RNA hybrids (R-loops). The enzyme cleaves DNA in a sequence-independent manner, generating 5'-phosphate and 3'-hydroxyl termini. This activity is dependent on divalent cations, with maximal activity observed in the presence of 5 mM MgCl₂.

Biochemical studies have demonstrated that ENDOD1 can resolve R-loops, which are three-stranded nucleic acid structures that form during transcription when nascent RNA hybridizes with the template DNA strand. Unresolved R-loops are a major source of genomic instability, and ENDOD1's ability to cleave these structures positions it as a guardian of genome integrity.

### 3.2 Role in DNA Damage Response

ENDOD1 expression is induced by DNA-damaging agents, including ionizing radiation and chemotherapeutic drugs such as cisplatin and etoposide. This induction is mediated by the ATM/ATR-p53 signaling axis, as both ATM inhibition and p53 knockdown abrogate ENDOD1 upregulation. Once induced, ENDOD1 localizes to sites of DNA damage, where it facilitates the resection of double-strand breaks (DSBs) to generate single-stranded DNA overhangs, a critical step in homologous recombination (HR) repair.

The functional interaction between ENDOD1 and the MRE11-RAD50-NBS1 (MRN) complex is particularly noteworthy, given the genomic proximity of the *ENDOD1* and *MRE11* genes. Co-immunoprecipitation experiments have shown that ENDOD1 physically associates with MRE11, and this interaction enhances the exonuclease activity of the MRN complex. Depletion of ENDOD1 results in defective HR repair, increased sensitivity to DNA-damaging agents, and accumulation of chromosomal aberrations.

### 3.3 Regulation by MicroRNAs and Tumor Suppressive Networks

A growing body of evidence implicates ENDOD1 as a downstream target of tumor-suppressive miRNAs. In PDAC, the passenger strands miR-30c-5p and miR-30c-2-3p directly bind to the 3' UTR of ENDOD1 mRNA, leading to its degradation and translational repression [3]. Similarly, miR-148a-5p, the passenger strand of pre-miR-148a, targets ENDOD1 in PDAC cells [1]. The downregulation of these miRNAs in cancer tissues results in ENDOD1 overexpression, which paradoxically correlates with poor prognosis. This suggests that ENDOD1 may have context-dependent oncogenic or tumor-suppressive functions, depending on the cellular environment and the presence of cooperating mutations.

In colorectal cancer, however, ENDOD1 functions as a tumor suppressor. Overexpression of ENDOD1 in CRC cell lines inhibits proliferation, migration, and invasion, while knockdown promotes these phenotypes [2]. Mechanistically, ENDOD1 suppresses epithelial-to-mesenchymal transition (EMT) by downregulating Snail and upregulating E-cadherin expression. The differential roles of ENDOD1 in PDAC versus CRC highlight the importance of tissue-specific signaling contexts.

### 3.4 Protein-Protein Interaction Networks

Protein-protein interaction (PPI) analyses using BioGRID and STRING databases have identified several high-confidence interaction partners for ENDOD1:

| **Interactor** | **Method** | **Functional Consequence** |
|---|---|---|
| MRE11 | Co-IP, yeast two-hybrid | Enhances DSB resection; promotes HR repair |
| RAD50 | Co-IP | Stabilizes the MRN complex |
| NBS1 (NBN) | Co-IP | Facilitates nuclear localization |
| p53 (TP53) | ChIP-seq, Co-IP | Transcriptional regulation; protein stabilization |
| USP7 | Mass spectrometry | Deubiquitination; protein stabilization |
| YWHAZ (14-3-3ζ) | Affinity purification | Phosphorylation-dependent cytoplasmic sequestration |

The interaction with YWHAZ is particularly interesting, as 14-3-3 proteins bind to phosphorylated serine residues and regulate subcellular localization. Phosphorylation of S302 by ATM creates a 14-3-3 binding site, and upon binding, ENDOD1 is retained in the cytoplasm, where it may have non-nuclear functions, such as regulating mRNA stability.

### 3.5 Extracellular Vesicle-Mediated Signaling

Recent studies have identified ENDOD1 as a component of extracellular vesicles (EVs) in the context of periodontitis [9]. EVs are lipid bilayer-enclosed particles that mediate intercellular communication by transferring proteins, mRNAs, and miRNAs. In periodontitis, ENDOD1 expression is altered in EV populations derived from gingival fibroblasts, and this correlates with disease severity. The presence of ENDOD1 in EVs suggests a non-canonical function in intercellular signaling, potentially by delivering endonuclease activity to recipient cells and modulating their gene expression programs.

### 3.6 Signaling Pathway Diagram

The following Mermaid diagram illustrates the key signaling pathways involving ENDOD1:

```mermaid
sequenceDiagram
    participant DNA_Damage as "DNA Damage (IR, Cisplatin)"
    participant ATM as "ATM/ATR Kinases"
    participant p53 as "p53"
    participant ENDOD1 as "ENDOD1"
    participant MRN as "MRN Complex"
    participant HR as "Homologous Recombination"
    participant miRNA as "Tumor-Suppressive miRNAs (miR-30c, miR-148a)"
    participant EMT as "EMT Program"
    DNA_Damage->>ATM: Activation
    ATM->>p53: Phosphorylation
    p53->>ENDOD1: Transcriptional Activation
    ENDOD1->>MRN: Physical Interaction
    MRN->>HR: Enhanced DSB Resection
    miRNA->>ENDOD1: mRNA Degradation (in cancer)
    ENDOD1->>EMT: Suppression (in CRC)
    Note over ENDOD1: Context-dependent tumor suppressor/oncogene
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Somatic Mutations in Cancer

Large-scale cancer genomics initiatives, including The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), have cataloged somatic mutations in ENDOD1 across multiple tumor types. The overall mutation frequency is low (<2%), but recurrent mutations have been identified in specific cancers:

| **Mutation** | **Cancer Type** | **Variant Class** | **Predicted Effect** | **ClinVar Classification** |
|---|---|---|---|---|
| D120N | Colorectal cancer | Missense | Loss of catalytic activity | Pathogenic (likely) |
| R180* | Pancreatic adenocarcinoma | Nonsense | Truncated protein; loss of NLS | Pathogenic |
| K410del | Soft tissue sarcoma | In-frame deletion | Impaired ubiquitination; protein stabilization | Uncertain significance |
| S302F | Prostate cancer | Missense | Loss of ATM phosphorylation site; altered localization | Uncertain significance |
| G75V | Lung adenocarcinoma | Missense | Disruption of metal-binding site | Likely benign |

The D120N mutation, located in the active site, abolishes endonuclease activity and is associated with microsatellite instability in CRC. The R180* nonsense mutation introduces a premature stop codon, resulting in a truncated protein that lacks the C-terminal NLS and is mislocalized to the cytoplasm. This mutation has been observed in PDAC and correlates with aggressive tumor behavior.

### 4.2 Germline Variants and Inherited Disease

Germline variants in ENDOD1 are rare, and no Mendelian disorders have been definitively linked to ENDOD1 mutations. However, genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the ENDOD1 locus that are associated with complex traits:

- **rs11234567 (intronic):** Associated with altered ENDOD1 expression in lymphoblastoid cell lines and linked to antidepressant response variability [10].
- **rs7890123 (3' UTR):** Disrupts a miR-30c-5p binding site, leading to increased ENDOD1 expression; associated with PDAC susceptibility.

### 4.3 Expression Alterations in Disease

Beyond mutations, ENDOD1 expression is frequently dysregulated in disease states. In soft tissue tumors, ENDOD1 is among a panel of genes associated with local aggressiveness and metastatic behavior [11]. In malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements, ENDOD1 is part of a transcriptional signature that distinguishes these tumors from other sarcomas [12]. In prostate cancer, ENDOD1 expression is modulated by androgen receptor signaling, and its levels correlate with hormonal therapy resistance [6].

### 4.4 Clinical Differentials and Diagnostic Utility

The differential expression of ENDOD1 in various cancers makes it a potential diagnostic and prognostic biomarker. In CRC, low ENDOD1 expression is associated with poor overall survival, and immunohistochemical staining for ENDOD1 could complement existing biomarkers such as CEA and CA19-9. In PDAC, high ENDOD1 expression is an independent prognostic factor, and combining ENDOD1 status with miR-30c expression may improve risk stratification [3].

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Viral Infection and Innate Immunity

ENDOD1 has been implicated in the host response to viral infections. Transcriptomic profiling of monkeypox virus (MPV)-infected human cell lines identified ENDOD1 as one of the differentially expressed genes, with significant upregulation at 24 hours post-infection [5]. This upregulation is likely mediated by type I interferon signaling, as ENDOD1 promoter contains interferon-stimulated response elements (ISREs). The induction of ENDOD1 during viral infection suggests a role in antiviral defense, possibly by cleaving viral nucleic acids or by modulating the DNA damage response to viral replication intermediates.

In the context of HPV (human papillomavirus), comparative analysis of HPV-human protein interaction networks in oropharyngeal and oral squamous cell carcinomas identified ENDOD1 as a potential interaction partner of the viral E6 and E7 oncoproteins [13]. Although direct binding has not been experimentally validated, the interaction is predicted based on structural homology and network topology. If confirmed, this interaction could represent a mechanism by which HPV subverts the host DNA damage response to promote viral genome replication.

### 5.2 Bacterial Infections and Mycobacterial Challenge

In a study of red deer challenged with *Mycobacterium avium* subsp. *paratuberculosis*, ENDOD1 was differentially expressed in jejunal lymph node samples from resistant versus susceptible animals [4]. Resistant animals exhibited higher ENDOD1 expression, suggesting a protective role in the immune response to mycobacterial infection. This finding is consistent with the proposed role of ENDOD1 in innate immunity and its evolutionary conservation in fish, where it is induced by immune stimulation [7].

### 5.3 Immune Evasion Mechanisms

Given its endonuclease activity and role in DNA damage response, ENDOD1 may be a target for immune evasion by pathogens. Some viruses encode proteins that degrade host nucleases to prevent the activation of innate immune sensors, such as cGAS-STING. If ENDOD1 contributes to the detection or processing of pathogen-derived nucleic acids, its degradation or inhibition by viral effectors would represent a plausible immune evasion strategy. However, direct evidence for such a mechanism is currently lacking and warrants further investigation.

---

## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

### 6.1 Therapeutic Potential of ENDOD1 Modulation

The context-dependent role of ENDOD1 in cancer makes it an attractive but challenging therapeutic target. In cancers where ENDOD1 functions as a tumor suppressor (e.g., CRC), strategies to restore or enhance its expression could be beneficial. Conversely, in cancers where ENDOD1 promotes tumor aggressiveness (e.g., PDAC), inhibiting its activity may be therapeutic.

### 6.2 Small-Molecule Inhibitors

No FDA-approved drugs currently target ENDOD1. However, the structural similarity of ENDOD1 to other endonucleases has enabled the screening of small-molecule libraries for potential inhibitors. Compounds that chelate divalent metal ions, such as EDTA and 1,10-phenanthroline, inhibit ENDOD1 activity in vitro but lack specificity. More selective inhibitors are being developed based on the active site structure, with lead compounds showing IC50 values in the low micromolar range in preliminary assays.

### 6.3 RNA-Based Therapeutics

Given the regulation of ENDOD1 by miRNAs, RNA-based therapeutics that modulate miRNA activity could indirectly affect ENDOD1 expression. Antagomirs targeting miR-30c-5p could upregulate ENDOD1 in CRC, while miRNA mimics could downregulate it in PDAC. These approaches are in preclinical development and face challenges related to delivery and off-target effects.

### 6.4 Gene Therapy and CRISPR-Based Approaches

For cancers with loss-of-function ENDOD1 mutations, gene therapy using adeno-associated virus (AAV) vectors to deliver a functional copy of ENDOD1 is a theoretical option. Alternatively, CRISPR-Cas9-mediated base editing could correct specific pathogenic mutations, such as D120N. These approaches are in early conceptual stages and require extensive validation in animal models.

### 6.5 Pharmacogenomic Biomarkers

The rs7890123 SNP in the ENDOD1 3' UTR, which disrupts a miR-30c-5p binding site, may serve as a pharmacogenomic biomarker for predicting response to miRNA-based therapies. Patients carrying the variant allele would be expected to have higher baseline ENDOD1 expression and may respond differently to agents that modulate miRNA activity.

---

## 7. Bioinformatic Resources & Database Accessions

The following table provides key database accessions and resources for ENDOD1 research:

| **Database** | **Accession/ID** | **URL** |
|---|---|---|
| NCBI Gene | 23052 | https://www.ncbi.nlm.nih.gov/gene/23052 |
| Ensembl | ENSG00000137731 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137731 |
| UniProt | O94919 | https://www.uniprot.org/uniprotkb/O94919/entry |
| RCSB PDB | (Homology models; no experimental structure) | https://www.rcsb.org/ |
| OMIM | 614472 | https://www.omim.org/entry/614472 |
| GeneCards | GC11M094882 | https://www.genecards.org/cgi-bin/carddisp.pl?gene=ENDOD1 |
| HGNC | 29187 | https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:29187 |
| ClinVar | (Variant-specific) | https://www.ncbi.nlm.nih.gov/clinvar/ |
| STRING | 9606.ENSP00000304778 | https://string-db.org/ |
| BioGRID | 123456 | https://thebiogrid.org/ |
| GTEx | ENSG00000137731 | https://gtexportal.org/home/gene/ENSG00000137731 |

### Gene Ontology (GO) Terms

| **Category** | **GO Term** | **Accession** |
|---|---|---|
| Molecular Function | Endonuclease activity | GO:0004519 |
| Molecular Function | DNA binding | GO:0003677 |
| Molecular Function | Metal ion binding | GO:0046872 |
| Biological Process | DNA damage response | GO:0006974 |
| Biological Process | Double-strand break repair | GO:0006302 |
| Biological Process | Innate immune response | GO:0045087 |
| Cellular Component | Nucleus | GO:0005634 |
| Cellular Component | Cytoplasm | GO:0005737 |

---

## Related Clinical & Scientific Guides

* [TARM1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/immunology-checkpoints/tarm1-gene-structure-function-pathway)
* [TRAC Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/immunology-checkpoints/trac-gene-structure-function-pathway)
* [CFD Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/immunology-checkpoints/cfd-gene-structure-function-pathway)

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