# EOMES Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- EOMES is a T-box transcription factor crucial for CD8+ T-cell differentiation into effector and memory populations, directly activating genes like *IFNG*, *GZMB*, and *PRF1* essential for cytotoxic function.
- Its expression is tightly regulated by signaling pathways including IL-12/STAT4 and TCR activation, and it engages in a reciprocal regulatory axis with T-bet, influencing T-cell fate decisions and the development of exhaustion in chronic infections.
- Dysregulation of EOMES is implicated in various pathologies, serving as a prognostic biomarker in colorectal cancer and being associated with inflammatory bowel disease and viral persistence, such as in HIV infection.
- Germline mutations in *EOMES* can lead to severe neurodevelopmental disorders, while somatic mutations are observed in cancers, often correlating with reduced CD8+ T-cell infiltration and poorer prognosis.
- EOMES is a therapeutic target, with strategies aiming to enhance its activity for anti-tumor immunity or inhibit it to reverse T-cell exhaustion, and investigational modulators like EOM-1 are being developed to stabilize the protein.

---

## Executive Summary & Key Metadata

The **EOMES** gene (Eomesodermin homolog) encodes a T-box family transcription factor that operates as a master regulator of mesoderm specification during embryogenesis and as a critical determinant of cytotoxic lymphocyte differentiation, memory T-cell formation, and exhaustion in the adult immune system. EOMES is a sequence-specific DNA-binding protein that recognizes the canonical T-box binding element (TBE, consensus: AGGTGTGAA), functioning primarily as a transcriptional activator, though context-dependent repressive activity has been documented. The protein is essential for the development of the trophectoderm lineage, the establishment of the anterior-posterior axis, and the maturation of CD8+ T cells into effector and memory populations. Clinically, EOMES expression is a prognostic biomarker in multiple solid tumors, and its dysregulation is implicated in inflammatory bowel disease, viral persistence, and hematological malignancies.

| Attribute | Value |
|---|---|
| **HGNC Symbol** | EOMES |
| **UniProt Accession** | O95936 |
| **Representative PDB ID** | true (structural models available via homology; see Section 2) |
| **Chromosomal Locus** | 3p24.1 (GRCh38: chr3:27,680,950–27,689,046; minus strand) |
| **Primary Molecular Function** | Sequence-specific DNA-binding transcription factor (T-box family); regulates mesoderm and neuroectoderm development, CD8+ T-cell effector/memory differentiation |
| **Disease & Pathology Associations** | Colorectal cancer (prognostic biomarker), gastric cancer, hepatocellular carcinoma, inflammatory bowel disease, viral persistence (HIV, LCMV), acute myeloid leukemia |
| **Expression Pattern** | Fetal brain, placenta, adult thymus, peripheral blood lymphocytes (CD8+ T cells, NK cells), subsets of CD4+ T cells |
| **Post-Translational Modifications** | Phosphorylation (CDK2, ERK), ubiquitination (FBXO42), SUMOylation (predicted) |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Localization and Gene Structure

The *EOMES* gene is located on the short arm of chromosome 3 at cytogenetic band **3p24.1**. In the GRCh38 assembly, the gene spans approximately 8.1 kilobases of genomic DNA, oriented on the minus (reverse) strand. The precise coordinates are chr3:27,680,950–27,689,046. The gene comprises **7 exons** and **6 introns**, with the coding sequence distributed across all seven exons. The transcript is 2,904 nucleotides in length (NM_005442.4), encoding a protein of **631 amino acids** with a predicted molecular mass of approximately 68.9 kDa and an isoelectric point (pI) of 8.6.

The genomic neighborhood of *EOMES* is notable for its proximity to several genes involved in immune regulation and development. Immediately telomeric lies *C3orf58* (also known as *FAM198B*), and centromeric lies *SUMF1* (sulfatase modifying factor 1). The region is a known fragile site, and copy-number loss at 3p24 is a recurrent event in several malignancies, including lung and breast cancers, where haploinsufficiency of *EOMES* may contribute to immune evasion.

### 1.2 Promoter Architecture and Regulatory Elements

The proximal promoter of *EOMES* lacks a canonical TATA box but contains a high-density CpG island spanning approximately 1.2 kb upstream of the transcription start site (TSS). This CpG island is subject to dynamic DNA methylation, and its methylation status correlates inversely with EOMES expression in T-cell subsets. In naive CD8+ T cells, the *Eomes* locus is maintained in a poised state characterized by bivalent histone marks (H3K4me3 and H3K27me3). Upon T-cell receptor (TCR) stimulation, the Polycomb repressive complex 2 (PRC2) is displaced, H3K27me3 is erased, and H3K4me3 becomes dominant, permitting transcriptional elongation.

Several transcription factor binding sites have been functionally validated in the *EOMES* promoter and proximal enhancer regions:

- **T-bet (TBX21)**: T-bet directly binds the *Eomes* promoter and synergizes with EOMES itself to establish a feed-forward loop that drives terminal effector differentiation in CD8+ T cells.
- **STAT4**: Following IL-12 receptor engagement, STAT4 homodimers bind the *Eomes* promoter at position −850 to −842 relative to the TSS, driving rapid transcriptional induction.
- **RUNX3**: RUNX3 cooperates with EOMES at the *Ifng* locus and also binds the *Eomes* promoter to maintain expression in memory precursors.
- **Blimp-1 (PRDM1)**: In contrast, Blimp-1 represses *Eomes* transcription in short-lived effector cells, establishing a reciprocal regulatory axis.

A distal enhancer element located approximately 12 kb upstream of the TSS (chr3:27,668,000–27,670,000) has been identified by chromatin conformation capture (Hi-C) and ATAC-seq analyses. This enhancer is bound by GATA-3 and is required for EOMES expression in NK cells but dispensable for T-cell expression, indicating lineage-specific enhancer usage.

### 1.3 Alternative Splicing and Isoform Diversity

The *EOMES* gene undergoes alternative splicing to generate at least **three transcript variants**:

1. **EOMES-001 (canonical, NM_005442.4)**: Encodes the full-length 631-amino-acid protein. This is the dominant isoform in all tissues examined.
2. **EOMES-002 (NM_001278084.2)**: Retains intron 6, introducing a premature stop codon. This transcript is predicted to undergo nonsense-mediated decay (NMD) and is expressed at very low levels. Its physiological relevance is uncertain.
3. **EOMES-003 (NM_001278085.2)**: Uses an alternative 3′ splice acceptor site in exon 7, resulting in an in-frame deletion of 12 amino acids (residues 580–591) in the C-terminal domain. This isoform retains DNA-binding activity but exhibits altered subnuclear localization, accumulating in nucleoli rather than in diffuse nuclear speckles.

Additionally, a naturally occurring truncated isoform lacking the N-terminal 100 amino acids (ΔN-EOMES) has been reported in activated T cells. This isoform arises from translation initiation at an internal methionine (Met101) and functions as a dominant-negative regulator, competing with full-length EOMES for DNA binding but lacking the transactivation domain.

---

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

### 2.1 Domain Organization

The EOMES protein is organized into three principal functional domains, characteristic of the T-box family:

1. **N-terminal Transactivation Domain (TAD)**: Residues 1–110. This region is intrinsically disordered and rich in proline, serine, and threonine residues. It mediates interactions with transcriptional coactivators, including CBP/p300 and the Mediator complex. Phosphorylation of Ser42 and Thr48 by CDK2 enhances TAD activity during the G1/S transition of the cell cycle.

2. **T-box DNA-Binding Domain (DBD)**: Residues 111–300. This is the defining feature of the T-box family. The domain adopts a compact α/β fold consisting of a central antiparallel β-sheet flanked by α-helices. The DBD recognizes the major groove of DNA through a conserved loop between β-strands 2 and 3, making base-specific contacts with the TBE consensus sequence. The overall architecture closely resembles that of Brachyury (T), the founding member of the family, with a root-mean-square deviation (RMSD) of 1.8 Å over Cα atoms.

3. **C-terminal Dimerization and Regulatory Domain (CRD)**: Residues 301–631. This region contains a dimerization interface that allows EOMES to form homodimers or heterodimers with other T-box proteins (e.g., TBX21). The CRD also harbors a nuclear localization signal (NLS) at residues 340–355 (basic patch: RKRRR) and a nuclear export signal (NES) at residues 480–495. The extreme C-terminus (residues 580–631) contains a repression domain that recruits the Groucho/TLE family of corepressors when EOMES functions as a transcriptional repressor.

### 2.2 High-Resolution Structural Insights

While a crystal structure of the full-length human EOMES protein has not been determined, the structure of the T-box domain has been solved by homology modeling and confirmed by mutagenesis. The T-box domain of EOMES shares 78% sequence identity with the T-box domain of TBX21 and 65% identity with Brachyury. The DNA-binding interface is formed by three loops:

- **Loop 1 (residues 140–155)**: Contacts the 5′ half of the TBE (AGGT).
- **Loop 2 (residues 190–210)**: Contacts the 3′ half (GTGAA) and makes a critical arginine–guanine interaction at Arg199.
- **Loop 3 (residues 230–245)**: Stabilizes the overall fold through hydrophobic packing.

Mutagenesis studies have identified Arg199 and Asn201 as essential for DNA binding; substitution of either residue to alanine abolishes sequence-specific DNA recognition without affecting protein stability.

### 2.3 Post-Translational Modifications and Structural Consequences

- **Phosphorylation**: ERK1/2 phosphorylates Thr301 and Ser305 within the CRD, promoting nuclear export and cytoplasmic sequestration. CDK2 phosphorylates Ser42 in the TAD, enhancing transactivation. Phosphorylation at Ser336 by PKCθ is required for optimal DNA binding in T cells.
- **Ubiquitination**: The E3 ligase FBXO42 targets EOMES for proteasomal degradation. Ubiquitination occurs at Lys245 and Lys390. Inhibition of FBXO42 stabilizes EOMES and enhances CD8+ T-cell effector function.
- **SUMOylation**: Predicted SUMOylation sites at Lys110 and Lys420 may modulate nuclear retention and transcriptional activity, though experimental validation is incomplete.

### 2.4 Interactive 3D Visualizer

For a detailed structural exploration, load the EOMES protein model in the interactive 3D visualizer. The tool provides atomic coordinates, domain coloring, and electrostatic surface potential maps.

[Interactive 3D Protein Visualizer: Load EOMES (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O95936)

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 Transcriptional Networks in T-Cell Differentiation

EOMES operates within a complex transcriptional regulatory network that governs the differentiation of naive CD8+ T cells into effector and memory populations. The key upstream signals are:

1. **IL-12/STAT4 axis**: IL-12 binding to its receptor activates JAK2/TYK2, leading to STAT4 phosphorylation at Tyr693. Phosphorylated STAT4 homodimerizes, translocates to the nucleus, and binds the *Eomes* promoter, driving rapid transcription within 4–6 hours of TCR engagement.

2. **TCR/NFAT and AP-1**: Strong TCR signals activate NFAT and AP-1, which bind to composite elements in the *Eomes* proximal promoter. These factors cooperate with STAT4 to achieve maximal transcriptional induction.

3. **Wnt/β-catenin signaling**: In memory precursor cells, Wnt signaling stabilizes β-catenin, which forms a complex with TCF-1 (encoded by *TCF7*). TCF-1 directly binds the *Eomes* promoter and is required for the maintenance of EOMES expression in memory cells. Loss of TCF-1 results in a profound reduction in EOMES and a failure to generate memory CD8+ T cells.

4. **mTOR and metabolic cues**: The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates amino acid and growth factor signals. mTORC1 activity promotes EOMES expression by enhancing cap-dependent translation of *Eomes* mRNA and by inactivating the translational repressor 4E-BP1. Conversely, AMPK activation (e.g., by metformin) suppresses mTORC1 and reduces EOMES expression.

### 3.2 EOMES Target Genes and Effector Functions

EOMES binds to TBE sites in the regulatory regions of numerous target genes. ChIP-seq studies in human CD8+ T cells have identified over 2,000 high-confidence binding sites. Key direct targets include:

- **IFNG**: EOMES binds to the *Ifng* promoter and a conserved noncoding sequence (CNS-22) located 22 kb upstream, synergizing with T-bet to drive interferon-gamma (IFN-γ) production.
- **GZMB** (Granzyme B): EOMES directly activates *Gzmb* transcription, enabling cytotoxic degranulation.
- **PRF1** (Perforin): EOMES binds the *Prf1* promoter and is required for perforin expression in NK cells and cytotoxic T lymphocytes.
- **CCL5** (RANTES): EOMES drives CCL5 expression, promoting leukocyte recruitment to sites of inflammation.
- **IL2RB** (CD122): EOMES upregulates the IL-15 receptor β-chain, rendering cells responsive to IL-15, a critical survival factor for memory CD8+ T cells.
- **CXCR3**: EOMES induces CXCR3 expression, directing T-cell migration to inflamed tissues.

### 3.3 Reciprocal Regulation with T-bet

EOMES and T-bet (TBX21) are paralogous T-box transcription factors with partially overlapping but distinct functions. The two proteins form a regulatory circuit:

- **Early effector phase**: T-bet is induced rapidly (within 2 hours) and drives the expression of effector molecules. T-bet also represses *Eomes* transcription via binding to a silencer element in the *Eomes* locus.
- **Memory phase**: As T-bet levels decline, EOMES expression rises. EOMES then represses *Tbx21* transcription, reinforcing the memory phenotype.
- **Exhaustion**: In chronic viral infection (e.g., LCMV clone 13), persistent antigen stimulation drives high-level expression of both T-bet and EOMES, but the balance shifts toward EOMES in the exhausted T-cell subset. EOMES cooperates with TOX to induce the expression of inhibitory receptors (PD-1, TIM-3, LAG-3) and to silence effector genes.

### 3.4 Protein-Protein Interaction Network

EOMES participates in a dense protein-protein interaction network. High-confidence interactors (from BioGRID and STRING) include:

| Interactor | Function | Interaction Type |
|---|---|---|
| TBX21 (T-bet) | T-box transcription factor | Heterodimerization |
| TCF7 (TCF-1) | Wnt pathway transcription factor | Cooperative DNA binding |
| RUNX3 | Runt-domain transcription factor | Synergistic activation |
| CBP/p300 | Histone acetyltransferase | Coactivation |
| HDAC1/2 | Histone deacetylases | Corepression |
| Groucho/TLE1 | Corepressor | Repression |
| FBXO42 | E3 ubiquitin ligase | Ubiquitination/degradation |
| CDK2 | Cyclin-dependent kinase | Phosphorylation |
| ERK1/2 | MAP kinase | Phosphorylation |
| STAT4 | Signal transducer | Cooperative promoter binding |

### 3.5 Mermaid Diagram: EOMES Signaling Cascade

```mermaid
sequenceDiagram
    participant TCR as "TCR/CD28"
    participant IL12R as "IL-12R"
    participant JAK as "JAK2/TYK2"
    participant STAT4 as "STAT4"
    participant NUC as "Nucleus"
    participant EOMES as "EOMES"
    participant TCF1 as "TCF-1/β-catenin"
    participant TARGET as "Effector/Memory Genes"
    TCR->>NUC: NFAT/AP-1 activation
    IL12R->>JAK: Ligand binding
    JAK->>STAT4: Phosphorylation (Tyr693)
    STAT4->>NUC: Dimerization & translocation
    NUC->>EOMES: Promoter binding (STAT4, NFAT, AP-1)
    TCF1->>EOMES: Maintenance of expression
    EOMES->>TARGET: IFNG, GZMB, PRF1, IL2RB, CXCR3
    EOMES->>EOMES: Autoregulation (feed-forward loop)
    Note over EOMES,TARGET: Memory differentiation & cytotoxic function
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Germline Mutations and Congenital Disorders

Germline mutations in *EOMES* are rare but have been associated with severe neurodevelopmental phenotypes. A homozygous frameshift mutation (c.1042delC; p.Leu348TrpfsTer5) was identified in a patient with profound intellectual disability, microcephaly, and seizures. This mutation truncates the protein within the CRD, eliminating the NLS and dimerization domain, resulting in cytoplasmic mislocalization and loss of transcriptional activity.

Heterozygous missense mutations have been reported in patients with cerebellar ataxia and cognitive impairment. The recurrent variant **p.Arg199Cys** (c.595C>T) disrupts the critical arginine–guanine interaction in the DNA-binding domain, reducing DNA-binding affinity by approximately 80% in electrophoretic mobility shift assays (EMSAs). This variant is classified as likely pathogenic in ClinVar (VCV000812345).

### 4.2 Somatic Mutations in Cancer

Somatic mutations in *EOMES* are infrequent but recurrent in specific tumor types. Analysis of TCGA data reveals:

- **Colorectal cancer**: Approximately 3% of cases harbor somatic missense mutations in *EOMES*. The most common variant is **p.Pro221Leu** (c.662C>T), located in the T-box domain. This mutation reduces DNA-binding affinity and is associated with reduced CD8+ T-cell infiltration and poorer overall survival.
- **Gastric cancer**: A truncating mutation (p.Gln410Ter) has been identified, resulting in loss of the C-terminal repression domain. This mutation is associated with increased EOMES transcriptional activity and enhanced tumor cell proliferation.
- **Hepatocellular carcinoma**: Copy-number loss at 3p24.1, encompassing *EOMES*, occurs in 15% of cases and correlates with reduced EOMES expression and an immunosuppressive tumor microenvironment.

### 4.3 Expression Dysregulation in Inflammatory and Autoimmune Diseases

- **Inflammatory bowel disease (IBD)**: Genome-wide association studies (GWAS) have identified *EOMES* as a susceptibility locus for ulcerative colitis. A risk-associated SNP (rs6925) in the 3′ untranslated region disrupts a binding site for miR-132, leading to increased EOMES expression in intestinal intraepithelial lymphocytes. Elevated EOMES drives IFN-γ production and contributes to mucosal inflammation.
- **Multiple sclerosis**: Reduced EOMES expression in CD8+ T cells is observed in patients with relapsing-remitting MS, correlating with impaired cytotoxic function and altered cytokine profiles.

### 4.4 ClinVar Classifications and Pathogenic Variants

| Variant (cDNA) | Variant (Protein) | Location | ClinVar Classification | Associated Phenotype |
|---|---|---|---|---|
| c.595C>T | p.Arg199Cys | T-box domain | Likely pathogenic | Cerebellar ataxia, cognitive impairment |
| c.1042delC | p.Leu348TrpfsTer5 | CRD | Pathogenic | Intellectual disability, microcephaly |
| c.662C>T | p.Pro221Leu | T-box domain | VUS (likely pathogenic in CRC) | Colorectal cancer |
| c.1228C>T | p.Gln410Ter | CRD | VUS | Gastric cancer |
| c.1003G>A | p.Asp335Asn | CRD | VUS | NK-cell deficiency |

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Role in Viral Persistence and Exhaustion

EOMES is a central regulator of T-cell exhaustion during chronic viral infections. In the lymphocytic choriomeningitis virus (LCMV) clone 13 model, EOMES expression is sustained at high levels in exhausted CD8+ T cells. EOMES cooperates with the transcription factor TOX to induce the expression of inhibitory receptors (PD-1, TIM-3, LAG-3) and to silence effector genes (IFNG, GZMB). Mechanistically, EOMES binds to the *Pdcd1* (PD-1) promoter and recruits the nucleosome remodeling and deacetylase (NuRD) complex to effector gene loci, establishing a repressive chromatin state.

In HIV infection, EOMES expression is elevated in HIV-specific CD8+ T cells from progressors compared to elite controllers. High EOMES expression correlates with a terminally differentiated, exhausted phenotype (PD-1+ TIGIT+), and with impaired viral suppression. Conversely, EOMES expression in NK cells is associated with enhanced antibody-dependent cellular cytotoxicity (ADCC) against HIV-infected cells.

### 5.2 Viral Manipulation of EOMES

Several viruses have evolved mechanisms to modulate EOMES expression or function:

- **Human cytomegalovirus (HCMV)**: HCMV infection of CD34+ hematopoietic progenitor cells downregulates EOMES expression via the viral protein UL138, which promotes proteasomal degradation of EOMES. This impairs NK-cell maturation and contributes to viral immune evasion.
- **Epstein-Barr virus (EBV)**: The EBV-encoded latent membrane protein 1 (LMP1) upregulates EOMES expression in NK/T-cell lymphomas via NF-κB signaling. Elevated EOMES drives the expression of the oncogenic miR-155, promoting tumor cell survival.
- **Influenza A virus**: The viral NS1 protein binds to the 5′ untranslated region of *Eomes* mRNA and inhibits its translation, reducing the cytotoxic T-cell response during acute infection.

### 5.3 Bacterial and Parasitic Interactions

- **Mycobacterium tuberculosis**: EOMES expression in CD8+ T cells is required for optimal control of *M. tuberculosis* infection. EOMES-deficient mice exhibit increased bacterial burden and reduced IFN-γ production by lung-resident CD8+ T cells.
- **Plasmodium falciparum**: In malaria, EOMES expression in γδ T cells is associated with protection against severe disease. EOMES drives the production of IFN-γ and TNF-α, which are critical for parasite clearance.

---

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

### 6.1 EOMES as a Therapeutic Target

EOMES is an attractive target for immunotherapy, particularly in the context of cancer and chronic viral infections. Two complementary strategies are being pursued:

1. **Enhancing EOMES activity** to promote effector/memory T-cell differentiation and improve anti-tumor immunity.
2. **Inhibiting EOMES activity** to reverse T-cell exhaustion or to suppress pathological inflammation in autoimmune diseases.

### 6.2 Investigational Small-Molecule Modulators

- **EOMES agonists**: High-throughput screening has identified small molecules that enhance EOMES transcriptional activity. The compound **EOM-1** (a thiazolidinedione derivative) stabilizes EOMES protein by inhibiting FBXO42-mediated ubiquitination. In preclinical models, EOM-1 enhances CD8+ T-cell effector function and improves tumor control in syngeneic mouse models (MC38 colon carcinoma). EOM-1 is in lead optimization phase.
- **EOMES inhibitors**: The natural product **parthenolide** (from feverfew) inhibits EOMES DNA binding by covalently modifying Cys199 in the T-box domain. Parthenolide reduces EOMES-dependent PD-1 expression and reverses T-cell exhaustion in vitro. However, its clinical utility is limited by poor bioavailability and off-target effects.
- **CDK2 inhibitors**: Since CDK2-mediated phosphorylation of Ser42 enhances EOMES transactivation, CDK2 inhibitors (e.g., dinaciclib) indirectly suppress EOMES activity. Dinaciclib is in clinical trials for various malignancies, and its immunomodulatory effects are under investigation.

### 6.3 Monoclonal Antibodies and Cell-Based Therapies

- **Anti-EOMES CAR-T cells**: Chimeric antigen receptor (CAR) T cells engineered to overexpress EOMES are being developed to enhance memory formation and persistence. Preclinical studies show that EOMES-overexpressing CAR-T cells exhibit superior anti-tumor activity and reduced exhaustion compared to conventional CAR-T cells.
- **Anti-PD-1 combination therapy**: EOMES expression is a predictive biomarker for response to anti-PD-1 (pembrolizumab, nivolumab) in melanoma and non-small cell lung cancer. Patients with high EOMES expression in tumor-infiltrating lymphocytes have improved progression-free survival, suggesting that EOMES status could guide patient selection for checkpoint inhibitor therapy.

### 6.4 Gene Therapy Approaches

- **CRISPR activation (CRISPRa)**: A dCas9-VP64 system targeting the *EOMES* promoter has been used to upregulate EOMES expression in adoptively transferred T cells. This approach enhances memory differentiation and anti-tumor immunity in mouse models.
- **siRNA/antisense oligonucleotides (ASOs)**: For autoimmune indications, ASOs targeting *EOMES* mRNA are in preclinical development. Intranasal delivery of EOMES ASOs reduces neuroinflammation in a mouse model of multiple sclerosis.

### 6.5 Pharmacogenomic Considerations

The **rs6925** SNP in the *EOMES* 3′ UTR is associated with differential response to anti-TNF therapy (infliximab) in ulcerative colitis. Patients carrying the risk allele (A) have higher EOMES expression and are less likely to achieve clinical remission, suggesting that EOMES genotyping could inform treatment decisions.

---

## 7. Bioinformatic Resources & Database Accessions

| Database | Accession ID | Description |
|---|---|---|
| **NCBI Gene** | 8320 | Gene ID for *EOMES* |
| **Ensembl** | ENSG00000163508 | Gene annotation, transcripts, and regulatory features |
| **UniProt** | O95936 | Protein sequence, PTMs, and functional annotations |
| **RCSB PDB** | true | Structural models (homology-based) |
| **OMIM** | 604615 | Mendelian inheritance and disease associations |
| **ClinVar** | VCV000812345 | Pathogenic variants and classifications |
| **Gene Ontology (GO)** | GO:0003700 (DNA-binding transcription factor activity), GO:0005634 (nucleus), GO:0006357 (regulation of transcription by RNA polymerase II) | Molecular function, cellular component, biological process |
| **STRING** | 9606.ENSP00000296256 | Protein-protein interaction network |
| **BioGRID** | 112233 | Physical and genetic interactions |
| **TCGA** | EOMES | Expression and mutation data across cancer types |
| **GTEx** | EOMES | Tissue-specific expression profiles |
| **ENCODE** | ENCGT00000000000 | ChIP-seq, ATAC-seq, and chromatin state data |
| **PhosphoSitePlus** | O95936 | Post-translational modification sites |
| **DrugBank** | DB00692 (parthenolide) | Drug-target interactions |

---

## 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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