# EYA2 Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- EYA2 functions as a dual-activity protein, acting as both a transcriptional co-activator for SIX family homeodomain proteins and a protein tyrosine phosphatase (EC 3.1.3.48), critical for development and cellular signaling. Its bifunctional nature, with a divergent N-terminal transactivation domain and a conserved C-terminal haloacid dehalogenase (HAD) phosphatase domain, positions it as a therapeutic target.
- The gene is located at 20q13.1, a region prone to amplification in solid tumors, and its expression is tightly regulated by epigenetic mechanisms like promoter methylation, which can lead to silencing in cancers such as pancreatic adenocarcinoma. Transcription is modulated by factors including PLZF, PAX6, FOXG1, and E2A-HLF.
- EYA2 plays context-dependent roles in oncogenesis, acting as a tumor suppressor in hepatocellular carcinoma by inducing SOCS3 to inhibit JAK/STAT signaling, but as an oncogene in breast cancer, promoting metastasis via TGF-β signaling and EMT. Somatic mutations, such as EYA2(A510E) in HCC, can abrogate its tumor-suppressive function.
- Germline variants in *EYA2* are associated with susceptibility to diabetic retinopathy, and the protein's homology to EYA1 suggests potential contributions to Branchio-Oto-Renal (BOR) spectrum disorders. Its role in myogenesis links it to congenital anomalies like abdominal wall defects.
- EYA2 is a critical component of the SIX1-EYA2 transcriptional complex, essential for myogenesis, sensory placode development, and nephrogenesis, and its phosphatase activity modulates pathways like TGF-β, JAK/STAT, and MYC expression. Viral oncoproteins like E2A-HLF and PLZF-RARA can hijack EYA2's transcriptional program to drive leukemogenesis.
- Small-molecule inhibitors targeting EYA2's phosphatase activity or its interaction with SIX1 are under development for therapeutic applications in leukemias (e.g., CALM-AF10), medulloblastoma, and breast cancer metastasis, with careful patient stratification based on EYA2 expression and mutation status being crucial for treatment efficacy.

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## Executive Summary & Key Metadata

The *EYA2* gene (Eyes Absent Homolog 2) encodes a multifunctional protein that operates as both a transcriptional co-activator and a tyrosine phosphatase. As a vertebrate ortholog of the *Drosophila* "eyes absent" (*eya*) gene, EYA2 is a critical node in the retinal determination gene network (RDGN), where it partners with SIX family homeodomain transcription factors to regulate developmental programs in the eye, muscle, kidney, ear, and craniofacial structures [1, 2, 3]. Beyond its developmental roles, EYA2 has emerged as a context-dependent modulator of oncogenesis, with both tumor-suppressive and tumor-promoting activities reported across distinct tissue types [4, 5, 6]. The protein's unique bifunctional architecture—combining a divergent N-terminal transactivation domain with a conserved C-terminal haloacid dehalogenase (HAD) phosphatase domain—positions it as an attractive target for small-molecule therapeutic intervention [5, 7].

| **Metadata Field** | **Value** |
|---|---|
| HGNC Symbol | EYA2 |
| UniProt Accession | O00167 |
| Representative PDB ID | true (see Section 2) |
| Chromosomal Locus | 20q13.1 |
| Primary Molecular Function | Transcriptional co-activator; protein tyrosine phosphatase (EC 3.1.3.48) |
| Disease & Pathology Associations | Breast cancer, ovarian cancer, leukemia (T-ALL, AML), medulloblastoma, hepatocellular carcinoma, pancreatic cancer, diabetic retinopathy, branchio-oto-renal spectrum disorders, congenital anomalies |

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Localization and Gene Structure

The human *EYA2* gene is located on the long arm of chromosome 20 at cytogenetic band 20q13.1, a region frequently amplified in various solid tumors [6, 8]. The gene spans approximately 160 kilobases of genomic DNA on the plus strand (GRCh38/hg38: chr20:46,890,000–47,050,000). The locus is gene-dense, with neighboring genes including *SLC9A8* (solute carrier family 9 member A8) telomerically and *ZNF335* (zinc finger protein 335) centromerically. The 20q13.1 region has been implicated in oculo-oto-dental syndrome through linkage analysis, although the causal gene in that disorder remains to be definitively identified [8].

The *EYA2* gene comprises 19 exons and 18 introns, with the translation initiation codon located in exon 2. The promoter region lacks a canonical TATA box but contains multiple GC-rich elements and putative binding sites for Sp1, AP-2, and members of the ETS family of transcription factors. Chromatin immunoprecipitation studies in embryonic stem cells and developing tissues have identified enhancer elements in introns 1 and 3 that are bound by PAX6, a master regulator of eye development [9, 10]. These intronic enhancers are evolutionarily conserved between human, mouse, and chicken, underscoring their functional importance [11, 12].

### 1.2 Promoter Architecture and Transcriptional Regulation

The *EYA2* promoter is subject to complex epigenetic regulation. In pancreatic adenocarcinoma, hypermethylation of CpG islands within the proximal promoter results in transcriptional silencing, and this methylation signature can be detected in circulating tumor DNA (ctDNA) from patient plasma [13, 14]. Conversely, in lung adenocarcinoma cells, promoter hypomethylation correlates with EYA2 overexpression, suggesting that the methylation status of this locus is dynamically regulated in a tissue-specific manner [15].

Several transcription factors have been shown to directly regulate *EYA2* expression:

- **PLZF (Promyelocytic Leukemia Zinc Finger)**: Directly activates *EYA2* transcription by binding to response elements in the proximal promoter. This regulation is critical for PLZF-RARA-induced leukemogenesis in acute promyelocytic leukemia [16].
- **PAX6**: Required for *Eya2* expression in the lens and nasal placode during mouse development, as demonstrated by *Pax6* mutant analysis [9].
- **FOXG1**: Represses *Eya2* in the developing neocortex, contributing to the temporal specification of glutamatergic neuronal subtypes [17].
- **E2A-HLF**: The chimeric transcription factor generated by the t(17;19) translocation in B-cell acute lymphoblastic leukemia activates *Eya2* expression, which is essential for its immortalization activity [18].

### 1.3 Alternative Splicing and Isoform Diversity

Alternative splicing of the *EYA2* primary transcript generates multiple mRNA isoforms. The canonical full-length transcript (NM_172110) encodes a 592-amino acid protein with a predicted molecular mass of approximately 66 kDa. A second major isoform (NM_172109) lacks exon 14, resulting in an in-frame deletion of 27 amino acids within the variable N-terminal region. This isoform retains the complete C-terminal Eya domain (eyaHR) but exhibits altered subcellular localization dynamics [19].

A novel splice variant expressed in the human eye has been characterized that utilizes an alternative 5' untranslated region (UTR) and produces a protein with an extended N-terminus [19]. The functional significance of this ocular-specific isoform remains under investigation, but its restricted expression pattern suggests tissue-specific regulatory roles.

The N-terminal region of EYA2 is highly divergent among EYA family members (EYA1-4) and is subject to extensive alternative splicing, whereas the C-terminal Eya domain is encoded by a single large exon (exon 19) that is conserved across all family members [3, 20]. This genomic organization—with the functional core encoded by one exon—may facilitate the generation of functionally distinct isoforms through N-terminal variation while preserving catalytic integrity.

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

### 2.1 Domain Organization

The EYA2 protein exhibits a modular architecture comprising two principal domains:

**N-Terminal Transactivation Domain (approximately residues 1–270):** This region is poorly conserved among EYA family members and is predicted to be largely intrinsically disordered. Despite the lack of defined tertiary structure, this domain mediates transcriptional activation through direct interactions with chromatin remodeling complexes, including SWI/SNF and histone acetyltransferases [2, 12]. The transactivation function is essential for SIX1-EYA2-mediated gene activation during development and oncogenesis [5].

**C-Terminal Eya Domain (eyaHR; approximately residues 271–592):** This ~270-amino acid region is highly conserved across species, from *Drosophila* to humans, and contains the catalytic core of the protein [3, 20]. The Eya domain adopts a two-lobed fold characteristic of the haloacid dehalogenase (HAD) superfamily. The larger lobe consists of a six-stranded parallel β-sheet flanked by α-helices, while the smaller lobe contains the active site residues.

> **[Interactive 3D Protein Visualizer: Load EYA2 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O00167)**

### 2.2 Catalytic Mechanism and Active Site Architecture

EYA2 possesses intrinsic protein tyrosine phosphatase (PTP) activity, a feature unique among transcriptional co-activators. The catalytic mechanism follows the canonical HAD family paradigm:

1. **Nucleophilic attack**: Aspartate 327 (Asp327) acts as the catalytic nucleophile, attacking the phosphorus atom of the phosphotyrosine substrate to form a phospho-aspartate intermediate.
2. **Aspartate-aspartate dyad**: Asp327 and Asp329 coordinate a magnesium ion (Mg²⁺) that stabilizes the transition state and activates a water molecule for hydrolysis.
3. **Substrate recognition**: The active site pocket accommodates phosphotyrosine but excludes phosphoserine and phosphothreonine, conferring tyrosine-specific phosphatase activity.

The active site is flanked by a substrate-binding cleft that recognizes the surrounding amino acid context, enabling selective dephosphorylation of specific protein substrates. Structural studies have identified a critical role for the "cap" region (residues 430–470) that gates access to the active site and contributes to substrate specificity [7].

### 2.3 Structural Basis for SIX1 Interaction

The Eya domain also mediates the physical interaction with SIX family homeodomain proteins. The SIX1-EYA2 interaction is essential for the nuclear translocation of EYA2 and the transcriptional activation of downstream target genes [2]. Structural and biochemical analyses have mapped the SIX1-binding surface to a hydrophobic groove on the Eya domain that is distinct from the phosphatase active site [7, 21]. This separation of functional surfaces enables the design of inhibitors that disrupt the SIX1-EYA2 interaction without affecting catalytic activity, or vice versa.

The interaction between SIX1 and EYA2 is regulated by the α subunits of heterotrimeric G proteins. Activated Gαz and Gαi subunits bind directly to EYA2 and prevent its association with SIX proteins, thereby inhibiting transcriptional activation [1, 2]. This regulatory mechanism links G protein-coupled receptor signaling to developmental gene expression programs.

### 2.4 Post-Translational Modifications and Structural Dynamics

EYA2 is subject to multiple post-translational modifications that modulate its structure and function:

- **Phosphorylation**: CDK6-mediated phosphorylation of EYA2 promotes its ubiquitination and proteasomal degradation [3, 4]. This regulatory axis connects cell cycle progression to EYA2 protein stability.
- **Ubiquitination**: The SCF^FBXW7 E3 ligase complex, in cooperation with FBXO7, targets EYA2 for degradation. FBXO7 binds and stabilizes EYA2, while FBXW7 promotes its ubiquitination, creating a dynamic equilibrium that regulates EYA2 protein levels [5].
- **Acetylation**: The N-terminal transactivation domain is acetylated by p300/CBP, enhancing its transcriptional activity [12].

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 The SIX1-EYA2 Transcriptional Complex

The canonical function of EYA2 is as a transcriptional co-activator for SIX family homeodomain proteins (SIX1, SIX2, SIX4, and SIX5). The SIX1-EYA2 complex regulates the expression of genes involved in:

- **Myogenesis**: EYA2 cooperates with SIX1 and DACH2 to activate muscle-specific gene expression, including *MyoD* and *Myf5* [1, 6, 7]. During somitic myogenesis, Eya2 expression is downregulated in response to teratogenic insults, linking EYA2 to congenital muscle defects [8].
- **Sensory placode development**: EYA2 is required for the formation of cranial sensory placodes, including the otic and olfactory placodes, where it activates downstream targets of SIX1 [9, 10, 11, 12].
- **Nephrogenesis**: EYA2 participates in the SIX1/SIX4-dependent genetic network required for kidney development [6].
- **Taste system development**: EYA2 is expressed in the developing and adult taste system, where it may regulate taste bud formation and maintenance [13].

The transcriptional activity of the SIX1-EYA2 complex requires the nuclear translocation of EYA2, which is mediated by its interaction with SIX proteins [2]. In the absence of SIX binding, EYA2 is retained in the cytoplasm, where it may exert non-transcriptional functions.

### 3.2 Tyrosine Phosphatase Signaling

The intrinsic tyrosine phosphatase activity of EYA2 represents a second, transcription-independent signaling modality. EYA2 dephosphorylates specific protein substrates, thereby modulating signaling cascades:

- **TGF-β signaling**: EYA2 promotes TGF-β signaling by dephosphorylating and activating components of the pathway, contributing to epithelial-mesenchymal transition (EMT) and cancer stem cell properties [5].
- **JAK/STAT signaling**: In hepatocellular carcinoma, EYA2 suppresses JAK/STAT signaling by upregulating SOCS3, a negative regulator of the pathway. The tumor-suppressive function of EYA2 in this context is dependent on its ability to induce SOCS3 expression [4].
- **MYC regulation**: EYA2 phosphatase activity promotes MYC expression in medulloblastoma, and pharmacological inhibition of EYA2 reduces MYC levels and prevents tumor progression [14].

### 3.3 Regulation by G Protein Signaling

EYA2 interacts directly with the α subunits of Gz and Gi heterotrimeric G proteins [1, 2]. This interaction has dual consequences:

1. **Sequestration**: Gα binding prevents EYA2 from interacting with SIX proteins, thereby inhibiting transcriptional activation.
2. **Signal integration**: The Gα-EYA2 interaction provides a direct link between G protein-coupled receptor signaling and developmental gene expression programs.

The reciprocal nature of this signaling—whereby EYA2 also influences Gα function—suggests a bidirectional regulatory circuit [2].

### 3.4 Protein-Protein Interaction Network

The EYA2 interactome includes:

| **Interacting Partner** | **Functional Consequence** | **Reference** |
|---|---|---|
| SIX1, SIX2, SIX4, SIX5 | Transcriptional activation; nuclear translocation | [2, 5] |
| DACH2 | Synergistic activation of myogenic genes | [1] |
| Gαz, Gαi | Inhibition of SIX interaction | [1, 2] |
| CDK6 | Phosphorylation and degradation | [3, 4] |
| FBXO7, FBXW7 | Ubiquitination and proteasomal degradation | [5] |
| p300/CBP | Acetylation; transcriptional activation | [12] |
| XPO1 | Nuclear export | [15] |

### 3.5 Signaling Pathway Diagram

```mermaid
flowchart TD
    A["Extracellular Signals"] --> B["GPCR Activation"]
    B --> C["Gαz/Gαi Activation"]
    C --> D["EYA2 Sequestration in Cytoplasm"]
    
    E["SIX1 Transcription Factor"] --> F["Nuclear Translocation of EYA2"]
    D -- Inhibition --> E
    
    F --> G["SIX1-EYA2 Transcriptional Complex"]
    G --> H["Target Gene Activation"]
    H --> I["Developmental Programs"]
    H --> J["Oncogenic Programs"]
    
    K["CDK6"] --> L["EYA2 Phosphorylation"]
    L --> M["Ubiquitination by SCF-FBXW7"]
    M --> N["Proteasomal Degradation"]
    
    O["EYA2 Phosphatase Activity"] --> P["TGF-β Signaling"]
    O --> Q["MYC Expression"]
    O --> R["SOCS3 Induction"]
    R --> S["JAK/STAT Inhibition"]
```

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Somatic Mutations in Cancer

Exome sequencing studies have identified recurrent somatic mutations in *EYA2* across multiple cancer types:

**EYA2(A510E) in Hepatocellular Carcinoma (HCC):** This missense mutation, located within the Eya domain, was identified through exome sequencing of HCC samples. Functional studies demonstrate that the A510E mutation abrogates the tumor-suppressive function of EYA2, leading to enhanced JAK/STAT signaling and accelerated tumor growth [4]. The mutation disrupts the ability of EYA2 to induce SOCS3 expression, thereby removing a critical brake on oncogenic signaling.

**Copy Number Alterations:** Focal amplifications of the 20q13.1 region, including *EYA2*, are observed in cervical carcinogenesis, where EYA2 functions as an oncogene [16]. Conversely, focal deletions and epigenetic silencing of EYA2 occur in pancreatic adenocarcinomas, where it acts as a tumor suppressor [13]. These contrasting roles highlight the context-dependence of EYA2 function.

### 4.2 Germline Variants and Disease Associations

**Diabetic Retinopathy:** Genome-wide association studies (GWAS) have identified *EYA2* as a susceptibility gene for diabetic retinopathy in type 2 diabetes [17, 18]. The associated variants are located in non-coding regions, suggesting regulatory effects on gene expression. The mechanism linking EYA2 to diabetic retinopathy may involve its role in retinal vascular development and maintenance.

**Branchio-Oto-Renal (BOR) Spectrum:** While mutations in *EYA1* are the primary cause of BOR syndrome, the structural and functional homology between EYA1 and EYA2 suggests that EYA2 variants may contribute to phenotypic variability or modifier effects [19, 20, 21]. Functional studies of SIX1 mutations in BOR demonstrate differential effects on target gene expression, and EYA2 may modulate these effects [1, 20].

**Congenital Anomalies:** Cadmium-induced omphalocele in chick embryos is associated with downregulation of Eya1 and Eya2 during somitic myogenesis, implicating EYA2 in congenital abdominal wall defects [8].

### 4.3 Expression Dysregulation in Malignancies

| **Cancer Type** | **EYA2 Status** | **Functional Role** | **Reference** |
|---|---|---|---|
| Breast cancer | Overexpressed | Promotes metastasis via TGF-β signaling, EMT, and cancer stem cell properties | [5] |
| Ovarian cancer | Overexpressed | Promotes tumor growth | [6] |
| T-ALL/AML | Overexpressed | Required for CALM-AF10 leukemogenesis | [2, 3, 4, 5, 6] |
| Medulloblastoma | Overexpressed | Promotes MYC expression and tumor progression | [14] |
| Hepatocellular carcinoma | Silenced/mutated | Tumor suppressor via SOCS3-JAK/STAT | [4] |
| Pancreatic adenocarcinoma | Epigenetically silenced | Tumor suppressor | [13, 14] |
| Lung adenocarcinoma | Overexpressed | Promotes migration and invasion | [7, 15] |
| Esophageal squamous cell carcinoma | Overexpressed | Molecular subtype marker | [8] |
| Endometrial cancer | Overexpressed | Biomarker for lymph node metastasis | [9] |

### 4.4 Clinical Differential Diagnosis

The clinical presentation of EYA2 dysregulation overlaps with that of other EYA family members (EYA1, EYA3, EYA4) and SIX family proteins. Differential diagnosis should consider:

- **BOR syndrome**: Primarily associated with EYA1 mutations, but SIX1 and SIX5 mutations can also cause the phenotype [19, 20, 21].
- **Leukemias with HOXA dysregulation**: CALM-AF10 leukemias are characterized by SIX1-EYA2 dependence, distinguishing them from other HOXA-driven leukemias [2, 4, 6].
- **Rhabdomyosarcoma**: The SIX1/EYA2 axis is part of the core regulatory circuit, and EYA inhibitors are being explored as therapeutic agents [10].

## 5. Host-Pathogen & Viral Interactions

### 5.1 Viral Oncoprotein Interactions

The EYA2 protein interacts with several viral oncoproteins that exploit its transcriptional and signaling functions:

**E2A-HLF Fusion Protein:** The t(17;19) translocation in B-cell acute lymphoblastic leukemia generates the E2A-HLF chimeric transcription factor, which directly activates *EYA2* expression. EYA2 is critical for E2A-HLF-mediated immortalization of hematopoietic stem/progenitor cells [18]. This represents a "hijacking" of the EYA2 transcriptional program by an oncogenic fusion protein.

**PLZF-RARA Fusion:** In acute promyelocytic leukemia, the PLZF-RARA fusion protein activates EYA2 expression through PLZF response elements. EYA2 is essential for PLZF-RARA-induced leukemogenesis, and its knockdown impairs leukemic cell proliferation [16].

### 5.2 Parasitic Infections

Transcriptomic analysis of *Trichinella spiralis* and *T. pseudospiralis* infected muscle tissues identified EYA2 as a differentially expressed gene, suggesting a role in the host response to parasitic infection [11]. The functional significance of EYA2 in this context remains to be fully characterized, but it may reflect the involvement of EYA2 in muscle regeneration and repair following parasite-induced damage.

### 5.3 Immune Evasion Mechanisms

The FBXO7/EYA2-SCF^FBXW7 axis promotes AXL-mediated maintenance of mesenchymal and immune evasion phenotypes in cancer cells [5]. This pathway links EYA2 to resistance to immunotherapy, as the mesenchymal phenotype is associated with reduced immune infiltration and checkpoint inhibitor resistance. Targeting EYA2 may therefore sensitize tumors to immunotherapy.

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

### 6.1 EYA2 Phosphatase Inhibitors

The unique tyrosine phosphatase activity of EYA2 has been exploited for therapeutic development:

**N-arylidenebenzohydrazide Compounds:** This class of allosteric inhibitors specifically targets the EYA2 phosphatase without affecting EYA3 activity [7]. These compounds inhibit EYA2-mediated cell migration and invasion in breast cancer models. The allosteric mechanism of action provides selectivity and reduces the likelihood of off-target effects.

**Benzoisothiazolone Derivatives:** High-throughput screening identified additional small-molecule inhibitors of EYA2 phosphatase activity that impair breast cancer cell proliferation [12].

### 6.2 SIX1-EYA2 Interaction Inhibitors

Disrupting the protein-protein interaction between SIX1 and EYA2 represents an alternative therapeutic strategy:

**Compound 1 (C1):** A novel small molecule that disrupts the SIX1/EYA2 complex and inhibits breast cancer metastasis in preclinical models [21]. This compound binds to the Eya domain at the SIX1 interaction surface, preventing complex formation and downstream transcriptional activation.

**EYA2 Inhibitor 1 (E2I1):** Identified through screening for inhibitors of the SIX1-EYA2 interaction, E2I1 impairs CALM-AF10 and Jurkat leukemia cell proliferation [5]. Treatment with E2I1 prolongs survival in murine models of SIX1-expressing T-cell leukemias [15].

### 6.3 Therapeutic Applications in Leukemia

The SIX1/EYA2 axis is a promising therapeutic target in CALM-AF10 leukemias:

- **Genetic interruption**: Knockdown of SIX1 or EYA2 impairs leukemia proliferation in vitro and in vivo [4, 6].
- **Pharmacological inhibition**: EYA2 inhibitors slow proliferation of SIX1-expressing pediatric leukemias [3].
- **Combination therapy**: EYA2 inhibitors may be combined with XPO1 inhibitors, as CALM-AF10 leukemias are dependent on nuclear export protein XPO1 [15].

### 6.4 Applications in Solid Tumors

**Medulloblastoma:** EYA2 tyrosine phosphatase inhibition reduces MYC expression and prevents medulloblastoma progression in preclinical models [14]. This approach targets the MYC oncogene indirectly through EYA2 inhibition.

**Breast Cancer:** EYA2 inhibitors block metastasis by inhibiting TGF-β signaling, EMT, and cancer stem cell properties [5, 21].

**Ovarian Cancer:** Targeting the SIX1/Eya transcriptional complex is being explored as a therapeutic strategy [13].

### 6.5 Pharmacogenomic Considerations

The dual role of EYA2 as both oncogene and tumor suppressor necessitates careful patient stratification:

- **Tumors with EYA2 overexpression**: May benefit from EYA2 inhibitor therapy.
- **Tumors with EYA2 silencing**: EYA2 inhibitors would be contraindicated, and strategies to restore EYA2 expression may be more appropriate.
- **Biomarker development**: EYA2 expression levels, methylation status, and mutation status should be assessed to guide therapeutic decisions.

## 7. Bioinformatic Resources & Database Accessions

| **Database** | **Identifier** | **URL** |
|---|---|---|
| NCBI Gene | 2139 | https://www.ncbi.nlm.nih.gov/gene/2139 |
| Ensembl | ENSG00000084710 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000084710 |
| UniProt | O00167 | https://www.uniprot.org/uniprotkb/O00167 |
| RCSB PDB | Multiple entries (see Section 2) | https://www.rcsb.org/ |
| OMIM | 601654 | https://www.omim.org/entry/601654 |
| GeneCards | EYA2 | https://www.genecards.org/cgi-bin/carddisp.pl?gene=EYA2 |
| STRING | EYA2 (human) | https://string-db.org/ |
| BioGRID | EYA2 | https://thebiogrid.org/ |
| ClinVar | EYA2 | https://www.ncbi.nlm.nih.gov/clinvar/?term=EYA2 |
| COSMIC | EYA2 | https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=EYA2 |
| GTEx | EYA2 | https://gtexportal.org/home/gene/EYA2 |
| Human Protein Atlas | EYA2 | https://www.proteinatlas.org/ENSG00000084710-EYA2 |

### Gene Ontology (GO) Terms

| **Category** | **GO Term** | **Accession** |
|---|---|---|
| Molecular Function | Protein tyrosine phosphatase activity | GO:0004725 |
| Molecular Function | Transcription co-activator activity | GO:0003713 |
| Molecular Function | Protein binding | GO:0005515 |
| Biological Process | Eye development | GO:0001654 |
| Biological Process | Skeletal muscle tissue development | GO:0007519 |
| Biological Process | Inner ear morphogenesis | GO:0042472 |
| Biological Process | Cell migration | GO:0016477 |
| Cellular Component | Nucleus | GO:0005634 |
| Cellular Component | Cytoplasm | GO:0005737 |

## Related Clinical & Scientific Guides

* [UTY Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/metabolic-pathways/uty-gene-structure-function-pathway)
* [ZBTB42 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/metabolic-pathways/zbtb42-gene-structure-function-pathway)
* [TTLL8 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/metabolic-pathways/ttll8-gene-structure-function-pathway)

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