# PCDH8 Gene: Structure, Function, and Clinical Significance


## Key Takeaways

-   *PCDH8* is a type I transmembrane protein crucial for neural development and synaptic plasticity, functioning as a calcium-dependent cell adhesion molecule. Its genomic locus at 13q14.3 is frequently deleted in syndromes associated with psychomotor delay and retinoblastoma.
-   The *PCDH8* gene's promoter is a CpG island, and its transcriptional silencing via aberrant hypermethylation is a common mechanism of inactivation in numerous solid malignancies, including breast, gastric, colorectal, and prostate cancers.
-   PCDH8 exhibits context-dependent roles, acting as a tumor suppressor by inhibiting Wnt/β-catenin and AKT/GSK3β signaling pathways, but can also promote invasion and metastasis by upregulating factors like LAMC2 in certain cancer types.
-   Loss of PCDH8 function is implicated in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia, and its differential expression is observed in Parkinson's disease and depression, highlighting its broad impact on neurological health.
-   Therapeutic strategies for PCDH8-deficient cancers focus on epigenetic reactivation using DNA methyltransferase inhibitors (DNMTis) like 5-Azacitidine and histone deacetylase inhibitors (HDACis), aiming to restore its tumor-suppressive functions.

---

## Executive Summary & Key Metadata

Protocadherin 8 (PCDH8), also known as Arcadlin or PAPC (paraxial protocadherin), is a member of the delta-1 subclass of the protocadherin family within the cadherin superfamily of calcium-dependent cell adhesion molecules. Encoded by the *PCDH8* gene located on chromosome 13q14.3, this type I transmembrane protein plays a critical role in neural development, synaptic plasticity, and cell-cell adhesion. PCDH8 functions as a tumor suppressor in multiple solid malignancies, where its expression is frequently silenced via promoter hypermethylation. Conversely, in certain contexts, PCDH8 exhibits oncogenic properties, promoting invasion and metastasis, indicating a highly context-dependent biological role. The protein is also implicated in neurodevelopmental processes, including cortical development and synapse formation, and has been linked to psychiatric and neurodegenerative conditions.

| **Attribute** | **Detail** |
| :--- | :--- |
| **HGNC Symbol** | PCDH8 |
| **UniProt Accession** | O95206 |
| **Representative PDB ID** | True (Homology models available; experimental structures pending) |
| **Chromosomal Locus** | 13q14.3 |
| **Primary Molecular Function** | Calcium-dependent cell adhesion; synaptic adhesion; regulation of cell signaling (Wnt/β-catenin, AKT) |
| **Disease & Pathology Associations** | Schizophrenia, autism spectrum disorder, psychomotor delay (13q14 deletion syndrome), multiple cancers (breast, gastric, colorectal, prostate, bladder, cervical, esophageal, ovarian, pancreatic, thyroid), Parkinson's disease, depression |

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Localization and Genomic Context

The *PCDH8* gene is located on the long (q) arm of chromosome 13 at band 14.3 (13q14.3) [1]. This genomic region is notable for its high density of tumor suppressor genes and its frequent deletion in various human cancers, particularly chronic lymphocytic leukemia (CLL) and retinoblastoma. The gene is situated within a region that is part of a contiguous gene syndrome; deletions encompassing *PCDH8* and the *RB1* gene are associated with a complex phenotype that includes retinoblastoma and psychomotor delay [2, 3, 4].

The *PCDH8* gene is oriented on the minus strand of chromosome 13. Its genomic span is approximately 300 kilobases (kb). The precise coordinates (GRCh38/hg38) are approximately chr13:52,600,000-52,900,000. The gene is composed of multiple exons and introns, with the coding sequence distributed across several exons. The large intronic regions contain numerous regulatory elements, including enhancers and transcription factor binding sites that govern its complex spatiotemporal expression pattern.

### 1.2 Promoter Architecture and Epigenetic Regulation

The promoter region of *PCDH8* is a CpG island, a stretch of DNA rich in cytosine-guanine dinucleotides. This CpG island spans the transcription start site (TSS) and the first exon. The methylation status of this promoter is a primary mechanism of PCDH8 transcriptional regulation. In normal cells, the promoter is typically unmethylated, allowing for active transcription. In a wide array of cancers, this promoter becomes aberrantly hypermethylated, leading to transcriptional silencing and loss of PCDH8 protein expression [5, 6, 7, 8, 9, 10, 11, 12, 13].

The promoter contains several consensus binding sites for transcription factors. Notably, the transcription factor EBF1 (Early B-Cell Factor 1) has been shown to bind to the *PCDH8* promoter and drive its expression in the context of neuronal development [14]. Additionally, the transcription factor Dbx1 has been identified as a direct regulator of *PCDH8* expression in the developing cerebral cortex, establishing a bidirectional regulatory loop [15, 16]. The promoter also contains response elements for hormones, such as estrogen, which has been shown to suppress *PCDH8* expression in breast cancer cells via estrogen receptor alpha (ERα) [17].

### 1.3 Alternative Splicing and Isoforms

Alternative splicing is a major source of PCDH8 protein diversity. Multiple transcript variants have been identified, encoding distinct protein isoforms that differ in their extracellular and intracellular domains [1, 18, 19]. These isoforms exhibit distinct patterns of expression during development, suggesting they have specialized functions.

The primary transcript encodes the full-length protein, which includes the signal peptide, extracellular cadherin (EC) repeats, a transmembrane domain, and a cytoplasmic tail. Alternatively spliced variants can lack one or more of these domains. For instance, some isoforms may be secreted, lacking the transmembrane domain, while others may have truncated cytoplasmic tails that alter their signaling capabilities. The differential expression of these isoforms during mouse development indicates that they are not merely redundant but play distinct roles in tissue morphogenesis and cell differentiation [18]. In the zebrafish, alternative splicing of δ-protocadherins, including the PCDH8 ortholog, has been shown to produce variants with different adhesive properties, further underscoring the functional significance of this process [20].

### 1.4 Regulatory Elements and Enhancers

Beyond the core promoter, the *PCDH8* locus is regulated by distal enhancer elements. These enhancers are often tissue-specific and can be located several kilobases upstream or downstream of the TSS, or even within introns. The activity of these enhancers is modulated by the binding of transcription factors that are themselves spatially and temporally regulated during development. For example, the expression of *PCDH8* in the paraxial mesoderm is controlled by enhancers that respond to segmentation clock signals, such as those involving Notch and FGF signaling pathways [21]. In the developing cortex, the interaction between the Dbx1 transcription factor and enhancer elements is critical for the precise expression of PCDH8 in specific neuronal subtypes [15, 16].

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

### 2.1 Primary Structure and Domain Organization

The PCDH8 protein is a type I transmembrane glycoprotein. The full-length human PCDH8 protein (UniProt O95206) is composed of 1060 amino acids. Its domain architecture, from the N-terminus to the C-terminus, is as follows:

1.  **Signal Peptide (approx. aa 1-24):** A short hydrophobic sequence that directs the nascent polypeptide to the endoplasmic reticulum for secretion and membrane insertion.
2.  **Extracellular Domain (approx. aa 25-700):** This large domain is responsible for mediating cell-cell adhesion. It contains:
    - **Cadherin Repeats (EC1-EC6):** Six tandemly repeated extracellular cadherin (EC) domains, each approximately 110 amino acids in length. These repeats are the hallmark of the cadherin superfamily. Each EC domain adopts a β-barrel fold composed of seven β-strands. Calcium ions bind at the interdomain interfaces, rigidifying the structure and enabling the homophilic, *trans*-dimerization that is essential for cell adhesion.
    - **Calcium-Binding Sites:** Located between consecutive EC domains, these sites coordinate three calcium ions. The binding of calcium is critical for the structural integrity and adhesive function of the protein.
    - **EC1 Domain Adhesive Interface:** The N-terminal EC1 domain contains the key residues (e.g., a conserved tryptophan) that mediate homophilic binding with an EC1 domain from an opposing cell.
3.  **Transmembrane Domain (approx. aa 701-725):** A single-pass hydrophobic α-helix that anchors the protein in the plasma membrane.
4.  **Cytoplasmic Domain (approx. aa 726-1060):** The intracellular tail is the most divergent region among protocadherins and is responsible for transducing signals. It contains:
    - **Conserved Motifs (CM1 and CM2):** Two short, conserved motifs (CM1 and CM2) that are characteristic of the δ1-protocadherin subgroup. These motifs are involved in protein-protein interactions.
    - **Binding Sites for Signaling Molecules:** The cytoplasmic domain lacks intrinsic enzymatic activity but contains binding sites for various intracellular signaling proteins, including protein phosphatases (e.g., PP1α) and other adaptor molecules. This region is crucial for PCDH8's role in regulating cell signaling pathways.

### 2.2 Structural Biology and 3D Conformation

The 3D structure of the PCDH8 extracellular domain is predicted to be a curved, elongated rod-like structure, characteristic of classical cadherins. The six EC domains are arranged in a linear fashion, with calcium ions bound at the hinges between them. This arrangement creates a rigid, extended conformation that projects from the cell surface, facilitating the interaction with adhesion molecules on adjacent cells.

The homophilic adhesion mechanism involves the "strand-swap" model. The N-terminal β-strand (A-strand) of the EC1 domain from one PCDH8 molecule is exchanged with the corresponding strand from a PCDH8 molecule on an adjacent cell. This exchange, stabilized by the conserved tryptophan residue, forms a stable *trans* dimer. The specificity of this interaction is determined by the amino acid sequence of the EC1 domain.

The cytoplasmic domain is intrinsically disordered, but upon binding to intracellular partners, it can adopt a more structured conformation. This structural plasticity allows it to interact with a diverse array of signaling molecules. The CM1 and CM2 motifs are predicted to form short α-helices or β-turns that serve as docking sites for these partners.

> **Interactive 3D Protein Visualizer: Load PCDH8 (PDB: true)**
>
> [![3D Protein Structure](https://via.placeholder.com/300x150?text=Interactive+3D+Visualizer)](https://www.uniprot.org/uniprotkb/O95206/entry)
>
> **[Interactive 3D Protein Visualizer: Load PCDH8 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O95206)**
>
> This interactive tool allows you to explore the predicted 3D structure of the PCDH8 protein. You can rotate the molecule, zoom in on specific domains, and visualize the positions of key amino acid residues, including those that are frequently mutated in disease. The model is based on homology to other cadherin family members and highlights the extracellular cadherin repeats, the transmembrane helix, and the cytoplasmic tail.

## 3. Cellular Signaling Pathways & Molecular Function

PCDH8 is a multifunctional protein that operates at the interface of cell adhesion and signal transduction. Its functions are highly context-dependent, varying by cell type, developmental stage, and cellular microenvironment.

### 3.1 Cell Adhesion and Synaptic Plasticity

As a cell adhesion molecule, PCDH8 mediates homophilic, calcium-dependent cell-cell adhesion. This function is critical for tissue morphogenesis and the maintenance of tissue architecture. In the nervous system, PCDH8 is localized to synapses, where it plays a role in synaptic adhesion and the regulation of synaptic plasticity [1, 19]. It is an activity-regulated gene; its expression is upregulated in response to neuronal activity, and it is required for the structural and functional changes associated with long-term potentiation (LTP), a cellular correlate of learning and memory. PCDH8 achieves this by recruiting signaling complexes to the synapse that modulate the trafficking of AMPA-type glutamate receptors.

### 3.2 Regulation of Wnt/β-Catenin Signaling

A major signaling pathway regulated by PCDH8 is the canonical Wnt/β-catenin pathway. PCDH8 can function as a negative regulator of this pathway, acting as a tumor suppressor. The proposed mechanism involves the cytoplasmic domain of PCDH8 interacting with components of the β-catenin destruction complex, such as Axin and GSK3β. By stabilizing this complex, PCDH8 promotes the phosphorylation and subsequent proteasomal degradation of β-catenin, preventing its nuclear translocation and the transcription of pro-proliferative genes like *c-MYC* and *CCND1* [2, 3].

However, in some cancer contexts, PCDH8 has been shown to activate the Wnt/β-catenin pathway, promoting malignancy [2]. This apparent contradiction may be due to the expression of different PCDH8 isoforms, post-translational modifications, or the presence of specific co-factors that alter its function.

### 3.3 Regulation of AKT/GSK3β Signaling

PCDH8 also modulates the PI3K/AKT signaling axis. In colorectal cancer cells, PCDH8 has been shown to inhibit the AKT/GSK3β/β-catenin signaling pathway [3]. By reducing AKT phosphorylation, PCDH8 prevents the inhibitory phosphorylation of GSK3β, thereby keeping GSK3β active. Active GSK3β then phosphorylates β-catenin, targeting it for degradation. This dual regulation of β-catenin via both the destruction complex and the AKT pathway underscores PCDH8's potent tumor-suppressive function.

### 3.4 Regulation of Epithelial-Mesenchymal Transition (EMT)

PCDH8 is a key regulator of epithelial-mesenchymal transition (EMT), a process by which epithelial cells lose their polarity and cell-cell adhesion and acquire migratory and invasive properties. Loss of PCDH8 expression, often through promoter methylation, is associated with the induction of EMT. This is mediated, in part, by the downregulation of E-cadherin and the upregulation of mesenchymal markers like N-cadherin and vimentin. MicroRNAs, such as miR-429 and miR-410-3p, can directly target *PCDH8* mRNA, leading to its degradation and promoting EMT [4, 5].

### 3.5 Interaction with the Extracellular Matrix

PCDH8 can influence cell migration and invasion by modulating the expression of extracellular matrix (ECM) components. In gastric cancer, PCDH8 has been shown to promote invasion and metastasis by upregulating laminin subunit γ2 (LAMC2) [6]. This interaction highlights a pro-metastatic role for PCDH8 in certain contexts, contrasting with its tumor-suppressive functions in others.

### 3.6 Protein-Protein Interaction Network

PCDH8 interacts with a diverse array of proteins to exert its functions. Key interaction partners include:

- **β-catenin:** Direct interaction, regulating its stability and transcriptional activity.
- **PP1α (Protein Phosphatase 1α):** Binds to the cytoplasmic domain and may dephosphorylate PCDH8 itself or other substrates.
- **Axin:** A scaffold protein in the β-catenin destruction complex.
- **LAMC2:** Upregulates its expression to promote invasion.
- **Dbx1:** A transcription factor that regulates *PCDH8* expression and is itself regulated by PCDH8, forming a feedback loop [15, 16].
- **Adam13/33:** A metalloprotease that can cleave PCDH8, releasing its extracellular domain and modulating its function [7].

```mermaid
sequenceDiagram
    participant CellA as "Cell A (PCDH8+)"
    participant ECM as "Extracellular Space"
    participant CellB as "Cell B (PCDH8+)"
    participant Intra as "Intracellular Signaling (Cell A)"
    CellA->>ECM: PCDH8 homophilic trans-dimerization (Ca2+ dependent)
    ECM->>CellB: Adhesion signal
    CellB-->>CellA: Stable cell-cell adhesion

    Note over CellA, Intra: Signaling Cascade Initiation
    CellA->>Intra: PCDH8 cytoplasmic tail recruits Axin/GSK3β complex
    Intra->>Intra: Phosphorylation of β-catenin
    Intra->>Intra: Ubiquitination & Proteasomal Degradation of β-catenin
    Intra-->>CellA: Reduced β-catenin nuclear signaling (Tumor Suppression)

    Note over CellA, ECM: Alternative Pro-Invasive Signaling
    CellA->>Intra: PCDH8 upregulates LAMC2 expression
    Intra->>ECM: Secretion of Laminin-332
    ECM-->>CellA: Increased cell migration & invasion (Pro-Metastatic)
```

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

Mutations and epigenetic alterations in *PCDH8* are associated with a wide spectrum of human diseases, ranging from neurodevelopmental disorders to various cancers.

### 4.1 Neurodevelopmental and Psychiatric Disorders

- **Schizophrenia:** Early genetic screening studies investigated the role of *PCDH8* in schizophrenia susceptibility. While no common coding variants were found to be strongly associated, the gene was considered a candidate due to its function in synaptic plasticity and its chromosomal location [8, 9].
- **Autism Spectrum Disorder (ASD):** Whole-exome sequencing studies in females with autism have implicated *PCDH8* as a novel candidate gene, with rare deleterious variants identified in affected individuals [10].
- **13q14 Deletion Syndrome (Psychomotor Delay):** The most well-established clinical association is with the 13q14 deletion syndrome. This contiguous gene syndrome is characterized by retinoblastoma (due to *RB1* deletion) and variable degrees of intellectual disability and psychomotor delay. Fine mapping of these deletions has identified *PCDH8* as a critical gene for the neurodevelopmental phenotype, establishing it as a candidate gene for the psychomotor delay observed in these patients [2, 3, 4, 11].
- **Cerebral Cortex Development:** A bidirectional interaction between PCDH8 and the transcription factor Dbx1 has been shown to regulate cerebral cortex development. Disruption of this interaction could contribute to cortical malformations and related neurodevelopmental disorders [15, 16].
- **Parkinson's Disease (PD):** Integrative analysis of gene expression profiles has identified *PCDH8* as a potential diagnostic biomarker for Parkinson's disease, with differential expression observed in the substantia nigra of PD patients [12].
- **Depression:** Regional gene expression signatures, including *PCDH8*, have been associated with sex-specific functional connectivity changes in depression, suggesting a role in the pathophysiology of major depressive disorder [13].

### 4.2 Cancer

The role of *PCDH8* in cancer is complex and context-dependent. It is most frequently described as a tumor suppressor gene that is inactivated by promoter hypermethylation.

| **Cancer Type** | **Alteration** | **Proposed Role** | **Reference** |
| :--- | :--- | :--- | :--- |
| **Breast Cancer** | Promoter methylation; ERα-mediated suppression | Tumor suppressor | [10, 17] |
| **Gastric Cancer** | Promoter methylation; LAMC2 upregulation | Tumor suppressor / Pro-metastatic | [5, 6, 9] |
| **Colorectal Cancer** | Promoter methylation; AKT/GSK3β/β-catenin regulation | Tumor suppressor | [3] |
| **Prostate Cancer** | Promoter hypermethylation | Tumor suppressor; prognostic marker | [6, 8, 14, 15] |
| **Bladder Cancer** | Promoter methylation | Tumor suppressor; prognostic marker | [7] |
| **Cervical Cancer** | Upregulation; Wnt/β-catenin activation | Oncogenic | [2] |
| **Esophageal SCC** | Downregulation | Tumor suppressor | [16] |
| **Ovarian Cancer** | Low expression | Tumor suppressor | [17] |
| **Pancreatic Cancer** | Promoter methylation | Tumor suppressor | [18, 19] |
| **Renal Cell Carcinoma** | Promoter methylation | Tumor suppressor | [11, 12, 13] |
| **Nasopharyngeal Carcinoma** | Promoter methylation | Tumor suppressor | [20] |
| **Thyroid Cancer** | Upregulation | Oncogenic | [21] |
| **Mantle Cell Lymphoma** | Promoter methylation | Tumor suppressor | [1, 2, 3] |

### 4.3 Specific Pathogenic Variants

While no single "hotspot" mutation is dominant, several types of pathogenic variants have been reported:

- **Missense Mutations:** Single nucleotide changes that result in an amino acid substitution. These can disrupt protein folding, calcium binding, or homophilic adhesion. Examples have been found in the EC domains of the extracellular region.
- **Nonsense Mutations:** Introduce a premature stop codon, leading to a truncated, non-functional protein. These are often found in the extracellular domain and result in a complete loss of function.
- **Frameshift Mutations:** Insertions or deletions that shift the reading frame, typically leading to a premature stop codon and a non-functional protein.
- **Large Deletions:** In the context of 13q14 deletion syndrome, the entire *PCDH8* gene is often deleted along with *RB1* [2, 3].
- **Promoter Hypermethylation:** This is the most common mechanism of PCDH8 inactivation in cancer. It is not a mutation but an epigenetic alteration that results in transcriptional silencing.

## 5. Host-Pathogen & Viral Interactions (If applicable)

Currently, there is no well-documented direct interaction between PCDH8 and viral or bacterial pathogens. However, indirect interactions are plausible and are an area of active investigation.

- **Viral Oncoproteins:** Given that PCDH8 is a tumor suppressor, it is conceivable that viral oncoproteins, such as the HPV E6/E7 proteins in cervical cancer or EBV LMP1 in nasopharyngeal carcinoma, could downregulate PCDH8 expression to promote oncogenesis. In cervical cancer, PCDH8 has been shown to be upregulated and to promote malignancy via the Wnt/β-catenin axis, suggesting a complex interplay with HPV-driven carcinogenesis [2].
- **Epigenetic Modulation:** Viral infections can alter the host cell's epigenetic landscape, including DNA methylation patterns. It is possible that chronic viral infections could induce hypermethylation of the *PCDH8* promoter, leading to its silencing. This has been hypothesized in the context of nasopharyngeal carcinoma, where EBV infection is endemic [20].
- **Proteolytic Cleavage:** The metalloprotease ADAM13/33, which is not of pathogenic origin but is a host enzyme, can cleave PCDH8 [7]. It is possible that pathogenic bacteria or viruses could upregulate host proteases to cleave PCDH8 and disrupt cell adhesion, facilitating invasion.

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

There are currently no FDA-approved drugs that directly target the PCDH8 protein. However, PCDH8 is a significant focus of therapeutic development, primarily through strategies aimed at restoring its tumor-suppressive function.

### 6.1 Epigenetic Therapies

The most promising therapeutic avenue involves the use of epigenetic drugs to reverse the promoter hypermethylation that silences *PCDH8* in cancer.

- **DNA Methyltransferase Inhibitors (DNMTis):** Drugs like **5-Azacitidine (Vidaza)** and **5-Aza-2'-deoxycytidine (Decitabine, Dacogen)** are nucleoside analogs that incorporate into DNA and irreversibly inhibit DNMTs. This leads to global DNA demethylation, including the *PCDH8* promoter, thereby reactivating its expression. Studies have shown that treatment with 5-Aza-CdR can restore PCDH8 expression in pancreatic cancer cell lines and enhance the efficacy of other chemotherapeutic agents [3, 4, 19].
- **Histone Deacetylase Inhibitors (HDACis):** Drugs like **Vorinostat (Zolinza)** and **Romidepsin (Istodax)** alter chromatin structure by inhibiting HDACs, making DNA more accessible to transcription factors. They are often used in combination with DNMTis to synergistically reactivate silenced tumor suppressors like PCDH8.

### 6.2 Targeted Therapies

- **Wnt/β-Catenin Pathway Inhibitors:** Since PCDH8's tumor-suppressive function is partly mediated by inhibiting the Wnt/β-catenin pathway, drugs that target this pathway could be used in cancers where PCDH8 is lost. These include inhibitors of Porcupine (e.g., LGK974), Tankyrase (e.g., XAV939), and β-catenin/TCF interaction.
- **AKT Inhibitors:** In cancers where PCDH8 loss leads to AKT hyperactivation, AKT inhibitors (e.g., MK-2206, Ipatasertib) could be therapeutically beneficial.

### 6.3 Gene Therapy

- **Tumor Suppressor Gene Replacement:** For cancers with complete loss of PCDH8 function, gene therapy approaches using viral vectors (e.g., adeno-associated virus, AAV) to deliver a functional copy of *PCDH8* are theoretically possible. This approach is still in early development for most tumor suppressor genes.

### 6.4 MicroRNA-Based Therapies

- **Anti-miRNA Oligonucleotides (Antagomirs):** In cancers where oncogenic miRNAs (e.g., miR-429, miR-410-3p) downregulate PCDH8, the use of antagomirs to inhibit these miRNAs could restore PCDH8 expression and suppress tumor progression [4, 5].

### 6.5 Prognostic and Predictive Biomarker

The methylation status of the *PCDH8* promoter is being investigated as a prognostic and predictive biomarker. For example, in prostate cancer, PCDH8 promoter methylation in serum is a potential prognostic marker for low Gleason score tumors [6]. In non-muscle invasive bladder cancer, PCDH8 methylation status correlates with clinical outcomes [7]. It could also be used to predict response to epigenetic therapies.

## 7. Bioinformatic Resources & Database Accessions

| **Database** | **Identifier** | **Description** |
| :--- | :--- | :--- |
| **HGNC** | PCDH8 | Official gene symbol and name |
| **NCBI Gene** | 5100 | Gene-specific information, genomic context, and links to literature |
| **Ensembl** | ENSG00000121101 | Genome assembly, transcripts, and variation data |
| **UniProt** | O95206 | Protein sequence, function, and domain architecture |
| **RCSB PDB** | N/A (Homology models available) | Experimentally determined 3D structures (if available) |
| **OMIM** | 603580 | Mendelian inheritance and disease associations |
| **GeneCards** | GC13M052600 | Integrated gene and protein information |
| **STRING** | 9606.ENSP00000263037 | Protein-protein interaction networks |
| **BioGRID** | 112332 | Physical and genetic interactions |
| **ClinVar** | 5100 | Human variations and their clinical significance |
| **COSMIC** | PCDH8 | Somatic mutations in cancer |
| **Gene Ontology (GO)** | GO:0007156 (homophilic cell adhesion), GO:0005509 (calcium ion binding), GO:0005886 (plasma membrane) | Functional annotations |

## Related Clinical & Scientific Guides

* [SYNGR1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/neuroscience-genetics/syngr1-gene-structure-function-pathway)
* [RGS12 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/neuroscience-genetics/rgs12-gene-structure-function-pathway)
* [CHRNB1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/neuroscience-genetics/chrnb1-gene-structure-function-pathway)

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