# SDC2 Gene: Structure, Function, and Clinical Significance
## Key Takeaways
- The *SDC2* gene encodes syndecan-2, a transmembrane heparan sulfate proteoglycan crucial for cell adhesion, growth factor signaling (e.g., VEGFA, FGF), and angiogenesis. Its N-terminal ectodomain contains Ser-Gly motifs for heparan sulfate chain attachment, and the cytoplasmic domain interacts with PDZ-domain proteins like syntenin, linking it to the actin cytoskeleton.
- Aberrant promoter hypermethylation of *SDC2* is a highly specific and early epigenetic event in colorectal carcinogenesis, making it a leading non-invasive biomarker detectable in stool and plasma DNA via methods like quantitative methylation-specific PCR.
- Syndecan-2 acts as a co-receptor for VEGFA165, critically enhancing its binding via 6-O sulfation of HS chains, which is essential for VEGFA-driven angiogenesis and endothelial cell migration. It also plays a role in Notch signaling in vascular smooth muscle cells and is implicated in fibrotic processes by regulating PAD2 activity.
- Beyond oncology, *SDC2* dysregulation is associated with neuropsychiatric disorders, including suicidal ideation, PTSD, and autism, potentially through modulation of synaptic plasticity or neuroinflammation. It also functions as a cell attachment receptor for Hepatitis B Virus (HBV), interacting with the preS1 domain of the viral envelope protein.
- Clinical utility of *SDC2* primarily lies in its methylation status for cancer screening; commercial assays like ColoClear™ detect fecal *SDC2* methylation for colorectal cancer screening. Investigational approaches include targeting SDC2 protein with monoclonal antibodies or HS mimetics to inhibit angiogenesis or using DNMT inhibitors like decitabine to restore *SDC2* expression.
---
## Executive Summary & Key Metadata
The **SDC2** gene encodes syndecan-2, a type I transmembrane heparan sulfate proteoglycan (HSPG) that operates at the interface between the extracellular matrix (ECM) and intracellular signaling cascades. Syndecan-2 is a critical regulator of cell adhesion, cytoskeletal organization, growth factor signaling, and angiogenesis. Its clinical relevance has expanded dramatically over the past decade, primarily due to the observation that **promoter hypermethylation of SDC2** is an early and highly specific epigenetic event in colorectal carcinogenesis, making it a leading non-invasive liquid biopsy biomarker. Beyond oncology, SDC2 has been implicated in neuropsychiatric disorders, fibrosis, viral entry, and vascular biology.
| **Attribute** | **Value** |
|---|---|
| HGNC Symbol | SDC2 |
| UniProt Accession | P34741 |
| Representative PDB ID | true (structural models available via AlphaFold and X-ray crystallography of ectodomain fragments) |
| Chromosomal Locus | 8q22.1 (human); cattle: 14q22 [1] |
| Primary Molecular Function | Transmembrane heparan sulfate proteoglycan; cell adhesion receptor; co-receptor for growth factors (VEGFA, FGF, TGF-β); regulator of integrin signaling and cytoskeletal dynamics |
| Disease & Pathology Associations | Colorectal cancer (methylation biomarker), gastric adenocarcinoma, osteosarcoma chemoresistance, prostate cancer, oral squamous cell carcinoma, radiation esophagitis, fibrosis (RA-ILD), suicidal ideation, PTSD, insomnia, autism, HBV attachment receptor |
---
## 1. Genomic Locus, Chromosomal Organization & Isoforms
### 1.1 Chromosomal Localization and Synteny
The human *SDC2* gene is located on the **long arm of chromosome 8 at band q22.1** (8q22.1). This region is notable for its frequent amplification and loss of heterozygosity in various malignancies. The gene spans approximately 35–40 kilobases of genomic DNA and is oriented on the minus strand. Comparative genomics has demonstrated strong evolutionary conservation; for instance, the bovine ortholog maps to chromosome 14q22, as determined by fluorescence *in situ* hybridization (FISH) [1]. The chromosomal neighborhood includes the GRPR (gastrin-releasing peptide receptor) gene, and a balanced translocation t(X;8) disrupting GRPR and positioned 3' to SDC2 has been reported in a patient with autism and multiple exostoses, suggesting potential long-range cis-regulatory effects [2].
### 1.2 Promoter Architecture and CpG Islands
The *SDC2* promoter region is characterized by a **large CpG island** spanning the transcription start site (TSS) and the first exon. This CpG island is the target of the aberrant hypermethylation observed in colorectal cancer (CRC) and other malignancies. In normal tissues, the promoter is largely unmethylated, permitting constitutive expression across many cell types, particularly fibroblasts, endothelial cells, and smooth muscle cells. In CRC, dense CpG methylation within this island leads to transcriptional silencing, a phenomenon that has been exploited for diagnostic purposes [3][4][5][6].
The promoter contains multiple consensus binding sites for transcription factors, including **Sp1**, **AP-1**, **Ets family members**, and **NF-κB**. The presence of these elements suggests that SDC2 expression is responsive to growth factor stimulation, inflammatory cytokines, and mechanical stress. Notably, **Notch signaling** has been shown to directly upregulate SDC2 transcription in vascular smooth muscle cells (VSMCs) via RBP-Jκ-dependent mechanisms, establishing a positive feedback loop wherein SDC2 acts as a Notch co-receptor [7].
### 1.3 Enhancer Elements and Long-Range Regulation
While detailed enhancer maps for SDC2 are still being refined, chromatin conformation capture studies (Hi-C) in endothelial cells have identified putative enhancer regions within intron 1 and approximately 50 kb upstream of the TSS. These regions are enriched for H3K27ac and H3K4me1 histone marks in cells expressing high levels of SDC2, such as human umbilical vein endothelial cells (HUVECs). The translocation breakpoint reported 3' to SDC2 in the autism/multiple exostoses case [2] may disrupt a boundary element or enhancer, although direct evidence of SDC2 dysregulation in that patient remains to be established.
### 1.4 Alternative Splicing and Isoforms
The *SDC2* gene undergoes alternative splicing, although the functional consequences are less well characterized than for SDC1 or SDC4. The canonical transcript (NM_002998.4) encodes a 201-amino-acid core protein. Minor splice variants have been reported that differ in the 5' untranslated region (UTR) and, in some cases, in the cytoplasmic domain. A variant lacking exon 5 (which encodes part of the extracellular domain) has been detected in certain cancer cell lines, potentially altering ligand-binding properties. However, the predominant isoform in most tissues is the full-length protein. The 3' UTR of SDC2 contains multiple conserved binding sites for microRNAs, including **miR-20a-5p**, which has been experimentally validated to repress SDC2 expression and modulate multidrug resistance in osteosarcoma [8].
---
## 2. 3D Protein Domain Architecture & Structural Biology
### 2.1 Domain Organization of the Syndecan-2 Core Protein
The syndecan-2 core protein (201 amino acids, ~22 kDa before glycosylation) is organized into three distinct structural domains, each with specialized functions:
1. **N-Terminal Extracellular Ectodomain (aa 1–131):** This domain contains the signal peptide (aa 1–18) and the mature ectodomain. It harbors **three conserved serine-glycine (Ser-Gly) motifs** that serve as attachment sites for heparan sulfate (HS) glycosaminoglycan (GAG) chains. The ectodomain is highly negatively charged due to the sulfated GAG chains, enabling electrostatic interactions with ECM components (fibronectin, collagen), growth factors (VEGFA, FGF-2), and cytokines. The N-terminal domain also contains a **C-type lectin-like fold** in some structural models, although this is not a canonical feature. Critically, the N-terminal domain of SDC2 has been shown to selectively enhance **6-O sulfation** of HS chains, a modification that is essential for VEGFA165 binding and pro-angiogenic signaling [9].
2. **Transmembrane Domain (aa 132–154):** A single-pass hydrophobic α-helix anchors the protein to the plasma membrane. This domain is highly conserved among syndecans and is involved in **homodimerization**. The transmembrane domain contains a GxxxG motif that mediates helix-helix interactions, stabilizing the dimeric form of the receptor. Dimerization is required for efficient signaling, as it brings the cytoplasmic domains into proximity for phosphorylation and scaffolding interactions.
3. **C-Terminal Cytoplasmic Domain (aa 155–201):** This is the most highly conserved region of the protein. It contains two conserved tyrosines (Tyr189 and Tyr192 in human SDC2) that can be phosphorylated by Src family kinases. The cytoplasmic domain also contains a **PDZ-binding motif** at the extreme C-terminus (EFYA), which mediates interactions with PDZ domain-containing scaffolding proteins such as **syntenin (SDCBP)**, **CASK**, and **synectin (GIPC1)**. These interactions link SDC2 to the actin cytoskeleton and to intracellular signaling complexes.
### 2.2 Post-Translational Modifications and 3D Conformation
The mature syndecan-2 protein is heavily glycosylated. The HS GAG chains attached to the ectodomain can reach lengths of 50–200 disaccharide units, extending the protein's reach up to 100 nm from the cell surface. This creates a large "glycocalyx" layer that modulates cell-cell and cell-matrix interactions. The 6-O sulfation pattern of these HS chains is dynamically regulated by sulfatases (SULF1/SULF2) and is critical for differential ligand binding. For example, 6-O sulfation is required for VEGFA165 binding but not for FGF-2 binding [9].
The cytoplasmic domain is intrinsically disordered in solution but adopts a structured conformation upon binding to PDZ domains. NMR studies of the cytoplasmic tail of syndecan-4 (a close homolog) suggest that the conserved C1 and C2 regions flanking the variable (V) region form transient α-helices. The V region of SDC2 is unique among syndecans and contains the tyrosine phosphorylation sites.
### 2.3 Structural Insights from PDB and AlphaFold
While a full-length X-ray crystal structure of human SDC2 is not yet available, high-confidence structural predictions are accessible via AlphaFold (UniProt P34741). The ectodomain is predicted to be largely unstructured, consistent with its role as a flexible scaffold for GAG attachment. The transmembrane domain is a well-defined α-helix, and the cytoplasmic domain is predicted to be disordered with a short helical segment near the PDZ-binding motif. Structural studies of the SDC2 ectodomain in complex with growth factors have been challenging due to the heterogeneity of the GAG chains. However, the N-terminal domain has been co-crystallized with VEGFA165 in a model system, revealing that the HS chains wrap around the growth factor dimer, stabilizing the interaction [9].
> **[Interactive 3D Protein Visualizer: Load SDC2 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=P34741)**
>
> Use the interactive 3D visualizer to explore the predicted structure of the SDC2 protein. The tool loads the AlphaFold model (UniProt P34741) and allows you to:
> * Color by domain (ectodomain, transmembrane, cytoplasmic).
> * Highlight the Ser-Gly GAG attachment sites.
> * Visualize the PDZ-binding motif (EFYA) at the C-terminus.
> * Overlay predicted post-translational modification sites.
---
## 3. Cellular Signaling Pathways & Molecular Function
### 3.1 Syndecan-2 as a Signaling Hub
Syndecan-2 functions as a **co-receptor** and **signaling platform**, integrating cues from the ECM and soluble growth factors to regulate cell behavior. Its functions are context-dependent, varying by cell type and developmental stage.
### 3.2 Angiogenesis and VEGFA Signaling
One of the best-characterized functions of SDC2 is its role in **developmental and pathological angiogenesis**. Global and endothelial-specific deletion of Sdc2 in mice results in marked angiogenic and arteriogenic defects, including reduced retinal vascular density and impaired response to ischemic injury [9]. Mechanistically, SDC2 binds VEGFA165 via its HS chains, presenting the ligand to VEGFR2 (KDR/Flk-1) and enhancing receptor activation. The N-terminal domain of SDC2 specifically promotes 6-O sulfation of its own HS chains, creating high-affinity binding sites for VEGFA165. This interaction is essential for VEGFA165-dependent neovascularization, as knockdown of SDC2 in endothelial cells abolishes VEGFA165-induced ERK1/2 phosphorylation and cell migration [9].
### 3.3 Notch Signaling and Vascular Smooth Muscle Cell Differentiation
SDC2 is reciprocally regulated by and regulates **Notch signaling** in vascular smooth muscle cells (VSMCs). Endothelial cells induce SDC2 expression in adjacent VSMCs through Notch ligand (Jagged1/DLL4) engagement. In turn, SDC2 acts as a Notch co-receptor, enhancing Notch1 and Notch3 signaling. This reciprocal regulation is critical for the maturation and stabilization of blood vessels during development [7]. Disruption of this loop contributes to vascular pathologies, including restenosis and atherosclerosis.
### 3.4 TGF-β and Fibrosis
SDC2 is a downstream target of **TGF-β signaling** and contributes to fibrotic processes. In a proteomic screen of TGF-β1-treated lung fibroblasts, SDC2 was identified as one of the most significantly upregulated proteins [10]. Furthermore, SDC2 is over-expressed in fibrotic tissues, including those from patients with systemic sclerosis and rheumatoid arthritis-associated interstitial lung disease (RA-ILD) [11][12]. SDC2 regulates the activity of **PAD2 (peptidylarginine deiminase 2)**, an enzyme that citrullinates arginine residues on proteins, contributing to the production of anti-citrullinated protein antibodies (ACPAs) in RA-ILD. Silencing SDC2 in RA-ILD fibroblasts reduces PAD2 expression and inhibits the pro-fibrotic phenotype [11]. Additionally, SDC2 is a direct transcriptional target of **IGFBP-3**, which is also implicated in fibrosis [12].
### 3.5 Cell Adhesion, Migration, and Invasion
SDC2 regulates cell adhesion and migration by modulating **integrin signaling** and the **actin cytoskeleton**. The cytoplasmic domain of SDC2 binds to syntenin and synectin, which link the receptor to the actin cytoskeleton via interactions with ARF6 and Rac1. SDC2 can promote or inhibit cell migration depending on the cellular context. In endothelial cells, SDC2 promotes migration by activating Rac1 and Cdc42. In contrast, in some cancer cell lines, SDC2 overexpression suppresses migration and invasion, suggesting a tumor-suppressive role in certain contexts.
### 3.6 Regulation of the Actin Cytoskeleton
The cytoplasmic domain of SDC2 interacts with **ezrin, radixin, and moesin (ERM) proteins**, which crosslink actin filaments to the plasma membrane. This interaction is regulated by tyrosine phosphorylation of the SDC2 cytoplasmic tail. Phosphorylation by Src family kinases promotes ERM binding and cytoskeletal reorganization, facilitating cell spreading and focal adhesion formation.
### 3.7 Protein-Protein Interaction Networks
The SDC2 interactome is complex and includes:
* **PDZ-domain scaffolding proteins:** Syntenin (SDCBP), CASK, synectin (GIPC1), and GOPC.
* **Cytoskeletal proteins:** Ezrin, moesin, α-actinin, and tubulin.
* **Growth factors and ECM proteins:** VEGFA, FGF-2, TGF-β, fibronectin, and collagen.
* **Signaling enzymes:** Src family kinases, PKCδ, and PAD2.
* **Viral proteins:** HBV preS1 domain (attachment receptor) [13].
STRING and BioGRID databases list over 50 high-confidence physical and functional interactors for SDC2.
### 3.8 Signaling Pathway Diagram
```mermaid
flowchart TD
A["ECM Ligands: VEGFA165, FGF-2, Fibronectin"] -->|"HS GAG chains"| B("SDC2 Ectodomain")
B --> C{"SDC2 Dimer"}
C -->|"Conformational change"| D["Cytoplasmic Domain"]
D -->|"PDZ-binding motif"| E["Syntenin / Synectin"]
E --> F["ARF6 / Rac1"]
F --> G["Actin Cytoskeleton Remodeling"]
C -->|"Co-receptor"| H["VEGFR2"]
H --> I["ERK1/2 / PI3K-Akt"]
I --> J["Angiogenesis / Cell Survival"]
C -->|"Co-receptor"| K["Notch1/3"]
K --> L["RBP-Jκ"]
L --> M["VSMC Differentiation / Maturation"]
D -->|"Tyr phosphorylation"| N["Src Family Kinases"]
N --> O["ERM Proteins"]
O --> G
B -->|"6-O sulfation"| P["Enhanced VEGFA165 Binding"]
P --> H
```
---
## 4. Pathogenic Hotspot Mutations & Clinical Differentials
### 4.1 Somatic Mutations in Cancer
While SDC2 is not a classic oncogene or tumor suppressor gene in the sense of frequent coding mutations, its expression is frequently dysregulated in cancer. The most common alteration is **epigenetic silencing via promoter hypermethylation**, which is observed in:
* **Colorectal Cancer (CRC):** Hypermethylation of the SDC2 promoter is one of the most sensitive and specific epigenetic biomarkers for CRC. It is present in ~70–90% of CRC tissues and ~50–60% of advanced adenomas, but rarely in normal colonic mucosa [3][4][5][6]. This methylation can be detected non-invasively in stool DNA, plasma cfDNA, and whole blood [5][14][15][16][17].
* **Gastric Adenocarcinoma:** SDC2 methylation is also elevated in gastric cancer and can be detected in plasma, offering a potential screening tool [18][19][20].
* **Other Cancers:** SDC2 methylation or altered expression has been reported in prostate cancer [1], oral squamous cell carcinoma [2], thyroid cancer [3], uveal melanoma [4][5], and lung adenocarcinoma [6][7].
### 4.2 Germline Variants and Neurodevelopmental Disorders
A rare balanced translocation t(X;8)(p22.13;q22.1) was identified in a patient with autism and multiple exostoses. The breakpoint on chromosome 8 was mapped to the GRPR gene, 3' to SDC2 [2]. While the translocation did not directly disrupt the SDC2 coding region, it was hypothesized to potentially affect its regulation. This case highlights a potential link between SDC2 locus integrity and neurodevelopmental phenotypes.
### 4.3 Genetic Variation and Radiation Toxicity
A study investigating genetic predictors of radiation esophagitis in patients with esophageal squamous cell carcinoma (ESCC) receiving radiotherapy identified a significant association with a single nucleotide polymorphism (SNP) in the SDC2 gene [8]. This suggests that common germline variants in SDC2 may modulate normal tissue response to DNA damage, potentially through altered ECM remodeling or inflammatory signaling.
### 4.4 GWAS and Neuropsychiatric Traits
A genome-wide association study (GWAS) implicated SDC2 in **suicidal ideation**, building on prior associations with PTSD, insomnia, and autism [9]. The mechanism is not yet clear, but SDC2 is expressed in the brain and may influence synaptic plasticity or neuroinflammation. Single-cell RNA sequencing of CD14+CD16+ monocytes identified a subpopulation with enhanced migratory and inflammatory phenotypes that may be relevant to neuroinflammation [10].
### 4.5 ClinVar and Pathogenic Variants
As of the latest data, ClinVar contains a limited number of variants in SDC2, most of which are of uncertain significance (VUS). No clear Mendelian disease has been linked to pathogenic SDC2 coding mutations, consistent with its role as a modifier gene rather than a primary disease gene. However, the functional impact of missense variants in the cytoplasmic PDZ-binding motif or the GAG attachment sites remains an active area of investigation.
### 4.6 Differential Diagnosis and Clinical Phenotypes
The clinical phenotypes associated with SDC2 dysregulation are primarily related to its methylation status:
| **Condition** | **SDC2 Alteration** | **Clinical Utility** |
|---|---|---|
| Colorectal Cancer | Promoter hypermethylation | Early detection, screening, prognosis [3][11][12][13][14][5][15][14][16][17][18][19][20][1][2][15][3][4][16][5][6][7][6][8][17][9][10][11][12][13][14][15][16][17][18][19][20][1][2] |
| Gastric Cancer | Promoter hypermethylation | Screening [18][19][20][3] |
| Osteosarcoma | Overexpression (mRNA) | Chemoresistance [8] |
| Prostate Cancer | Altered expression | Prognosis [1] |
| Oral Squamous Cell Carcinoma | Altered expression | Biomarker [2][4] |
| Radiation Esophagitis | Germline SNP | Toxicity prediction [8] |
| Suicidal Ideation | GWAS locus | Risk assessment [9] |
| RA-ILD | Overexpression | Fibrosis progression [11] |
---
## 5. Host-Pathogen & Viral Interactions
### 5.1 Hepatitis B Virus (HBV) Attachment Receptor
Syndecan-2 has been identified as a **cell attachment receptor for Hepatitis B Virus (HBV)**. HBV particles, which are enveloped and contain apolipoprotein E (apoE) on their surface, require initial attachment to cell surface heparan sulfate proteoglycans (HSPGs). While SDC1 was previously identified as a major receptor for Hepatitis C Virus (HCV) [5], a recent study demonstrated that SDC2 serves as a critical attachment factor for HBV. The interaction is mediated by the HS chains of SDC2 binding to the preS1 domain of the HBV large envelope protein and/or apoE. Silencing SDC2 in hepatocyte cell lines significantly reduces HBV attachment and infection [13]. This finding has implications for understanding HBV tropism and for developing entry inhibitors.
### 5.2 Hepatitis E Virus (HEV)
While not directly shown to use SDC2, the closely related HSPG family is known to be involved in HEV attachment. A study using an A549-derived subclonal cell line with enhanced HEV replication showed altered expression of cell surface molecules, potentially including HSPGs [6]. The role of SDC2 specifically in HEV entry remains to be determined.
### 5.3 Polyethyleneimine (PEI)-Mediated Gene Delivery
Syndecans are the primary cell-surface receptors for PEI-DNA polyplexes used in non-viral gene therapy. A study demonstrated that SDC1 and SDC2 have **opposing roles** in PEI-mediated transfection. SDC1 promotes polyplex uptake, while SDC2 inhibits it. This differential effect is likely due to differences in their cytoplasmic domains and intracellular trafficking pathways [7]. This has implications for the design of more efficient gene delivery vectors.
### 5.4 Human Immunodeficiency Virus (HIV) and Neuroinflammation
SDC2 is expressed on a subpopulation of CD14+CD16+ monocytes that exhibit enhanced migratory and inflammatory phenotypes. These cells are implicated in HIV-associated neuroinflammation. The expression of SDC2 on these cells may facilitate their transmigration across the blood-brain barrier [10].
---
## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors
### 6.1 SDC2 Methylation as a Pharmacodynamic Biomarker
The primary clinical application of SDC2 is as a **methylation biomarker** for cancer screening and monitoring. Several commercial assays have been developed and are in clinical use, particularly in China:
* **ColoClear™ (Kangwei Biotech):** A stool DNA test that detects methylated SDC2. It has received approval from the China National Medical Products Administration (NMPA) for CRC screening [15][16][18].
* **LungMe™ / Plasma SDC2 assays:** Various laboratory-developed tests (LDTs) detect SDC2 methylation in plasma cfDNA [5][14][7][20][1].
The sensitivity and specificity of SDC2 methylation for CRC detection are consistently high. A meta-analysis reported a pooled sensitivity of ~80% and specificity of ~90% for CRC, with lower sensitivity for advanced adenomas (~50%) [16][19][17]. Combining SDC2 with other methylation markers (e.g., SEPT9, SFRP2, VIM, NDRG4, BCAT1, IKZF1, KCNQ5) improves diagnostic performance [3][11][8][14][17][18][20][3][4][7][8][9][11][12][13][2].
### 6.2 Investigational Drugs and Compounds
* **Quercetin:** A natural flavonoid that has been shown to reduce fecal SDC2 gene methylation levels in CRC patients in a retrospective study. The mechanism is hypothesized to involve inhibition of DNA methyltransferases (DNMTs) [9].
* **Decitabine (5-aza-2'-deoxycytidine):** A DNMT inhibitor used in the treatment of myelodysplastic syndromes. In CRC cell lines (e.g., HCT-116), decitabine treatment demethylates the SDC2 promoter and restores gene expression [19]. This suggests that SDC2 expression could be used as a pharmacodynamic marker for DNMT inhibitor therapy.
### 6.3 Therapeutic Targeting of SDC2 Protein
Direct therapeutic targeting of SDC2 is an emerging area. Potential strategies include:
* **Monoclonal Antibodies:** Antibodies targeting the SDC2 ectodomain could be used to block ligand binding (e.g., VEGFA165) or to deliver cytotoxic payloads to SDC2-expressing tumor cells.
* **HS Mimetics:** Small molecules or glycomimetics that compete with SDC2 HS chains for growth factor binding could inhibit angiogenesis. For example, agents that block 6-O sulfation could selectively inhibit VEGFA165 signaling [9].
* **siRNA/ASO Therapies:** In fibrosis, silencing SDC2 in fibroblasts could reduce PAD2 expression and ACPA production, potentially ameliorating RA-ILD [11]. In osteosarcoma, targeting SDC2 could reverse multidrug resistance [8].
### 6.4 Gene Therapy Vectors
The opposing roles of SDC1 and SDC2 in PEI-mediated transfection suggest that modulating SDC2 expression could enhance the efficiency of non-viral gene delivery. For example, transiently silencing SDC2 in target cells could increase polyplex uptake [7].
---
## 7. Bioinformatic Resources & Database Accessions
| **Database** | **Accession / ID** | **URL** |
|---|---|---|
| HGNC | 10665 | https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10665 |
| NCBI Gene | 6383 | https://www.ncbi.nlm.nih.gov/gene/6383 |
| Ensembl | ENSG00000169439 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000169439 |
| UniProt | P34741 | https://www.uniprot.org/uniprotkb/P34741/entry |
| RCSB PDB | true (AlphaFold model available) | https://www.rcsb.org/search?q=sdC2 |
| OMIM | 142461 | https://www.omim.org/entry/142461 |
| ClinVar | SDC2 | https://www.ncbi.nlm.nih.gov/clinvar/?term=SDC2%5Bgene%5D |
| STRING | 9606.ENSP00000307087 | https://string-db.org/network/9606.ENSP00000307087 |
| BioGRID | 112590 | https://thebiogrid.org/112590 |
| Gene Ontology (GO) | GO:0005886 (plasma membrane), GO:0007155 (cell adhesion), GO:0001934 (angiogenesis), GO:0043235 (receptor complex) | https://www.ebi.ac.uk/QuickGO/ |
| GTEx | SDC2 | https://gtexportal.org/home/gene/SDC2 |
| CCLE | SDC2 | https://portals.broadinstitute.org/ccle |
---
## Related Clinical & Scientific Guides
* [PMCH Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/developmental-biology/pmch-gene-structure-function-pathway)
* [CYLC1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/developmental-biology/cylc1-gene-structure-function-pathway)
* [CRX Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/developmental-biology/crx-gene-structure-function-pathway)
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