PDPN (Podoplanin) - A Key Player in Lymphangiogenesis and Cancer
Comprehensive gene card, expression data, mutations, and clinical relevance of PDPN
Gene Information Card
| Symbol | PDPN |
|---|---|
| Full Name | Podoplanin |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.21 |
| NCBI Gene ID | 10630 ncbi.nlm.nih.gov/gene/10630 |
| Ensembl ID | ENSG00000162493 |
| UniProt ID | Q86YL7 |
| OMIM ID | 608863 |
| HGNC ID | 29602 |
| Aliases | T1A, T1A-2, AGGRUS, GP36, Gp38, HT1A-1, OTS8, PA2.26, gp38 |
Description
The PDPN gene encodes podoplanin, a type I integral membrane glycoprotein with extensive O-glycosylation. It is a well-established marker for lymphatic endothelial cells but is also expressed in various other cell types, including kidney podocytes, alveolar type I cells, and mesothelial cells. Podoplanin plays a critical role in the development of the lymphatic system, particularly in the separation of blood and lymphatic vessels during embryonic development. It is also involved in platelet aggregation via its interaction with the C-type lectin-like receptor 2 (CLEC-2) on platelets. In cancer, PDPN is frequently overexpressed and is associated with tumor invasion, metastasis, and poor prognosis. It is also a key component of the tumor microenvironment, where it is expressed on cancer-associated fibroblasts (CAFs).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lymphedema (Nonne-Milroy-like) | Mutations in PDPN can disrupt lymphatic vessel development, leading to lymphatic dysfunction and edema. | OMIM, PubMed |
| Various Cancers (e.g., squamous cell carcinoma, mesothelioma, brain tumors) | Overexpression of PDPN promotes tumor cell invasion, migration, and metastasis. It also induces platelet aggregation, which may facilitate tumor cell emboli formation and immune evasion. | COSMIC, PubMed |
| Lung Cancer | PDPN expression in lung squamous cell carcinoma is associated with poor differentiation and advanced stage. | COSMIC, PubMed |
| Oral Squamous Cell Carcinoma (OSCC) | High PDPN expression in OSCC is correlated with invasive tumor front and lymph node metastasis. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph Node | Not detected | Low |
| Lung | Not detected | Low |
| Kidney | Not detected | Low |
| Skin | Not detected | Low |
| Esophagus | Not detected | Low |
| Salivary Gland | Not detected | Low |
| Thyroid | Not detected | Low |
| Adrenal Gland | Not detected | Low |
| Appendix | Not detected | Low |
| Bone Marrow | Not detected | Low |
| Brain | Not detected | Low |
| Breast | Not detected | Low |
| Cervix | Not detected | Low |
| Colon | Not detected | Low |
| Duodenum | Not detected | Low |
| Endometrium | Not detected | Low |
| Fallopian Tube | Not detected | Low |
| Gallbladder | Not detected | Low |
| Heart | Not detected | Low |
| Liver | Not detected | Low |
| Ovary | Not detected | Low |
| Pancreas | Not detected | Low |
| Placenta | Not detected | Low |
| Prostate | Not detected | Low |
| Rectum | Not detected | Low |
| Skeletal Muscle | Not detected | Low |
| Small Intestine | Not detected | Low |
| Smooth Muscle | Not detected | Low |
| Spleen | Not detected | Low |
| Stomach | Not detected | Low |
| Testis | Not detected | Low |
| Thymus | Not detected | Low |
| Urinary Bladder | Not detected | Low |
| White Blood Cells | Not detected | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung Carcinoma) | Not detected | Low |
| MCF7 (Breast Carcinoma) | Not detected | Low |
| HeLa (Cervical Carcinoma) | Not detected | Low |
| K562 (Leukemia) | Not detected | Low |
| HepG2 (Liver Carcinoma) | Not detected | Low |
| U2OS (Osteosarcoma) | Not detected | Low |
| SH-SY5Y (Neuroblastoma) | Not detected | Low |
| THP-1 (Monocyte) | Not detected | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.346C>T (p.Arg116Ter) | Nonsense | Rare | Predicted to result in a truncated protein lacking the transmembrane and cytoplasmic domains, likely leading to loss of function. |
| c.412G>A (p.Gly138Arg) | Missense | Rare | May affect protein folding or glycosylation, potentially altering its function. |
| c.523A>G (p.Thr175Ala) | Missense | Rare | Located in the extracellular domain, may affect interactions with binding partners like CLEC-2. |
| c.601C>T (p.Arg201Cys) | Missense | Rare | May disrupt disulfide bond formation, affecting protein stability. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in PDPN are rare but are predicted to impair lymphatic vessel development and function, potentially contributing to lymphedema. These mutations often result in truncated or misfolded proteins.
Gain of Function (GOF)
Gain-of-function is primarily observed at the expression level rather than through specific mutations. Overexpression of wild-type PDPN in cancers leads to enhanced tumor cell migration, invasion, and platelet aggregation, which are hallmarks of its oncogenic role.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for PDPN. Given its role as a membrane receptor, a mutant protein could potentially interfere with wild-type function, but this has not been demonstrated.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 (protein binding) | • GO:0005886 (plasma membrane) |
| • GO:0016021 (integral component of membrane) | • GO:0001944 (vasculature development) |
| • GO:0001945 (lymph vessel development) | • GO:0007155 (cell adhesion) |
| • GO:0030198 (extracellular matrix organization) | • GO:0043062 (extracellular structure organization) |
| • GO:0048870 (cell motility) | • GO:0030335 (positive regulation of cell migration) |
Pathways
• Podoplanin/CLEC-2 signaling pathway
• Lymphatic vessel development pathway
• Tumor metastasis pathway
Protein Summary
Podoplanin is a small, heavily O-glycosylated type I transmembrane protein. It consists of a large extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. The extracellular domain contains multiple tandem repeats of a platelet aggregation-stimulating (PLAG) domain, which is crucial for its interaction with CLEC-2 on platelets. This interaction induces platelet activation and aggregation. Podoplanin is essential for the normal development of the lymphatic system, where it is required for the separation of blood and lymphatic vessels. In pathological conditions, particularly cancer, podoplanin is overexpressed in tumor cells and cancer-associated fibroblasts, promoting tumor progression, invasion, and metastasis. Its expression is often associated with a poor prognosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDPN Knockout HEK293 Cell Line | EDJ-KQ2700 | Human | 10630 | Details Get a Quote |
| PDPN Knockout HeLa Cell Line | EDJ-KQ55447 | Human | 10630 | Details Get a Quote |
| PDPN Knockout A-549 Cell Line | EDJ-KQ63929 | Human | 10630 | Details Get a Quote |
| PDPN Knockout HCT 116 Cell Line | EDJ-KQ72386 | Human | 10630 | Details Get a Quote |
| PDPN Knockdown LX-2 stable cell line | EDJ-KD009 | Human | 10630 | Details Get a Quote |
| PDPN Overexpression LX-2 Stable Cell Line | EDC90051 | Human | 10630 | Details Get a Quote |
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