TP63 Gene - Tumor Protein P63
Key regulator of epithelial development and stem cell maintenance, implicated in ectodermal dysplasias and cancer
Gene Information Card
| Symbol | TP63 |
|---|---|
| Full Name | Tumor protein p63 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q28 |
| NCBI Gene ID | 8626 ncbi.nlm.nih.gov/gene/8626 |
| Ensembl ID | ENSG00000073282 |
| UniProt ID | Q9H3D4 |
| OMIM ID | 603273 |
| HGNC ID | 11979 |
| Aliases | p63, KET, LMS, EEC3, SHFM4, TP73L, TP53CP, TP53L, p73L, p40 |
Description
The TP63 gene encodes a member of the p53 family of transcription factors. It is essential for the development and maintenance of stratified epithelial tissues, including skin, limbs, and craniofacial structures. TP63 regulates cell proliferation, differentiation, and apoptosis, and plays a critical role in stem cell identity. Mutations in TP63 cause several autosomal dominant developmental disorders, and its dysregulation is implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3) | Missense mutations in the DNA-binding domain disrupt transcriptional activity | OMIM #604292 |
| Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome | Mutations in the SAM domain impair protein-protein interactions | OMIM #106260 |
| Split-hand/foot malformation 4 (SHFM4) | Missense mutations in the DNA-binding domain | OMIM #605289 |
| Limb-mammary syndrome (LMS) | Mutations in the transactivation domain | OMIM #603543 |
| Rapp-Hodgkin syndrome | Mutations in the SAM domain | OMIM #129400 |
| Squamous cell carcinoma | Overexpression and gain-of-function mutations promote oncogenesis | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | High |
| Esophagus | 8.2 | Medium |
| Cervix | 6.1 | Medium |
| Breast | 4.3 | Low |
| Prostate | 3.8 | Low |
| Lung | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 15.0 | High expression in epithelial cells |
| A431 (epidermoid carcinoma) | 12.3 | Overexpressed |
| MCF7 (breast cancer) | 2.5 | Low expression |
| HeLa (cervical cancer) | 4.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1037C>T (p.Pro346Leu) | Missense | Common in EEC3 | Disrupts DNA binding |
| c.1682G>A (p.Arg561His) | Missense | Common in AEC | Impairs SAM domain function |
| c.722C>T (p.Thr241Met) | Missense | Reported in SHFM4 | Reduces transactivation |
| c.953G>A (p.Arg318Gln) | Missense | Found in LMS | Alters transactivation domain |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the DNA-binding domain (e.g., p.Arg204Gln) reduce transcriptional activity, leading to developmental defects.
Gain of Function (GOF)
Overexpression or mutations in the N-terminal transactivation domain can promote cell proliferation and tumorigenesis in squamous cell carcinomas.
Dominant Negative (DN)
Mutations in the oligomerization domain (e.g., p.Arg561His) produce proteins that interfere with wild-type p63 function, causing dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity (GO:0003700) | • RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977) |
| • Protein homodimerization activity (GO:0042803) | • Apoptotic process (GO:0006915) |
| • Cell differentiation (GO:0030154) | • Epithelial cell development (GO:0002064) |
Pathways
• p53 signaling pathway (KEGG hsa04115)
• Apoptosis (Reactome R-HSA-109581)
• Transcriptional regulation by TP53 (Reactome R-HSA-3700989)
• Developmental biology (Reactome R-HSA-1266738)
Protein Summary
The p63 protein is a transcription factor with multiple isoforms due to alternative promoter usage and splicing. The major isoforms, TAp63 and ΔNp63, have distinct roles: TAp63 is involved in tumor suppression and apoptosis, while ΔNp63 is crucial for epithelial stem cell maintenance and proliferation. The protein contains a transactivation domain, a DNA-binding domain, a tetramerization domain, and a sterile alpha motif (SAM) domain. Mutations in these domains lead to various developmental disorders and contribute to cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TP63 Knockout HEK293 Cell Line | EDJ-KQ2948 | Human | 8626 | Details Get a Quote |
| TP63 Knockout A-549 Cell Line | EDJ-KQ25454 | Human | 8626 | Details Get a Quote |
| TP63 Knockout HeLa Cell Line | EDJ-KQ54958 | Human | 8626 | Details Get a Quote |
| TP63 Knockout HCT 116 Cell Line | EDJ-KQ71911 | Human | 8626 | Details Get a Quote |
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