TFAP2A: Transcription Factor AP-2 Alpha
A master regulator of development, cell cycle, and cancer, implicated in Char syndrome and various malignancies.
Gene Information Card
| Symbol | TFAP2A |
|---|---|
| Full Name | Transcription Factor AP-2 Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 6p24.3 |
| NCBI Gene ID | 7020 ncbi.nlm.nih.gov/gene/7020 |
| Ensembl ID | ENSG00000137203 |
| UniProt ID | P05549 |
| OMIM ID | 107580 |
| HGNC ID | 11742 |
| Aliases | AP-2, AP2TF, AP2, TFAP2, BOFS, AP-2alpha |
Description
TFAP2A encodes transcription factor AP-2 alpha, a member of the AP-2 family of sequence-specific DNA-binding proteins. It regulates gene expression during embryonic development, particularly in neural crest, craniofacial, and limb formation. Postnatally, it modulates cell proliferation, apoptosis, and differentiation. Dysregulation is linked to Char syndrome (autosomal dominant) and multiple cancers (e.g., melanoma, breast, gastric).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Char Syndrome | Loss-of-function mutations in TFAP2A disrupt neural crest development, leading to patent ductus arteriosus, facial dysmorphism, and hand anomalies. | OMIM #169100; ClinVar |
| Melanoma | TFAP2A acts as a tumor suppressor; loss of expression promotes metastasis and poor prognosis. | COSMIC; NCBI Gene |
| Breast Cancer | TFAP2A overexpression correlates with ERBB2/HER2 amplification and endocrine therapy resistance. | NCBI Gene; PubMed |
| Gastric Cancer | TFAP2A hypermethylation and reduced expression associated with aggressive tumor behavior. | COSMIC; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Breast | 8.3 | Low |
| Stomach | 6.1 | Low |
| Brain | 4.2 | Low |
| Lung | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (Breast) | 15.2 | High expression |
| A375 (Melanoma) | 9.7 | Moderate expression |
| HeLa (Cervical) | 7.1 | Low expression |
| K562 (Leukemia) | 2.3 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.715C>T (p.Arg239*) | Nonsense | <0.1% in general population; pathogenic in Char syndrome | Loss of function; premature truncation |
| c.632G>A (p.Arg211Gln) | Missense | Rare; reported in Char syndrome | Impaired DNA binding |
| c.1A>G (p.Met1?) | Start loss | Very rare | Loss of protein expression |
| Amplification (6p24.3) | Copy number gain | ~5% in breast cancer | Potential gain of function; overexpression |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and start-loss mutations (e.g., p.Arg239*, p.Met1?) cause haploinsufficiency or complete loss of AP-2 alpha function, leading to Char syndrome.
Gain of Function (GOF)
Gene amplification in breast cancer may lead to increased TFAP2A activity, promoting HER2 signaling.
Dominant Negative (DN)
Missense mutations in the DNA-binding domain (e.g., p.Arg211Gln) can produce a protein that interferes with wild-type AP-2 alpha function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• AP-2 transcription factor network
• Neural crest differentiation
• ERBB2/HER2 signaling in breast cancer
• p53 pathway (indirect regulation)
Protein Summary
TFAP2A encodes a 451-amino acid transcription factor (AP-2 alpha) with a C-terminal basic helix-span-helix domain and an N-terminal proline-rich transactivation domain. It forms homodimers or heterodimers with other AP-2 family members, binding to GC-rich consensus sequences (5'-GCCNNNGGC-3') in target gene promoters. The protein regulates genes involved in cell cycle (e.g., CDKN1A), apoptosis (e.g., BCL2), and differentiation (e.g., KRT14). Post-translational modifications include phosphorylation and sumoylation, modulating its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TFAP2A Knockout HEK293 Cell Line | EDJ-KQ5917 | Human | 7020 | Details Get a Quote |
| TFAP2A Knockout A-549 Cell Line | EDJ-KQ29448 | Human | 7020 | Details Get a Quote |
| TFAP2A Knockout HCT 116 Cell Line | EDJ-KQ29449 | Human | 7020 | Details Get a Quote |
| TFAP2A Knockout HeLa Cell Line | EDJ-KQ29450 | Human | 7020 | Details Get a Quote |
| Tfap2a Knockout NIH 3T3 Cell Line | EDJ-KZ504 | Mouse | 21418 | Details Get a Quote |
