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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TFAP2C
transcription factor AP-2 gamma
Chromosome 20 · 20q13.31
NCBI Gene: 7022Ensembl: ENSG00000087510.8HGNC: HGNC:11744UniProt: Q92754
110PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of gene expression, epigeneticpositive regulation of transcription by RNA polymerase IIprotein bindingsequence-specific double-stranded DNA bindingneurodegenerative diseaseandrogenetic alopeciaalopeciadiverticular disease
✦AI Summary

TFAP2C is a sequence-specific DNA-binding transcription factor that plays critical roles in early embryonic development, germ cell specification, and cellular stress responses. During early embryonic development, TFAP2C works with TEAD4 to establish a bistable switch that drives robust lineage diversification by promoting both inner cell mass and trophectoderm fates in totipotent embryos 1. TFAP2C is essential for primordial germ cell specification, where it functions alongside GATA transcription factors and SOX17 to drive the human germ-cell specification program 2. In germ cell tumors like seminoma, TFAP2C promotes tumor invasion and migration 3. The protein also responds to cellular stress, particularly ferroptosis, where it coordinates with SP1 to activate selenoprotein transcription including antioxidant GPX4, providing neuroprotection against oxidative damage 4. In cancer contexts, TFAP2C can be regulated by epigenetic mechanisms - EZH2 normally represses TFAP2C expression through H3K27 methylation, and loss of this repression contributes to gastric squamous cell carcinoma development 5. Additionally, TFAP2C binds to androgen receptor enhancer elements in prostate cancer, contributing to treatment resistance 6.

Sources cited
1
TFAP2C works with TEAD4 to establish a bistable switch for lineage diversification in embryos
PMID: 38789684
2
TFAP2C is essential for primordial germ cell specification alongside GATA factors and SOX17
PMID: 33608411
3
TFAP2C promotes tumor invasion and migration in seminoma
PMID: 38123589
4
TFAP2C coordinates with SP1 to activate selenoprotein transcription for neuroprotection
PMID: 31056284
5
EZH2 represses TFAP2C expression via H3K27 methylation, and loss contributes to gastric squamous cell carcinoma
PMID: 40595652
6
TFAP2C binds androgen receptor enhancer elements in prostate cancer
PMID: 39954255
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.53Moderate
androgenetic alopeciaOpen Targets
0.25Weak
alopeciaOpen Targets
0.20Weak
diverticular diseaseOpen Targets
0.20Weak
breast carcinomaOpen Targets
0.18Weak
tricuspid valve diseaseOpen Targets
0.17Weak
microcephalyOpen Targets
0.14Weak
breast benign neoplasmOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
hair colorOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.09Suggestive
seminomaOpen Targets
0.09Suggestive
bladder exstrophyOpen Targets
0.09Suggestive
non-small cell lung carcinomaOpen Targets
0.09Suggestive
cervical carcinomaOpen Targets
0.09Suggestive
Genu varumOpen Targets
0.08Suggestive
alcohol drinkingOpen Targets
0.08Suggestive
Genu valgumOpen Targets
0.08Suggestive
Abnormality of refractionOpen Targets
0.08Suggestive
prostate cancerOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
WWOXProtein interaction99%MYCProtein interaction96%CITED2Protein interaction95%ESR1Protein interaction94%KCTD1Protein interaction94%TFAP2AProtein interaction93%
Tissue Expression6 tissues
Brain
100%
Lung
45%
Bone Marrow
19%
Heart
16%
Ovary
12%
Liver
3%
Gene Interaction Network
Click a node to explore
TFAP2CWWOXMYCCITED2ESR1KCTD1TFAP2A
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q92754
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.42Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.23 [0.14–0.42]
RankingsWhere TFAP2C stands among ~20K protein-coding genes
  • #4,338of 20,598
    Most Researched110 · top quartile
  • #2,189of 17,882
    Most Constrained (LOEUF)0.42 · top quartile
Genes detectedTFAP2C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke.
PMID: 31056284
Cell · 2019
1.00
2
EZH2 loss promotes gastric squamous cell carcinoma.
PMID: 40595652
Nat Commun · 2025
0.90
3
Single-cell multi-omics analysis of human testicular germ cell tumor reveals its molecular features and microenvironment.
PMID: 38123589
Nat Commun · 2023
0.80
4
Transcription factors in ferroptotic cell death.
PMID: 32123318
Cancer Gene Ther · 2020
0.70
5
Efficient derivation of embryonic stem cells and primordial germ cell-like cells in cattle.
PMID: 38355134
J Reprod Dev · 2024
0.60