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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TFAP4
transcription factor AP-4
Chromosome 16 · 16p13.3
NCBI Gene: 7023Ensembl: ENSG00000090447.13HGNC: HGNC:11745UniProt: Q01664
100PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
transcription cis-regulatory region bindinghost-mediated suppression of viral transcriptionhost-mediated activation of viral transcriptionnegative regulation of cyclin-dependent protein serine/threonine kinase activityBurkitts lymphomaprostate carcinomabenign prostatic hyperplasianeurodegenerative disease
✦AI Summary

TFAP4 (transcription factor AP-4) is a sequence-specific DNA-binding transcription factor that regulates gene expression by binding to symmetrical DNA sequences, particularly E-box motifs 1. The protein functions as both a transcriptional activator and repressor depending on cellular context. TFAP4 plays critical roles in cancer progression across multiple tumor types, where it is frequently upregulated in malignant epithelial cells and associated with poor patient survival 2. Mechanistically, TFAP4 promotes oncogenesis through multiple pathways: it activates IGF2BP1 to stabilize TK1 expression via m6A modification in lung cancer 3, regulates MCM5 to activate PI3K/AKT signaling in gastric cancer 4, and controls mechanotransduction by directly activating mechanosensors like Itga11 and Piezo2 in cardiac fibrosis 5. In T-cell malignancies, TFAP4 serves as a key regulator of Galectin-9 expression 6. The transcription factor also influences therapeutic responses, as TFAP4 knockdown enhances chemotherapy efficacy and is downregulated following anti-PD-1 treatment 2. Paradoxically, TFAP4 can enhance CAR-T cell fitness under chr16 stimulation conditions 7. These diverse functions establish TFAP4 as both a prognostic biomarker and potential therapeutic target across multiple diseases.

Sources cited
1
TFAP4 binds to symmetrical DNA sequences and influences MLH1 promoter methylation
PMID: 31530880
2
TFAP4 is upregulated in malignant epithelial cells and associated with poor survival
PMID: 40653182
3
TFAP4 activates IGF2BP1 and promotes NSCLC progression by stabilizing TK1 via m6A modification
PMID: 36074102
4
TFAP4 regulates MCM5 to activate PI3K/AKT pathway in gastric cancer
PMID: 39971831
5
TFAP4 controls mechanotransduction by activating Itga11 and Piezo2 in cardiac fibrosis
PMID: 40612272
6
TFAP4 serves as key regulator of Galectin-9 expression in T-ALL
PMID: 40106574
7
TFAP4 enhances CAR-T cell fitness under chronic stimulation
PMID: 37714135
Disease Associationsⓘ20
Burkitts lymphomaOpen Targets
0.45Moderate
prostate carcinomaOpen Targets
0.39Weak
benign prostatic hyperplasiaOpen Targets
0.38Weak
neurodegenerative diseaseOpen Targets
0.31Weak
Varicose veinsOpen Targets
0.29Weak
non-Hodgkins lymphomaOpen Targets
0.26Weak
Umbilical herniaOpen Targets
0.13Weak
colorectal carcinomaOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
neuroblastomaOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
hereditary spastic paraplegiaOpen Targets
0.09Suggestive
cancerOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
adenomaOpen Targets
0.08Suggestive
posterior cortical atrophyOpen Targets
0.08Suggestive
pachyonychia congenitaOpen Targets
0.07Suggestive
acute lymphoblastic leukemiaOpen Targets
0.07Suggestive
infectionOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CDKN1AProtein interaction92%HBS1LProtein interaction76%HBG2Protein interaction75%BPTFProtein interaction74%DCLRE1AProtein interaction72%PRM1Protein interaction71%
Tissue Expression6 tissues
Ovary
100%
Liver
62%
Brain
51%
Lung
50%
Heart
26%
Bone Marrow
24%
Gene Interaction Network
Click a node to explore
TFAP4CDKN1AHBS1LHBG2BPTFDCLRE1APRM1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q01664
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.36Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.19 [0.11–0.36]
RankingsWhere TFAP4 stands among ~20K protein-coding genes
  • #4,817of 20,598
    Most Researched100 · top quartile
  • #1,580of 17,882
    Most Constrained (LOEUF)0.36 · top 10%
Genes detectedTFAP4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Modular pooled discovery of synthetic knockin sequences to program durable cell therapies.
PMID: 37714135
Cell · 2023
1.00
2
Temporal evolution reveals bifurcated lineages in aggressive neuroendocrine small cell prostate cancer trans-differentiation.
PMID: 37995683
Cancer Cell · 2023
0.90
3
The immunological and prognostic landscape of TFAP4 in cancer: A single-cell RNA sequencing perspective.
PMID: 40653182
Arch Biochem Biophys · 2025
0.80
4
Genome-wide CRISPR screen identifies IRF1 and TFAP4 as transcriptional regulators of Galectin-9 in T cell acute lymphoblastic leukemia.
PMID: 40106574
Sci Adv · 2025
0.70
5
TFAP4 Regulation of MCM5 Activates the PI3K/AKT Pathway to Promote Invasion and Metastasis of Gastric Cancer.
PMID: 39971831
Dig Dis Sci · 2025
0.60