TFAP2E

Chr 1

transcription factor AP-2 epsilon

Also known as: AP-2epsilon, AP2E

NCBI Gene: 339488ENSG00000116819UniProt: Q6VUC0

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II and regulation of cell population proliferation. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

108
ClinVar variants
9
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TFAP2E
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 86 VUS of 108 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.16LOEUF
pLI 0.000
Z-score 1.15
OE 0.66 (0.40–1.16)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.02Z-score
OE missense 0.81 (0.72–0.92)
184 obs / 227.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.66 (0.40–1.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.72–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 9 / 13.6Missense obs/exp: 184 / 227.2Syn Z: 0.12

ClinVar Variant Classifications

108 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS86
Conflicting1
7
Pathogenic
2
Likely Pathogenic
86
VUS
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
79
7
0
86
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Conflicting
—1
Total07916096

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TFAP2E · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TFAP2E is implicated in central nervous system, orofacial and maxillofacial anomalies.
Kalanithy JC et al.·J Med Genet
2025
SQLE-catalyzed squalene metabolism promotes mitochondrial biogenesis and tumor development in K-ras-driven cancer.
Pan J et al.·Cancer Lett
2025
TFAP2E methylation status and prognosis of patients with radically resected colorectal cancer.
Park SJ et al.·Oncology
2015Cohort
TFAP2E-DKK4 and chemoresistance in colorectal cancer.
Ebert MP et al.·N Engl J Med
2012
TFAP2E hypermethylation was associated with survival advantage in patients with colorectal cancer.
Zhang ZM et al.·J Cancer Res Clin Oncol
2014Cohort
Intratumoral Microbiota Correlates with AP-2 Expression: A Pan-Cancer Map with Cohort-Specific Prognostic and Molecular Footprints.
Kołat D et al.·Int J Mol Sci
2025Cohort
Differentiation of zebrafish melanophores depends on transcription factors AP2 alpha and AP2 epsilon.
Van Otterloo E et al.·PLoS Genet
2010Functional
CpG Island Methylator Phenotype and Methylation of Wnt Pathway Genes Together Predict Survival in Patients with Colorectal Cancer.
Kim SH et al.·Yonsei Med J
2018Cohort
DNA methylation biomarkers of prostate cancer: confirmation of candidates and evidence urine is the most sensitive body fluid for non-invasive detection.
Payne SR et al.·Prostate
2009
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools