TFAP2E

Chr 1

transcription factor AP-2 epsilon

Also known as: AP-2epsilon, AP2E

NCBI Gene: 339488 ENSG00000116819 UniProt: Q6VUC0 OMIM: 614428

TFAP2E encodes a sequence-specific DNA-binding transcription factor that regulates genes involved in eye, face, body wall, limb and neural tube development, and plays a role in CNS development and cartilage differentiation. Mutations cause neurodevelopmental disorders with intellectual disability and multiple congenital anomalies, inherited in an autosomal dominant pattern. The gene shows low constraint against loss-of-function variants, suggesting tolerance to complete gene loss.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.16

Clinical Summary— TFAP2E

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

80 VUS of 93 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

1.02Z-score

OE missense 0.81 (0.72–0.92)

184 obs / 227.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.40–1.16)

0≤0.351.4

Missense OE?0.81 (0.72–0.92)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 9 / 13.6Missense obs/exp: 184 / 227.2Syn Z: 0.12

This gene — mechanism propensity

0.7036th %ile

GOF

0.2994th %ile

LOF

0.59top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

93 submitted variants in ClinVar

ClinVar

Classification Summary

VUS80

Conflicting1

VUS

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	80	0	0	80
Likely Benign	0	0	0	0	0
Benign	0	0	0	0	0
Conflicting	—				1
Total	0	80	0	0	81

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap TFAP2E — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →