TFAP2A

Chr 6

transcription factor AP-2 alpha

Also known as: AP-2, AP-2alpha, AP2TF, BOFS, TFAP2

NCBI Gene: 7020ENSG00000137203UniProt: P05549

The protein encoded by this gene is a transcription factor that binds the consensus sequence 5'-GCCNNNGGC-3'. The encoded protein functions as either a homodimer or as a heterodimer with similar family members. This protein activates the transcription of some genes while inhibiting the transcription of others. Defects in this gene are a cause of branchiooculofacial syndrome (BOFS). Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]

Primary Disease Associations & Inheritance

UniProtBranchiooculofacial syndrome
351
ClinVar variants
83
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TFAP2A
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
83 Pathogenic / Likely Pathogenic· 139 VUS of 351 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.26LOEUF
pLI 0.990
Z-score 3.73
OE 0.06 (0.02–0.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
2.59Z-score
OE missense 0.54 (0.47–0.62)
136 obs / 251.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.06 (0.02–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.54 (0.47–0.62)
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.1.16
0≤1.21.6
LoF obs/exp: 1 / 18.2Missense obs/exp: 136 / 251.4Syn Z: -1.36

ClinVar Variant Classifications

351 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic36
VUS139
Likely Benign94
Benign27
Conflicting8
47
Pathogenic
36
Likely Pathogenic
139
VUS
94
Likely Benign
27
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
13
31
0
47
Likely Pathogenic
10
18
8
0
36
VUS
3
117
17
2
139
Likely Benign
0
2
42
50
94
Benign
0
1
22
4
27
Conflicting
—8
Total1615112056351

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

View in ClinVar →

Protein Context — Lollipop Plot

TFAP2A · protein map & ClinVar variants

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

Gene2Phenotype Curations

TFAP2A-related branchiooculofacial syndrome

definitive
ADUndeterminedAltered Gene Product Structure
Dev. DisordersEye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — TFAP2A
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
[Branchio-oculo-facial syndrome].
Frascari F et al.·Ann Dermatol Venereol
2012Case report
A neonatal case report of branchiooculofacial syndrome caused by a novel mutation in the TFAP2A gene and literature review.
Luo F et al.·Medicine (Baltimore)
2023Review
TFAP2A-mediated downregulation of UBE2C is crucial for endometrial decidualization and embryo implantation.
Yu L et al.·Cell Signal
2025
Toward an orofacial gene regulatory network.
Kousa YA et al.·Dev Dyn
2016Review
TFAP2A potentiates lung adenocarcinoma metastasis by a novel miR-16 family/TFAP2A/PSG9/TGF-β signaling pathway.
Xiong Y et al.·Cell Death Dis
2021
TFAP2A downregulation mediates tumor-suppressive effect of miR-8072 in triple-negative breast cancer via inhibiting SNAI1 transcription.
Fang Y et al.·Breast Cancer Res
2024
Clinical presentation and the presence of hearing impairment in branchio-oculo-facial syndrome: a new mutation in the TFAP2A gene.
Thomeer HG et al.·Ann Otol Rhinol Laryngol
2010Review
TFAP2A promotes cervical cancer via a positive feedback pathway with PD‑L1.
Yang J et al.·Oncol Rep
2023
TFAP2A regulates nasopharyngeal carcinoma growth and survival by targeting HIF-1α signaling pathway.
Shi D et al.·Cancer Prev Res (Phila)
2014
TFAP2A Upregulates SKA3 to Promote Glycolysis and Reduce the Sensitivity of Lung Adenocarcinoma Cells to Cisplatin.
Liu G et al.·Pharmacology
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
TFAP2A transcriptionally regulates B3GALT2 to affect gouty arthritis progression through pyroptosis: a study based on machine learning and multi-omics integration analysis.
Han HL et al.·J Orthop Surg Res
2026
TFAP2A facilitates aerobic glycolysis and metastasis of pancreatic cancer via IGF2BP2-mediated LDHA m6A modification.
Xu Z et al.·Pathol Res Pract
2026
Transcription factor TFAP2A drives EMT progress by activating BDKRB1 transcription: The potential mechanism by which TFAP2A promotes idiopathic pulmonary fibrosis.
Zhang J et al.·Toxicol Appl Pharmacol
2026Functional
TFAP2A Transcriptionally Activates CST2 to Promote the Malignant Progression of Non-Small Cell Lung Cancer.
Li C et al.·J Biochem Mol Toxicol
2026
CES3 promotes NSCLC progression via lipid metabolic reprogramming regulated by TFAP2A.
Luo P et al.·J Cancer
2026🔓 Open Access
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