Transcription factor AP4 is a basic helix-loop-helix-zipper transcription factor that activates viral and cellular genes by binding to the symmetrical DNA sequence 5'-CAGCTG-3'. Mutations cause autosomal dominant developmental and epileptic encephalopathy with microcephaly. This gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.17
Clinical SummaryTFAP4
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.17LOEUF
pLI 0.997
Z-score 3.86
OE 0.00 (0.000.17)
Highly constrained

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

Missense Constraint
1.60Z-score
OE missense 0.70 (0.610.80)
152 obs / 218.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.17)
00.351.4
Missense OE0.70 (0.610.80)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 0 / 17.4Missense obs/exp: 152 / 218.4Syn Z: -0.28
DN
0.3396th %ile
GOF
0.2597th %ile
LOF
0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TFAP4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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