EP300

Chr 22AD

EP300 lysine acetyltransferase

Also known as: KAT3B, MKHK2, RSTS2, p300

The protein functions as a histone acetyltransferase that regulates transcription via chromatin remodeling and is essential for cell proliferation and differentiation. Heterozygous loss-of-function mutations cause Rubinstein-Taybi syndrome 2 and Menke-Hennekam syndrome 2 through autosomal dominant inheritance. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the underlying pathogenic mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.103 OMIM phenotypes
Clinical SummaryEP300
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Gene-Disease Validity (ClinGen)
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.10LOEUF
pLI 1.000
Z-score 9.65
OE 0.05 (0.030.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.03Z-score
OE missense 0.84 (0.800.89)
1119 obs / 1327.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.030.10)
00.351.4
Missense OE0.84 (0.800.89)
00.61.4
Synonymous OE1.42
01.21.6
LoF obs/exp: 6 / 120.1Missense obs/exp: 1119 / 1327.6Syn Z: -7.05
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveEP300-related Rubinstein-Taybi syndromeLOFAD
limitedEP300-related retinitis pigmentosaOTHERAD
DN
0.2698th %ile
GOF
0.3392th %ile
LOF
0.87top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.10

Literature Evidence

LOFRTS is caused by haploinsufficiency of CREBBP or EP300 gene.PMID:30566799

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

EP300 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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