EP300

Chr 22

EP300 lysine acetyltransferase

Also known as: KAT3B, MKHK2, RSTS2, p300

NCBI Gene: 2033 ENSG00000100393 UniProt: Q09472

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.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein. It functions as histone acetyltransferase that regulates transcription via chromatin remodeling and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and thus plays a role in the stimulation of hypoxia-induced genes such as VEGF. Defects in this gene are a cause of Rubinstein-Taybi syndrome and may also play a role in epithelial cancer. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.10

Clinical Summary— EP300

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Gene-Disease Validity (ClinGen)

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

Explore recent and relevant literature in Research Assistant →

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?

0.10LOEUF

pLI 1.000

Z-score 9.65

OE 0.05 (0.03–0.10)

Highly constrained

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

Missense Constraint?

2.03Z-score

OE missense 0.84 (0.80–0.89)

1119 obs / 1327.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.05 (0.03–0.10)

0≤0.351.4

Missense OE?0.84 (0.80–0.89)

0≤0.61.4

Synonymous OE?1.42

0≤1.21.6

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

This gene — mechanism propensity

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 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFRTS is caused by haploinsufficiency of CREBBP or EP300 gene.1

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

References