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…

Primary Disease Associations & Inheritance

UniProtRubinstein-Taybi syndrome 2

UniProtMenke-Hennekam syndrome 2

Clinical highlights

Gene-disease validity (ClinGen)

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

362

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.10

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)