EP400

protein-coding

E1A binding protein p400, the group of Tip60/Nua4 histone acetyltransferase complex subunits|Myb/SANT domain containing|Small nucleolar RNA protein coding host genes

Gene summary

Predicted to enable chromatin binding activity. Involved in nervous system development; positive regulation of double-strand break repair via homologous recombination; and regulation of cell cycle. Located in nucleoplasm. Part of NuA4 histone acetyltransferase complex and Swr1 complex. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

TNRC12

MANE transcript

NM_015409.5

Inheritance

AD, AR

ClinVar variants

U:501B:132

Top phenotype

neurodevelopmental disorder with or without early-onset generalized epilepsy

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr12:131,949,942-132,080,460

External References & Databases

Ensembl (ENSG00000183495)

Transcript & Mutation Effects

hg38 • Region Span ~130.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

neurodevelopmental disorder with or without early-onset generalized epilepsySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030930

Submitter: PanelApp Australia

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EP400 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 466

not providedTotal: 107

EP400-related disorderTotal: 80

Neurodevelopmental disorderTotal: 2

EP400-associated neurodevelopmental disorderTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015409.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	57 clinvar	24 clinvar	85
missense			455 clinvar	47 clinvar	3 clinvar	505
nonsense			15 clinvar			15
start loss			1 clinvar			1
frameshift			15 clinvar	1 clinvar		16
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	501	105	27	633

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015409.5	RefSeq	NP_056224.3	52	MANE Select
ENST00000389561.7	Ensembl	ENSP00000374212.2	52	MANE Select
ENST00000330386.7	Ensembl	ENSP00000330620.7	7	Standard
ENST00000332482.8	Ensembl	ENSP00000331737.5	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Formation of Senescence-Associated Heterochromatin Foci (SAHF)
DNA Damage/Telomere Stress Induced Senescence
Cellular Senescence
Cellular responses to stress
Chromatin modifying enzymes

Biological Process

histone H4 acetylation
histone H2A acetylation

Molecular Function

DNA binding
chromatin binding
helicase activity
protein binding
ATP binding

Cellular Component

Swr1 complex
nucleoplasm
nuclear speck
NuA4 histone acetyltransferase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389561
Coding exons: 52
Length: 130498
Individuals with no LoFs: 125606
Homozygous LoFs: 7
Heterozygous LoFs: 135
Defined: 125748
p: 0.000565

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.56	1535	1.84e+3	0.832	0.000121	20033
Missense (PolyPhen)		78	145.77	0.53509		1465
Synonymous	-2.32	905	820	1.10	0.0000606	6528
Loss of Function	9.90	23	157	0.147	0.00000812	1626

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0015	0.0014	notable
Latino/Admixed American	0.00065	0.00061	rare
Ashkenazi Jewish	0.00091	0.00079	rare
East Asian	0.00017	0.00016	rare
Finnish	0.00029	0.00028	rare
European (Non-Finnish)	0.00039	0.00034	rare
South Asian	0.0013	0.0013	notable
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. May be required for transcriptional activation of E2F1 and MYC target genes during cellular proliferation. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. May regulate ZNF42 transcription activity. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AFZ from the nucleosome. {ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:24463511}.;

Recessive Scores

pRec: 0.279

Intolerance Scores

LoFtool: 0.00889
RVIS EVS: -3.86
RVIS percentile EVS: 0.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.976

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	Medium
Primary Immunodeficiency	High	High	High
Cancer	High	High	High