EPC1
protein-codingenhancer of polycomb homolog 1, the group of Tip60/Nua4 histone acetyltransferase complex subunits
Gene summary
This gene encodes a member of the polycomb group (PcG) family. The encoded protein is a component of the NuA4 histone acetyltransferase complex and can act as both a transcriptional activator and repressor. The encoded protein has been linked to apoptosis, DNA repair, skeletal muscle differentiation, gene silencing, and adult T-cell leukemia/lymphoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~111.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EPC1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001272004.3. 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 | 2 | 1 | 3 | |||
| missense | 76 | 2 | 78 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 84 | 3 | 0 | 87 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001258933.1 | 14 | MANE Select | |
| Ensembl | ENSP00000318559.6 | 14 | MANE Select | |
| RefSeq | NP_001258948.1 | 13 | Standard | |
| RefSeq | NP_001269320.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- Transcriptional Regulation by E2F6
- Generic Transcription Pathway
- RNA Polymerase II Transcription
- Chromatin modifying enzymes
Biological Process
- negative regulation of transcription by RNA polymerase II
- transcription, DNA-templated
- regulation of transcription by RNA polymerase II
- vascular smooth muscle cell differentiation
- regulation of growth
Molecular Function
- histone acetyltransferase activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- nuclear membrane
- Piccolo NuA4 histone acetyltransferase complex
- NuA4 histone acetyltransferase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000263062
- Coding exons
- 15
- Length
- 111048
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125748
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.67 | 299 | 460 | 0.649 | 0.0000243 | 5464 |
| Missense (PolyPhen) | 109 | 223.18 | 0.48839 | 2532 | ||
| Synonymous | 0.737 | 162 | 174 | 0.929 | 0.00000939 | 1618 |
| Loss of Function | 6.30 | 2 | 50.2 | 0.0399 | 0.00000321 | 512 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the NuA4 histone acetyltransferase (HAT) 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. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. {ECO:0000269|PubMed:14966270}.;
Recessive Scores
- pRec
- 0.0951
Intolerance Scores
- LoFtool
- 0.0677
- RVIS EVS
- -0.62
- RVIS percentile EVS
- 17.4
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.908
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |