EPC1

Chr 10

enhancer of polycomb 1

Also known as: Epl1

NCBI Gene: 80314 ENSG00000120616 UniProt: Q9H2F5 OMIM: 610999

The EPC1 protein is a component of the NuA4 histone acetyltransferase complex that acetylates histones H4 and H2A to regulate gene transcription and plays a direct role in DNA double-strand break repair through homologous recombination. Mutations cause autosomal dominant neurodevelopmental disorder with intellectual disability, behavioral abnormalities, and variable features including seizures and autism spectrum disorder. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely pathogenic when they occur.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.13

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.13LOEUF

pLI 1.000

Z-score 6.30

OE 0.04 (0.01–0.13)

Highly constrained

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

Missense Constraint?

2.67Z-score

OE missense 0.65 (0.59–0.71)

299 obs / 460.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.13)

0≤0.351.4

Missense OE?0.65 (0.59–0.71)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 2 / 50.2Missense obs/exp: 299 / 460.4Syn Z: 0.74

Background carrier burden — how many people carry a rare variant somewhere in EPC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

811 rare PASS variants

Rare truncating (LoF)

1 in 5,700

45 rare PASS variants

Rare synonymous (reference)

1 in 120

398 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EPC1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 5,400
South Asian	~43k	1 in 84	1 in 7,100
Remaining (unassigned)	~30k	1 in 65	≈ 1 in 10,000
European (Finnish)	~27k	1 in 390	1 in 2,700
Admixed American	~22k	1 in 110	≈ 1 in 10,000
African / African American	~21k	1 in 85	≈ 1 in 4,500
East Asian	~20k	1 in 99	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 500	none seen
Middle Eastern	~2,884	1 in 68	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 14 coding exons well covered in gnomAD exomes and genomes.? see exons ↓