EPC1

Chr 10

enhancer of polycomb 1

Also known as: Epl1

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.

Summary from RefSeq, UniProt
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2
Active trials
13
Pubs (1 yr)
12
P/LP submissions
0%
P/LP missense
0.13
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryEPC1
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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ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 73 VUS of 105 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.13LOEUF
pLI 1.000
Z-score 6.30
OE 0.04 (0.010.13)
Highly constrained

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

Missense Constraint
2.67Z-score
OE missense 0.65 (0.590.71)
299 obs / 460.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.010.13)
00.351.4
Missense OE0.65 (0.590.71)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 2 / 50.2Missense obs/exp: 299 / 460.4Syn Z: 0.74
DN
0.3495th %ile
GOF
0.2597th %ile
LOF
0.85top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.13

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

ClinVar Variant Classifications

105 submitted variants in ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS73
Likely Benign3
Benign1
11
Pathogenic
1
Likely Pathogenic
73
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
1
0
1
VUS
2
68
3
0
73
Likely Benign
0
2
0
1
3
Benign
0
0
1
0
1
Total27016189

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EPC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
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