EED

Chr 11AD

embryonic ectoderm development

Also known as: COGIS, HEED, WAIT1

NCBI Gene: 8726ENSG00000074266UniProt: O75530

This gene encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein interacts with enhancer of zeste 2, the cytoplasmic tail of integrin beta7, immunodeficiency virus type 1 (HIV-1) MA protein, and histone deacetylase proteins. This protein mediates repression of gene activity through histone deacetylation, and may act as a specific regulator of integrin function. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Cohen-Gibson syndromeMIM #617561
AD
184
ClinVar variants
32
Pathogenic / LP
1.00
pLI score· haploinsufficient
4
Active trials
Clinical Summary— EED
🧬
Gene-Disease Validity (ClinGen)
Cohen-Gibson syndrome · ADModerate

Moderate evidence — consider for supplementary testing

⚡
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.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 82 VUS of 184 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 0.999
Z-score 4.48
OE 0.04 (0.01–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.73Z-score
OE missense 0.50 (0.43–0.58)
118 obs / 236.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.04 (0.01–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.50 (0.43–0.58)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 1 / 25.4Missense obs/exp: 118 / 236.3Syn Z: -0.12

ClinVar Variant Classifications

184 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic10
VUS82
Likely Benign36
Benign33
Conflicting1
22
Pathogenic
10
Likely Pathogenic
82
VUS
36
Likely Benign
33
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
18
0
22
Likely Pathogenic
0
9
1
0
10
VUS
1
68
12
1
82
Likely Benign
0
2
14
20
36
Benign
0
1
28
4
33
Conflicting
—1
Total1847325184

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

View in ClinVar →

Protein Context — Lollipop Plot

EED · protein map & ClinVar variants

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

Gene2Phenotype Curations

EED-related Weaver-like overgrowth syndrome

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cohen-Gibson syndrome

MIM #617561

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — EED
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mediterranean-style diet for the primary and secondary prevention of cardiovascular disease.
Rees K et al.·Cochrane Database Syst Rev
2019Meta-analysis
Mutations in Epigenetic Regulation Genes Are a Major Cause of Overgrowth with Intellectual Disability.
Tatton-Brown K et al.·Am J Hum Genet
2017
Imagawa-Matsumoto syndrome: SUZ12-related overgrowth disorder.
Imagawa E et al.·Clin Genet
2023Review
Environmental Enteric Dysfunction in Children.
Syed S et al.·J Pediatr Gastroenterol Nutr
2016Review
EZH2 function in immune cell development.
Nutt SL et al.·Biol Chem
2020Review
PRC2-complex related dysfunction in overgrowth syndromes: A review of EZH2, EED, and SUZ12 and their syndromic phenotypes.
Cyrus S et al.·Am J Med Genet C Semin Med Genet
2019Review
Environmental enteric dysfunction: an overview.
Crane RJ et al.·Food Nutr Bull
2015Review
Targeting EED as a key PRC2 complex mediator toward novel epigenetic therapeutics.
Bao Q et al.·Drug Discov Today
2024Review
Clinical and cost-effectiveness of left ventricular assist devices as destination therapy for advanced heart failure: systematic review and economic evaluation.
Beese S et al.·Health Technol Assess
2024Review
Recent strategies targeting Embryonic Ectoderm Development (EED) for cancer therapy: Allosteric inhibitors, PPI inhibitors, and PROTACs.
Zhao Y et al.·Eur J Med Chem
2022Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Environmental Enteric Dysfunction

Maternal Probiotic Intervention to Improve Gut Health - Trial II - Bangladesh

ENROLLING BY INVITATION
NCT06817031Phase PHASE2International Centre for Diarrhoeal Disease Research, BangladeshStarted 2025-04-20
VE818PlaceboOral Vancomycin
Environmental Enteric Dysfunction (EED)

Maternal Probiotic Intervention to Improve Gut Health - Trial II - Burkina Faso (MPIGH-II)

RECRUITING
NCT07134790Phase PHASE2University GhentStarted 2025-07-30
VE818PlaceboOral Vancomycin
Malnutrition PregnancyMalnutrition in ChildrenMalnutrition (Calorie)

Early Life Malnutrition, Environmental Enteric Dysfunction and Microbiome Trajectories

RECRUITING
NCT07195006University of ZimbabweStarted 2025-01-27
Malnutrition in pregnancy as exposurePoor WASH living conditions as exposure
Environmental Enteric Dysfunction (EED)Stunting

Maternal Probiotic Intervention to Improve Gut Health-Trial II-Pakistan

RECRUITING
NCT07207434Phase PHASE2Aga Khan UniversityStarted 2025-08-30
Oral VancomycinVE818Placebo

External Resources

Links to major genomics databases and tools