EED

Chr 11AD

embryonic ectoderm development

Also known as: COGIS, HEED, WAIT1

The protein is a component of the PRC2/EED-EZH2 complex that methylates histones H3 and H1 to repress gene transcription, including developmental genes like HOX genes. Mutations cause Cohen-Gibson syndrome, which is inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI = 0.999, LOEUF = 0.187), indicating that even single functional copies are critical for normal development.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.191 OMIM phenotype
Clinical SummaryEED
🧬
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.
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — EED
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 0.999
Z-score 4.48
OE 0.04 (0.010.19)
Highly constrained

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

Missense Constraint
2.73Z-score
OE missense 0.50 (0.430.58)
118 obs / 236.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.010.19)
00.351.4
Missense OE0.50 (0.430.58)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 1 / 25.4Missense obs/exp: 118 / 236.3Syn Z: -0.12
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongEED-related Weaver-like overgrowth syndromeOTHERAD
DN
0.2698th %ile
GOF
0.2397th %ile
LOF
0.81top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.19

Literature Evidence

LOFMaintenance of the functional integrity of mouse hematopoiesis by EED and promotion of leukemogenesis by EED haploinsufficiencyPMID:27432459

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

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →