EED

Chr 11

embryonic ectoderm development

Also known as: COGIS, HEED, WAIT1

NCBI Gene: 8726 ENSG00000074266 UniProt: O75530

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCohen-Gibson syndrome

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · Cohen-Gibson syndrome · AD · ClinGen 2022

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

172

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

GeneReview available — EED

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.04 (0.01–0.19)

0≤0.351.4

Missense OE?0.50 (0.43–0.58)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 1 / 25.4Missense obs/exp: 118 / 236.3Syn Z: -0.12

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 93

489 rare PASS variants

Rare truncating (LoF)

1 in 2,700

39 rare PASS variants

Rare synonymous (reference)

1 in 160

276 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EED. 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 120	1 in 2,300
South Asian	~43k	1 in 110	1 in 520
Remaining (unassigned)	~30k	1 in 100	1 in 2,500
European (Finnish)	~27k	1 in 180	≈ 1 in 9,600
Admixed American	~22k	1 in 110	1 in 3,200
African / African American	~21k	1 in 120	1 in 3,400
East Asian	~20k	1 in 91	1 in 610
Ashkenazi Jewish	~13k	1 in 1,100	1 in 530
Middle Eastern	~2,884	1 in 130	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): 9 of 12 coding exons well covered in gnomAD exomes; exons 8, 10, 11 marginal. Genomes: all 12.? see exons ↓