EED

embryonic ectoderm development, the group of Polycomb repressive complex 2|WD repeat domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:86201212-86279807

Links

ENSG00000074266 ∙ NCBI:8726 ∙ OMIM:605984 ∙ HGNC:3188 ∙ Uniprot:O75530 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Cohen-Gibson syndrome (Moderate), mode of inheritance: AD
• Cohen-Gibson syndrome (Strong), mode of inheritance: AD
• Weaver syndrome (Supportive), mode of inheritance: AD
• Cohen-Gibson syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cohen-Gibson syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	25787343; 27193220; 27868325; 28229514

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EED gene.

• Cohen-Gibson syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EED gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				19	3	22
missense	1	5	39	2		47
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	3	1	6
non coding				6	26	32
Total	1	5	40	27	29

Variants in EED

This is a list of pathogenic ClinVar variants found in the EED region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-86244421-G-C			Benign (May 23, 2021)
11-86245105-G-T			Likely benign (May 01, 2024)
11-86245106-G-C			Likely benign (Jun 01, 2024)
11-86245145-G-A			Likely benign (Aug 01, 2023)
11-86245217-G-A			Likely benign (Jul 01, 2024)
11-86245233-T-C		Cohen-Gibson syndrome	Uncertain significance (May 17, 2022)
11-86245235-C-T		Cohen-Gibson syndrome	Likely benign (Dec 02, 2021)
11-86245238-G-T		Cohen-Gibson syndrome	Uncertain significance (Sep 01, 2021)
11-86245240-G-A		Cohen-Gibson syndrome	Uncertain significance (Mar 23, 2020)
11-86245240-G-T		Cohen-Gibson syndrome • Inborn genetic diseases	Uncertain significance (Jun 16, 2023)
11-86245241-G-T		Inborn genetic diseases	Uncertain significance (Jun 27, 2022)
11-86245243-A-G		Inborn genetic diseases	Uncertain significance (Nov 01, 2022)
11-86245245-G-A		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
11-86245246-T-C		Cohen-Gibson syndrome	Uncertain significance (Jul 02, 2021)
11-86245256-G-A			Likely benign (Jul 26, 2017)
11-86245265-A-G		Cohen-Gibson syndrome	Likely benign (Sep 19, 2022)
11-86245272-A-G		Inborn genetic diseases	Uncertain significance (Apr 04, 2023)
11-86245273-T-G		Cohen-Gibson syndrome	Uncertain significance (Oct 29, 2021)
11-86245279-C-T		Cohen-Gibson syndrome	Uncertain significance (Feb 01, 2023)
11-86245302-A-G		Cohen-Gibson syndrome	Uncertain significance (Apr 02, 2020)
11-86245307-C-T		Cohen-Gibson syndrome	Likely benign (Dec 31, 2023)
11-86245310-G-A			Likely benign (Sep 01, 2022)
11-86245325-C-T		Cohen-Gibson syndrome	Likely benign (Jun 18, 2019)
11-86245347-A-C		Cohen-Gibson syndrome • EED-related disorder	Uncertain significance (Apr 25, 2023)
11-86245361-C-T		Cohen-Gibson syndrome	Benign (May 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EED	protein_coding	protein_coding	ENST00000263360	12	34270

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000708	125154	0	3	125157	0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.73	118	236	0.499	0.0000115	2963
Missense in Polyphen		8	71.005	0.11267		916
Synonymous	-0.121	79	77.6	1.02	0.00000392	763
Loss of Function	4.48	1	25.4	0.0394	0.00000132	304

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000280	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Polycomb group (PcG) protein. Component of the PRC2/EED- EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A. {ECO:0000269|PubMed:10581039, ECO:0000269|PubMed:14532106, ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:20974918, ECO:0000269|PubMed:28229514, ECO:0000269|PubMed:9584199}.
• Disease: DISEASE: Cohen-Gibson syndrome (COGIS) [MIM:617561]: An autosomal dominant overgrowth disorder characterized by accelerated osseous maturation, advanced bone age, skeletal abnormalities including flaring of the metaphyses of the long bones, large hands with long fingers and camptodactyly, scoliosis, cervical spine anomalies, dysmorphic facial features, and variable intellectual disability. {ECO:0000269|PubMed:25787343, ECO:0000269|PubMed:27193220, ECO:0000269|PubMed:27868325, ECO:0000269|PubMed:28229514, ECO:0000269|PubMed:28475857}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Histone Modifications;Interactome of polycomb repressive complex 2 (PRC2);Oxidative Stress Induced Senescence;Tumor suppressor activity of SMARCB1;EMT transition in Colorectal Cancer;Signal Transduction;Epigenetic regulation of gene expression;Gene expression (Transcription);the prc2 complex sets long-term gene silencing through modification of histone tails;Transcriptional Regulation by E2F6;Generic Transcription Pathway;Oxidative Stress Induced Senescence;Cellular Senescence;Cellular responses to stress;PKMTs methylate histone lysines;RNA Polymerase II Transcription;Chromatin modifying enzymes;Cellular responses to external stimuli;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Chromatin organization;TNFalpha;Intracellular signaling by second messengers;PRC2 methylates histones and DNA (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.15

Haploinsufficiency Scores

• pHI: 0.922
• hipred: Y
• hipred_score: 0.777
• ghis: 0.717

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.972

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Eed
• Phenotype: hematopoietic system phenotype; pigmentation phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chromatin silencing;regulation of gene expression by genetic imprinting;spinal cord development;negative regulation of gene expression, epigenetic;negative regulation of transcription, DNA-templated;positive regulation of histone H3-K27 methylation;negative regulation of G0 to G1 transition;histone H3-K27 methylation;cellular response to leukemia inhibitory factor;regulation of adaxial/abaxial pattern formation
• Cellular component: sex chromatin;nucleus;nucleoplasm;cytosol;ESC/E(Z) complex;pronucleus
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;protein binding;nucleosome binding;histone methyltransferase activity;identical protein binding;histone methyltransferase activity (H3-K27 specific)