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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
EZH2
enhancer of zeste 2 polycomb repressive complex 2 subunit
Chromosome 7 Β· 7q36.1
NCBI Gene: 2146Ensembl: ENSG00000106462.13HGNC: HGNC:3527UniProt: A0A090N8E9
1,553PubMed Papers
21Diseases
3Drugs
39Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneTranscription Factor
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
promoter-specific chromatin bindingprotein-lysine N-methyltransferase activitychromatin DNA bindingnucleosome bindingWeaver syndromediffuse large B-cell lymphomaneurodegenerative diseasefollicular lymphoma
✦AI Summary

EZH2 is the catalytic subunit of the PRC2 (Polycomb Repressive Complex 2), mediating histone H3 methylation at lysines 9 and 27 (H3K9me and H3K27me) to drive transcriptional repression 1. EZH2 catalyzes mono-, di-, and trimethylation of H3K27, with preference for less-methylated substrates (H3K27me0 > H3K27me1 > H3K27me2) 23. In embryonic stem cells, EZH2-containing PRC2 complexes predominantly generate H3K27me3, essential for stem cell identity and differentiation 4. Beyond canonical histone methylation, EZH2 exhibits non-canonical functions, including binding c-Myc at non-PRC2 targets via a cryptic transactivation domain to activate genes in acute leukemias 5. EZH2 overexpression correlates with poor prognosis across multiple cancersβ€”triple-negative breast cancer, ovarian cancer, and glioblastomaβ€”and promotes metastasis and therapeutic resistance 6789. In immune contexts, T cell EZH2 drives atherosclerosis by suppressing anti-inflammatory responses and Il-4 expression 10. EZH2 also regulates ferroptosis in kidney injury by suppressing SLC7A11 through H3K27me3 deposition 11. Both catalytic inhibitors and PROTAC-based EZH2 degraders represent therapeutic strategies for EZH2-dependent malignancies.

Sources cited
1
EZH2 catalyzes H3K9me and H3K27me methylation for transcriptional repression
PMID: 14532106
2
EZH2 catalyzes H3K27me1/2/3 with preference for less-methylated substrates
PMID: 22323599
3
EZH2 demonstrates progressive activity loss with increased H3K27 methylation
PMID: 30923826
4
EZH2-PRC2 predominates in embryonic stem cells and generates H3K27me3 for stem cell identity
PMID: 19026781
5
EZH2 exhibits non-canonical function binding c-Myc via cryptic transactivation domain in acute leukemias
PMID: 35210568
6
EZH2-H3K27me3 promotes TNBC peritoneal metastasis via KRT14 upregulation
PMID: 36446780
7
EZH2 overexpression correlates with poor prognosis and therapeutic resistance in multiple cancers
PMID: 38331087
8
EZH2 upregulation in ovarian cancer correlates with HCMV infection and oncogenic transformation
PMID: 37634008
9
EZH2 and Myc drive glioblastoma development in HCMV-infected astrocytes
PMID: 37147437
10
T cell EZH2 suppresses anti-inflammatory Il-4 expression and drives atherosclerosis
PMID: 39917842
11
EZH2 regulates ferroptosis in kidney injury by H3K27me3-mediated SLC7A11 suppression
PMID: 38169402
Disease Associationsβ“˜21
Weaver syndromeOpen Targets
0.83Strong
diffuse large B-cell lymphomaOpen Targets
0.61Moderate
neurodegenerative diseaseOpen Targets
0.52Moderate
follicular lymphomaOpen Targets
0.51Moderate
viral diseaseOpen Targets
0.49Moderate
neoplasmOpen Targets
0.46Moderate
melanomaOpen Targets
0.45Moderate
breast carcinomaOpen Targets
0.45Moderate
lymphomaOpen Targets
0.44Moderate
acute myeloid leukemiaOpen Targets
0.43Moderate
goutOpen Targets
0.41Moderate
cancerOpen Targets
0.40Moderate
myelodysplastic syndromeOpen Targets
0.40Weak
neoplasm of mature B-cellsOpen Targets
0.39Weak
chronic myelogenous leukemiaOpen Targets
0.39Weak
sarcomaOpen Targets
0.38Weak
myeloid neoplasmOpen Targets
0.38Weak
non-Hodgkins lymphomaOpen Targets
0.38Weak
chronic myelomonocytic leukemiaOpen Targets
0.38Weak
myelofibrosisOpen Targets
0.37Weak
Weaver syndromeUniProt
Pathogenic Variants39
NM_004456.5(EZH2):c.2050C>T (p.Arg684Cys)Pathogenic
Weaver syndrome|not provided|EZH2-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 684
NM_004456.5(EZH2):c.2035G>C (p.Val679Leu)Likely pathogenic
Weaver syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 679
NM_004456.5(EZH2):c.2187dup (p.Asp730Ter)Pathogenic
Weaver syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 730
NM_004456.5(EZH2):c.1876G>A (p.Val626Met)Pathogenic
Weaver syndrome|EZH2-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 626
NM_004456.5(EZH2):c.2084C>T (p.Ser695Leu)Pathogenic
Weaver syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 695
NM_004456.5(EZH2):c.2233G>A (p.Glu745Lys)Pathogenic
Weaver syndrome|not provided|Neoplasm|EZH2-related disorder
β˜…β˜…β˜†β˜†2023β†’ Residue 745
NM_004456.5(EZH2):c.398A>G (p.Tyr133Cys)Pathogenic
Weaver syndrome|not provided
β˜…β˜…β˜†β˜†2020β†’ Residue 133
NM_004456.5(EZH2):c.434T>G (p.Phe145Cys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 145
NM_004456.5(EZH2):c.1969G>A (p.Asp657Asn)Likely pathogenic
Weaver syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 657
NM_004456.5(EZH2):c.394C>A (p.Pro132Thr)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 132
NM_004456.5(EZH2):c.1882G>A (p.Gly628Ser)Likely pathogenic
Weaver syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 628
NM_004456.5(EZH2):c.835C>T (p.His279Tyr)Likely pathogenic
EZH2-related disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 279
NM_004456.5(EZH2):c.2185T>C (p.Phe729Leu)Pathogenic
Weaver syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 729
NM_004456.5(EZH2):c.1730C>T (p.Pro577Leu)Likely pathogenic
not provided|Medulloblastoma SHH activated and TP53 wild-type
β˜…β˜†β˜†β˜†2022β†’ Residue 577
NM_004456.5(EZH2):c.472C>T (p.His158Tyr)Likely pathogenic
Weaver syndrome
β˜…β˜†β˜†β˜†2020β†’ Residue 158
NM_004456.5(EZH2):c.457T>C (p.Tyr153His)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2020β†’ Residue 153
NM_004456.5(EZH2):c.2132A>T (p.His711Leu)Likely pathogenic
Weaver syndrome
β˜…β˜†β˜†β˜†2020β†’ Residue 711
NM_004456.5(EZH2):c.2048C>A (p.Thr683Asn)Likely pathogenic
Weaver syndrome
β˜…β˜†β˜†β˜†2019β†’ Residue 683
NM_004456.5(EZH2):c.1891del (p.Ile631fs)Likely pathogenic
Childhood neoplasm;Hereditary cancer-predisposing syndrome
β˜…β˜†β˜†β˜†2019β†’ Residue 631
NM_004456.5(EZH2):c.2235A>T (p.Glu745Asp)Pathogenic
Weaver syndrome
β˜…β˜†β˜†β˜†2019β†’ Residue 745
View on ClinVar β†—
Drug Targets3
GSK2816126Phase I
Histone-lysine N-methyltransferase EZH2 inhibitor
TAZEMETOSTATApproved
Histone-lysine N-methyltransferase EZH2 inhibitor
follicular lymphoma
TAZEMETOSTAT HYDROBROMIDEApproved
Histone-lysine N-methyltransferase EZH2 inhibitor
follicular lymphoma
Related Genes
RNF2Protein interaction100%H2AC8Protein interaction100%TET2Protein interaction100%ASXL2Protein interaction100%LCORProtein interaction100%EZHIPProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
13%
Lung
8%
Liver
6%
Ovary
5%
Heart
2%
Gene Interaction Network
Click a node to explore
EZH2RNF2H2AC8TET2ASXL2LCOREZHIP
PROTEIN STRUCTURE
Preparing viewer…
PDB5U5T Β· 1.60 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.27Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.17 [0.11–0.27]
RankingsWhere EZH2 stands among ~20K protein-coding genes
  • #80of 20,598
    Most Researched1,553 Β· top 1%
  • #492of 1,025
    FDA-Approved Drug Targets2
  • #1,554of 5,498
    Most Pathogenic Variants39
  • #924of 17,882
    Most Constrained (LOEUF)0.27 Β· top 10%
Genes detectedEZH2
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
EZH2-H3K27me3 mediated KRT14 upregulation promotes TNBC peritoneal metastasis.
PMID: 36446780
Nat Commun Β· 2022
1.00
2
EZH2-mediated development of therapeutic resistance in cancer.
PMID: 38331087
Cancer Lett Β· 2024
0.90
3
EZH2 inhibits senescence-associated inflammation and attenuates intervertebral disc degeneration by regulating the cGAS/STING pathway via H3K27me3.
PMID: 39938633
Osteoarthritis Cartilage Β· 2025
0.86
4
EZH2 promotes B-cell autoimmunity in primary Sjogren's syndrome via METTL3-mediated m6A modification.
PMID: 39577129
J Autoimmun Β· 2024
0.82
5
EZH2 noncanonically binds cMyc and p300 through a cryptic transactivation domain to mediate gene activation and promote oncogenesis.
PMID: 35210568
Nat Cell Biol Β· 2022
0.80