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EZH2

Chr 7q36.1

enhancer of zeste 2 polycomb repressive complex 2 subunit

Aliases:
EZH1, ENX-1, KMT6, KMT6A
MANE:
ENST00000320356.7
OMIM: 601573 ↗NCBI: 2146 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

  • Childhood solid tumours

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

  • DDG2P

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

  • Embryonal tumour of possible germline origin

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

  • Fetal anomalies

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

  • Intellectual disability

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

  • Skeletal dysplasia

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

  • Childhood solid tumours cancer susceptibility

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

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Disease associations (Open Targets)

  • Weaver syndrome

    0.84

  • diffuse large B-cell lymphoma

    0.61

  • neurodegenerative disease

    0.52

  • follicular lymphoma

    0.52

  • viral infectious disease

    0.49

  • melanoma

    0.46

  • breast carcinoma

    0.45

  • lymphoma

    0.44

  • acute myeloid leukemia

    0.43

  • neoplasm

    0.43

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Histone-lysine N-methyltransferase EZH2

Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene (PubMed:14532106, PubMed:15225548, PubMed:15385962, PubMed:16618801, PubMed:16936726, PubMed:17344414, PubMed:22323599, PubMed:24474760, PubMed:26581166, PubMed:30026490, PubMed:30923826). Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively (PubMed:15231737, PubMed:17210787, PubMed:18285464, PubMed:22323599, PubMed:30923826). Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2 (PubMed:22323599, PubMed:30923826). Compared to EZH1-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation (PubMed:19026781). The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (PubMed:16357870, PubMed:17200670). Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes (PubMed:16179254, PubMed:18086877, PubMed:20935635). EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA (PubMed:23063525). Regulates the circadian clock via histone methylation at the promoter of the circadian genes (PubMed:16717091). Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription (By similarity)

Diseases associated with EZH2

Curated MONDO disease pages that list EZH2 among their top associated genes.

Data sources: HGNC (CC BY 4.0), AlphaFold (CC BY 4.0, Jumper et al. Nature 2021), Genomics England PanelApp (CC BY 4.0), ClinGen, Open Targets (CC0), UniProt.

Not for sole clinical decision-making. Always verify against primary sources.