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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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EHMT2
euchromatic histone lysine methyltransferase 2
Chromosome 6 Β· 6p21.33
NCBI Gene: 10919Ensembl: ENSG00000204371.12HGNC: HGNC:14129UniProt: A0A024RCN9
330PubMed Papers
0Diseases
0Drugs
7Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of DNA replicationnucleoplasmpeptidyl-lysine dimethylationchromosome condensation
✦AI Summary

EHMT2 is a histone methyltransferase that catalyzes mono- and dimethylation of histone H3 lysine 9 (H3K9me1/me2), establishing epigenetic marks for transcriptional repression through HP1 protein recruitment 1. Beyond histones, EHMT2 methylates non-histone proteins including p53 and DNMT1, linking histone and DNA methylation pathways 2. EHMT2 also mediates H3K56me1 methylation, regulating DNA replication and histone-PCNA interactions 3. Clinically, EHMT2 dysregulation associates with multiple malignancies. In colorectal cancer, EHMT2 inhibition enhances anti-PD1 immunotherapy efficacy by upregulating galectin-7 and converting immunosuppressive microenvironments to T-cell-inflamed ones 4. EHMT2 contributes to epithelial-mesenchymal transition, cancer stemness, and drug resistance across cancer types 5. In Wilms tumor, EHMT2 functions as a prognostic biomarker linked to Wnt/Ξ²-catenin pathway activation 6. Additionally, EHMT2-mediated H3K9me2 balance at the MLL/KMT2A locus controls leukemic amplifications and rearrangements, particularly therapy-induced events 7. In neuronal development, transient EHMT2 inhibition at the progenitor stage accelerates human cortical neuron maturation by releasing epigenetic developmental barriers 8.

Sources cited
1
H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins
PMID: 11316813
2
EHMT2 mediates dimethylation of p53/TP53 at lysine 373
PMID: 20118233
3
EHMT2 mediates monomethylation of H3K56me1 in G1 phase, regulating DNA replication
PMID: 22387026
4
EHMT2 inhibition enhances anti-PD1 immunotherapy by upregulating galectin-7 in microsatellite stable colorectal cancer
PMID: 38065340
5
EHMT1/EHMT2 are aberrantly expressed in cancers and associated with EMT, cellular plasticity and therapy resistance
PMID: 34954891
6
EHMT2 is a prognostic biomarker in Wilms tumor associated with epigenetic regulation and Wnt/Ξ²-catenin pathway
PMID: 40830093
7
EHMT2-mediated H3K9me1/2 balance at MLL/KMT2A locus regulates leukemic amplifications and rearrangements
PMID: 37788669
8
Transient EHMT2 inhibition at progenitor stage primes neurons for rapid acquisition of mature properties
PMID: 38297124
Pathogenic Variants7
NM_006709.5(EHMT2):c.3229G>A (p.Ala1077Thr)Pathogenic
Kleefstra-like syndrome|EHMT2-related Kleefstra-like syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 1077
NM_006709.5(EHMT2):c.3335A>G (p.Asn1112Ser)Pathogenic
Kleefstra-like syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1112
NM_006709.5(EHMT2):c.3472T>C (p.Phe1158Leu)Pathogenic
Kleefstra-like syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1158
NM_006709.5(EHMT2):c.3225_3236del (p.Glu1076_Val1079del)Pathogenic
Kleefstra-like syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1076
NM_006709.5(EHMT2):c.3487_3492del (p.Ser1163_Lys1164del)Pathogenic
Kleefstra-like syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1163
NM_006709.5(EHMT2):c.3485A>G (p.Lys1162Arg)Pathogenic
Kleefstra-like syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1162
NM_006709.5(EHMT2):c.3229G>T (p.Ala1077Ser)Pathogenic
Kleefstra-like syndrome
β˜…β˜†β˜†β˜†β†’ Residue 1077
View on ClinVar β†—
Related Genes
H3-5Protein interaction100%H3C13Protein interaction100%MIER1Protein interaction100%JARID2Protein interaction100%KDM5AProtein interaction100%BANF1Protein interaction100%
Tissue Expression

No tissue expression data available for this gene.

Gene Interaction Network
Click a node to explore
EHMT2H3-5H3C13MIER1JARID2KDM5ABANF1
PROTEIN STRUCTURE
Preparing viewer…
PDB5VSC Β· 1.40 Γ… Β· X-ray
View on RCSB β†—
RankingsWhere EHMT2 stands among ~20K protein-coding genes
  • #992of 20,598
    Most Researched330 Β· top 5%
  • #3,150of 5,498
    Most Pathogenic Variants7
Genes detectedEHMT2
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
An epigenetic barrier sets the timing of human neuronal maturation.
PMID: 38297124
Nature Β· 2024
1.00
2
Galectin-7 Induction by EHMT2 Inhibition Enhances Immunity in Microsatellite Stability Colorectal Cancer.
PMID: 38065340
Gastroenterology Β· 2024
0.90
3
BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility.
PMID: 36864760
Nucleic Acids Res Β· 2023
0.80
4
Mechanism of EHMT2-mediated genomic imprinting associated with Prader-Willi syndrome.
PMID: 40610428
Nat Commun Β· 2025
0.72
5
EHMT1/EHMT2 in EMT, cancer stemness and drug resistance: emerging evidence and mechanisms.
PMID: 34954891
FEBS J Β· 2022
0.70