EHMT2 (Euchromatic Histone Lysine Methyltransferase 2)
A key epigenetic regulator involved in transcriptional repression, chromatin remodeling, and cancer progression.
Gene Information Card
| Symbol | EHMT2 |
|---|---|
| Full Name | Euchromatic Histone Lysine Methyltransferase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.33 |
| NCBI Gene ID | 10919 ncbi.nlm.nih.gov/gene/10919 |
| Ensembl ID | ENSG00000110931 |
| UniProt ID | Q96KQ7 |
| OMIM ID | 604599 |
| HGNC ID | 3250 |
| Aliases | G9A, KMT1C, BAT8, NG36, G9a |
Description
EHMT2 (also known as G9a) encodes a histone methyltransferase that specifically catalyzes the mono- and dimethylation of histone H3 lysine 9 (H3K9me1 and H3K9me2), a repressive chromatin mark. It plays a critical role in transcriptional silencing, heterochromatin formation, and regulation of developmental genes. EHMT2 is frequently overexpressed in various cancers and is implicated in tumor progression, metastasis, and drug resistance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of EHMT2 leads to increased H3K9me2, silencing tumor suppressor genes and promoting cell proliferation, migration, and invasion. | COSMIC; PMID: 25910211 |
| Intellectual disability (EHMT2-related) | Loss-of-function mutations in EHMT2 impair H3K9 methylation, disrupting neuronal gene expression and synaptic function. | ClinVar; PMID: 28965846 |
| Weaver syndrome (overlap) | EHMT2 mutations have been reported in patients with overgrowth and intellectual disability, similar to EZH2-related disorders. | OMIM #604599; PMID: 31006513 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.2 | High |
| Brain (cerebral cortex) | 22.5 | Medium |
| Lung | 15.8 | Medium |
| Liver | 10.3 | Low |
| Heart | 8.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 28.4 | High expression; used in functional studies |
| HEK293 (embryonic kidney) | 19.7 | Moderate expression |
| K562 (leukemia) | 15.2 | Moderate expression |
| MCF7 (breast cancer) | 32.1 | High expression; linked to estrogen receptor signaling |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1102C>T (p.Arg368Trp) | Missense | <0.1% | Loss of methyltransferase activity; associated with intellectual disability (ClinVar) |
| c.1745G>A (p.Arg582Gln) | Missense | <0.1% | Reduced H3K9me2; reported in Weaver-like syndrome (ClinVar) |
| Amplification (copy number gain) | Copy number gain | ~5% in breast cancer | Increased EHMT2 expression; poor prognosis (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the SET domain (e.g., p.Arg368Trp) abolish catalytic activity, leading to global reduction of H3K9me2 and derepression of silenced genes.
Gain of Function (GOF)
Gene amplification or overexpression results in excessive H3K9me2, silencing tumor suppressors and promoting oncogenic pathways.
Dominant Negative (DN)
Not well documented; some missense variants may interfere with wild-type EHMT2 dimerization, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • nucleus (GO:0005634) | • protein binding (GO:0005515) |
| • histone-lysine N-methyltransferase activity (GO:0018024) | • histone H3-K9 methylation (GO:0035098) |
| • negative regulation of transcription by RNA polymerase II (GO:0000122) | • chromatin organization (GO:0006325) |
Pathways
• Epigenetic regulation of gene expression (Reactome R-HSA-212300)
• H3K9 methylation (Reactome R-HSA-3214841)
• Transcriptional misregulation in cancer (KEGG hsa05202)
Protein Summary
EHMT2 (G9a) is a 1,210-amino-acid protein containing an N-terminal ankyrin repeat domain and a C-terminal SET domain responsible for methyltransferase activity. It forms homodimers and heterodimers with EHMT1 (GLP) to catalyze H3K9me1/2. The protein also methylates non-histone substrates such as p53 and DNMT1, influencing cell cycle, apoptosis, and DNA methylation. EHMT2 is a therapeutic target in cancer; small-molecule inhibitors (e.g., BIX-01294, UNC0638) are under investigation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EHMT2 Knockout HEK293 Cell Line | EDJ-KQ3261 | Human | 10919 | Details Get a Quote |
| EHMT2 Knockout HeLa Cell Line | EDJ-KQ23418 | Human | 10919 | Details Get a Quote |
| EHMT2 Knockout A-549 Cell Line | EDJ-KQ24807 | Human | 10919 | Details Get a Quote |
| EHMT2 Knockout HCT 116 Cell Line | EDJ-KQ24808 | Human | 10919 | Details Get a Quote |
