EHMT2 — Euchromatic Histone Lysine Methyltransferase 2

EHMT2 — Euchromatic Histone Lysine Methyltransferase 2

<div class="infobox infobox-gene">
<div class="infobox-header">EHMT2</div>
<div class="infobox-image"> [@tachibana2002]
[Structure](https://www.uniprot.org/uniprot/Q96KQ7)
</div>
<table>
<tr><th>Full Name</th><td>Euchromatic Histone Lysine Methyltransferase 2</td></tr>
<tr><th>Symbol</th><td>EHMT2 (also G9a)</td></tr>
<tr><th>Chromosomal Location</th><td>6p21.1</td></tr>
<tr><th>NCBI Gene ID</th><td>[10993](https://www.ncbi.nlm.nih.gov/gene/10993)</td></tr>
<tr><th>OMIM</th><td>[618586](https://www.omim.org/entry/618586)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000108799</td></tr>
<tr><th>UniProt ID</th><td>[Q96KQ7](https://www.uniprot.org/uniprot/Q96KQ7)</td></tr>
<tr><th>Associated Diseases</th><td>Congenital disorder of glycosylation, neurodegeneration, intellectual disability</td></tr>
</table>
</div>

Overview

EHMT2 — Euchromatic Histone Lysine Methyltransferase 2

<div class="infobox infobox-gene">
<div class="infobox-header">EHMT2</div>
<div class="infobox-image"> [@tachibana2002]
[Structure](https://www.uniprot.org/uniprot/Q96KQ7)
</div>
<table>
<tr><th>Full Name</th><td>Euchromatic Histone Lysine Methyltransferase 2</td></tr>
<tr><th>Symbol</th><td>EHMT2 (also G9a)</td></tr>
<tr><th>Chromosomal Location</th><td>6p21.1</td></tr>
<tr><th>NCBI Gene ID</th><td>[10993](https://www.ncbi.nlm.nih.gov/gene/10993)</td></tr>
<tr><th>OMIM</th><td>[618586](https://www.omim.org/entry/618586)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000108799</td></tr>
<tr><th>UniProt ID</th><td>[Q96KQ7](https://www.uniprot.org/uniprot/Q96KQ7)</td></tr>
<tr><th>Associated Diseases</th><td>Congenital disorder of glycosylation, neurodegeneration, intellectual disability</td></tr>
</table>
</div>

Overview

EHMT2 (also known as G9a or KMT1C) is a histone lysine methyltransferase that catalyzes the mono- and dimethylation of histone H3 at lysine 9 (H3K9me1/2). It is a crucial epigenetic regulator involved in transcriptional repression, embryonic development, and cellular differentiation. EHMT2 forms a heterodimer with EHMT1 (GLP) and together they constitute the G9a/GLP complex, which is the primary H3K9 methyltransferase in mammalian cells.

In the central nervous system, EHMT2 plays critical roles in neuronal development, synaptic plasticity, and memory formation. Dysregulation of EHMT2 activity has been implicated in multiple neurodegenerative diseases, making it a potential therapeutic target.

Function

EHMT2 (also known as G9a or KMT1C) is a histone lysine methyltransferase that catalyzes the mono- and dimethylation of histone H3 at lysine 9 (H3K9me1/2). It is a crucial epigenetic regulator involved in transcriptional repression, embryonic development, and cellular differentiation.

Enzymatic Activity

• H3K9 Methylation: Adds H3K9me1/2 marks associated with gene silencing
• H3K27 Methylation: Can also methylate H3K27
• Non-histone Targets: Methylates various non-histone proteins including [TP53](/genes/tp53), [RELA](/genes/rela), and [WIZ](/genes/wiz)

Protein Domains

• SET domain: Catalytic methyltransferase domain
• Ankyrin repeat domains: Protein-protein interactions
• Pre-SET domain: Required for activity

Disease Associations

Neurodegeneration

• Elevated G9a activity observed in AD brain tissue
• Contributes to epigenetic silencing of synaptic plasticity genes
• H3K9me2 marks increase at promoters of memory-related genes
• References: [Lubitz et al., 2022](https://doi.org/10.1038/s41593-022-01024-6), [Zh 2018](/eng et al.,https://doi.org/10.1016/j.neurobiolaging.2018.01.018)

• G9a-mediated repression affects dopamine neuron survival
• May contribute to [alpha-synuclein](/proteins/alpha-synuclein) toxicity
• References: [Pifl et al., 2014](https://doi.org/10.1007/s00401-014-1251-9)

• Dysregulated H3K9 methylation in HD models
• Contributes to transcriptional dysfunction
• References: [Vashishtha et al., 2013](https://doi.org/10.1016/j.neuron.2013.04.036)

• Altered epigenetic regulation in motor [neurons](/entities/neurons)
• References: [Chestnut et al., 2011](https://doi.org/10.1016/j.neurobiolaging.2010.03.004)

Other Conditions

• Congenital Disorder of Glycosylation (CDG): EHMT2 mutations cause CDG
• Intellectual Disability: Epigenetic dysregulation affects neurodevelopment
• Cancer: Overexpression in various cancers

Expression

Brain Expression

• Cerebral [Cortex](/brain-regions/cortex): Moderate to high expression in pyramidal neurons
• [Hippocampus](/brain-regions/hippocampus): High expression in CA1-CA3 regions and dentate gyrus
• Basal Ganglia: Present in striatal neurons
• Cerebellum: Expressed in Purkinje cells
• Allen Brain Atlas: [EHMT2 expression data](https://human.brain-map.org/molecule/show?molecule_id=126957522)

Cellular Localization

• Nuclear: Primary localization in euchromatin
• Cytoplasmic: Minor fraction in cytoplasm

Therapeutic Targeting

G9a/EHMT2 inhibitors are being explored as therapeutic agents:

Potential Applications

• Memory Enhancement: G9a inhibition reverses age-related memory decline in mice
• Neuroprotection: May protect against [amyloid-beta](/proteins/amyloid-beta) toxicity
• Transcription Therapy: Restoring expression of silenced genes

See Also

• [G9a Protein](/proteins/atg9a)
• [Epigenetic Mechanisms in Neurodegeneration](/content/mechanisms)
• [H3K9 Methylation Pathway](/genes/th)
• [Transcription Factors in AD](/diseases/alzheimers-disease#transcriptional-dysregulation)

External Links

• [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/)
• [UniProt](https://www.uniprot.org/)
• [OMIM](https://www.omim.org/)
• [GeneCards](https://www.genecards.org/)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving EHMT2 — Euchromatic Histone Lysine Methyltransferase 2 discovered through SciDEX knowledge graph analysis: