EHMT2

Chr 6

euchromatic histone lysine methyltransferase 2

Also known as: BAT8, C6orf30, G9A, GAT8, KMT1C, NG36

NCBI Gene: 10919ENSG00000204371UniProt: Q96KQ7

This gene encodes a methyltransferase that methylates lysine residues of histone H3. Methylation of H3 at lysine 9 by this protein results in recruitment of additional epigenetic regulators and repression of transcription. This gene was initially thought to be two different genes, NG36 and G9a, adjacent to each other in the HLA locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

156
ClinVar variants
13
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EHMT2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 127 VUS of 156 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.45LOEUF
pLI 0.000
Z-score 5.19
OE 0.31 (0.21–0.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.71Z-score
OE missense 0.62 (0.58–0.67)
483 obs / 773.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.31 (0.21–0.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.62 (0.58–0.67)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.90
0≤1.21.6
LoF obs/exp: 20 / 65.2Missense obs/exp: 483 / 773.5Syn Z: 1.41

ClinVar Variant Classifications

156 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic2
VUS127
Likely Benign9
Benign7
11
Pathogenic
2
Likely Pathogenic
127
VUS
9
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
7
0
11
Likely Pathogenic
0
0
2
0
2
VUS
0
123
4
0
127
Likely Benign
0
2
2
5
9
Benign
0
1
1
5
7
Total01301610156

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EHMT2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
EHMT1/EHMT2 in EMT, cancer stemness and drug resistance: emerging evidence and mechanisms.
Nachiyappan A et al.·FEBS J
2022Review
Epigenetic balance ensures mechanistic control of MLL amplification and rearrangement.
Gray ZH et al.·Cell
2023
Novel Truncated Peptide Derived From circCDYL Exacerbates Cardiac Hypertrophy.
Li M et al.·Circ Res
2025
EHMT2-mediated transcriptional reprogramming drives neuroendocrine transformation in non-small cell lung cancer.
Yang C et al.·Proc Natl Acad Sci U S A
2024
EHMT2-mediated R-loop formation promotes the malignant progression of prostate cancer via activating Aurora B.
Zhang Y et al.·Clin Transl Med
2025
Recently discovered EZH2 and EHMT2 (G9a) inhibitors.
Soumyanarayanan U et al.·Future Med Chem
2016Review
Targeting EHMT2/ G9a for cancer therapy: Progress and perspective.
Jan S et al.·Eur J Pharmacol
2021
Expression and prognostic significance of chromatin modulators EHMT2/G9a and KDM2b in acute myeloid leukemia.
Gouda MBY et al.·J Cell Biochem
2022
EHMT2 as a Candidate Gene for an Autosomal Recessive Neurodevelopmental Syndrome.
Carvalho LML et al.·Mol Neurobiol
2025Case report
Targeting EHMT2 reverses EGFR-TKI resistance in NSCLC by epigenetically regulating the PTEN/AKT signaling pathway.
Wang L et al.·Cell Death Dis
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Gut microbiota modulation of epigenetic target EHMT2: Lacticaseibacillus rhamnosus Fb7-311 regulated renal cell carcinoma apoptosis and metastasis.
Lee J et al.·Exp Mol Med
2026
YiQi GuBen formula targets EHMT2 and enhances NEDD4L transcription to combat epithelial-mesenchymal transition and airway remodeling in asthma.
Kong Y et al.·J Ethnopharmacol
2026Functional
Loss of EHMT2 enhances NK cell-driven anti-tumor immunity through TGF-β1 suppression.
Chava S et al.·EMBO Mol Med
2026🔓 Open Access
Coordinated repression of totipotency-associated gene loci by histone methyltransferase EHMT2 via LINE1 regulatory elements.
Chatterjee K et al.·EMBO Rep
2026🔓 Open Access
Gut microbiota-mediated targeting of EHMT2 in individuals of European ancestry: A novel therapeutic approach for Alzheimer's disease.
Yan Y et al.·J Alzheimers Dis
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools