EHMT1

Chr 9AD

euchromatic histone lysine methyltransferase 1

Also known as: EHMT1-IT1, EUHMTASE1, Eu-HMTase1, FP13812, GLP, GLP1, KLEFS1, KMT1D

NCBI Gene: 79813ENSG00000181090UniProt: Q9H9B1OMIM: 607001

The encoded histone methyltransferase methylates lysine-9 of histone H3 to repress gene transcription and may regulate MYC- and E2F-responsive genes involved in cell cycle transition. Loss-of-function mutations cause Kleefstra syndrome 1, an autosomal dominant neurodevelopmental disorder. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the disease mechanism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.071 OMIM phenotype
Clinical Summary— EHMT1
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Gene-Disease Validity (ClinGen)
Kleefstra syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
92 unique Pathogenic / Likely Pathogenic· 341 VUS of 800 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — EHMT1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.07LOEUF
pLI 1.000
Z-score 7.42
OE 0.02 (0.00–0.07)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.16Z-score
OE missense 0.88 (0.83–0.94)
713 obs / 805.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.02 (0.00–0.07)
0≤0.351.4
Missense OE0.88 (0.83–0.94)
0≤0.61.4
Synonymous OE1.22
0≤1.21.6
LoF obs/exp: 1 / 66.1Missense obs/exp: 713 / 805.9Syn Z: -3.17
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveEHMT1-related Kleefstra syndromeLOFAD
DN
0.2299th %ile
GOF
0.3392th %ile
LOF
0.81top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 51% of P/LP variants are LoF · LOEUF 0.07

Literature Evidence

LOFSuch information processing deficits are likely paramount to our understanding of the cognitive and neurological dysfunctions shared across the neurodevelopmental disorders associated with EHMT1 haploinsufficiency.PMID:32954001

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

800 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic63
Likely Pathogenic29
VUS341
Likely Benign283
Benign44
Conflicting20
63
Pathogenic
29
Likely Pathogenic
341
VUS
283
Likely Benign
44
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
33
2
28
0
63
Likely Pathogenic
14
3
11
1
29
VUS
9
305
23
4
341
Likely Benign
0
52
120
111
283
Benign
0
20
3
21
44
Conflicting
—20
Total56382185137780

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

View in ClinVar →

Protein Context — Lollipop Plot

EHMT1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
EHMT1 mediates cellular motility in embryonal rhabdomyosarcoma by activating SOX8 expression.
Bajaj U et al.·Br J Cancer
2025
A Novel Frameshift Variant and a Partial EHMT1 Microdeletion in Kleefstra Syndrome 1 Patients Resulting in Variable Phenotypic Severity and Literature Review.
Tzetis M et al.·Genes (Basel)
2025Open AccessReview
The Histone Methyltransferases EHMT1 and EHMT2 Repress the Expression of Genes Related to Excitability and Cell Death in Oligodendrocyte Progenitors.
Pruvost M et al.·Glia
2025
EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell-Dependent Manner.
Nguyen LL et al.·Mol Cancer Res
2024
Essential roles of histone lysine methyltransferases EZH2 and EHMT1 in male embryo development of Phenacoccus solenopsis.
Tong H et al.·Commun Biol
2024Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients