protein
Histone-lysine N-methyltransferase EHMT1
Gene
EHMT1
Organism
Homo sapiens(9606)
Length
1298 aa
Mass
141,466 Da
EHMT1 is a histone-lysine N-methyltransferase that catalyzes mono-, di-, and trimethylation of histone H3 lysine 9 (H3K9me1/2/3) to establish repressive chromatin marks, recruiting HP1 proteins for transcriptional silencing (UniProt: Q9H9B1). The enzyme also weakly methylates H3K27 and methylates non-histone substrates including p53, while functioning independently in DNA methylation processes. EHMT1 participates in cell cycle regulation by silencing MYC- and E2F-responsive genes during G0 phase and contributes to brown and beige adipocyte differentiation through chromatin targeting by PRDM16.
Mutations in EHMT1 cause Kleefstra syndrome 1 (KLEFS1), an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, psychomotor developmental delay, seizures, behavioral abnormalities, facial dysmorphisms, brachymicrocephaly, and congenital cardiac and urogenital defects (UniProt: Q9H9B1). The epigenetic dysfunction resulting from loss of histone methyltransferase activity disrupts normal neuronal development and patterning.
EHMT1 is classified as a syndromic autism-associated gene by SFARI (SFARI Cat S), reflecting its established link to autism spectrum features within the context of Kleefstra syndrome's broader neurodevelopmental phenotype.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Histone methyltransferase that specifically mono-, di- and trimethylates 'Lys-9' of histone H3 (H3K9me1, H3K9me2 and H3K9me3, respectively) in euchromatin (PubMed:12004135). H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones (PubMed:12004135). Also weakly methylates 'Lys-27' of histone H3 (H3K27me) (PubMed:12004135). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently (By similarity). Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1 (PubMed:12004135). During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle (PubMed:12004135). Involved in the differentiation of myoblastic precursors into brown adipose cells: following recruitment to chromatin by PRDM16, mediates formation of H3K9me2 and H3K9me3, inhibiting the expression of white adipose-selective genes (By similarity). Also involved in the differentiation of beige adipocytes from white adipose cells following recruitment by PRDM16 (By similarity). EHMT1 also promotes protein stabilization of PRDM16, by preventing PRDM16 ubiquitination and degradation (By similarity). In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53 (PubMed:20118233). Represses the expression of mitochondrial function-related genes, perhaps by occupying their promoter regions, working in concert with probable chromatin reader BAZ2B (By similarity)
Disease associations
Kleefstra syndrome 1KLEFS1
A form of Kleefstra syndrome, an autosomal dominant disease characterized by variable intellectual disability, psychomotor developmental delay, seizures, behavioral abnormalities, and facial dysmorphisms. KLEFS1 patients additionally manifest brachy(micro)cephaly, congenital heart defects, and urogenital defects.
Sources
Last updated 5/6/2026, 5:24:37 AM