Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

EHMT1

HGNC:24650 (protein-coding gene)

euchromatic histone lysine methyltransferase 1

Unique Cases:
30
Disorders:
ID, ASD, EP, SCZ, CP
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
EHMT1 is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probab... (Source: Uniprot)
Previous symbols
EHMT1-IT1
Alias symbols
Eu-HMTase1, FLJ12879, KIAA1876, bA188C12.1, KMT1D, FLJ40292, GLP
Chromosomal Location
9q34.3
Genomic Coordinates
GRCh37:chr9:140513444-140730579
GRCh38:chr9:137619001-137836127
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

62.96

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.07

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Definitive

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Strong2 Definitive1

Publications:

Verhoeven WM et. al., Kleefstra syndrome in three adult patients: further delineation of the behavioral and neurological phenotype shows aspects of a neurodegenerative course., Am J Med Genet A, 2011
Rump A et. al., A mosaic maternal splice donor mutation in the EHMT1 gene leads to aberrant transcripts and to Kleefstra syndrome in the offspring., Eur J Hum Genet, 2013
Snoeijen-Schouwenaars FM et. al., Diagnostic exome sequencing in 100 consecutive patients with both epilepsy and intellectual disability., Epilepsia, 2019
Kleefstra T et. al., Loss-of-function mutations in euchromatin histone methyl transferase 1 (EHMT1) cause the 9q34 subtelomeric deletion syndrome., Am J Hum Genet, 2006
Trump N et. al., Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis., J Med Genet, 2016
Willemsen MH et. al., Update on Kleefstra Syndrome., Mol Syndromol, 2012
Matthews AM et. al., Atypical cerebral palsy: genomics analysis enables precision medicine., Genet Med, 2019
Stojanovic JR et. al., Diagnostic and Clinical Utility of Clinical Exome Sequencing in Children With Moderate and Severe Global Developmental Delay / Intellectual Disability., J Child Neurol, 2020
Yang L et. al., Clinical and genetic spectrum of a large cohort of children with epilepsy in China., Genet Med, 2019
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Aspromonte MC et. al., Characterization of intellectual disability and autism comorbidity through gene panel sequencing., Hum Mutat, 2019
Helsmoortel C et. al., Challenges and opportunities in the investigation of unexplained intellectual disability using family-based whole-exome sequencing., Clin Genet, 2015
Grozeva D et. al., Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability., Hum Mutat, 2015
Kirov G et. al., De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia., Mol Psychiatry, 2012
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021
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NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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