ArticleAmerican journal of human genetics2018
Histone Lysine Methylases and Demethylases in the Landscape of Human Developmental Disorders.
Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 5 of them syntheses that pooled it.
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Who cites it
182 citing papers in PubMed, 5 syntheses or guidelines pooled it, 271 citations in OpenAlex.
- Meta-analysis of activated neurons reveals dynamic regulation of diverse classes of alternative splicing.Genome research · 2025Pooled it
- Sequencing in over 50,000 cases identifies coding and structural variation underlying atrial fibrillation risk.Nature genetics · 2025Pooled it
- Role of Ash1l in Tourette syndrome and other neurodevelopmental disorders.Developmental neurobiology · 2021Pooled it
- Identification of a novel de novo KMT2B variant in a Greek dystonia patient via exome sequencing genotype-phenotype correlations of all published cases.Molecular biology reports · 2021Pooled it
- Systematic Review and Bioinformatic Analysis of microRNA Expression in Autism Spectrum Disorder Identifies Pathways Associated With Cancer, Metabolism, Cell Signaling, and Cell Adhesion.Frontiers in psychiatry · 2021Pooled it
- Genetic analysis of childhood-onset dystonia-28 caused by a variant (c.5076G>A) in theGlobal medical genetics · 2026Article
- Identification and characterisation of a novel homozygous KDM5A variant associated with severe axial hypotonia, seizures, and cardiac anomalies.Journal of human genetics · 2026Article
- Variable Expressiveness of a Novel PathogenicDiseases (Basel, Switzerland) · 2026Article
- Biallelic inactivating variants in the chromatin remodeler DMAP1 cause a syndromic neurodevelopmental disorder.The Journal of clinical investigation · 2026Article
- Uncultured Amniocytes Enable Rapid and Clinically Informative Prenatal RNA Sequencing for Genetic Diagnosis.International journal of molecular sciences · 2026Article
- Ultra-low oxygen tension duringbioRxiv : the preprint server for biology · 2026Article
- Monoallelic and biallelic KDM5A variants identified in patients with autism spectrum disorder.HGG advances · 2026Article
- Autism-like phenotypes and increased NMDAR2D expression in mice with KDM5B histone lysine demethylase deficiency.Science advances · 2026Article
- MLL3/4 methyltransferases regulate the differentiation of pluripotent stem cells through coordinating glycolysis and mitochondrial respiration.bioRxiv : the preprint server for biology · 2026Article
- Chromatinopathies: clinically overlapping disorders, revealing novel variants and their DNA methylation signatures.Clinical epigenetics · 2026Article
- Novel Variants in KMT2C Further Support a Neurodevelopmental Disorder Distinct From Kleefstra and Kabuki Syndromes.Molecular genetics & genomic medicine · 2026Article
- Review
- De Novo HeterozygousGenes · 2026Review
- Discovery of a Potent, Selective, and In Vivo Efficacious Covalent Inhibitor for Lysine Methyltransferase SETD8.Journal of medicinal chemistry · 2026Article
- Individuals with reported and novel KDM5C variants present with seizures, a feature recapitulated in a Drosophila model.Human molecular genetics · 2026Article
122 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 16 institutions in 4 countries.
Funding
Abstract
Histone lysine methyltransferases (KMTs) and demethylases (KDMs) underpin gene regulation. Here we demonstrate that variants causing haploinsufficiency of KMTs and KDMs are frequently encountered in individuals with developmental disorders. Using a combination of human variation databases and existing animal models, we determine 22 KMTs and KDMs as additional candidates for dominantly inherited developmental disorders. We show that KMTs and KDMs that are associated with, or are candidates for, dominant developmental disorders tend to have a higher level of transcription, longer canonical transcripts, more interactors, and a higher number and more types of post-translational modifications than other KMT and KDMs. We provide evidence to firmly associate KMT2C, ASH1L, and KMT5B haploinsufficiency with dominant developmental disorders. Whereas KMT2C or ASH1L haploinsufficiency results in a predominantly neurodevelopmental phenotype with occasional physical anomalies, KMT5B mutations cause an overgrowth syndrome with intellectual disability. We further expand the phenotypic spectrum of KMT2B-related disorders and show that some individuals can have severe developmental delay without dystonia at least until mid-childhood. Additionally, we describe a recessive histone lysine-methylation defect caused by homozygous or compound heterozygous KDM5B variants and resulting in a recognizable syndrome with developmental delay, facial dysmorphism, and camptodactyly. Collectively, these results emphasize the significance of histone lysine methylation in normal human development and the importance of this process in human developmental disorders. Our results demonstrate that systematic clinically oriented pathway-based analysis of genomic data can accelerate the discovery of rare genetic disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.