protein
Histone-lysine N-methyltransferase ASH1L
Gene
ASH1L
Organism
Homo sapiens(9606)
Length
2969 aa
Mass
332,790 Da
ASH1L (Histone-lysine N-methyltransferase ASH1L) is a histone methyltransferase that catalyzes trimethylation of histone H3 at lysine 36 (H3K36me3), a key epigenetic modification involved in transcriptional regulation (UniProt: Q9NR48). The protein also exhibits in vitro monomethylase activity at histone H3 lysine 9, though the physiological relevance of this activity remains unclear.
ASH1L is associated with intellectual developmental disorder, autosomal dominant 52 (MRD52), characterized by significantly below-average general intellectual functioning with impairments in adaptive behavior during development (MIM 617796). Loss-of-function or missense variants in ASH1L disrupt normal chromatin remodeling processes critical for neurodevelopmental gene expression.
ASH1L is classified as SFARI Category 1 (high confidence ASD risk gene), indicating strong evidence for involvement in autism spectrum disorder pathogenesis (SFARI Cat 1). The epigenetic dysfunction caused by ASH1L mutations likely contributes to both intellectual disability and autistic features through altered chromatin structure affecting neurodevelopmental pathways.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
High confidence — strong genetic evidence from multiple studies
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 specifically trimethylating 'Lys-36' of histone H3 forming H3K36me3 (PubMed:21239497). Also monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro (By similarity). The physiological significance of the H3K9me1 activity is unclear (By similarity)
Disease associations
Intellectual developmental disorder, autosomal dominant 52MRD52
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
Sources
Last updated 5/6/2026, 5:25:51 AM