protein
ATP-dependent chromatin remodeler CHD8
Gene
CHD8
Organism
Homo sapiens(9606)
Length
2581 aa
Mass
290,519 Da
CHD8 is an ATP-dependent chromatin remodeler that functions as a transcriptional regulator by sliding nucleosomes along DNA and remodeling chromatin structure (UniProt: Q9HCK8). The protein acts primarily as a transcription repressor, suppressing p53-mediated apoptosis and negatively regulating Wnt signaling through beta-catenin activity. Additionally, CHD8 regulates alternative splicing of genes involved in neuronal differentiation, cell cycle, and DNA repair, and facilitates RNA polymerase III transcription through interaction with ZNF143.
CHD8 plays important roles in neurodevelopmental contexts, regulating alternative splicing critical for neuronal differentiation. Mutations in CHD8 cause intellectual developmental disorder with autism and macrocephaly (IDDAM), an autosomal dominant condition characterized by impaired intellectual development, autism spectrum phenotype, macrocephaly, tall stature, gastrointestinal symptoms, and sleep disturbances (UniProt: Q9HCK8).
CHD8 is classified as SFARI Category 1, indicating high confidence as an autism risk gene (SFARI Cat 1). The strong association between CHD8 mutations and autism spectrum phenotypes, combined with the protein's roles in neuronal gene regulation and splicing, underscores its importance in neurodevelopmental biology.
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
ATP-dependent chromatin-remodeling factor, it slides nucleosomes along DNA; nucleosome sliding requires ATP (PubMed:28533432). Acts as a transcription repressor by remodeling chromatin structure and recruiting histone H1 to target genes. Suppresses p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity. Acts as a negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity. Negatively regulates CTNNB1-targeted gene expression by being recruited specifically to the promoter regions of several CTNNB1 responsive genes. Involved in both enhancer blocking and epigenetic remodeling at chromatin boundary via its interaction with CTCF. Acts as a suppressor of STAT3 activity by suppressing the LIF-induced STAT3 transcriptional activity. Also acts as a transcription activator via its interaction with ZNF143 by participating in efficient U6 RNA polymerase III transcription. Regulates alternative splicing of a core group of genes involved in neuronal differentiation, cell cycle and DNA repair. Enables H3K36me3-coupled transcription elongation and co-transcriptional RNA processing likely via interaction with HNRNPL
Disease associations
Intellectual developmental disorder with autism and macrocephalyIDDAM
An autosomal dominant disorder characterized by impaired intellectual development, a highly penetrant autism spectrum phenotype, and macrocephaly. Other common features include tall stature, gastrointestinal symptoms, distinct facial features, sleep problems, and attention problems.
Sources
Last updated 5/6/2026, 5:25:42 AM