Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

CHD8

HGNC:20153 (protein-coding gene)

chromodomain helicase DNA binding protein 8

Unique Cases:
89
Disorders:
ID, ASD, EP, ADHD, SCZ, CP
Last Updated:
January 24, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
CHD8 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
DNA helicase that acts as a chromatin remodeling factor and regulates transcription. 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 th... (Source: Uniprot)
Previous symbols
HELSNF1
Alias symbols
KIAA1564, DUPLIN
Chromosomal Location
14q11.2
Genomic Coordinates
GRCh37:chr14:21853353-21905457
GRCh38:chr14:21385199-21456123
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

11.24

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.08

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

No Classification

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Strong3 Limited1 Definitive1

Publications:

Howrigan DP et. al., Exome sequencing in schizophrenia-affected parent-offspring trios reveals risk conferred by protein-coding de novo mutations., Nat Neurosci, 2020
Husson T et. al., Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use., Transl Psychiatry, 2020
Alotaibi M et. al., A de novo variant of CHD8 in a patient with autism spectrum disorder., Discoveries (Craiova), 2020
Wang T et. al., Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders., Nat Commun, 2020
McCarthy SE et. al., De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability., Mol Psychiatry, 2014
Lee H et. al., Clinical exome sequencing for genetic identification of rare Mendelian disorders., JAMA, 2014
Iossifov I et. al., The contribution of de novo coding mutations to autism spectrum disorder., Nature, 2014
De Rubeis S et. al., Synaptic, transcriptional and chromatin genes disrupted in autism., Nature, 2014
O'Roak BJ et. al., Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders., Science, 2012
Bernier R et. al., Disruptive CHD8 mutations define a subtype of autism early in development., Cell, 2014
Du X et. al., Genetic Diagnostic Evaluation of Trio-Based Whole Exome Sequencing Among Children With Diagnosed or Suspected Autism Spectrum Disorder., Front Genet, 2018
Guo H et. al., Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model., Mol Autism, 2018
Wu H et. al., Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort., Clin Genet, 2020
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Wang T et. al., De novo genic mutations among a Chinese autism spectrum disorder cohort., Nat Commun, 2016
Feliciano P et. al., Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes., NPJ Genom Med, 2019
Beighley JS et. al., Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes., Biol Psychiatry, 2020
Ruzzo EK et. al., Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks., Cell, 2019
Tatton-Brown K et. al., Mutations in Epigenetic Regulation Genes Are a Major Cause of Overgrowth with Intellectual Disability., Am J Hum Genet, 2017
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021
et. al., , ,

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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Autism & Developmental Medicine Institute