CHD8

chromodomain helicase DNA binding protein 8, the group of Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 14:21385194-21456126

Previous symbols: [ "HELSNF1" ]

Links

ENSG00000100888

∙ NCBI:57680 ∙ OMIM:610528 ∙ HGNC:20153 ∙ Uniprot:Q9HCK8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autism (Strong), mode of inheritance: AD
intellectual disability (Strong), mode of inheritance: AD
congenital myasthenic syndrome (Limited), mode of inheritance: AD
intellectual developmental disorder with autism and macrocephaly (Strong), mode of inheritance: AD
complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with autism and macrocephaly	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	21572417; 22495306; 22495309; 22495311; 22521361; 23160955; 24998929; 31001818

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHD8 gene.

not_provided (1277 variants)
Inborn_genetic_diseases (341 variants)
Intellectual_developmental_disorder_with_autism_and_macrocephaly (197 variants)
CHD8-related_disorder (67 variants)
not_specified (46 variants)
Intellectual_disability (16 variants)
Autism_spectrum_disorder (15 variants)
Neurodevelopmental_disorder (7 variants)
Complex_neurodevelopmental_disorder (5 variants)
See_cases (5 variants)
Autism (2 variants)
Macrocephaly (2 variants)
Developmental_disorder (2 variants)
Motor_delay (1 variants)
CHD8-associated_Neurodevelopmental_syndrome (1 variants)
Congenital_ptosis (1 variants)
Delayed_speech_and_language_development (1 variants)
Marfanoid_habitus_and_intellectual_disability (1 variants)
Rare_genetic_intellectual_disability (1 variants)
Genetic_developmental_and_epileptic_encephalopathy (1 variants)
Tall_stature (1 variants)
Overgrowth (1 variants)
Neurodevelopmental_delay (1 variants)
Developmental_delay (1 variants)
Fatigable_weakness (1 variants)
Increased_muscle_fatiguability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHD8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001170629.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	2 clinvar		13 clinvar	269 clinvar	13 clinvar	297
missense	8 clinvar	27 clinvar	711 clinvar	134 clinvar	3 clinvar	883
nonsense	51 clinvar	20 clinvar	3 clinvar			74
start loss			1			1
frameshift	55 clinvar	25 clinvar	4 clinvar			84
splice donor/acceptor (+/-2bp)	10 clinvar	15 clinvar	6 clinvar			31
Total	126	87	738	403	16

Highest pathogenic variant AF is 0.00000827495

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHD8	protein_coding	protein_coding	ENST00000399982	37	70933

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.62e-18	124641	0	12	124653	0.0000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.95	806	1.44e+3	0.559	0.0000827	16853
Missense in Polyphen		166	516.11	0.32164		5933
Synonymous	1.03	473	502	0.941	0.0000254	5048
Loss of Function	10.1	5	129	0.0388	0.00000800	1415

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000154	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.0000465	0.0000464
European (Non-Finnish)	0.0000267	0.0000265
Middle Eastern	0.0000556	0.0000556
South Asian	0.0000984	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: 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 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. {ECO:0000255|HAMAP- Rule:MF_03071, ECO:0000269|PubMed:17938208, ECO:0000269|PubMed:18378692}.;
Disease: DISEASE: Autism 18 (AUTS18) [MIM:615032]: A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation. {ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:26637798}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Pathway: Wnt signaling pathway - Homo sapiens (human);Wnt Signaling Pathway;Signaling by WNT;Signal Transduction;Deactivation of the beta-catenin transactivating complex;Regulation of nuclear beta catenin signaling and target gene transcription;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

pRec: 0.120

Intolerance Scores

loftool: 0.121
rvis_EVS: -2.34
rvis_percentile_EVS: 1.18

Haploinsufficiency Scores

pHI: 0.711
hipred: Y
hipred_score: 0.785
ghis: 0.621

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: N
essential_gene_gene_trap: K
gene_indispensability_pred: E
gene_indispensability_score: 0.948

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Chd8
Phenotype: growth/size/body region phenotype; cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: chd8
Affected structure: enteric neuron
Phenotype tag: abnormal
Phenotype quality: decreased amount

Gene ontology

Biological process: negative regulation of transcription by RNA polymerase II;in utero embryonic development;brain development;Wnt signaling pathway;DNA duplex unwinding;social behavior;ATP-dependent chromatin remodeling;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of transcription by RNA polymerase III;digestive tract development;prepulse inhibition;negative regulation of canonical Wnt signaling pathway;negative regulation of fibroblast apoptotic process
Cellular component: nucleus;nucleoplasm;protein-containing complex;MLL1 complex
Molecular function: p53 binding;DNA binding;DNA helicase activity;chromatin binding;protein binding;ATP binding;beta-catenin binding;DNA-dependent ATPase activity;methylated histone binding;histone binding;armadillo repeat domain binding