CHD8

Chr 14AD

chromodomain helicase DNA binding protein 8

Also known as: AUTS18, HELSNF1, IDDAM

NCBI Gene: 57680ENSG00000100888UniProt: Q9HCK8OMIM: 610528

This gene encodes a member of the chromodomain-helicase-DNA binding protein family, which is characterized by a SNF2-like domain and two chromatin organization modifier domains. The encoded protein also contains brahma and kismet domains, which are common to the subfamily of chromodomain-helicase-DNA binding proteins to which this protein belongs. This gene has been shown to function in several processes that include transcriptional regulation, epigenetic remodeling, promotion of cell proliferation, and regulation of RNA synthesis. Allelic variants of this gene are associated with autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2016]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder with autism and macrocephalyMIM #615032
AD

Clinical highlights

Gene-disease validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
68
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.08
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — CHD8
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.08LOEUF
pLI 1.000
Z-score 10.12
OE 0.04 (0.02–0.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
5.95Z-score
OE missense 0.56 (0.53–0.59)
806 obs / 1441.3 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?
LoF OE?0.04 (0.02–0.08)
0≤0.351.4
Missense OE?0.56 (0.53–0.59)
0≤0.61.4
Synonymous OE?0.94
0≤1.21.6
LoF obs/exp: 5 / 129.0Missense obs/exp: 806 / 1441.3Syn Z: 1.03

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CHD8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients