CHD8 (Q9HCK8) variants and mutations

CHD8 (also known as Q9HCK8) is a human protein-coding gene encoding an ATP-dependent chromatin remodeler protein. It remodels chromatin at neurodevelopmental and cell-cycle regulatory genes and influences expression of many autism-associated pathways. Haploinsufficiency causes a neurodevelopmental syndrome frequently marked by autism-related features, developmental delay, and macrocephaly. This analysis covers 3,741 CHD8 variants and mutations. Of these, 71% have computational variant effect predictions. Disease context includes autism, hereditary disease, and autism spectrum disorder. Example CHD8 variants include M1I, A2V, and D3G.

Variant analysis overview

Gene: CHD8
Protein: Q9HCK8
UniProt accession: Q9HCK8
Organism: Homo sapiens
Variants analyzed: 3741
Variant scope: all variants
Completed: 2026-08-18

Variant and mutation evidence

Variant composition: 3,322 unspecified-consequence records; 1 stop retained variant; 247 missense variants; 125 synonymous variants; 15 frameshift variants; 17 in-frame deletions; 8 in-frame insertions; 2 stop-gained variants; 2 splice-region variants; 2 substitution
Prediction scores: 2,645 variants have prediction scores (71% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: autism, hereditary disease, autism spectrum disorder, Intellectual disability, neurodevelopmental disorder, complex neurodevelopmental disorder, Macrocephaly, Neurodevelopmental delay, developmental disability, Fatigable weakness, Overgrowth, marfanoid habitus and intellectual disability.

Protein structure and variant hotspots

Protein features: 4 domains; 1 binding sites; 22 post-translational modification sites.
Structural context: 515 variants have structural context.
PTM context: 29 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable CHD8 variants

Examples include M1I, A2V, D3G, D3N, P4S, I5M, I5N, D7E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

CHD8 analysis run — CHD8 (3,741 variants) — completed 2026-08-18