CHD8
Chr 14ADchromodomain helicase DNA binding protein 8
Also known as: AUTS18, HELSNF1, IDDAM
This gene encodes a chromodomain-helicase-DNA binding protein that regulates transcription, promotes cell proliferation, and controls RNA synthesis through epigenetic remodeling. Loss-of-function mutations cause autosomal dominant intellectual developmental disorder with autism and macrocephaly. The protein's critical role in transcriptional regulation explains how haploinsufficiency leads to the neurodevelopmental phenotype.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGExploring the Physiological Mechanisms of Austism Through Organoids
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools