Intellectual developmental disorder with autism and macrocephaly: genes and variants
Intellectual developmental disorder with autism and macrocephaly is linked to 1 analyzed protein (CHD8). 10 DNA variants are known to cause it; 89 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Intellectual developmental disorder with autism and macrocephaly
CHD8: ATP-dependent chromatin remodeler CHD8
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.
10 disease-causing and 89 uncertain variants in CHD8 are linked to Intellectual developmental disorder with autism and macrocephaly.
Where Intellectual developmental disorder with autism and macrocephaly variants cluster
- CHD8 Helicase C-terminal (positions 1137–1288): 3 of 10 disease-causing changes, 5.1× more than its size predicts.
Known disease-causing variants in Intellectual developmental disorder with autism and macrocephaly
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CHD8 V644A | 644 | Chromo 1 | Disease-causing (★) |
| CHD8 L1100P | 1100 | Disease-causing (★) | |
| CHD8 R1242Q | 1242 | Helicase C-terminal | Disease-causing (★) |
| CHD8 E1480D | 1480 | Disease-causing (★) | |
| CHD8 R812Q | 812 | Disease-causing (★) | |
| CHD8 E837K | 837 | Helicase ATP-binding | Disease-causing (★) |
| CHD8 R2333C | 2333 | Disease-causing (★) | |
| CHD8 E2099K | 2099 | Interaction with FAM124B | Disease-causing (★) |
| CHD8 Y1168N | 1168 | Helicase C-terminal | Disease-causing |
| CHD8 C1208F | 1208 | Helicase C-terminal | Disease-causing |
Which prediction tools work for Intellectual developmental disorder with autism and macrocephaly
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- PolyPhen-2: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 90 out of 100
- CATVariant: 80 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Diseases related to Intellectual developmental disorder with autism and macrocephaly
- Complex neurodevelopmental disorder, also linked to CHD8
- Autism, also linked to CHD8
- Paediatric disorders, also linked to CHD8
Frequently asked questions
Which genes are linked to Intellectual developmental disorder with autism and macrocephaly?
In CATVariant, Intellectual developmental disorder with autism and macrocephaly is linked to 1 analyzed protein: CHD8 (ATP-dependent chromatin remodeler CHD8).
How many genetic variants are linked to Intellectual developmental disorder with autism and macrocephaly?
103 variants: 10 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 89 are of uncertain significance or have conflicting reports.
Which uncertain variants in Intellectual developmental disorder with autism and macrocephaly look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Intellectual developmental disorder with autism and macrocephaly?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.90, based on 8 disease-causing and 107 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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