EDT1. Novel genes with suggestive evidence for a role in DD.

Six genes with suggestive evidence to be novel DD genes. The number of unrelated patients with independent functional or LoF mutations in the DDD cohort or the wider meta-analysis dataset including DDD patients is listed. The p value reported is the minimum p value from the testing of the DDD dataset and the meta-analysis dataset. The dataset that gave this minimal p value is also reported. Mutations are considered to be clustered if the p value of clustering of functional SNVs is less than 0.01. Predicted haploinsufficiency is reported as a percentile of all genes in the genome, with ~0% being highly likely to be haploinsufficient and 100% very unlikely to be haploinsufficient, based on the prediction score described in Huang et al ²⁶ updated to enable predictions for a higher fraction of genes in the genome. NAA10 is already known to cause an X-linked recessive DD in males, but here we identified missense mutations in females, suggesting a different, X-linked dominant, disorder.

Evidence	Gene	de novos DDD (Missense, LoF)	de novos Meta (Missense, LoF)	P Value	Test	Mutation Clustering	Predicted Haploinsufficiency
De novo enrichment + additional evidence	NAA15	1 (0,1)	3 (0,3)	1.64E-06	Meta	No	7.5%
	ZBTB20	3 (1,2)	3 (1,2)	4.84E-06	DDD	No	0.2%
	NAA10	2 (2,0)	3 (3,0)	8.28E-06	Meta	No	34.1%
	TRIP12	3 (1,2)	4(2,2)	2.13E-05	Meta	No	3.8%
	USP9X	3 (1,2)	3 (1,2)	5.14E-05	DDD	No	3.8%
	KAT6A	2 (0,2)	2 (0,2)	7.91E-05	DDD	No	19.0%