. Author manuscript; available in PMC: 2022 Jun 27.

Published in final edited form as: Nat Rev Cardiol. 2021 Jul 16;19(1):26–42. doi: 10.1038/s41569-021-00587-4

Table 2 |.

Functional assignment of 132 definitive and candidate genes for CHD

Category	Functional class	CHD-associated genes enriched for variant type (%)		Example genes associated with syndromic and non-syndromic CHD
Category	Functional class	Loss of function	Damaging missense	Gene	Phenotype^a
Gene regulation	Chromatin modification	15	19	KMT2D	Kabuki syndrome
				CHD7	CHARGE syndrome
				KAT6B	Genitopatellar syndrome
	Transcription factor	8	8	GATA4	Isolated atrial, ventricular or atrioventricular septal defect, tetralogy of Fallot
	Transcription factor	8	8	TBX5	Holt–Oram syndrome
	mRNA processing	8	3	CDK13	Distinctive faces, intellectual disability
	DNA binding	3	1	CLSPN	Xeroderma pigmentosa
Signalling	Extracellular matrix	8	12	COL3A1	Polymicrogyria
	Cilia	0	1	AMBRA1	Corpus callosum agenesis, seizures, cataracts, pigmentation defects, cardiomyopathy, variable immune defects
	Cytoskeleton	12	13	NF1	Neurofibromatosis
	Signal transduction	29	23	PTPN11	Noonan syndrome
	Signal transduction	29	23	JAG1	Alagille syndrome
Other	Ion binding, transmembrane transport, oxidoreductase activity	18	21	CLCN7	Hypopigmentation, organomegaly, delayed myelination, developmental delays

Genes associated with congenital heart disease (CHD) identified in the analysis shown in FIGS 3 and 4 were mapped to gene ontology terms found in the Gene Ontology database. The gene ontology categorization of 132 genes and the identified variants are provided in Supplementary Table 1.

Phenotypes are detailed at Online Mendelian Inheritance in Man.