Paediatric disorders - additional genes

Gene: RBFOX2

Green List (high evidence)

Comment on list classification: Details on patient cases in the literature are limited, however, the same clinical phenotype of hypoplastic left heart syndrome is reported in multiple unrelated individuals with monoallelic variants in the RBFOX2 gene.

ClinGen have classified this association as definitive (assessed 14/05/2024) - https://search.clinicalgenome.org/CCID:008203

On this basis, this gene should be promoted to Green at the next GMS panel update.

Created: 20 Oct 2025, 3:36 p.m. | Last Modified: 20 Oct 2025, 3:41 p.m.

Panel Version: 7.17

- PMID: 25205790 - de novo copy number loss that encompasses RBFOX2 in another proband with hypoplastic left heart syndrome

- PMID: 26785492 - three unrelated cases with distinct de novo LOF variants in the RBFOX2 gene and hypoplastic left heart syndrome

- PMID: 28991257 - de novo missense variant identified in a patient with congenital heart disease (conotruncal defects)

- PMID: 36198703 - zebrafish model lacking two Rbfox2 orthologs exhibited ventricular size and contractility deficits, which were rescued by injection of human RBFOX2 mRNA

- PMID: 35137168 - Rbfox2 conditional knockout mouse model showed embryonic heart developmental defects and recapitulated several molecular and phenotypic features hypoplastic left heart syndrome

- PMID: 37165897 - de novo missense variant identified in patient with hypoplastic left heart syndrome
Sources: ClinGen, Literature

Created: 20 Oct 2025, 3:30 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Congenital heart disease, MONDO:0005453; hypoplastic left heart syndrome

Publications

• 26785492
• 25205790
• 28991257
• 35137168
• 37165897