Submission Details

GATA binding protein 6 (GATA6) was evaluated for autosomal dominant dilated cardiomyopathy (DCM). GATA6 is a member of the GATA family of zinc finger transcription factors. Its role is to direct tissue-specific gene expression during formation of the mammalian heart where it is highly expressed (Huggon IC et al. 1997; PMID: 9294001). To date, defects in GATA6 have been associated with various types of congenital heart disease (Kodo K et al. 2009; PMID: 19666519) and atrial fibrillation (Yang YQ et al. 2012; PMID: 22257684). In a study by Xu L et al. 2014 (PMID: 25119427), two missense GATA6 variants (c.1340G>A; p.C447Y and c.1424A>G; p.H475R) were reported in two DCM pedigrees from China. Dual-luciferase reporter assays in HEK-293 cells showed significantly reduced transcriptional activation by GATA6 proteins with the p.C447Y and p.H475R variants (Xu L et al. 2014; PMID: 25119427). However, due to concerns related to suspect data from the authors, a decision was made by the expert DCM curation panel not to score evidence in this publication. Another study screened a family with DCM by WES and Sanger sequencing and reported a novel GATA6 missense variant (c.985C>T, p.H329Y) in four affected individuals (Khazamipour A et al. 2022; PMID: 35962153). The authors performed in silico molecular dynamics simulation of the wild-type GATA6 structure and the H329Y variant which indicated that the H329Y variant could affect the protein structure (Khazamipour A et al. 2022; PMID: 35962153). There are no other genetic or functional studies implicating GATA6 with DCM. Based on this evidence, the approved classification for this gene is No known disease relationship. This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group on 12/13/2024 (SOP Version 10).