Submission Details

Autosomal dominant

04/09/2019

The ABCC9 gene is located on chromosome 12 at 12p12.1 and encodes the ATP binding cassette subfamily C member 9 protein, which is a subunit of ATP-sensitive potassium channels along with KCNJ11 in cardiac and smooth muscle. The ABCC9 gene was first reported in relation to dilated cardiomyopathy in 2004 (15034580: Bienengraeber et al. 2004). Evidence supporting this gene-disease relationship includes limited case-level and experimental data. Three heterozygous variants (one frameshift, one stop-gained, and one missense) in this gene were reported in three unrelated patients (15034580: Bienengraeber et al. 2004; 24503780: Pugh et al. 2014). The mechanism of disease is unknown, but in vitro analyses of the identified variants suggested they result in partial protein mislocalization and abnormal Katp channel responses to ATP and ADP (15034580: Bienengraeber et al. 2004). ABCC9 is expressed in cardiac tissue and homozygous mice with an exon 5 deletion die prematurely and have decreased ejection fraction and cardiac fraction shortening (24648545: Fahrenbach et al. 2014). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.

15034580 24503780 24648545