ATP-binding cassette, subfamily C, member 9 (ABCC9) was first reported in relation to autosomal dominant Brugada Syndrome in 2014 (Hu et al., PMID 24439875). Variation in ABCC9 has been reported in Cantú Syndrome (ClinGen curated definitive) cases as well as non-syndromic cardiac disease cases. For the non-syndromic cardiac disease cases curated here, features of Brugada Syndrome, atrial fibrillation, early repolarization syndrome, and sudden cardiac arrest have been reported in at least seven cases. All but one of the reported variants are missense with the remaining being a short frame shifting indel. Most of the curated variants have a high population frequency in gnomAD v4.1, and what functional data that is available is not conclusive. Evidence disputing this gene-disease relationship includes case-level data and experimental data. There are two primary isoforms of the coding product, SUR2A and SUR2B. SUR2A is considered to be a primarily cardiac specific isoform; however, while it is expressed in cardiac tissue, expression is not entirely unique to the heart (PMID 8798681). In summary, the evidence supporting the relationship between ABCC9 and autosomal dominant Brugada syndrome has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role ABCC9 plays in this disease. This classification was approved by the ClinGen Hereditary Cardiovascular Disease GCEP on the meeting date October 28, 2025 (SOP Version 11).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.