SLC4A3 encodes a plasma membrane anion exchange protein. Genetic evidence supporting SLC4A3 as a SQTS-causing gene is derived from a single publication in which exome sequencing was performed in 2 families, including one large pedigree (PMID 29167417). The same rare genetic variant (p.Arg370His, c.1109G>A) was identified in both families, suggesting they are possibly distantly related. Experimental evidence from in vitro and zebrafish models suggests reduced membrane localization of the mutated protein leads to intracellular alkalinization and shortening of the cardiomyocyte action potential duration. The genetic evidence, including the unbiased gene discovery approach of whole exome sequencing and segregation of the identified genetic variant with a large number of affected individuals within the presented pedigree, was considered strong. However, lack of other publications supporting this gene-disease relationship led to a score in the “moderate” range using the gene curation template. The Expert Panel discussed upgrading the final classification but was divided on this issue with 4 panelists voting for “strong” and 5 for “moderate”.
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.