The serotonin transporter gene (SLC6A4) was considered a candidate gene in autism spectrum disorder (ASD) based on the purported association of common coding and noncoding variants in this gene with ASD. However, these association studies, many of which were performed almost two decades ago, were underpowered, and their findings were not validated when larger samples were analyzed (2006, PMID: 16616719; meta-analysis 2008, PMID: 18286633). Several inherited missense variants identified in unrelated multiplex autism families and initially reported as rare (PMID: 15995945) are observed in gnomAD at high frequency and were not scored as evidence. Experimental evidence is available, including mouse models, but in the absence of human genetic evidence were not utilized in the scoring. In summary, there is no valid genetic evidence to support an association between SLC6A4 and autism spectrum disorder. Approved by the ClinGen ID/Autism Expert Panel 1/6/2021. Note that this gene-disease relationship was originally curated in May 2018 and given a Limited classification. Changes in scoring practices resulted in the classification being updated.
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.