AP1G1 was first reported in relation to autosomal recessive complex neurodevelopmental disorder in 2021 (Usmani et al., PMID: 34102099). Of note, AP1G1 has also been implicated in autosomal dominant complex neurodevelopmental disorder (Usmani-Riazuddin syndrome, autosomal dominant). The split curation for Usmani-Riazuddin syndrome, autosomal dominant, is assessed separately.
AP1G1-related autosomal recessive complex neurodevelopmental disorder (also known as Usmani-Riazuddin syndrome, autosomal recessive) has been reported in three affected individuals from two unrelated consanguineous families carrying homozygous missense variants functionally characterized in cell culture and zebrafish models (PMID: 34102099). Common features in affected individuals included global developmental delay, hypotonia, speech delay, moderately to severely impaired intellectual development, and spasticity. This gene-disease relationship is also supported by experimental evidence. AP1G1 interacts with other adaptor protein complex 1 (AP-1) proteins, AP1S1/AP1S2, which have been definitively implicated in neurodevelopmental disorders. AP complexes mediate selective intracellular vesicular trafficking and polarized localization of somatodendritic proteins in neurons.
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. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on November 2, 2022 (SOP Version 9).
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.