Fig. 1

SHANK3 orthologues are conserved in zebrafish and CRISPR/Cas9-induced frameshift mutations are similar to those found in people with Phelan-McDermid syndrome. a shank3a on chromosome 18 (teal) and shank3b on chromosome 4 (purple) retain synteny with different genes surrounding SHANK3 on chromosome 22 in humans. b Shank3a and Shank3b retain protein binding domains found in humans including Shank/ProSAP N-terminal (SPN), ankyrin repeats, SRC Homology 3 (SH3), postsynaptic density protein/disc large tumor suppressor/zonula occludens-1 protein (PDZ), proline-rich region (PRR), Homer-interaction, cortactin-interaction, actin-binding protein 1 (Abp1), and sterile alpha motif (SAM). Individuals with SHANK3 mutations show a C-terminal bias affecting the largest coding exon preceding the SAM-domain encoding exon (gray cylinder). All indicated mutations show frameshift mutations from people with Phelan-McDermid syndrome above and the two CRISPR generated mutations in zebrafish below. c Raw sequence traces show insertion mutations highlighted in red with corresponding changes in downstream amino acids. Mutations were named according to changes in amino acids (e.g., shank3b isoleucine 915 changed to histidine with 31 frame-shifted amino acids terminating in a stop codon)