SHANK3 the Synapse and Autism Martha R Herbert M D Ph D Autism spectrum disorders present a paradox of great heterogeneity and great specificity Well over 100 genetic disorders yield an autism phenotype 1 most through specific but distinct mechanisms and many of which affect the synapse SHANK3 SH3 and multiple ankyrin repeat do 24 11 2013 nbsp 0183 32 Both the SHANK2 and SHANK3 genes have strong ties with autism not only as strong candidate genes in terms of mutations but also research reported just this month has shown that approximately 15 of autistic brains in their study sample exhibited hypermethylation of the SHANK3 gene 1 Research on OCD suggests a disturbed essentially 16 10 2007 nbsp 0183 32 Autism MIM 209850 is a neurodevelopmental disorder that manifests within the first 3 years of life Narrowly defined autism has a population prevalence of 1 5–2 cases per 1 000 children and represents the classic pervasive developmental disorder PDD 1 1 The three core characteristics of autism are impairments of reciprocal social 1 2 2013 nbsp 0183 32 1 Introduction Autism spectrum disorder ASD is a neurodevelopmental disorder characterized by two main phenotypic expressions impairments in reciprocal interaction and communication and restricted and stereotyped patterns of interests and behaviors reviewed in Ref ASD affects about 1–2 of children and it is about four times more common in males 15 7 2019 nbsp 0183 32 The results of the behavioral tests therefore showed that SHANK 3 mutants displayed an autism like behavior and impaired social interaction two typical features of

SHANK3 as an autism spectrum disorder associated gene SHANK3 is a synaptic scaffolding protein enriched in the postsynaptic density of excitatory synapses and plays important roles in the formation maturation and maintenance of synapses 23 2 2019 nbsp 0183 32 It s just that zebrafish seem so far removed from real life autism it s heterogeneity complexity and also its humanness The findings published by David James and colleagues 2 kinda changed my mind a little bit Their findings supporting quot mutations in SHANK3 as causal for GI gastrointestinal transit and motility abnormalities quot caught The Shank protein family Shank proteins which include Shanks 1 2 and 3 were first identified in a yeast two hybrid assay using the gua nylate kinase associated protein GKAP also called SAPAP1 DLGAP1 and DAP 1 as bait 1 GKAP is a PSD 95 binding protein that forms an important compo nent of the postsynaptic density PSD where protein 24 5 2011 nbsp 0183 32 Furthermore the Shank complex could be linked to several other proteins regulating actin cytoskeleton dynamics such as β Pix a guanine nucleotide exchange factor for Rac1 and cdc42 small GTPases 18 Abp1 a member of the Arp2 3 complex 17 and cortactin 35 Indeed depletion of the Arp2 3 complex including cortactin Abi2 WAVE–1 N–WASP and Abp1 18 9 2014 nbsp 0183 32 This nearly doubles the previously estimated rate making SHANK3 a top autism gene candidate For comparison a deletion of chromosomal region 16p11 2 one of the strongest risk factors for autism is found in about 1 percent of people with autism

1 2 2013 nbsp 0183 32 SHANK3 is a synaptic scaffolding protein enriched in the postsynaptic density of excitatory synapses and plays important roles in the formation maturation and maintenance of synapses Haploinsufficiency of the SHANK3 gene causes a developmental disorder 22q13 3 deletion syndrome known as Phelan–McDermid syndrome that is characterized Autism spectrum disorders present a paradox of great heterogeneity and great specificity Well over 100 genetic disorders yield an autism phenotype 1 most through specific but distinct mechanisms and many of which affect the synapse SHANK3 SH3 and multiple ankyrin repeat do mains 3 is known to be disrupted in the 22q1327 4 2020 nbsp 0183 32 The mood stabilizing drug lithium eases repetitive behaviors seen in mice missing SHANK3 an autism gene according to a new study The findings 1 suggest lithium merits further study as a treatment for some people with autism even though the drug has troublesome side effects including tremors and impaired memory Lithium is of course a rather difficult A SHANK3 point mutation in three siblings with Autism Spectrum Disorder A Family pedigree depicting the three probands III 1 III 2 III 3 parents their siblings and grandparents Shank 3 Mouse Model of Autism Confidential 2 Background About 2 of people with autism carry harmful mutations in SHANK3 a protein that helps organize the

4 1 2019 nbsp 0183 32 Leblond CS Nava C Polge A Gauthier J Huguet G Lumbroso S et al Meta analysis of SHANK mutations in autism spectrum disorders a gradient of severity in cognitive impairments PLoS Genet Here we present an example of this by studying a missense variant in a well known autism spectrum disorder ASD causing gene SHANK3 We analyzed Shank3 s in vivo phosphorylation profile and identified S685 as one phosphorylation site 12 6 2020 nbsp 0183 32 A mouse study by Craig Powell M D Ph D and colleagues suggests that early genetic rescue may be a potential therapy in autism spectrum disorder or ASD Powell looked at one gene called SHANK3 whose alteration is seen in about 0 5 percent of ASD patients The study is published in eNeuro and was highlighted on the ASD news site Spectrum 11 12 2015 nbsp 0183 32 One such gene known as Shank3 has been linked to both autism and schizophrenia MIT neuroscientists have now shed some light on how a single gene can play a role in more than one disease In a study appearing in the online edition of Neuron they revealed that two different mutations of the Shank3 gene produce some distinct molecular and SHANK3 encodes a protein that is essential for communication between neurons Disruptions in the SHANK3 gene have been shown to lead to autism Joseph Buxbaum of the Mount Sinai School of Medicine and his colleagues have created a