Human genes SHANK1, SHANK2, and SHANK3 have been implicated as susceptibility loci for autism spectrum disorder or related phenotypes in a number of studies (see discussion in MIM:604999). They encode members of a family of postsynaptic scaffolding proteins that are present in the postsynaptic density of glutamatergic synapses. There is a single orthologous gene in Drosophila, Prosap, for which RNAi-targeting constructs, alleles caused by insertional mutagenesis, and amorphic alleles created by targeted recombination have been generated.
None of the human SHANK genes has been introduced into flies.
Animals homozygous for amorphic mutations of Dmel\Prosap are viable and fertile; they exhibit neuroanatomy defective, neurophysiology defective, and locomotor defective phenotypes in larval and adult stages. Examination of the role of Prosap in synapse development at the larval neuromuscular junctions and the adult mushroom body calyx has demonstrated that, in addition to its postsynaptic function, Prosap acts presynaptically in synapse development in the brain.
[updated Mar. 2019 by FlyBase; FBrf0222196]
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996, pubmed:8655659; Risch et al., 1999, pubmed:10417292). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (MIM:608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008; pubmed:18698615). [from MIM:209850; 2017.03.18]
The SFARI Gene autism database ( https:gene.sfari.org ) rates the gene-autism associations for SHANK2 and SHANK3 as high confidence (score 1); for SHANK1 as strong candidate (score 2). [2020.11.05]
SHANK2 is implicated in susceptibility to autism (AUTS17, MIM:613436). SHANK3 is associated with intelligence and cognitive ability in multiple GWAS studies (see GWAS Catalog, below in 'External links').
Shank family proteins contain multiple domains for protein-protein interaction, including ankyrin repeats, and an SH3 domain. They are synaptic proteins that may function as molecular scaffolds in the postsynaptic density of excitatory synapses.
SHANK1, SHANK2 and SHANK3 encode members of a family of postsynaptic scaffolding proteins that are present at glutamatergic synapses in the CNS (Monteiro and Feng, 2017; pubmed:28179641).
Many to one: 3 human to 1 Drosophila. The human genes are SHANK1, SHANK2, and SHANK3.
Many to one: 3 human to 1 Drosophila. The human genes are SHANK1, SHANK2, and SHANK3.
Many to one: 3 human to 1 Drosophila. The human genes are SHANK1, SHANK2, and SHANK3.
Moderate- to high-scoring ortholog of human SHANK1, SHANK2, and SHANK3 (1 Drosophila to 3 human). Dmel\Prosap shares 25-26% identity and 36-38% similarity with the human genes.
