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General Information
Name
autism spectrum disorder, susceptibility to, SHANK-related
FlyBase ID
FBhh0000793
OMIM
Overview

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 OMIM: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]

Disease Summary Information
Parent Disease Summary: autism spectrum disorder, susceptibility to
Symptoms and phenotype
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 (OMIM: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 OMIM:209850; 2017.03.18]
Specific Disease Summary: autism spectrum disorder, susceptibility to, SHANK-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
SHANK2 is implicated in susceptibility to autism (AUTS17, OMIM:613436). SHANK3 is associated with intelligence and cognitive ability in multiple GWAS studies (see GWAS Catalog, below in 'External links').
Cellular phenotype and pathology
Molecular information
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).
External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)
    Many to one: 3 human to 1 Drosophila. The human genes are SHANK1, SHANK2, and SHANK3.
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)
    Many to one: 3 human to 1 Drosophila. The human genes are SHANK1, SHANK2, and SHANK3.
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)
    Many to one: 3 human to 1 Drosophila. The human genes are SHANK1, SHANK2, and SHANK3.
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      Prosap (Prosap) encodes a member of SH3 and multiple ankyrin repeat domain (SHANK) family of genes that encode synaptic scaffolding proteins. It regulates synaptic growth and development, including the structure of the neuromuscular junction and synapses of the calyx, and olfactory acuity. [Date last reviewed: 2019-03-21]
      Gene Groups / Pathways
        Comments on ortholog(s)
        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.
        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Synthetic Gene(s) Used (0)
        Summary of Physical Interactions (1 groups)
        protein-protein
        Interacting group
        Assay
        References
        Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
        Models Based on Experimental Evidence ( 0 )
        Allele
        Disease
        Evidence
        References
        Modifiers Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Interaction
        References
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Selected mammalian transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        amorphic allele - molecular evidence
        ends-out gene targeting
        amorphic allele - molecular evidence
        TALEN
        amorphic allele - molecular evidence
        CRISPR/Cas9
        amorphic allele - genetic evidence
        minos activity
        References (9)