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General Information
Name
autism spectrum disorder, susceptibility to (postulated), MAPK3-related
FlyBase ID
FBhh0000842
OMIM
Overview

Copy number variants (CNVs) affecting a number of different chromosomal regions have been implicated in the development of autism and schizophrenia. One such region, 16p11.2, includes approximately 25 genes, including mitogen-activated protein kinase 3 (MAPK3), which plays a key role in the MAPK/ERK kinase cascade. MAPK3 is also associated with schizophrenia and/or autism in several GWAS studies. There is a single high-scoring ortholog is Drosophila, rolled (Dmel\rl), for which an extensive number of mutations, including classical amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\rl is also orthologous to the human gene MAPK1.

Several UAS constructs of the wild-type human Hsap\MAPK3 gene have been introduced into flies as part of a large-scale study of human synaptic genes.

In an RNAi-based screen of Drosophila genes orthologous to human genes within the 16p11.2 region, knockdown of Dmel\rl was observed to result in neuroanatomy defects in larval neuromuscular junctions, including multiple and ectopic innervations of presynaptic motor axons into postsynaptic body-wall muscles. A large number of physical and genetic interactions for Dmel\rl have been described; see below and in the rl gene report.

[updated Jun. 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 (postulated), MAPK3-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
MAPK3 is associated with schizophrenia and/or autism in several GWAS studies (see GWAS Catalog, below in 'External links').
Cellular phenotype and pathology
Molecular information
MAPK3 encodes a serine/threonine kinase that is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. MAPK1 (ERK2) and MAPK3 (ERK1) play key roles in this cascade. The activation of MAPK1 or MAPK3 kinase requires its phosphorylation by upstream kinases; upon activation, the MAP kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. [Gene Cards, MAPK3, MAPK1; 2018.07.11]
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 (2 human to 1 Drosophila); multiple more distantly related genes in both species. Dmel\rl is most closely related to MAPK1 and MAPK3.
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      rolled (rl) encodes the mitogen activated protein (MAP) kinase, core component of the RAS/MAPK pathway. It is inactivated by the phosphatases encoded by PTP-ER and Mkp3. It phosphorylates a diverse set of downstream cytoplasmic and nuclear effectors, which impact cell fate decisions in a wide array of tissues. [Date last reviewed: 2019-03-14]
      Gene Groups / Pathways
      Comments on ortholog(s)
      High-scoring ortholog of human MAPK1 and MAPK3 (1 Drosophila to 2 human); multiple more distantly related genes in both species. Dmel\rl shares 76-82% identity and 84-90% 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 (24 groups)
      protein-protein
      Interacting group
      Assay
      References
      pull down, autoradiography, enzymatic study
      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot, pull down, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting
      two hybrid, pull down, autoradiography, comigration in non denaturing gel electrophoresis, western blot, cross-linking study, Identification by mass spectrometry
      anti tag coimmunoprecipitation, anti tag western blot, pull down, autoradiography, anti bait coimmunoprecipitation, western blot
      proximity ligation assay, fluorescence microscopy, anti tag coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      enzymatic study, autoradiography
      enzymatic study, autoradiography
      anti tag coimmunoprecipitation, anti tag western blot, western blot
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti bait coimmunoprecipitation, western blot
      enzymatic study, autoradiography
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      pull down, autoradiography, anti tag coimmunoprecipitation, western blot
      RNA-protein
      Interacting group
      Assay
      References
      rna three hybrid
      Alleles Reported to Model Human Disease (Disease Ontology) (3 alleles)
      Models Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 3 )
      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 - genetic evidence
      ethyl methanesulfonate
      loss of function allele
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      loss of function allele
      loss of function allele
      spontaneous
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      X ray
      amorphic allele - genetic evidence
      X ray
      loss of function allele
      ethyl methanesulfonate
      References (5)