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General Information
Name
autism spectrum disorder, susceptibility to, CSDE1-related
FlyBase ID
FBhh0001161
OMIM
Overview

The human RNA-binding protein (RBP) gene CSDE1 was identified in a genome-wide association study as a potential susceptibility locus for an autism spectrum disorder (ASD; FBhh0000514.)

There is a high-ranking ortholog of human CSDE1 in Drosophila, Unr. Several alleles of Unr have been generated, including RNAi targeting constructs, fluorescently tagged constructs, and misexpression constructs generated by insertional mutagenesis.

The human gene Hsap\CSDE1 has been introduced into flies.

In Unr loss-of-function hypomorphs, the neuromuscular junction (NMJ) of A1-7 lateral longitudinal muscle 1 shows an increase in both total bouton number and satellite bouton number, as well as defective endocytosis. Electrophysiological assays show that Unr hypomorphs have impaired synaptic transmission (lower excitatory junction potential frequency). Pan-neuronal RNAi knockdown shows a similar synaptic overgrowth phenotype to the hypomorph. This can be rescued by overexpression of Unr or the human gene Hsap\CSDE1, indicating that Hsap\CSDE1 it is capable of heterologous rescue (functional complementation).

[updated Jan 2020 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, CSDE1-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

The most consistent phenotypes of individuals with CSDE1 mutations include ASD, intellectual disability (ID), delayed speech, and delayed motor development. Of the 16 individuals for whom cognitive ability was assessed, 14 had a diagnosis of mild-to-severe ID and the remaining 2 patients had cognitive performance in the below-average range of intellectual functioning. In addition, we noted several common comorbidities : recurrent seizures or epilepsy (44%), increased head circumference or macrocephaly (43%), anxiety behavior (54%), attention-deficit/hyperactivity disorder (69%), variable ocular abnormalities (54%), hand development abnormalities (40%), and hypotonia (46%). (Adapted from Guo et al. 2019 and references therein, FBrf0243646.)

Genetics

The SFARI Gene autism database ( https:gene.sfari.org ) rates the gene-autism association for CSDE1 as high confidence (score 1). [2020.11.05]

Cellular phenotype and pathology
Molecular information

Enrichment and pathway analyses have shown that ASD risk genes are frequently associated with transcriptional regulation, especially targets of RNA binding proteins (RBPs) such as CSDE1. RBPs mainly function in posttranscriptional gene regulation, which is essential to sustain cellular metabolism, and to coordinate maturation, transport, stability, and degradation of all classes of RNAs. CSDE1, also known as UNR, encodes a highly conserved RBP containing five cold-shock domains and has been implicated in both neuronal migration and differentiation. (Adapted from Guo et al. 2019 and references therein, FBrf0243646.)

External links
Disease synonyms
ASD
autism spectrum disorder, susceptibility to (postulated), CSDE1-related
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human gene to 1 Drosophila gene.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    Upstream of N-ras (Unr) encodes an RNA binding protein that functions as an RNA chaperone and translation regulator. It performs opposing, sex-specific, roles in X-chromosome dosage compensation by regulating lncRNA:roX2 RNA conformation in males and msl-2 mRNA translation in females. [Date last reviewed: 2019-03-21]
    Gene Groups / Pathways
      Comments on ortholog(s)

      Single, high-scoring ortholog of Hsap\CSDE1.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (17 groups)
        RNA-protein
        Interacting group
        Assay
        References
        anti bait coimmunoprecipitation, quantitative reverse transcription pcr
        anti bait coimmunoprecipitation, quantitative reverse transcription pcr, clip-seq
        anti bait coimmunoprecipitation, quantitative reverse transcription pcr
        anti bait coimmunoprecipitation, quantitative reverse transcription pcr
        anti bait coimmunoprecipitation, quantitative reverse transcription pcr, electrophoretic mobility shift assay, autoradiography, pull down, western blot
        pull down, western blot, electrophoretic mobility shift assay, autoradiography, affinity chromatography technology, static light scattering, Identification by mass spectrometry, isothermal titration calorimetry, predetermined participant, anti bait coimmunoprecipitation, quantitative reverse transcription pcr, x-ray crystallography, nucleic acid uv cross-linking assay
        anti bait coimmunoprecipitation, quantitative reverse transcription pcr
        anti bait coimmunoprecipitation, quantitative reverse transcription pcr
        protein-protein
        Interacting group
        Assay
        References
        anti bait coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot
        pull down, western blot, anti bait coimmunoprecipitation
        anti bait coimmunoprecipitation, autoradiography, electrophoretic mobility shift assay, affinity chromatography technology, Identification by mass spectrometry, pull down, western blot
        Alleles Reported to Model Human Disease (Disease Ontology) (3 alleles)
        Models Based on Experimental Evidence ( 2 )
        Allele
        Disease
        Evidence
        References
        Modifiers Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Interaction
        References
        Models Based on Experimental Evidence ( 0 )
        Allele
        Disease
        Evidence
        References
        Modifiers Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Interaction
        References
        Alleles Representing Disease-Implicated Variants
        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
        References (3)