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General Information
Name
atrial septal defect 4
FlyBase ID
FBhh0000102
Disease Ontology Term
Parent Disease
Overview

This report describes atrial septal defect 4 (ASD4), which is a sub-type of atrial septal defect (ASD); ASD exhibits autosomal dominant inheritance. The human gene implicated in this disease is TBX20, which encodes a T-box transcription factor. There are 2 high-scoring fly orthologs, H15 and mid, for which classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. The two Drosophila orthologs map within 60kb of each other. They exhibit different expression patterns: H15 is more specifically expressed in cardiac tissues, especially in adults; mid is more broadly expressed, including in early embryos.

The human TBX20 gene has not been introduced into flies.

Most animals homozygous for amorphic mutations of Dmel\mid die during late embryogenesis; among other embryonic phenotypes, a partially penetrant heart phenotype is observed. Mutations of Dmel\H15 have not been well characterized. The penetrance of heart morphogenesis defects in embryos observed for RNAi-induced knockdown of mid is increased in an H15 mutant background.

[updated Apr. 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: atrial septal defect
Symptoms and phenotype
Congenital heart defect characterized by defects of atrial septation; additional heart abnormalities, such as other defects in septation, defects in chamber growth, or insufficiency of the cardiac valves may be present. [from OMIM:611363; 2015.12.18]
Atrial septal defect is characterized by a defect in the interatrial septum allowing pulmonary venous return from the left atrium to pass directly to the right atrium. Depending on the size of the defect, this can result in a spectrum of disease; diagnosis may not occur until adulthood. [from Medscape, http://emedicine.medscape.com/article/162914-overview, 2015.12.18]
Specific Disease Summary: atrial septal defect 4
OMIM report
[ATRIAL SEPTAL DEFECT 4; ASD4](https://omim.org/entry/611363)
Human gene(s) implicated
[T-BOX 20; TBX20](https://omim.org/entry/606061)
Symptoms and phenotype
Atrial septal defect with other congenital heart disease but no conduction defects or noncardiac abnormalities. [from OMIM:611363; 2015.12.18]
Genetics
ASD4 is inherited as an autosomal dominant; it is associated with mutations in the TBX20 gene. [from OMIM:611363; 2015.12.18]
Cellular phenotype and pathology
Molecular information
TBX20 is a member of the T-box family of transcription factors; it has been shown to interact with known cardiac transcription factors. Both long and short isoforms of the Tbx20 protein are produced, differing in the presence or absence of a C-terminal domain (beyond the T-box). [from OMIM:606061; 2015.12.18]
External links
Disease synonyms
ASD4
atrial septal defect
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)
    One to many: 1 human to 2 Drosophila.
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (2)
      Gene Snapshot
      H15 (H15) encodes a T-box transcription factor that regulates the specification of cell fate in the heart and central nervous system. [Date last reviewed: 2019-07-11]
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)
      Ortholog of human TBX20 (2 Drosphila to 1 human). Dmel\H15 shares 35% identity and 47% similarity with the human gene. The 2 fly genes differ in expression patterns: H15 is highly expressed in the heart of the adult fly; low levels of expression are observed in late embryos, primarily in the embryonic dorsal vessel.
      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      In progress.Contributions welcome.
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)
      Ortholog of human TBX20 (2 Drosphila to 1 human). Dmel\mid shares 40% identity and 54% similarity with the human gene. The 2 fly genes differ in expression patterns: mid is expressed in a variety of tissues, including epidermal and neural; among other embryonic structures, expression is observed in the embryonic dorsal vessel.
      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 (18 groups)
      protein-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
      anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
      protein-protein
      Interacting group
      Assay
      References
      bimolecular fluorescence complementation, fluorescence microscopy
      bimolecular fluorescence complementation, fluorescence microscopy
      bimolecular fluorescence complementation, fluorescence microscopy
      bimolecular fluorescence complementation, fluorescence microscopy
      pull down, autoradiography, anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation
      pull down, autoradiography
      bimolecular fluorescence complementation, fluorescence microscopy
      Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
      Models Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Models Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 0 )
      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
      loss of function allele
      Delta2-3 transposase
      loss of function allele
      Delta2-3 transposase
      amorphic allele - molecular evidence
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      loss of function allele
      ethyl methanesulfonate
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      amorphic allele - molecular evidence
      ethyl methanesulfonate
      amorphic allele - molecular evidence
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      References (5)