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General Information
Name
Coffin-Siris syndrome 3
FlyBase ID
FBhh0001092
Disease Ontology Term
Parent Disease
Overview

This report describes Coffin-Siris syndrome 3 (CSS3), which is a subtype of Coffin-Siris syndrome; it is also called mental retardation autosomal dominant 15 (MRD15). CSS3 exhibits autosomal dominant inheritance. The human gene implicated in this disease is SMARCB1, which encodes a component of SWI/SNF complexes; these complexes regulate transcription via chromatin remodeling. SMARCB1 encodes a core subunit of SWI/SNF complexes and is thought to be a component of all types of SWI/SNF complexes. There is a single Drosophila gene orthologous to SMARCB1, Dmel\Snr1, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

The human SMARCB1 gene has not been introduced into flies.

Animals homozygous for a loss-of-function mutations of Snr1 typically die during early stages. RNAi-targeted knockdown of Snr1 in the mushroom body (a brain region associated with learning and memory) causes male flies not to reduce courtship attempts after being rejected by a female, a measure of memory formation in flies. Both short-term and long-term memory impairment are observed. Defects in mushroom body morphology are observed, including defects in pruning of the MBγ neurons during pupal morphogenesis. Many physical and genetic interactions have been reported for Dmel\Snr1; see below and in the Snr1 gene report.

[updated Jul. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: Coffin-Siris syndrome
Symptoms and phenotype

Coffin-Siris syndrome is a multiple malformation syndrome characterized by mental retardation associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. Other more variable features may include poor overall growth, craniofacial abnormalities, spinal anomalies, and congenital heart defects (review by Vergano and Deardorff, 2014; pubmed:25169447). [from OMIM:135900; 2019.07.19]

Coffin-Siris syndrome is a multiple malformation syndrome characterized by intellectual disability associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. Other more variable features may include poor overall growth, craniofacial abnormalities, spinal anomalies, and congenital heart defects (review by Vergano and Deardorff, 2014; pubmed:25169447). [from OMIM:135900; 2019.07.19]

Specific Disease Summary: Coffin-Siris syndrome 3
OMIM report

[COFFIN-SIRIS SYNDROME 3; CSS3](https://omim.org/entry/614608)

Human gene(s) implicated

[SWI/SNF-RELATED, MATRIX-ASSOCIATED, ACTIN-DEPENDENT REGULATOR OF CHROMATIN, SUBFAMILY B, MEMBER 1; SMARCB1](https://omim.org/entry/601607)

Symptoms and phenotype
Genetics

Coffin-Siris syndrome-3 (CSS3) is caused by heterozygous mutation in the SMARCB1 gene. [from OIMI:614608 ; 2019.07.20]

Cellular phenotype and pathology
Molecular information

SMARCB1 encodes a core component of the SWI/SNF complex, an ATP-dependent chromatin-remodeling complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively.

Disease synonyms
CSS3
mental retardation autosomal dominant 15
MRD15
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 to 1 Drosophila.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      Snf5-related 1 (Snr1) encodes a core component of the ATP-dependent SWI/SNF chromatin-remodeling complex (Brahma complex). It functions as a tumor suppressor and is required for maintaining normal endosomal trafficking-mediated signaling cascades. [Date last reviewed: 2018-09-13]
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human SMARCB1 (1 Drosophila to 1 human). Dmel\Snr1 shares 63% identity and 74% similarity with the human gene.

      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 (30 groups)
        protein-protein
        Interacting group
        Assay
        References
        experimental knowledge based
        anti tag coimmunoprecipitation, Identification by mass spectrometry, experimental knowledge based, protein cross-linking with a bifunctional reagent
        experimental knowledge based
        anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, pull down, molecular weight estimation by staining, ion exchange chromatography, molecular sieving, peptide massfingerprinting, coimmunoprecipitation, experimental knowledge based
        two hybrid, anti bait coimmunoprecipitation, anti tag western blot, pull down, western blot
        experimental knowledge based
        experimental knowledge based
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        experimental knowledge based, anti bait coimmunoprecipitation, western blot
        pull down, western blot, anti bait coimmunoprecipitation
        anti tag coimmunoprecipitation, protein cross-linking with a bifunctional reagent, Identification by mass spectrometry
        experimental knowledge based
        enzymatic study, autoradiography, western blot, anti tag coimmunoprecipitation, anti tag western blot, two hybrid
        experimental knowledge based
        anti bait coimmunoprecipitation, western blot
        experimental knowledge based
        anti tag coimmunoprecipitation, anti tag western blot, pull down
        anti tag coimmunoprecipitation, western blot
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        experimental knowledge based
        enzymatic study, western blot, anti tag coimmunoprecipitation, anti tag western blot, autoradiography
        two hybrid, experimental knowledge based, protein cross-linking with a bifunctional reagent, Identification by mass spectrometry
        coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, molecular weight estimation by staining
        pull down, western blot, anti bait coimmunoprecipitation
        anti tag coimmunoprecipitation, peptide massfingerprinting
        two hybrid, pull down, western blot
        Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)
        Models Based on Experimental Evidence ( 4 )
        Modifiers Based on Experimental Evidence ( 2 )
        Allele
        Disease
        Interaction
        References
        is exacerbated by LKK102438
        is exacerbated by PtrHM05184
        is exacerbated by aHMC03685
        is exacerbated by biHMS02815
        is exacerbated by FsHMC04698
        is exacerbated by sliJF01229
        is exacerbated by dppJF02455
        is exacerbated by hbKK106631
        is exacerbated by Mmp2GD9489
        is exacerbated by Ndae1GD967
        is exacerbated by NetAGD6299
        is exacerbated by ocHMS01314
        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
        loss of function allele
        P-element activity
        loss of function allele
        CRISPR/Cas9
        References (6)