FB2025_01 , released February 20, 2025
Human Disease Model Report: Robinow syndrome, autosomal dominant 2
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General Information
Name
Robinow syndrome, autosomal dominant 2
FlyBase ID
FBhh0001513
Disease Ontology Term
Parent Disease
Overview

This report describes Robinow syndrome, autosomal dominant 2. The human gene implicated is DVL1, which encodes a cytoplasmic phosphoprotein that regulates cell proliferation by transducing Wnt signaling to down-stream effectors. There is one high-scoring fly ortholog, Dmel\dsh, for which multiple genetic reagents, including amorphic or loss of function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis, have been generated.

Multiple UAS constructs of Hsap\DVL1 have been introduced into flies, including wild-type DVL1 and genes carrying frameshift variants implicated in disease; see the 'Disease-Implicated Variants' table below. Overexpression of both wild-type and mutant Hsap\DVL1 isoforms in the developing wing results in disruptions of planar cell polarity; while expression of mutant isoforms result in additional wing structure phenotypes including thickening of the wing veins, absence of the anterior crossvein, ectopic bristles, and creases. Hsap\DVL1 variants also induce ectopic JNK signalling, and disrupt endogenous canonical WNT signalling.

[updated Mar.2024 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: Robinow syndrome, autosomal dominant 2
OMIM report

[ROBINOW SYNDROME, AUTOSOMAL DOMINANT 2; DRS2](https://omim.org/entry/616331)

Human gene(s) implicated

[DISHEVELLED 1; DVL1](https://omim.org/entry/601365)

Symptoms and phenotype

Robinow syndrome is a skeletal dysplasia characterized by distinctive facial features, including midface hypoplasia, hypertelorism, a short nose, and a broad mouth, known collectively as 'fetal facies.' Additional features include mesomelic dwarfism, macrocephaly, gingival hypertrophy, dental malocclusion, genital hypoplasia, and brachydactyly (summary by Bunn et al., 2015, pmid:25817014). Additionally, increased skull bone density and appendicular osteosclerosis are present in patients with DRS2 (White et al., 2015, pmid:25817016; Bunn et al., 2015, pmid:25817014). [from MIM:616331; 2023.04.28]

Genetics

Autosomal dominant Robinow syndrome 2 (DRS2) is caused by heterozygous mutation in the DVL1 gene on chromosome 1p36. [from MIM:616331; 2023.04.28]

Cellular phenotype and pathology
Molecular information

DVL1, the human homolog of the Drosophila dishevelled gene (dsh) encodes a cytoplasmic phosphoprotein that regulates cell proliferation, acting as a transducer molecule for developmental processes, including segmentation and neuroblast specification. [provided by RefSeq, Jul 2008]

The DVL1 gene encodes dishevelled-1, a member of a family of intracellular scaffolding proteins that act downstream of transmembrane WNT receptors. [from MIM:601365; 2023.04.28]

External links
Disease synonyms
autosomal dominant Robinow syndrome-2
DSR2
fetal face syndrome
osteosclerotic Robinow syndrome
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 2 Drosophila); DVL1 has one high-scoring Drosophila ortholog, dsh.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human DVL3, DVL2, and DVL1 (1 Drosophila to 3 human).

    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 (72 groups)
      protein-protein
      Interacting group
      Assay
      References
      pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot, enzymatic study
      anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot
      pull down, western blot
      pull down, western blot, autoradiography
      experimental knowledge based
      anti tag coimmunoprecipitation, anti tag western blot
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      two hybrid, anti tag coimmunoprecipitation, autoradiography, pull down, anti tag western blot, anti bait coimmunoprecipitation, western blot
      experimental knowledge based
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot, pull down
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot, pull down, autoradiography, two hybrid
      anti tag coimmunoprecipitation, western blot, pull down, anti tag western blot
      experimental knowledge based
      experimental knowledge based
      anti tag coimmunoprecipitation, anti tag western blot
      pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot
      two hybrid, anti tag coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, anti tag western blot, two hybrid
      pull down, western blot, two hybrid
      experimental knowledge based
      experimental knowledge based
      anti tag coimmunoprecipitation, anti tag western blot
      anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, western blot
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      anti tag coimmunoprecipitation, anti tag western blot
      experimental knowledge based
      anti tag coimmunoprecipitation, anti tag western blot
      pull down, western blot, autoradiography, two hybrid, anti bait coimmunoprecipitation
      anti tag coimmunoprecipitation, western blot, enzymatic study, autoradiography, peptide massfingerprinting
      pull down, autoradiography, two hybrid, anti bait coimmunoprecipitation, anti tag western blot
      experimental knowledge based
      anti tag coimmunoprecipitation, western blot
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      anti tag coimmunoprecipitation, anti tag western blot
      two hybrid, anti tag coimmunoprecipitation, anti tag western blot
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      pull down, anti tag western blot, anti tag coimmunoprecipitation, autoradiography
      anti tag coimmunoprecipitation, tag visualisation
      Alleles Reported to Model Human Disease (Disease Ontology) (8 alleles)
      Models Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 5 )
      Models Based on Experimental Evidence ( 3 )
      Modifiers Based on Experimental Evidence ( 0 )
      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
      Related mammalian, viral, bacterial, or synthetic 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
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      loss of function allele
      ethyl nitrosourea
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      methyl methanesulfonate
      loss of function allele
      ethyl methanesulfonate
      References (6)