Human Disease Model Report: Robinow syndrome, autosomal dominant 2

General Information

Name

Robinow syndrome, autosomal dominant 2

FlyBase ID

FBhh0001513

Disease Ontology Term

autosomal dominant Robinow syndrome 2

Parent Disease

OMIM

ROBINOW SYNDROME, AUTOSOMAL DOMINANT 2; DRS2

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]

(OMIM, 2013-)

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]

(OMIM, 2013-)

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]

(FlyBase Curators, 2013-)

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]

(OMIM, 2013-)

External links

Gene2Function (human gene): DVL1
Gene Cards: DVL1
GeneReviews, NCBI Bookshelf: Autosomal Dominant Robinow Syndrome
MedlinePlus (condition): Robinow syndrome
MedlinePlus (gene): DVL1
MARRVEL (human gene): DVL1
NCBI MedGen: Autosomal dominant Robinow syndrome 2 (DRS2)
NCBI (Entrez) gene: DVL1; dishevelled segment polarity protein 1
National Organization for Rare Disorders: Robinow syndrome

Disease synonyms

autosomal dominant Robinow syndrome-2

DSR2

fetal face syndrome

osteosclerotic Robinow syndrome

Related Diseases

Related human health report(s)

Ortholog Information

Human gene(s) in FlyBase

Hsap\DVL1

Human gene (HGNC)

Symbol / Name

DVL1; dishevelled segment polarity protein 1

D. melanogaster ortholog (based on DIOPT)

Dmel\dsh

(DIOPT, 2013-)

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)

Dmel\dsh

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

WNT-TCFC

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

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (72 groups)

dsh

protein-protein

Interacting group

Assay

References

dsh - Abl

pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot, enzymatic study

(Singh et al., 2010)

dsh - arm

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot

(Vuong et al., 2014)

dsh - arr

pull down, western blot

(Yamazaki and Yanagawa, 2003)

dsh - Axn

pull down, western blot, autoradiography

(Capilla et al., 2012, Yamazaki and Yanagawa, 2003)

dsh - Bap60

experimental knowledge based

(Guruharsha et al., 2011)

dsh - baz

anti tag coimmunoprecipitation, anti tag western blot

(Banerjee et al., 2017)

dsh - boca

experimental knowledge based

(Guruharsha et al., 2011)

dsh - brm

experimental knowledge based

(Guruharsha et al., 2011)

dsh - CAP

two hybrid

(Yamazaki and Yanagawa, 2003)

dsh - Cdk8

experimental knowledge based

(Guruharsha et al., 2011)

dsh - CG3008

experimental knowledge based

(Guruharsha et al., 2011)

dsh - CG17002

experimental knowledge based

(Guruharsha et al., 2011)

dsh - CG34159

experimental knowledge based

(Guruharsha et al., 2011)

dsh - cno

two hybrid, anti tag coimmunoprecipitation, autoradiography, pull down, anti tag western blot, anti bait coimmunoprecipitation, western blot

(Johnston et al., 2013, Carmena et al., 2006)

dsh - Cpsf6

experimental knowledge based

(Guruharsha et al., 2011)

dsh - CycA

anti tag coimmunoprecipitation, anti tag western blot

(Darnat et al., 2022)

dsh - DAAM

anti tag coimmunoprecipitation, anti tag western blot, pull down

(Gombos et al., 2015)

dsh - dbo

anti tag coimmunoprecipitation, anti tag western blot

(Strutt et al., 2013)

dsh - dgo

anti tag coimmunoprecipitation, anti tag western blot, pull down, autoradiography, two hybrid

(Jenny et al., 2005)

dsh - dlg1

anti tag coimmunoprecipitation, western blot, pull down, anti tag western blot

(Liu et al., 2016, Garcia et al., 2014)

dsh - ebi

experimental knowledge based

(Guruharsha et al., 2011)

dsh - enc

experimental knowledge based

(Guruharsha et al., 2011)

dsh - ens

anti tag coimmunoprecipitation, anti tag western blot

(Kikuchi et al., 2018)

dsh - Frl

pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot

(Dollar et al., 2016)

dsh - frtz

two hybrid, anti tag coimmunoprecipitation, western blot

(Wang et al., 2017)

dsh - fy

anti tag coimmunoprecipitation, anti tag western blot, two hybrid

(Wang et al., 2017)

dsh - fz

two hybrid

(Wong et al., 2003)

dsh - fz2

pull down, western blot, two hybrid

(Wong et al., 2003, Yamazaki and Yanagawa, 2003)

dsh - Gtpbp2

experimental knowledge based

(Guruharsha et al., 2011)

dsh - ix

experimental knowledge based

(Guruharsha et al., 2011)

dsh - kel

anti tag coimmunoprecipitation, anti tag western blot

(Sun et al., 2024, Strutt et al., 2013)

dsh - Klp64D

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot

(Vuong et al., 2014)

dsh - l(2)gl

anti tag coimmunoprecipitation, western blot

(Kaplan and Tolwinski, 2010)

dsh - Larp4B

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED4

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED6

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED7

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED8

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED10

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED11

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED14

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED15

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED16

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED17

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED18

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED20

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED23

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED25

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED27

experimental knowledge based

(Guruharsha et al., 2011)

dsh - MED30

experimental knowledge based

(Guruharsha et al., 2011)

dsh - meru

anti tag coimmunoprecipitation, anti tag western blot

(Banerjee et al., 2017)

dsh - mor

experimental knowledge based

(Guruharsha et al., 2011)

dsh - mud

anti tag coimmunoprecipitation, anti tag western blot

(Ségalen et al., 2010)

dsh - N

pull down, western blot, autoradiography, two hybrid, anti bait coimmunoprecipitation

(Capilla et al., 2012, Muñoz-Descalzo et al., 2010, Hayward et al., 2005, Ramain et al., 2001, Axelrod et al., 1996)

dsh - Nek2

anti tag coimmunoprecipitation, western blot, enzymatic study, autoradiography, peptide massfingerprinting

(Schertel et al., 2013)

dsh - nkd

pull down, autoradiography, two hybrid, anti bait coimmunoprecipitation, anti tag western blot

(Chan et al., 2008, Waldrop et al., 2006, Rousset et al., 2002, Rousset et al., 2001, Wharton et al., 2001)

dsh - osa

experimental knowledge based

(Guruharsha et al., 2011)

dsh - otk

anti tag coimmunoprecipitation, western blot

(Peradziryi et al., 2011)

dsh - Pa1

experimental knowledge based

(Guruharsha et al., 2011)

dsh - pk

pull down, autoradiography

(Dollar et al., 2016, Jenny et al., 2005, Tree et al., 2002)

dsh - Psi

experimental knowledge based

(Guruharsha et al., 2011)

dsh - Ptip

experimental knowledge based

(Guruharsha et al., 2011)

dsh - RhoGEF2

anti tag coimmunoprecipitation, anti tag western blot

(Warrington et al., 2013)

dsh - sano

two hybrid, anti tag coimmunoprecipitation, anti tag western blot

(Chung et al., 2009)

dsh - Sec24AB

experimental knowledge based

(Guruharsha et al., 2011)

dsh - skd

experimental knowledge based

(Guruharsha et al., 2011)

dsh - Snr1

experimental knowledge based

(Guruharsha et al., 2011)

dsh - Ssdp

experimental knowledge based

(Guruharsha et al., 2011)

dsh - Ubx

two hybrid

(Hsiao et al., 2014)

dsh - Usp10

experimental knowledge based

(Guruharsha et al., 2011)

dsh - Vang

pull down, anti tag western blot, anti tag coimmunoprecipitation, autoradiography

(Humphries et al., 2023, Humphries et al., 2020, Jenny et al., 2005, Bastock et al., 2003)

dsh - yki

anti tag coimmunoprecipitation, tag visualisation

(Varelas et al., 2010)

Alleles Reported to Model Human Disease (Disease Ontology) (8 alleles)

dsh

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

dsh^Q108.UAS

model of neurodegenerative disease

CEA

(Lee et al., 2004)

Modifiers Based on Experimental Evidence ( 5 )

Allele

Disease

Interaction

References

dsh¹

ameliorates autosomal recessive intellectual developmental disorder

modeled by Nab2^ex3

(Corgiat et al., 2022)

ameliorates Schimke immuno-osseous dysplasia

modeled by Marcal1^UAS.cBa

(Morimoto et al., 2016)

dsh³

ameliorates Schimke immuno-osseous dysplasia

modeled by Marcal1^UAS.cBa

(Morimoto et al., 2016)

exacerbates cancer

modeled by Axn^{FGmut.UAS.GFP}

(Mendoza-Topaz et al., 2011)

ameliorates familial adenomatous polyposis 1

modeled by Apc2^f90, Apc^Q8

(Mendoza-Topaz et al., 2011)

dsh⁶

ameliorates Schimke immuno-osseous dysplasia

modeled by Marcal1^UAS.cBa

(Morimoto et al., 2016)

dsh^Q108.UAS

model of neurodegenerative disease

is exacerbated by Hsap\HTT^{N548.Q128.UAS}

(Lee et al., 2004)

dsh^UAS.Tag:MYC

ameliorates tauopathy

modeled by Hsap\MAPT^UAS.1N4R

(Folwell et al., 2010)

ameliorates neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures

modeled by Hsap\IRF2BPL^UAS.cBa

(Marcogliese et al., 2022)

Hsap\DVL1

Models Based on Experimental Evidence ( 3 )

Allele

Disease

Evidence

References

Hsap\DVL1^{1529ΔG.UAS.Tag:FLAG}

model of autosomal dominant Robinow syndrome 2

CEC

(Gignac et al., 2023)

Hsap\DVL1^{1519ΔT.UAS.Tag:FLAG}

model of autosomal dominant Robinow syndrome 2

CEC

(Gignac et al., 2023)

Hsap\DVL1^{1615ΔA.UAS.Tag:FLAG}

model of autosomal dominant Robinow syndrome 2

CEC

(Gignac et al., 2023)

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

Hsap\DVL1^UAS.Tag:FLAG

P{UAS-hDVL1.FLAG}

Hsap\DVL1^{1529ΔG.UAS.Tag:FLAG}

P{UAS-hDVL1.1529DeltaG.FLAG}

Hsap\DVL1^{1519ΔT.UAS.Tag:FLAG}

P{UAS-hDVL1.1519DeltaT.FLAG}

Hsap\DVL1^{1615ΔA.UAS.Tag:FLAG}

P{UAS-hDVL1.1615DeltaA.FLAG}

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

dsh^UAS.Tag:MYC

P{UAS-dsh.myc}

w^*; P{UAS-dsh.myc}1-16

dsh^Q108.UAS

P{UAS-dsh.Q108}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

y¹ v¹; P{TRiP.JF01253}attP2

dsh^JF01254

P{TRiP.JF01254}

y¹ v¹; P{TRiP.JF01254}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMC05863}attP40

dsh^VSH330205

P{VSH330205}

P{VSH330205}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

dsh^b117

loss of function allele

dsh⁸

amorphic allele - genetic evidence

ethyl methanesulfonate

dsh⁶

loss of function allele

ethyl nitrosourea

dsh⁶/FM7a

dsh⁷

amorphic allele - genetic evidence

ethyl methanesulfonate

dsh⁴

loss of function allele

ethyl methanesulfonate

dsh⁷⁵

loss of function allele

dsh⁷⁵ P{neoFRT}19A/FM7a

dsh¹

methyl methanesulfonate

w¹ dsh¹

dsh³

loss of function allele

ethyl methanesulfonate

y¹ w¹ dsh³ f^36a/FM7a

References (6)

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