FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: Cornelia de Lange syndrome 3
Open Close
General Information
Name
Cornelia de Lange syndrome 3
FlyBase ID
FBhh0001588
Disease Ontology Term
Parent Disease
OMIM
CORNELIA DE LANGE SYNDROME 3 WITH OR WITHOUT MIDLINE BRAIN DEFECTS; CDLS3
Overview

This report describes Cornelia de Lange syndrome 3, a subtype of Cornelia de Lange syndrome. The human gene implicated is SMC3, which encodes structural maintenance of chromosomes 3, a member of the cohesin multiprotein complex required for sister chromatid cohesion. There is one high-scoring fly ortholog, Dmel\SMC3, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

The human gene SMC3 has not yet been introduced into flies.

Ubiquitous RNAi knockdown of Dmel\SMC3 resulted in an increase in startle response time, an increase in spontaneous locomotor activity, and a decrease in night sleep.

[updated July 2024 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: Cornelia de Lange syndrome
Symptoms and phenotype

Cornelia de Lange syndrome (CDLS) is a multisystem malformation syndrome recognized primarily on the basis of characteristic facial dysmorphism, in association with prenatal and postnatal growth retardation, mental retardation and, in many cases, upper limb anomalies. However, there is wide clinical variability in this disorder, with milder phenotypes that may be difficult to ascertain on the basis of physical features (summary by Rohatgi et al., 2010; pubmed:20583156). [from MIM:122470; 2017.09.08]

(OMIM, 2013-)
Specific Disease Summary: Cornelia de Lange syndrome 3
OMIM report

[CORNELIA DE LANGE SYNDROME 3 WITH OR WITHOUT MIDLINE BRAIN DEFECTS; CDLS3](https://omim.org/entry/610759)

Human gene(s) implicated

[STRUCTURAL MAINTENANCE OF CHROMOSOMES 3; SMC3](https://omim.org/entry/606062)

Symptoms and phenotype

See general description of Cornelia de Lange syndrome.

(FlyBase Curators, 2013-)
Genetics

Cornelia de Lange syndrome-3 CDLS3) is caused by heterozygous mutation in the SMC3 gene on chromosome 10q25. [from MIM:610759; 2024.07.02]

(OMIM, 2013-)
Cellular phenotype and pathology
Molecular information

SMC3 belongs to the SMC3 subfamily of SMC proteins. The encoded protein occurs in certain cell types as either an intracellular, nuclear protein or a secreted protein. The nuclear form, known as structural maintenance of chromosomes 3, is a component of the multimeric cohesin complex that holds together sister chromatids during mitosis, enabling proper chromosome segregation. Post-translational modification of the encoded protein by the addition of chondroitin sulfate chains gives rise to the secreted proteoglycan bamacan, an abundant basement membrane protein. [provided by RefSeq, Jul 2008]

(FlyBase Curators, 2013-)

The SMC3 gene encodes a subunit of the evolutionarily conserved multimeric cohesin complex, which has been implicated in a wide range of functions, including sister chromatid cohesion, DNA repair mechanisms, gene regulation, and maintenance of genome stability (summary by Gil-Rodriguez et al., 2015, pubmed: 25655089). [from MIM:606062 2024.07.02]

(OMIM, 2013-)
External links
Disease synonyms
CDLS3
Cornelia de Lange syndrome 3 with or without midline brain defects
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    Symbol / Name
    SMC3; structural maintenance of chromosomes 3
    D. melanogaster ortholog (based on DIOPT)
    Dmel\SMC3
    (DIOPT, 2013-)
    Comments on ortholog(s)

    One to one (1 human to 1 Drosophila); SMC3 has one high-scoring Drosophila ortholog, SMC3.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Dmel\SMC3
      Gene Snapshot
      Structural maintenance of chromosomes 3 (SMC3) encodes a subunit of the cohesin complex. It is involved in planar cell polarity by regulating the membrane enrichment of the transmembrane cadherin encoded by stan. [Date last reviewed: 2019-07-11]
      Molecular function (GO)
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human SMC3 (1 Drosophila to 1 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 (9 groups)
        SMC3
        protein-protein
        Interacting group
        Assay
        References
        SMC3 - Brca2
        ion exchange chromatography, peptide massfingerprinting
        (Kusch, 2015)
        SMC3 - c(2)M
        anti tag coimmunoprecipitation, anti tag western blot
        (Meyer et al., 2014, Heidmann et al., 2004)
        SMC3 - Cp190
        pull down, Identification by mass spectrometry
        (Kaushal et al., 2022)
        SMC3 - CTCF
        pull down, Identification by mass spectrometry
        (Kaushal et al., 2022)
        SMC3 - Nap1
        pull down, autoradiography
        (Moshkin et al., 2013)
        SMC3 - Pc
        pull down, peptide massfingerprinting, anti bait coimmunoprecipitation, western blot
        (Strübbe et al., 2011)
        SMC3 - solo
        two hybrid
        (Krishnan et al., 2014)
        SMC3 - vtd
        anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry, anti bait coimmunoprecipitation
        (Ribeiro et al., 2016, Meyer et al., 2014, Heidmann et al., 2004, Vass et al., 2003)
        SMC3 - yem
        anti bait coimmunoprecipitation, anti tag western blot, anti tag coimmunoprecipitation, western blot
        (Meyer et al., 2014)
        Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
        SMC3
        Models Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Evidence
        References
        SMC3HMC05010
        model of  Cornelia de Lange syndrome 3
        CEA
        (MacPherson 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
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        SMC3GD14684
        P{GD14684}
        w1118; P{GD14684}v39205
        SMC3KK108887
        P{KK108887}
        P{KK108887}VIE-260B
        SMC3HMS00318
        P{TRiP.HMS00318}
        y1 sc* v1 sev21; P{TRiP.HMS00318}attP2
        SMC3GL00518
        P{TRiP.GL00518}
        y1 sc* v1 sev21; P{TRiP.GL00518}attP40
        SMC3NIG.9802R
        P{NIG.9802R}
        P{NIG.9802R}1
        SMC3HMJ03116
        P{TRiP.HMJ03116}
        y1 v1; P{TRiP.HMJ03116}attP40
        SMC3HMC05010
        P{TRiP.HMC05010}
        y1 sc* v1 sev21; P{TRiP.HMC05010}attP2/TM3, Sb1
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        References (4)