Human Disease Model Report: Cornelia de Lange syndrome 4

General Information

Name

Cornelia de Lange syndrome 4

FlyBase ID

FBhh0001589

Disease Ontology Term

Cornelia de Lange syndrome 4

Parent Disease

Cornelia de Lange syndrome

OMIM

CORNELIA DE LANGE SYNDROME 4 WITH OR WITHOUT MIDLINE BRAIN DEFECTS; CDLS4

Overview

This report describes Cornelia de Lange syndrome 4, a subtype of Cornelia de Lange syndrome. The human gene implicated is RAD21, which encodes RAD21 cohesion complex component, a member of the cohesin multiprotein complex required for sister chromatid cohesion. RAD21 is also associated with Mungan syndreom (MIM:611376). There is one high-scoring fly ortholog, Dmel\vtd, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

The human gene RAD21 has not yet been introduced into flies.

Ubiquitous RNAi knockdown of Dmel\vtd resulted in an increase in startle response time, an increase in spontaneous locomotor activity, and a decrease in night sleep. Knockdown of Dmel\vtd also results in a 'tapping' phenotype, in which flies exhibit a repetitive extension and retraction of individual legs as though preparing to walk, but without progressive movement.

[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 4

OMIM report

[CORNELIA DE LANGE SYNDROME 4 WITH OR WITHOUT MIDLINE BRAIN DEFECTS; CDLS4](https://omim.org/entry/614701)

Human gene(s) implicated

[RAD21 COHESIN COMPLEX COMPONENT; RAD21](https://omim.org/entry/606462)

Symptoms and phenotype

See general description of Cornelia de Lange syndrome.

(FlyBase Curators, 2013-)

Genetics

Cornelia de Lange syndrome-4 CDLS4) is caused by heterozygous mutation in the RAD21 gene (606462), which encodes a component of the cohesin complex, on chromosome 8q24. [from MIM:614701; 2024.07.02]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

RAD21 encodes a protein highly similar to the gene product of Schizosaccharomyces pombe rad21, a gene involved in the repair of DNA double-strand breaks, as well as in chromatid cohesion during mitosis. This protein is a nuclear phospho-protein, which becomes hyperphosphorylated in cell cycle M phase. The highly regulated association of this protein with mitotic chromatin specifically at the centromere region suggests its role in sister chromatid cohesion in mitotic cells. [provided by RefSeq, Jul 2008]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): RAD21
Gene Cards: RAD21
GeneReviews, NCBI Bookshelf: Cornelia de Lange Syndrome
MedlinePlus (condition): Cornelia de Lange syndrome
MedlinePlus (gene): RAD21
MARRVEL (human gene): RAD21
NCBI MedGen: Cornelia de Lange syndrome 4 (CDLS4)
NCBI (Entrez) gene: RAD21; RAD21 cohesin complex component

Disease synonyms

CDLS4

Cornelia de Lange syndrome 4 with or without midline brain defects

RAD21-Related Cornelia de Lange Syndrome

Related Diseases

Related human health report(s)

Cornelia de Lange syndrome

Related Specific Diseases

OMIM phenotypic series

Cornelia de Lange syndrome

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[CDLS1](https://omim.org/entry/122470)

[NIPBL](https://omim.org/entry/608667)

Cornelia de Lange syndrome 1

[CDLS2](https://omim.org/entry/300590)

[SMC1A](https://omim.org/entry/300040)

Cornelia de Lange syndrome 2

[CDLS3](https://omim.org/entry/610759)

[SMC3](https://omim.org/entry/606062)

Cornelia de Lange syndrome 3

[CDLS4](https://omim.org/entry/614701)

[RAD21](https://omim.org/entry/606462)

Cornelia de Lange syndrome 4

[CDLS5](https://omim.org/entry/300882)

[HDAC8](https://omim.org/entry/300269)

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

RAD21; RAD21 cohesin complex component

D. melanogaster ortholog (based on DIOPT)

Dmel\vtd

(DIOPT, 2013-)

Comments on ortholog(s)

Two to one (2 human to 1 Drosophila); RAD21 has one high-scoring Drosophila ortholog, vtd.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\vtd

Gene Snapshot

verthandi (vtd) encodes a subunit of the cohesin complex, which encircles sister chromatids after DNA replication and has multiple roles in the regulation of gene expression and DNA repair. [Date last reviewed: 2019-03-21]

Molecular function (GO)

chromatin binding

Cellular component (GO)

Gene Groups / Pathways

COHSN

Comments on ortholog(s)

High-scoring ortholog of human RAD21 and RAD21L1 (1 Drosophila to 2 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 (29 groups)

vtd

protein-protein

Interacting group

Assay

References

vtd

anti bait coimmunoprecipitation, Identification by mass spectrometry, anti tag coimmunoprecipitation

(Ribeiro et al., 2016)

vtd - ATPsynβ

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Ribeiro et al., 2016)

vtd - Brca2

ion exchange chromatography, peptide massfingerprinting

(Kusch, 2015)

vtd - c(2)M

anti tag coimmunoprecipitation, anti tag western blot, autoradiography, western blot

(Meyer et al., 2014, Urban et al., 2014)

vtd - Cp190

pull down, Identification by mass spectrometry

(Kaushal et al., 2022)

vtd - CTCF

pull down, molecular weight estimation by staining, Identification by mass spectrometry

(Kaushal et al., 2022, Kaushal et al., 2021)

vtd - dmt

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Yamada et al., 2017)

vtd - Fib

anti bait coimmunoprecipitation, Identification by mass spectrometry

(Ribeiro et al., 2016)

vtd - Haspin

anti bait coimmunoprecipitation, anti tag western blot

(Fresán et al., 2020)

vtd - His4

anti bait coimmunoprecipitation, Identification by mass spectrometry, anti tag coimmunoprecipitation

(Ribeiro et al., 2016)

vtd - lark

pull down, western blot

(Swain et al., 2016)

vtd - mts

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

(Kim et al., 2019, Moshkin et al., 2013)

vtd - Nap1

pull down, autoradiography, anti bait coimmunoprecipitation, western blot

(Moshkin et al., 2013)

vtd - Nipped-B

anti tag coimmunoprecipitation, anti tag western blot

(Gause et al., 2008)

vtd - nonC

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Ribeiro et al., 2016)

vtd - Pc

pull down, peptide massfingerprinting, anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation

(Strübbe et al., 2011)

vtd - pds5

anti tag coimmunoprecipitation, western blot

(Kusch, 2015)

vtd - Psc

anti tag coimmunoprecipitation, western blot

(Strübbe et al., 2011)

vtd - Ran

anti tag coimmunoprecipitation, Identification by mass spectrometry, anti bait coimmunoprecipitation

(Ribeiro et al., 2016)

vtd - SA1

anti tag coimmunoprecipitation, Identification by mass spectrometry, anti bait coimmunoprecipitation, western blot, anti tag western blot

(Ribeiro et al., 2016, Moshkin et al., 2013, Gause et al., 2008, Vass et al., 2003)

vtd - san

acetylase assay, autoradiography

(Ribeiro et al., 2016)

vtd - Sce

anti tag coimmunoprecipitation, western blot

(Strübbe et al., 2011)

vtd - sesB

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Ribeiro et al., 2016)

vtd - SMC1

anti bait coimmunoprecipitation, Identification by mass spectrometry, anti tag coimmunoprecipitation, anti tag western blot, western blot

(Ribeiro et al., 2016, Eichinger et al., 2013, Strübbe et al., 2011, Gause et al., 2010, Gause et al., 2008, Vass et al., 2003)

vtd - SMC3

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)

vtd - Su(var)205

anti tag coimmunoprecipitation, peptide massfingerprinting

(Alekseyenko et al., 2014)

vtd - TBPH

pull down, western blot

(Swain et al., 2016)

vtd - tws

anti tag coimmunoprecipitation, anti tag western blot

(Kim et al., 2019)

vtd - yem

anti bait coimmunoprecipitation, western blot

(Meyer et al., 2014)

Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)

vtd

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

vtd^GL00522

model of Cornelia de Lange syndrome 4

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

w¹¹¹⁸; P{GD4260}v13669/CyO

vtd^GL00522

P{TRiP.GL00522}

y¹ sc^* v¹ sev²¹; P{TRiP.GL00522}attP2/TM3, Sb¹

vtd^HMC06090

P{TRiP.HMC06090}

y¹ sc^* v¹ sev²¹; P{TRiP.HMC06090}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

References (4)

Report Sections

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