Human Disease Model Report: Coffin-Siris syndrome 3

General Information

Name

Coffin-Siris syndrome 3

FlyBase ID

FBhh0001092

Disease Ontology Term

Coffin-Siris syndrome 3

Parent Disease

Coffin-Siris syndrome

OMIM

COFFIN-SIRIS SYNDROME 3; CSS3

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 MIM:135900; 2019.07.19]

(OMIM, 2013-)

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 MIM:135900; 2019.07.19]

(FlyBase Curators, 2013-)

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]

(OMIM, 2013-)

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.

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): SMARCB1
Gene Cards: SMARCB1
MedlinePlus (gene): SMARCB1
MARRVEL (human gene): SMARCB1
NCBI MedGen: Mental retardation, autosomal dominant 15 (CSS3)
NCBI (Entrez) gene: SMARCB1; SWI/SNF related BAF chromatin remodeling complex subunit B1

Disease synonyms

CSS3

mental retardation autosomal dominant 15

MRD15

Related Diseases

Related human health report(s)

Related Specific Diseases

OMIM phenotypic series

Coffin-Siris syndrome

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[CSS1](https://omim.org/entry/135900)

[ARID1B](https://omim.org/entry/614556)

Coffin-Siris syndrome 1

[CSS2](https://omim.org/entry/614607)

[ARID1A](https://omim.org/entry/603024)

Coffin-Siris syndrome 2

[CSS3](https://omim.org/entry/614608)

[SMARCB1](https://omim.org/entry/601607)

Coffin-Siris syndrome 3

[CSS4](https://omim.org/entry/614609)

[SMARCA4](https://omim.org/entry/603254)

Coffin-Siris syndrome 4

[CSS5](https://omim.org/entry/616938)

[SMARCE1](https://omim.org/entry/603111)

[CSS6](https://omim.org/entry/617808)

[ARID2](https://omim.org/entry/609539)

[CSS7](https://omim.org/entry/618027)

[DPF2](https://omim.org/entry/601671)

[CSS8](https://omim.org/entry/618362)

[SMARCC2](https://omim.org/entry/601734)

Coffin-Siris syndrome 8

[CSS11](https://omim.org/entry/618779)

[SMARCD1](https://omim.org/entry/601735)

Coffin-Siris syndrome 11

[CSS12](https://omim.org/entry/619325)

[BICRA](https://omim.org/entry/605690)

Coffin-Siris syndrome 12

[IDDMOH](https://omim.org/entry/615866)

[SOX11](https://omim.org/entry/600898)

[IDDSDF](https://omim.org/entry/618506)

[SOX4](https://omim.org/entry/184430)

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

SMARCB1; SWI/SNF related BAF chromatin remodeling complex subunit B1

D. melanogaster ortholog (based on DIOPT)

Dmel\Snr1

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Snr1

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]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

BAP
PBAP

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

H. sapiens (Human)

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

Summary of Physical Interactions (31 groups)

Snr1

protein-protein

Interacting group

Assay

References

Snr1 - Bap55

experimental knowledge based

(Guruharsha et al., 2011)

Snr1 - Bap60

experimental knowledge based, anti tag coimmunoprecipitation, Identification by mass spectrometry, protein cross-linking with a bifunctional reagent

(Barish et al., 2020, Mashtalir et al., 2018, Guruharsha et al., 2011)

Snr1 - Bap111

experimental knowledge based

(Guruharsha et al., 2011)

Snr1 - brm

experimental knowledge based, pull down, western blot, anti bait coimmunoprecipitation, ion exchange chromatography, molecular sieving, molecular weight estimation by staining, coimmunoprecipitation, Identification by mass spectrometry, peptide massfingerprinting, anti tag coimmunoprecipitation

(Tilly et al., 2021, Guruharsha et al., 2011, Mohrmann et al., 2004, Zraly et al., 2004, Marenda et al., 2003, Kal et al., 2000, Collins et al., 1999, Papoulas et al., 1998, Dingwall et al., 1995)

Snr1 - Cdk2

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

(Zraly et al., 2004)

Snr1 - CG14207

experimental knowledge based

(Guruharsha et al., 2011)

Snr1 - Clk

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Kwok et al., 2015)

Snr1 - Cpsf6

anti bait coimmunoprecipitation, western blot, experimental knowledge based

(Yu et al., 2018, Guruharsha et al., 2011)

Snr1 - CycE

pull down, western blot, anti bait coimmunoprecipitation

(Zraly et al., 2004)

Snr1 - d4

anti tag coimmunoprecipitation, protein cross-linking with a bifunctional reagent, Identification by mass spectrometry

(Mashtalir et al., 2018)

Snr1 - dsh

experimental knowledge based

(Guruharsha et al., 2011)

Snr1 - Dyrk2

enzymatic study, autoradiography, two hybrid, anti tag coimmunoprecipitation, anti tag western blot, western blot

(Kinstrie et al., 2006)

Snr1 - E(spl)m3-HLH

experimental knowledge based

(Guruharsha et al., 2011)

Snr1 - e(y)3

anti bait coimmunoprecipitation, western blot

(Chalkley et al., 2008)

Snr1 - ebi

experimental knowledge based

(Guruharsha et al., 2011)

Snr1 - erm

anti tag coimmunoprecipitation, anti tag western blot, pull down

(Koe et al., 2014)

Snr1 - geminin

anti tag coimmunoprecipitation, western blot

(Herr et al., 2010)

Snr1 - Gtpbp2

experimental knowledge based

(Guruharsha et al., 2011)

Snr1 - MED7

experimental knowledge based

(Guruharsha et al., 2011)

Snr1 - MED8

experimental knowledge based

(Guruharsha et al., 2011)

Snr1 - MED14

experimental knowledge based

(Guruharsha et al., 2011)

Snr1 - MED17

experimental knowledge based

(Guruharsha et al., 2011)

Snr1 - MED18

experimental knowledge based

(Guruharsha et al., 2011)

Snr1 - mnb

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

(Kinstrie et al., 2006)

Snr1 - mor

protein cross-linking with a bifunctional reagent, Identification by mass spectrometry, anti bait coimmunoprecipitation, western blot, anti tag western blot, two hybrid, experimental knowledge based

(Tilly et al., 2021, Mashtalir et al., 2018, Curtis et al., 2011, Guruharsha et al., 2011)

Snr1 - net

two hybrid

(Marenda et al., 2004)

Snr1 - osa

anti bait coimmunoprecipitation, western blot, coimmunoprecipitation, molecular weight estimation by staining

(Marenda et al., 2003, Collins et al., 1999)

Snr1 - psq

anti bait coimmunoprecipitation, western blot

(Chetverina et al., 2022)

Snr1 - Su(var)3-3

anti bait coimmunoprecipitation, western blot, pull down

(Curtis et al., 2011)

Snr1 - Trl

anti tag coimmunoprecipitation, peptide massfingerprinting

(Nakayama et al., 2012)

Snr1 - trx

pull down, western blot, two hybrid

(Tie et al., 2014, Marenda et al., 2003)

Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)

Snr1

Models Based on Experimental Evidence ( 4 )

Allele

Disease

Evidence

References

Snr1^RNAi.UAS.cUa

model of atypical teratoid rhabdoid tumor

CEA

(Jeibmann et al., 2014)

Snr1^GD4140

model of rhabdoid cancer

CEA with BacA\p35^UAS.cHa

(Xie et al., 2017)

Snr1^KK101602

model of atypical teratoid rhabdoid tumor

CEA

(Federico et al., 2022, Tegeder et al., 2019)

Snr1^HMS00363

model of rhabdoid cancer

CEA

(Xie et al., 2017)

CEA with BacA\p35^UAS.cHa

(Xie et al., 2017)

model of Coffin-Siris syndrome 3

CEA

(MacPherson et al., 2023, Chubak et al., 2019)

Modifiers Based on Experimental Evidence ( 2 )

Allele

Disease

Interaction

References

Snr1^RNAi.UAS.cUa

model of atypical teratoid rhabdoid tumor

is ameliorated by CycD^RNAi.UAS.cUa

(Jeibmann et al., 2014)

is ameliorated by Mer^GD1484

(Jeibmann et al., 2014)

is ameliorated by kibra^RNAi.UAS.cUa

(Jeibmann et al., 2014)

is ameliorated by ex^VDRC.cUa

(Jeibmann et al., 2014)

is ameliorated by ex^RNAi.UAS.cUa

(Jeibmann et al., 2014)

is ameliorated by ci^RNAi.UAS.cUa

(Jeibmann et al., 2014)

is ameliorated by ci^RNAi.UAS.cUa

(Jeibmann et al., 2014)

Snr1^KK101602

model of atypical teratoid rhabdoid tumor

is exacerbated by CG4968^GL00459

(Tegeder et al., 2019)

is exacerbated by Dlst^HMC03051

(Tegeder et al., 2019)

is exacerbated by CG5334^KK112373

(Tegeder et al., 2019)

is exacerbated by Kpc1^KK101455

(Tegeder et al., 2019)

is exacerbated by CG6805^HMS01290

(Tegeder et al., 2019)

is exacerbated by CG7656^KK108673

(Tegeder et al., 2019)

is exacerbated by CG7987^KK104367

(Tegeder et al., 2019)

is exacerbated by Atf6^GD14782

(Tegeder et al., 2019)

is exacerbated by Bub1^HMC04961

(Tegeder et al., 2019)

is exacerbated by CG8243^KK107797

(Tegeder et al., 2019)

is exacerbated by CG9265^KK111700

(Tegeder et al., 2019)

is exacerbated by CAH1^KK108727

(Tegeder et al., 2019)

is exacerbated by CG10185^KK102859

(Tegeder et al., 2019)

is exacerbated by CG10348^HMS02808

(Tegeder et al., 2019)

is exacerbated by CG11151^KK111988

(Tegeder et al., 2019)

is exacerbated by Dred^KK101241

(Tegeder et al., 2019)

is exacerbated by CG9386^HMS00236

(Tegeder et al., 2019)

is exacerbated by CycD^KK108447

(Tegeder et al., 2019)

is exacerbated by CG15012^KK102332

(Tegeder et al., 2019)

is exacerbated by CycG^JF02474

(Tegeder et al., 2019)

is exacerbated by ECSIT^KK102897

(Tegeder et al., 2019)

is exacerbated by Eip75B^KK108982

(Tegeder et al., 2019)

is exacerbated by Fs^HMC04698

(Tegeder et al., 2019)

is exacerbated by CG15803^HMC03179

(Tegeder et al., 2019)

is exacerbated by CG31637^KK109079

(Tegeder et al., 2019)

is exacerbated by CG3662^GLC01437

(Tegeder et al., 2019)

is exacerbated by CG40006^HMS01170

(Tegeder et al., 2019)

is exacerbated by GluRIB^KK114418

(Tegeder et al., 2019)

is exacerbated by GluRIIA^KK105437

(Tegeder et al., 2019)

is exacerbated by Sph242^KK115684

(Tegeder et al., 2019)

is exacerbated by CG41378^GLC01600

(Tegeder et al., 2019)

is exacerbated by CG42271^KK105173

(Tegeder et al., 2019)

is exacerbated by GluRIIB^JF03145

(Tegeder et al., 2019)

is exacerbated by Hs3st-B^KK108793

(Tegeder et al., 2019)

is exacerbated by Klf15^JF02420

(Tegeder et al., 2019)

is exacerbated by CG42541^KK109685

(Tegeder et al., 2019)

is exacerbated by CG44836^KK112207

(Tegeder et al., 2019)

is exacerbated by LpR1^HMS02973

(Tegeder et al., 2019)

is exacerbated by Mmp2^GD9489

(Tegeder et al., 2019)

is exacerbated by Ndae1^GD967

(Tegeder et al., 2019)

is exacerbated by NetA^GD6299

(Tegeder et al., 2019)

is exacerbated by NetB^HMS01177

(Tegeder et al., 2019)

is exacerbated by L^KK102438

(Tegeder et al., 2019)

is exacerbated by Optix^HMC03993

(Tegeder et al., 2019)

is exacerbated by Sik2^HMC04153

(Tegeder et al., 2019)

is exacerbated by Smox^KK111163

(Tegeder et al., 2019)

is exacerbated by Snx21^KK101320

(Tegeder et al., 2019)

is exacerbated by Socs44A^KK112370

(Tegeder et al., 2019)

is exacerbated by Osbp^KK107784

(Tegeder et al., 2019)

is exacerbated by Pcyt2^KK110819

(Tegeder et al., 2019)

is exacerbated by Pi3K21B^KK109296

(Tegeder et al., 2019)

is exacerbated by Ptr^HM05184

(Tegeder et al., 2019)

is exacerbated by Sod2^HMS00499

(Tegeder et al., 2019)

is exacerbated by Spn28Da^KK106224

(Tegeder et al., 2019)

is exacerbated by Spn43Ab^HMS02759

(Tegeder et al., 2019)

is exacerbated by Spn88Eb^GD12821

(Tegeder et al., 2019)

is exacerbated by Zasp52^KK101276

(Tegeder et al., 2019)

is exacerbated by Rab6^KK108556

(Tegeder et al., 2019)

is exacerbated by Rgk2^KK112136

(Tegeder et al., 2019)

is exacerbated by Rip11^HMS01792

(Tegeder et al., 2019)

is exacerbated by a^HMC03685

(Tegeder et al., 2019)

is exacerbated by bi^HMS02815

(Tegeder et al., 2019)

is exacerbated by bowl^JF02419

(Tegeder et al., 2019)

is exacerbated by daw^KK110248

(Tegeder et al., 2019)

is exacerbated by dia^KK101745

(Tegeder et al., 2019)

is exacerbated by dlp^HMS00903

(Tegeder et al., 2019)

is exacerbated by dpn^HMC03154

(Tegeder et al., 2019)

is exacerbated by dpp^JF02455

(Tegeder et al., 2019)

is exacerbated by hb^KK106631

(Tegeder et al., 2019)

is exacerbated by l(3)72Dr^KK106580

(Tegeder et al., 2019)

is exacerbated by RpS5b^GL01864

(Tegeder et al., 2019)

is exacerbated by Sema1b^KK104666

(Tegeder et al., 2019)

is exacerbated by lin-28^HMC03080

(Tegeder et al., 2019)

is exacerbated by mfr^KK102150

(Tegeder et al., 2019)

is exacerbated by ninaD^HMC02392

(Tegeder et al., 2019)

is exacerbated by nanos^KK105687

(Tegeder et al., 2019)

is exacerbated by oc^HMS01314

(Tegeder et al., 2019)

is exacerbated by pdm2^KK110854

(Tegeder et al., 2019)

is exacerbated by ph-d^JF01705

(Tegeder et al., 2019)

is exacerbated by pyd^HMS00263

(Tegeder et al., 2019)

is exacerbated by robo2^HMS01063

(Tegeder et al., 2019)

is exacerbated by scramb1^KK105750

(Tegeder et al., 2019)

is exacerbated by slgA^KK109194

(Tegeder et al., 2019)

is exacerbated by sli^JF01229

(Tegeder et al., 2019)

is exacerbated by sob^HMS01123

(Tegeder et al., 2019)

is exacerbated by tsg^KK109596

(Tegeder et al., 2019)

is exacerbated by vis^HMS01480

(Tegeder et al., 2019)

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

Snr1^GD4140

P{GD4140}

w¹¹¹⁸; P{GD4140}v12645/TM3

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00363}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMS05749}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Snr1^SR21

loss of function allele

P-element activity

Snr1^19-21

loss of function allele

CRISPR/Cas9

References (7)

Report Sections

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