Human Disease Model Report: myopathy, FLNC-related

General Information

Name

myopathy, FLNC-related

FlyBase ID

FBhh0000670

Disease Ontology Term

myopathy

Parent Disease

OMIM

Overview

This report describes fly models relevant to myopathies that are FLNC-related. The human gene implicated in these diseases is filamin C (FLNC), a muscle-specific filamin associated with the sarcomeric Z disk. FLNC is implicated in several forms of myopathy, 'myopathy, myofibrillar, 5' (MIM:609524, FBhh0000672), 'cardiomyopathy, familial hypertrophic 26' (MIM:617047, FBhh0000671) and 'myopathy, distal, 4' (MIM:614065, FBhh0000673); all are inherited as autosomal dominants. There is a single orthologous gene in Drosophila, cher, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\cher is also orthologous to the human genes FLNA and FLNB.

The human FLNC gene has not been introduced into flies.

Since expression of cher is not restricted to muscle, a number of phenotypes observed for cher mutations are not related to muscle. Animals homozygous for an amorphic allele of Dmel\cher are viable; females are sterile. RNAi-effected loss of cher in muscle results in a decrease in adult viability, a flightless phenotype, and severe sarcomere phenotypes. Physical and genetic interactions of Dmel\cher have been described; see below and in the cher gene report.

[updated Dec. 2017 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: myopathy, FLNC-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

One of a group of 'Z-disk diseases' that typically manifests as distal myopathy, but may also affect proximal muscles and the heart (Selcen and Carpen, 2008; pubmed:19181098).

(FlyBase Curators, 2013-)

Genetics

Cellular phenotype and pathology

The morphological findings are typical of myofibrillar myopathy (MFM) and include Z-disk alterations and aggregation of dense filamentous material visible in trichrome staining(Selcen and Carpen, 2008; pubmed:19181098).

(FlyBase Curators, 2013-)

Molecular information

FLNC is muscle-specific filamin; filamin proteins crosslink actin filaments into orthogonal networks in cortical cytoplasm and participate in the anchoring of membrane proteins for the actin cytoskeleton. FLNC is critical for normal myogenesis and for maintaining the structural integrity of the muscle fibers; may also display structural functions at the Z lines in muscle cells. [from Gene Cards, FLNC; 2017.12.01]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): FLNC
Gene Cards: FLNC
MedlinePlus (gene): FLNC
MARRVEL (human gene): FLNC
NCBI (Entrez) gene: FLNC; filamin C

Disease synonyms

autosomal dominant myopathy

Related Diseases

Related human health report(s)

cardiomyopathy, familial hypertrophic 26

myopathy, distal, 4

myopathy, myofibrillar

myopathy, myofibrillar, 5

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

FLNC; filamin C

D. melanogaster ortholog (based on DIOPT)

Dmel\cher

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one (3 human to 1 Drosophila); the other human genes are FLNA and FLNB.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\cher

Gene Snapshot

cheerio (cher) encodes a dimeric F-actin crosslinking protein of the filamin protein family. It functions to organize the F-actin cytoskeleton in multiple contexts including ovarian germline ring canals, migrating somatic cells, and neuronal growth cones. [Date last reviewed: 2019-03-07]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Moderate- to high-scoring ortholog of human FLNA, FLNC, and FLNB (1 Drosophila to 3 human); Dmel\cher shares 45-46% identity and 59-61% similarity with the human genes.

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 (21 groups)

cher

protein-protein

Interacting group

Assay

References

cher - 14-3-3ε

anti bait coimmunoprecipitation, western blot, Identification by mass spectrometry

(Külshammer et al., 2022)

cher - Actin

phenotype-based detection assay, fluorescence microscopy, inferred by author

(Green et al., 2018)

cher - bbg

anti bait coimmunoprecipitation, Identification by mass spectrometry, western blot

(Külshammer et al., 2022)

cher - CG44250

two hybrid

(Hu et al., 2017.6.13)

cher - dos

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

cher - hts

proximity ligation assay, fluorescence microscopy, proximity-dependent biotin identification, Identification by mass spectrometry

(Mannix et al., 2019)

cher - ihog

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

(Lalioti et al., 2025)

cher - InR

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

cher - kel

proximity-dependent biotin identification, western blot, Identification by mass spectrometry

(Mannix et al., 2019)

cher - l(2)efl

anti bait coimmunoprecipitation, anti tag western blot, peptide massfingerprinting

(Wójtowicz et al., 2015)

cher - Nuak

two hybrid

(Brooks et al., 2020)

cher - Pak

proximity ligation assay, fluorescence microscopy

(Lee and Schwarz, 2016)

cher - pll

two hybrid

(Edwards et al., 1997)

cher - Rab11

pull down, peptide massfingerprinting

(Ramel et al., 2013)

cher - Sema1a

two hybrid, anti bait coimmunoprecipitation, anti tag western blot

(Jeong et al., 2017)

cher - sls

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

(González-Morales et al., 2017)

cher - Ten-m

two hybrid, pull down, autoradiography

(Zheng et al., 2011)

cher - tub

two hybrid

(Edwards et al., 1997)

cher - Vinc

phenotype-based detection assay, fluorescence microscopy, inferred by author

(Green et al., 2018)

cher - wash

phenotype-based detection assay, fluorescence microscopy, inferred by author

(Green et al., 2018)

cher - zip

anti bait coimmunoprecipitation, western blot, Identification by mass spectrometry

(Külshammer et al., 2022, Külshammer and Uhlirova, 2013)

Alleles Reported to Model Human Disease (Disease Ontology) (23 alleles)

cher

Models Based on Experimental Evidence ( 22 )

Allele

Disease

Evidence

References

cher¹

model of myopathy

CEA with Act88F⁶

(González-Morales et al., 2017)

cher^EPSΔ5

model of myopathy

CEA

(González-Morales et al., 2017)

CEA with sls^j1D7

(González-Morales et al., 2017)

CEA with Act88F⁶

(González-Morales et al., 2017)

cher^Q1042X

model of myopathy

CEA

(González-Morales et al., 2017)

DOES NOT model myopathy

CEA with sls^j1D7

(González-Morales et al., 2017)

cher^sko

model of myopathy

CEA

(González-Morales et al., 2017)

CEA with sls^j1D7

(González-Morales et al., 2017)

DOES NOT model myopathy

CEA with Act88F⁶

(González-Morales et al., 2017)

cher^CPTI001403

model of myopathy

CEA with Act88F⁶

(González-Morales et al., 2017)

DOES NOT model myopathy

CEA with sls^ZCL2144

(González-Morales et al., 2017)

cher^KK107518

model of distal myopathy 4

CEA

(Ader et al., 2022)

model of myofibrillar myopathy 5

CEA

(Ader et al., 2022)

model of myopathy

CEA

(González-Morales et al., 2017)

CEA with cher^JF02077

(González-Morales et al., 2017)

cher^JF02077

model of myopathy

CEA

(González-Morales et al., 2017)

CEA with cher^KK107518

(González-Morales et al., 2017)

model of distal myopathy 4

CEA

(Ader et al., 2022)

model of myofibrillar myopathy 5

CEA

(Ader et al., 2022)

cher^I1849T.STOP

model of myopathy

CEA

(Ader et al., 2022)

cher^V1865L.STOP

DOES NOT model myopathy

CEA

(Ader et al., 2022)

cher^G1789S.STOP

model of myopathy

CEA

(Ader et al., 2022)

cher^I1849T

DOES NOT model myopathy

CEA

(Ader et al., 2022)

cher^V1865L

DOES NOT model myopathy

CEA

(Ader et al., 2022)

cher^G1789S

DOES NOT model myopathy

CEA

(Ader et al., 2022)

cher^{closedMSR.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^ΔMSR.mGFP6

model of myopathy

CEA

(Fisher et al., 2024)

cher^{ΔIg14-22.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^{ΔIg14-21.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^{ΔIg15-21.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^{ΔIg16-17.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^{ΔIg18-19.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^{ΔIg20-21.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^ΔIg22.mGFP6

model of myopathy

CEA

(Fisher et al., 2024)

Modifiers Based on Experimental Evidence ( 2 )

Allele

Disease

Interaction

References

cher^EP3715

exacerbates tauopathy

modeled by Hsap\MAPT^V337M.UAS

(Shulman and Feany, 2003)

cher^JF02077

model of myopathy

is exacerbated by sls¹

(González-Morales et al., 2017)

is exacerbated by sls^j1D7

(González-Morales et al., 2017)

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

Cardiovascular Diseases

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

y¹ v¹; P{TRiP.JF02077}attP2

y¹ v¹; P{TRiP.HMS01501}attP2/TM3, Sb¹

cher^NIG.3937R

P{NIG.3937R}

P{NIG.3937R}2

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

P-element activity

CRISPR/Cas9

CRISPR/Cas9

CRISPR/Cas9

piggyBac activity

piggyBac activity

piggyBac activity

cher^{closedMSR.mGFP6}

phiC31 integrase

cher^ΔMSR.mGFP6

phiC31 integrase

cher^{ΔIg14-22.mGFP6}

cher^{ΔIg14-21.mGFP6}

cher^{ΔIg15-21.mGFP6}

cher^{ΔIg16-17.mGFP6}

cher^{ΔIg18-19.mGFP6}

cher^{ΔIg20-21.mGFP6}

cher^ΔIg22.mGFP6

cher^sko

ethyl methanesulfonate

cher^sko e^*/TM3, Sb¹

cher¹

amorphic allele - genetic evidence

cher¹/TM3, Sb¹

cher^EPSΔ5

Delta2-3 transposase

cher^EPSΔ12.1

amorphic allele - molecular evidence

Delta2-3 transposase

cher^Q1042X

cher^CPTI001403

piggyBac activity

w¹¹¹⁸; PBac{681.P.FSVS-1}cher^CPTI001403

References (8)

Report Sections

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