Human Disease Model Report: laminopathies

General Information

Name

laminopathies

FlyBase ID

FBhh0000264

Disease Ontology Term

myopathy

Parent Disease

OMIM

Overview

A number of disorders of cardiac and striated muscles, neuromuscular disorders, lipodystrophy syndromes, and premature aging syndromes are associated with mutations of the LMNA gene, which encodes lamins A and C, and are described as laminopathies. This report includes general information about laminopathies; reports on specific diseases that have been investigated in flies may be accessed via the links in the 'Related diseases' section, below.

[updated May 2016 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: laminopathies

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Different mis-splicing events of the LMNA pre-mRNA are associated with different disorders.

(Scotti and Swanson, 2016)

Mutations in the human gene LMNA (Lamin A/C) are implicated in multiple diseases classified as laminopathies. [From MIM:150330, 2016.05.23]

(OMIM, 2013-)

Cellular phenotype and pathology

Cells isolated from human and mouse tissue from the various laminopathies, all display abnormal nuclear structure. These phenotypes range from abnormal nuclear shape to nuclear blebbing and even dispersal of DNA into the cytoplasm.

(Schreiber and Kennedy, 2013)

Molecular information

The LMNA gene encodes lamin A and lamin C. Lamins are structural protein components of the nuclear lamina, a protein network underlying the inner nuclear membrane that determines nuclear shape and size. The lamins constitute a class of intermediate filaments. Three types of lamins, A, B (see LMNB1; MIM:150340), and C, have been described in mammalian cells (Fisher et al., 1986, pubmed:3462705). [From MIM:150330, 2016.05.23]

(OMIM, 2013-)

External links

Gene2Function (human gene): LMNA
Gene Cards: LMNA
GeneReviews, NCBI Bookshelf: Laminopathies: One Gene, Two Proteins, Five Diseases..
MedlinePlus (gene): LMNA
MARRVEL (human gene): LMNA
NCBI MedGen: Laminopathy
NCBI (Entrez) gene: LMNA; lamin A/C

Disease synonyms

Related Diseases

Related human health report(s)

dilated cardiomyopathy 1A

Hutchinson-Gilford progeria syndrome

leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy

lipodystrophy, familial partial, type 2

muscular dystrophy, Emery-Dreifuss

muscular dystrophy, lamin-related

muscular dystrophy, limb-girdle, autosomal recessive

Ortholog Information

Human gene(s) in FlyBase

Hsap\LMNA

Human gene (HGNC)

Symbol / Name

LMNA; lamin A/C

D. melanogaster ortholog (based on DIOPT)

Dmel\Lam

(DIOPT, 2013-)

Dmel\LamC

(DIOPT, 2013-)

Comments on ortholog(s)

Many to many: 3 human to 2 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (2)

Dmel\Lam

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Ortholog of human LMNB2, LMNA, and LMNB1 (2 Drosophila to 3 human).

Dmel\Lam shares 36% identity and 57% similarity with human LMNB2, 37% identity and 60% similarity with human LMNA, and 37% identity and 59% similarity with human LMNB1.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\LamC

Gene Snapshot

Lamin C (LamC) encodes a type V intermediate filament that is essential for development. It contributes to the shape and structural integrity of the nucleus and plays roles in genome integrity and gene regulation, through contacts made with chromatin. [Date last reviewed: 2019-03-14]

Molecular function (GO)

structural constituent of cytoskeleton

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Ortholog of human LMNB2, LMNA, and LMNB1 (2 Drosophila to 3 human).

Dmel\LamC shares 38% identity and 58% similarity with human LMNB2, 35% identity and 54% similarity with human LMNA, and 37% identity and 58% similarity with human LMNB1.

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 (42 groups)

Lam

protein-protein

Interacting group

Assay

References

Lam

cosedimentation, western blot, inferred by author, two hybrid

(Zaremba-Czogalla et al., 2012, Schulze et al., 2009, Stuurman et al., 1999, Goldberg et al., 1998)

Lam - AGO2

anti bait coimmunoprecipitation, Identification by mass spectrometry

(Nazer et al., 2018)

Lam - baf

anti tag coimmunoprecipitation, anti tag western blot

(Mehsen et al., 2018)

Lam - BicD

two hybrid, pull down, western blot

(Stuurman et al., 1999)

Lam - bocks

experimental knowledge based, two hybrid

(Guruharsha et al., 2011, Schulze et al., 2009)

Lam - Brca2

anti tag coimmunoprecipitation, western blot, pull down, anti tag western blot, ion exchange chromatography, peptide massfingerprinting, anti bait coimmunoprecipitation

(Kusch, 2015)

Lam - cnn

anti bait coimmunoprecipitation, peptide massfingerprinting

(Habermann et al., 2012)

Lam - Dlc90F

experimental knowledge based

(Guruharsha et al., 2011)

Lam - dod

anti bait coimmunoprecipitation, western blot, proximity ligation assay, fluorescence microscopy

(Napoletano et al., 2021)

Lam - dysf

proximity ligation assay, fluorescence microscopy

(Wu et al., 2022)

Lam - fs(1)Ya

two hybrid

(Goldberg et al., 1998)

Lam - JIL-1

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

(Bao et al., 2005)

Lam - Keap1

pull down, western blot, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, bimolecular fluorescence complementation, fluorescence microscopy

(Carlson et al., 2024)

Lam - LamC

two hybrid

(Schulze et al., 2009)

Lam - LBR

solid phase assay, anti bait coimmunoprecipitation, western blot, autoradiography

(Wagner et al., 2004)

Lam - MAN1

anti bait coimmunoprecipitation, western blot, two hybrid

(Pinto et al., 2008, Wagner et al., 2006)

Lam - Mkrn1

experimental knowledge based

(Guruharsha et al., 2011)

Lam - mud

affinity chromatography technology, Identification by mass spectrometry, anti bait coimmunoprecipitation, anti tag western blot

(Capalbo et al., 2011)

Lam - Nup153

anti bait coimmunoprecipitation, western blot

(Chen et al., 2013)

Lam - nxf2

anti bait coimmunoprecipitation, western blot

(Iwasaki et al., 2021)

Lam - Ote

two hybrid, pull down, Identification by mass spectrometry, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot, experimental knowledge based

(Emond-Fraser et al., 2023, Habermann et al., 2012, Guruharsha et al., 2011, Goldberg et al., 1998)

Lam - p38a

anti tag coimmunoprecipitation, western blot

(Ryan et al., 2021)

Lam - Pen

affinity chromatography technology, Identification by mass spectrometry

(Virágh et al., 2012)

Lam - PIG-B

anti tag coimmunoprecipitation, Identification by mass spectrometry, phenotype-based detection assay, inferred by author, proximity-dependent biotin identification, western blot, coimmunoprecipitation

(Yamamoto-Hino et al., 2020)

Lam - Polr2A

anti bait coimmunoprecipitation, Identification by mass spectrometry

(Nazer et al., 2018)

Lam - Rab5

pull down, western blot, affinity chromatography technology, Identification by mass spectrometry

(Capalbo et al., 2011)

Lam - RPA1

experimental knowledge based

(Guruharsha et al., 2011)

Lam - RPA2

experimental knowledge based

(Guruharsha et al., 2011)

Lam - sphe

experimental knowledge based

(Guruharsha et al., 2011)

Lam - Sse

pull down, western blot

(Cipressa et al., 2025)

Lam - stv

anti tag coimmunoprecipitation, western blot

(Ryan et al., 2021)

Lam - Su(var)205

anti bait coimmunoprecipitation, western blot

(Napoletano et al., 2021)

Lam - Sumo

anti tag coimmunoprecipitation, comigration in sds page, anti tag western blot

(Pirone et al., 2017)

Lam - Topors

two hybrid, anti bait coimmunoprecipitation, western blot

(Capelson and Corces, 2005)

Lam - tws

anti tag coimmunoprecipitation, anti tag western blot

(Mehsen et al., 2018)

Lam - wash

anti bait coimmunoprecipitation, western blot, blue native page, pull down, autoradiography, proximity ligation assay

(Verboon et al., 2020, Verboon et al., 2015)

Lam - wge

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

(Masuko et al., 2018, Masuko et al., 2018)

RNA-protein

Interacting group

Assay

References

Lam - nonA

anti bait coimmunoprecipitation, quantitative reverse transcription pcr

(Kozlova et al., 2006)

LamC

protein-protein

Interacting group

Assay

References

LamC

two hybrid, cosedimentation, western blot, inferred by author

(Zaremba-Czogalla et al., 2012, Schulze et al., 2009)

LamC - bocks

two hybrid

(Schulze et al., 2009)

LamC - Lam

two hybrid

(Schulze et al., 2009)

LamC - MAN1

two hybrid, anti bait coimmunoprecipitation, western blot

(Pinto et al., 2008, Wagner et al., 2006)

LamC - Sse

pull down, western blot

(Cipressa et al., 2025)

Alleles Reported to Model Human Disease (Disease Ontology) (29 alleles)

Lam

Models Based on Experimental Evidence ( 4 )

Allele

Disease

Evidence

References

Lam^A25

model of myopathy

CEA

(Frost et al., 2016, Patterson et al., 2004)

Lam^Ari3

model of myopathy

CEA

(Patterson et al., 2004)

Lam^GD1478

model of myopathy

CEA

(Oyston et al., 2018)

Lam^KK102399

model of myopathy

CEA

(Oyston et al., 2018)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

Lam^GL00577

exacerbates tauopathy

modeled by Hsap\MAPT^R406W.UAS

(Frost et al., 2016)

LamC

Models Based on Experimental Evidence ( 20 )

Allele

Disease

Evidence

References

LamC^ΔN.UAS

model of autosomal dominant Emery-Dreifuss muscular dystrophy 2

CEC

(Shaw et al., 2022)

LamC^R401K.hs

model of autosomal dominant Emery-Dreifuss muscular dystrophy 2

CEA

(Schulze et al., 2005)

LamC^G489V.UAS

model of myopathy

CEA

(Dialynas et al., 2012)

model of muscular dystrophy

CEA

(Shaw et al., 2022, Dialynas et al., 2015)

model of congenital muscular dystrophy due to LMNA mutation

CEA

(Chandran et al., 2019)

model of dilated cardiomyopathy 1A

CEC

(Bhide et al., 2018)

LamC^N496I.UAS

model of myopathy

CEA

(Dialynas et al., 2012)

model of muscular dystrophy

CEA

(Dialynas et al., 2015)

LamC^V528P.UAS

model of myopathy

CEA

(Dialynas et al., 2012)

model of muscular dystrophy

CEA

(Dialynas et al., 2015)

model of congenital muscular dystrophy due to LMNA mutation

CEA

(Chandran et al., 2019)

LamC^M553R.UAS

model of myopathy

CEA

(Dialynas et al., 2012)

model of muscular dystrophy

CEA

(Dialynas et al., 2015)

LamC^ΔN.UAS.cSa

model of muscular dystrophy

CEA

(Dialynas et al., 2015, Zwerger et al., 2013)

LamC^E174K.UAS

model of progeria

CEA with LamC^unspecified

(Li et al., 2016)

LamC^unspecified

model of progeria

CEA with LamC^E174K.UAS

(Li et al., 2016)

LamC^R205W.UAS

model of congenital muscular dystrophy due to LMNA mutation

CEA

(Chandran et al., 2019)

model of dilated cardiomyopathy 1A

CEC

(Shaw et al., 2022, Bhide et al., 2018)

LamC^A177P.UAS

model of congenital muscular dystrophy due to LMNA mutation

CEA

(Chandran et al., 2019)

LamC^R264W.UAS

model of congenital muscular dystrophy due to LMNA mutation

CEA

(Hinz et al., 2021)

LamC^R264Q.UAS

model of congenital muscular dystrophy due to LMNA mutation

CEA

(Hinz et al., 2021)

LamC^S37L.UAS

model of dilated cardiomyopathy 1A

CEC

(Shaw et al., 2022)

LamC^ΔK47.UAS

model of autosomal dominant Emery-Dreifuss muscular dystrophy 2

CEC

(Shaw et al., 2022)

LamC^L74R.UAS

model of dilated cardiomyopathy 1A

CEC

(Shaw et al., 2022)

LamC^R237P.UAS

model of congenital muscular dystrophy due to LMNA mutation

CEA

(Shaw et al., 2022)

LamC^K521Q.UAS

model of autosomal recessive Emery-Dreifuss muscular dystrophy 3

CEC

(Shaw et al., 2022)

LamC^R564P.UAS

model of autosomal dominant Emery-Dreifuss muscular dystrophy 2

CEA

(Walker et al., 2023)

CEC

(Shaw et al., 2022)

LamC^K521W.UAS

model of familial partial lipodystrophy type 2

CEA

(Walker et al., 2023)

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

LamC^G00158

exacerbates Huntington's disease

modeled by Hsap\HTT^{128Q.1-336.UAS}

(Kaltenbach et al., 2007)

LamC^k11904

exacerbates Huntington's disease

modeled by Hsap\HTT^{128Q.1-336.UAS}

(Kaltenbach et al., 2007)

LamC^G489V.UAS

model of congenital muscular dystrophy due to LMNA mutation

is exacerbated by AMPKα^HMC04979

(Chandran et al., 2019)

is ameliorated by AMPKα^UAS.cMa

(Chandran et al., 2019)

is ameliorated by S6k^KQ.UAS

(Chandran et al., 2019)

is exacerbated by Thor^KK108272

(Chandran et al., 2019)

is ameliorated by Thor^UAS.cMa

(Chandran et al., 2019)

is exacerbated by foxo^KK108485

(Chandran et al., 2019)

is ameliorated by foxo^UASp.GFP

(Chandran et al., 2019)

is ameliorated by srl^UAS.cRa

(Chandran et al., 2019)

is exacerbated by srl^KK100201

(Chandran et al., 2019)

model of dilated cardiomyopathy 1A

is exacerbated by Atg1^K38Q.UAS

(Bhide et al., 2018)

is ameliorated by Atg1^UAS.cSa

(Bhide et al., 2018)

is ameliorated by cnc^GD4437

(Bhide et al., 2018)

is ameliorated by cnc^KK103976

(Bhide et al., 2018)

Hsap\LMNA

Models Based on Experimental Evidence ( 2 )

Allele

Disease

Evidence

References

Hsap\LMNA^UAS.A

model of progeria

CEA

(Beard et al., 2008)

Hsap\LMNA^{progerin.UAS.A}

model of progeria

CEA

(Beard et al., 2008)

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\LMNA^UAS.Tag:HA

PBac{UAS-hLMNA.HA}

y¹ w^*; PBac{UAS-hLMNA.HA}VK00033

Hsap\LMNA^{progerin.UAS.A}

P{UAS-LMNA.A.progerin}

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

w¹¹¹⁸; P{GD1478}v45635/TM3

y¹ v¹; P{TRiP.JF01389}attP2

Lam^GL00577

P{TRiP.GL00577}

y¹ sc^* v¹ sev²¹; P{TRiP.GL00577}attP2

Lam^HMC04816

P{TRiP.HMC04816}

y¹ sc^* v¹ sev²¹; P{TRiP.HMC04816}attP40

y¹ v¹; P{TRiP.JF01406}attP2

LamC^NIG.10119R

P{NIG.10119R}

P{NIG.10119R}1

LamC^{RNAi.Sym.UTR.UAS}

P{UAS-LamC.UTR.RNAi}

LamC^{RNAi.Sym.tail.UAS}

P{UAS-LamC.tail.RNAi}

LamC^RNAi.UAS.cUa

P{UAS-LamC.RNAi.U}

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Lam⁰⁴⁶⁴³

loss of function allele

P-element activity

P{PZ}Lam⁰⁴⁶⁴³ cn¹/CyO; ry⁵⁰⁶

Lam¹⁴

amorphic allele - genetic evidence

P-element activity

Lam^Ari3

loss of function allele

ethyl methanesulfonate

Lam⁹

amorphic allele - genetic evidence

P-element activity

Lam⁸³

loss of function allele

X ray

Lam^A25

loss of function allele

X ray

Lam^A25 pr¹/CyO; st¹

Lam^Ari7

loss of function allele

ethyl methanesulfonate

Lam^K2

loss of function allele

X ray

Lam^K2 pr¹/CyO; st¹

LamC^k11904

P-element activity

y^d2 w¹¹¹⁸ P{ey-FLP.N}2 P{5xglBS-lacZ.38-1}TPN1; P{neoFRT}42D P{lacW}ttv^k11904 /CyO y⁺

LamC^G00158

P-element activity

y^* w^* P{PTT-GB}LamC^G00158

LamC^LC10

amorphic allele - molecular evidence

Delta2-3 transposase

LamC^LC58

amorphic allele - molecular evidence

Delta2-3 transposase

LamC^unspecified

References (21)

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