Human Disease Model Report: attention deficit hyperactivity disorder, susceptibility to (postulated), MEF2C-related

General Information

Name

attention deficit hyperactivity disorder, susceptibility to (postulated), MEF2C-related

FlyBase ID

FBhh0001217

Disease Ontology Term

attention deficit hyperactivity disorder

Parent Disease

OMIM

Overview

The human gene MEF2C has been identified as a candidate susceptibility locus for attention deficit hyperactivity disorder. MEF2C is a member of the Mef2 family of transcription factors, involved in myogenesis and heart development. There are four Mef2 family paralogs in humans, MEF2A-MEF2D. There is a single orthologous gene in Drosophila, Dmel\Mef2, for which classical loss-of-function alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated.

MEF2C has also been identified as the locus behind a disorder of mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations (MIM:613443), which is contained in a region removed by chromosome 5q14.3 deletion syndrome (same entry, MIM:613443).

The human gene MEF2C has not been introduced into flies.

Mef2 is expressed in dopaminergic and circadian neurons in Drosophila. When Mef2 is knocked down pan-neuronally, flies show increased increased night activity and reduced sleep, both measures of ADHD-associated behavior in Drosophila (see other fly models of ADHD at FBhh0000653). This effect is exacerbated when flies are kept in a fully dark environment, causing further sleep disruptions and less activity during awake periods.

[updated Jun. 2020 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: attention deficit hyperactivity disorder, susceptibility to (postulated), MEF2C-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

The role of circadian genes and circuits in ADHD has been implicated, as ADHD often goes together with sleep disturbances, and abnormal circadian rhythms of melatonin secretion have been observed in children and adult patients with ADHD. Notably, positive genetic correlations between insomnia and sleep-related traits and ADHD exist. Abnormal circadian rhythms of melatonin secretion have been observed in children and adult patients with ADHD. Notably, positive genetic correlations between insomnia and sleep-related traits and ADHD exist. (Adapted from Klein et al. 2020 and references therein, FBrf0245813.)

(FlyBase Curators, 2013-)

Genetics

Cellular phenotype and pathology

Molecular information

MEF2 proteins belong to MADS-box family of transcription factors. MADS-box is named from the four proteins minichromosome maintenance genes (MCM1), agamous (AG), deficiens (DEFA) and serum response factor (SRF), which share a contiguous conserved motif in eukaryotic organisms. MEF2 proteins were initially identified as a vital factor for skeletal muscle development that have the ability to bind A/T-rich sequences within gene promoter of muscle creatine kinase (MCK). (Chen et al. 2017 and references therein, pubmed:29340119.)

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): MEF2C
Gene2Function (human gene): MEF2C
Gene Cards: MEF2C
MedlinePlus (condition): attention-deficit-hyperactivity-disorder
MedlinePlus (gene): MEF2C
MARRVEL (human gene): MADS BOX TRANSCRIPTION ENHANCER FACTOR 2, POLYPEPTIDE C; MEF2C
MARRVEL (human gene): MEF2C
NCBI MedGen: Attention deficit hyperactivity disorder (ADHD)
NCBI (Entrez) gene: MEF2C; myocyte enhancer factor 2C

Disease synonyms

ADHD

Search term: ADD

Related Diseases

Related human health report(s)

attention deficit hyperactivity disorder, susceptibility to

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

MEF2C; myocyte enhancer factor 2C

D. melanogaster ortholog (based on DIOPT)

Dmel\Mef2

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 4 human gene. to 1 Drosophila gene.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Mef2

Gene Snapshot

Myocyte enhancer factor 2 (Mef2) encodes a protein that belongs to the MADS-box family of transcription factors and is required for muscle development. It directly activates a large number of muscle protein genes. It also regulates gene expression in other tissues, including the fat body and neural tissue. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

nucleus

Gene Groups / Pathways

MADSTF

Comments on ortholog(s)

High-ranking ortholog for three of the four human MEF2 family genes: MEFA, MEFC, and MEF2. Moderately-ranking ortholog for human MEF2B.

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)

Mef2

protein-protein

Interacting group

Assay

References

Mef2

electrophoretic mobility shift assay, autoradiography

(Lovato et al., 2009)

Mef2 - abd-A

bimolecular fluorescence complementation, fluorescence microscopy, anti tag coimmunoprecipitation, anti tag western blot

(Bischof et al., 2018, Baëza et al., 2015)

Mef2 - Abd-B

bimolecular fluorescence complementation, fluorescence microscopy

(Baëza et al., 2015)

Mef2 - Ada2b

anti tag coimmunoprecipitation, peptide massfingerprinting

(Weake et al., 2011)

Mef2 - Antp

bimolecular fluorescence complementation, fluorescence microscopy

(Baëza et al., 2015)

Mef2 - Eip78C

two hybrid array

(Shokri et al., 2019)

Mef2 - Hsdl2

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

Mef2 - nej

two hybrid

(Lin and Baines, 2019)

Mef2 - Paics

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

Mef2 - Rel

two hybrid array

(Shokri et al., 2019)

Mef2 - Scr

bimolecular fluorescence complementation, fluorescence microscopy

(Baëza et al., 2015)

Mef2 - sd

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

(Bernard et al., 2009, Deng et al., 2009)

Mef2 - Svil

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

Mef2 - Tbp

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation

(Clark et al., 2013)

Mef2 - TfIIFβ

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

Mef2 - TfIIS

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

Mef2 - twi

pull down, autoradiography

(Bernard et al., 2009)

Mef2 - Ubx

bimolecular fluorescence complementation, fluorescence microscopy

(Bischof et al., 2018, Baëza et al., 2015)

Mef2 - vg

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

(Deng et al., 2009)

RNA-RNA

Interacting group

Assay

References

Mef2 - mir-92b

quantitative reverse transcription pcr, luminiscence technology, necessary binding region, western blot

(Chen et al., 2012)

Mef2 - mir-124

quantitative reverse transcription pcr

(Sun et al., 2012)

Alleles Reported to Model Human Disease (Disease Ontology) (5 alleles)

Mef2

Models Based on Experimental Evidence ( 2 )

Allele

Disease

Evidence

References

Mef2^GD5039

model of attention deficit hyperactivity disorder

CEA

(Klein et al., 2020)

Mef2^UAS.cUa

model of carcinoma

CEA with N^ICN.UAS

(Pallavi et al., 2012)

model of cancer

CEA with N^ICN.UAS

(Harsh and Eleftherianos, 2020)

Modifiers Based on Experimental Evidence ( 4 )

Allele

Disease

Interaction

References

Mef2^22-21

ameliorates alveolar rhabdomyosarcoma

modeled by Hsap\FOXO1::Hsap\PAX7^UAS.cGa

(Galindo et al., 2014)

Mef2^KG01211a

ameliorates Huntington's disease

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

(Kaltenbach et al., 2007)

Mef2^X1

ameliorates cardiomyopathy

modeled by Pp2B-14D^{act.tin.C.Tag:FLAG}

(Lee et al., 2014)

modeled by Pp2B-14D^act.UAS.EYFP

(Lee et al., 2014)

ameliorates Huntington's disease

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

(Kaltenbach et al., 2007)

Mef2^GD5039

ameliorates Friedreich ataxia

modeled by fh¹

(Chen et al., 2016)

DOES NOT exacerbate neurodegenerative disease

modeled by Zzzz\CAG^{CAA.94.UAS.Tag:MYC,Tag:FLAG}

(van Eyk et al., 2011)

modeled by Zzzz\CAG^{93.UAS.Tag:MYC,Tag:FLAG}

(van Eyk et al., 2011)

exacerbates neurodegenerative disease

modeled by Zzzz\CTG^{86.UAS.Tag:MYC,Tag:FLAG}

(van Eyk et al., 2011)

ameliorates amyotrophic lateral sclerosis type 8

modeled by Vap33^{P58S.UAS.Tag:FLAG}

(Sanhueza et al., 2015)

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

Mef2^UAS.cUa

P{UAS-Mef2.U}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

Mef2^GD5039

P{GD5039}

w¹¹¹⁸; P{GD5039}v15549/TM3

Mef2^JF03115

P{TRiP.JF03115}

y¹ v¹; P{TRiP.JF03115}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01691}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Mef2^P544

loss of function allele

Delta2-3 transposase

Mef2^KG01211a

P-element activity

y¹ w^67c23; P{SUPor-P}Mef2^KG01211a, P{SUPor-P}KG01211b

Mef2^S0283

loss of function allele

y¹ w^*; P{org-1.SM-RFP}Jon25Bi^18a P{tinC-GFP}cn^13b Mef2^S0283 P{HLH54F.LVM-RFP}Sin3A^16b/CyO, P{GAL4-twi.G}2.2, P{UAS-2xEGFP}AH2.2

Mef2^S1801

loss of function allele

y¹ w^*; P{org-1.SM-RFP}Jon25Bi^18a P{tinC-GFP}cn^13b Mef2^S1801 P{HLH54F.LVM-RFP}16c/CyO, P{GAL4-twi.G}2.2, P{UAS-2xEGFP}AH2.2

Mef2^22-21

amorphic allele - genetic evidence

diepoxybutane

Adh^fn23 cn¹ pr¹ Mef2^22-21/CyO

Mef2^26-7

amorphic allele - genetic evidence

diepoxybutane

Mef2^X1

amorphic allele - genetic evidence

X ray

Df(2R)X1, Mef2^X1/CyO, Adh^nB

References (4)

Report Sections

Open Close