This gene is a member of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors. Members of this family are involved in control of muscle and neuronal cell differentiation and development, and are regulated by class II histone deacetylases. Fusions of the encoded protein with Deleted in Azoospermia-Associated Protein 1 (DAZAP1) due to a translocation have... See more...

Aliases for MEF2D Gene

Aliases for MEF2D Gene

  • Myocyte Enhancer Factor 2D 2 3 5
  • Myocyte-Specific Enhancer Factor 2D 3 4
  • MADS Box Transcription Enhancer Factor 2, Polypeptide D 3

External Ids for MEF2D Gene

Previous GeneCards Identifiers for MEF2D Gene

  • GC01M154302
  • GC01M152201
  • GC01M153213
  • GC01M153650
  • GC01M153246
  • GC01M154700
  • GC01M156433
  • GC01M127793

Summaries for MEF2D Gene

Entrez Gene Summary for MEF2D Gene

  • This gene is a member of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors. Members of this family are involved in control of muscle and neuronal cell differentiation and development, and are regulated by class II histone deacetylases. Fusions of the encoded protein with Deleted in Azoospermia-Associated Protein 1 (DAZAP1) due to a translocation have been found in an acute lymphoblastic leukemia cell line, suggesting a role in leukemogenesis. The encoded protein may also be involved in Parkinson disease and myotonic dystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

GeneCards Summary for MEF2D Gene

MEF2D (Myocyte Enhancer Factor 2D) is a Protein Coding gene. Diseases associated with MEF2D include Migraine Without Aura and Brachydactyly, Type E1. Among its related pathways are Development Angiotensin activation of ERK and Mitochondrial Gene Expression. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and DNA-binding transcription factor activity, RNA polymerase II-specific. An important paralog of this gene is MEF2A.

UniProtKB/Swiss-Prot Summary for MEF2D Gene

  • Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific, growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. Plays a critical role in the regulation of neuronal apoptosis (By similarity).

Gene Wiki entry for MEF2D Gene

Additional gene information for MEF2D Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MEF2D Gene

Genomics for MEF2D Gene

GeneHancer (GH) Regulatory Elements for MEF2D Gene

Promoters and enhancers for MEF2D Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MEF2D on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MEF2D

Top Transcription factor binding sites by QIAGEN in the MEF2D gene promoter:
  • aMEF-2
  • CREB
  • deltaCREB
  • MEF-2A
  • p300
  • Sp1
  • STAT1
  • STAT3

Genomic Locations for MEF2D Gene

Genomic Locations for MEF2D Gene
chr1:156,463,721-156,500,842
(GRCh38/hg38)
Size:
37,122 bases
Orientation:
Minus strand
chr1:156,433,519-156,470,620
(GRCh37/hg19)
Size:
37,102 bases
Orientation:
Minus strand

Genomic View for MEF2D Gene

Genes around MEF2D on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MEF2D Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MEF2D Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MEF2D Gene

Proteins for MEF2D Gene

  • Protein details for MEF2D Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14814-MEF2D_HUMAN
    Recommended name:
    Myocyte-specific enhancer factor 2D
    Protein Accession:
    Q14814
    Secondary Accessions:
    • D3DVC0
    • Q14815
    • Q5T9U5
    • Q5T9U6

    Protein attributes for MEF2D Gene

    Size:
    521 amino acids
    Molecular mass:
    55938 Da
    Quaternary structure:
    • Interacts with MYOG (By similarity). Forms a complex with class II HDACs in undifferentiating cells. On myogenic differentiation, HDACs are released into the cytoplasm allowing MEF2s to interact with other proteins for activation. Interacts with HDAC4 (in undifferentiating cells); the interaction translocates MEF2D to nuclear dots. Forms a heterodimer with MEF2A. Interacts with MAPK7; the interaction phosphorylates but does not activate MEF2D (By similarity). Interacts with CCAR2 and HDAC3.

    Alternative splice isoforms for MEF2D Gene

neXtProt entry for MEF2D Gene

Post-translational modifications for MEF2D Gene

  • Phosphorylated on Ser-444 by CDK5 is required for Lys-439 sumoylation and inhibits transcriptional activity. In neurons, enhanced CDK5 activity induced by neurotoxins promotes caspase 3-mediated cleavage leading to neuron apoptosis. Phosphorylation on Ser-180 can be enhanced by EGF. Phosphorylated and activated by CaMK4.
  • Acetylated on Lys-439 by CREBBP. Acetylated by EP300. Deacetylated by SIRT1 and HDAC3.
  • Sumoylated on Lys-439 with SUMO2 but not SUMO1; which inhibits transcriptional activity and myogenic activity. Desumoylated by SENP3.
  • Proteolytically cleaved in cerebellar granule neurons on several sites by caspase 7 following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation (By similarity).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for MEF2D Gene

Domains & Families for MEF2D Gene

Gene Families for MEF2D Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for MEF2D Gene

Blocks:
  • Transcription factor, MADS-box
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for MEF2D Gene

GenScript: Design optimal peptide antigens:
  • Myocyte-specific enhancer factor 2D (MEF2D_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q14814

UniProtKB/Swiss-Prot:

MEF2D_HUMAN :
  • The beta domain, missing in a number of isoforms, is required for enhancement of transcriptional activity.
  • Belongs to the MEF2 family.
Domain:
  • The beta domain, missing in a number of isoforms, is required for enhancement of transcriptional activity.
Family:
  • Belongs to the MEF2 family.
genes like me logo Genes that share domains with MEF2D: view

Function for MEF2D Gene

Molecular function for MEF2D Gene

UniProtKB/Swiss-Prot Function:
Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific, growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. Plays a critical role in the regulation of neuronal apoptosis (By similarity).
GENATLAS Biochemistry:
myocyte-specific enhancer binding factor 2D,interacting with members of the MyoD family of transcriptional activator,also interacting with TWIST to inhibit myogenesis,negatively regulated by MITR in association with HDAC1,also expressed in muscle cells

Phenotypes From GWAS Catalog for MEF2D Gene

Gene Ontology (GO) - Molecular Function for MEF2D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA,IEA 20590529
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IBA 21873635
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS,IDA 19274049
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IEA --
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with MEF2D: view
genes like me logo Genes that share phenotypes with MEF2D: view

Animal Models for MEF2D Gene

MGI Knock Outs for MEF2D:

Animal Model Products

CRISPR Products

miRNA for MEF2D Gene

miRTarBase miRNAs that target MEF2D
Targeted motifs for MEF2D Gene
HOMER Transcription Factor Regulatory Elements motif MEF2D
  • Consensus sequence: GCTATTTTTAGC Submotif: canonical Cell Type: Retina GEO ID: GSE61391

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MEF2D

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology and Transcription Factor Targets for MEF2D Gene

Localization for MEF2D Gene

Subcellular locations from UniProtKB/Swiss-Prot for MEF2D Gene

Nucleus. Note=Translocated by HDAC4 to nuclear dots.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MEF2D gene
Compartment Confidence
nucleus 5
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
cytosol 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (4)
  • Vesicles (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MEF2D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IDA,IEA 20590529
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA --
GO:0043231 intracellular membrane-bounded organelle IDA --
genes like me logo Genes that share ontologies with MEF2D: view

Pathways & Interactions for MEF2D Gene

PathCards logo

SuperPathways for MEF2D Gene

SuperPathway Contained pathways
1 NFAT and Cardiac Hypertrophy
.42
.42
.37
2 CREB Pathway
.68
.50
3 Myogenesis
1.00
4 Mitochondrial Gene Expression
5 Immune response Function of MEF2 in T lymphocytes
.36
.36
genes like me logo Genes that share pathways with MEF2D: view

Pathways by source for MEF2D Gene

5 GeneGo (Thomson Reuters) pathways for MEF2D Gene
  • Development Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis
  • Immune response Function of MEF2 in T lymphocytes
  • Signal transduction Activation of PKC via G-Protein coupled receptor
  • Signal transduction Calcium signaling
  • Signal transduction IP3 signaling
17 Qiagen pathways for MEF2D Gene
  • Calcium Mediated T-Cell Apoptosis
  • CCKBR-Gastrin Stimulated Signaling
  • CRHR Pathway
  • Crosstalk Between CARM1 and ESRs
  • ERK5 Signaling

SIGNOR curated interactions for MEF2D Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MEF2D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001649 osteoblast differentiation IEA --
GO:0001958 endochondral ossification IEA --
GO:0002062 chondrocyte differentiation IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006915 apoptotic process IEA --
genes like me logo Genes that share ontologies with MEF2D: view

Drugs & Compounds for MEF2D Gene

(1) Drugs for MEF2D Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(2) Additional Compounds for MEF2D Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with MEF2D: view

Transcripts for MEF2D Gene

mRNA/cDNA for MEF2D Gene

2 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MEF2D

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MEF2D Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6a · 6b · 6c ^ 7a · 7b ^ 8a · 8b · 8c ^ 9a · 9b ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17
SP1: -
SP2:
SP3:
SP4:
SP5: - - -
SP6: -
SP7: -
SP8:
SP9:

Relevant External Links for MEF2D Gene

GeneLoc Exon Structure for
MEF2D

Expression for MEF2D Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MEF2D Gene

mRNA differential expression in normal tissues according to GTEx for MEF2D Gene

This gene is overexpressed in Muscle - Skeletal (x4.3).

Protein differential expression in normal tissues from HIPED for MEF2D Gene

This gene is overexpressed in Retina (14.8), Peripheral blood mononuclear cells (11.5), CD8 Tcells (9.9), and NK cells (7.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MEF2D Gene



Protein tissue co-expression partners for MEF2D Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MEF2D

SOURCE GeneReport for Unigene cluster for MEF2D Gene:

Hs.314327

Evidence on tissue expression from TISSUES for MEF2D Gene

  • Muscle(4.7)
  • Heart(4.6)
  • Eye(4.4)
  • Liver(4.2)
  • Nervous system(3.9)
genes like me logo Genes that share expression patterns with MEF2D: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for MEF2D Gene

Orthologs for MEF2D Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MEF2D Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MEF2D 31
  • 100 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MEF2D 31
  • 94 (a)
OneToOne
cow
(Bos Taurus)
Mammalia MEF2D 31 30
  • 93.43 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Mef2d 17 31 30
  • 91.06 (n)
rat
(Rattus norvegicus)
Mammalia Mef2d 30
  • 90.73 (n)
dog
(Canis familiaris)
Mammalia MEF2D 31 30
  • 88.21 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MEF2D 31
  • 73 (a)
OneToOne
chicken
(Gallus gallus)
Aves MEF2D 31 30
  • 75.2 (n)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia mef2d 30
  • 73.37 (n)
Str.7341 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.19991 30
zebrafish
(Danio rerio)
Actinopterygii mef2d 31 30 30
  • 69.22 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Mef2 31
  • 31 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea mef-2 32
  • 74 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SMP1 31
  • 19 (a)
ManyToMany
RLM1 31
  • 17 (a)
ManyToMany
rice
(Oryza sativa)
Liliopsida Os.4153 30
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 96 (a)
OneToMany
Species where no ortholog for MEF2D was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MEF2D Gene

ENSEMBL:
Gene Tree for MEF2D (if available)
TreeFam:
Gene Tree for MEF2D (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MEF2D: view image

Paralogs for MEF2D Gene

Paralogs for MEF2D Gene

(7) SIMAP similar genes for MEF2D Gene using alignment to 2 proteins:

  • MEF2D_HUMAN
  • Q05BX2_HUMAN
genes like me logo Genes that share paralogs with MEF2D: view

Variants for MEF2D Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MEF2D Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
rs2274315 - p.Pro434Ser

Additional dbSNP identifiers (rs#s) for MEF2D Gene

Structural Variations from Database of Genomic Variants (DGV) for MEF2D Gene

Variant ID Type Subtype PubMed ID
nsv1078835 CNV deletion 25765185

Variation tolerance for MEF2D Gene

Residual Variation Intolerance Score: 14.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.79; 16.66% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MEF2D Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
MEF2D

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MEF2D Gene

Disorders for MEF2D Gene

MalaCards: The human disease database

(3) MalaCards diseases for MEF2D Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
migraine without aura
  • common migraine
brachydactyly, type e1
  • bde1
migraine with or without aura 1
  • migraine with or without aura, susceptibility to, 1
- elite association - COSMIC cancer census association via MalaCards
Search MEF2D in MalaCards View complete list of genes associated with diseases

Additional Disease Information for MEF2D

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with MEF2D: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MEF2D Gene

Publications for MEF2D Gene

  1. A fourth human MEF2 transcription factor, hMEF2D, is an early marker of the myogenic lineage. (PMID: 8269842) Breitbart RE … Nadal-Ginard B (Development (Cambridge, England) 1993) 2 3 4 23 54
  2. Control of MEF2 transcriptional activity by coordinated phosphorylation and sumoylation. (PMID: 16356933) Grégoire S … Yang XJ (The Journal of biological chemistry 2006) 3 4 23 54
  3. Big mitogen-activated kinase regulates multiple members of the MEF2 protein family. (PMID: 10849446) Kato Y … Lee JD (The Journal of biological chemistry 2000) 3 4 23 54
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41 54
  5. Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program. (PMID: 20682687) Jablonski KA … Diabetes Prevention Program Research Group (Diabetes 2010) 3 41 54

Products for MEF2D Gene

Sources for MEF2D Gene