This gene encodes a mitochondrial NAD-dependent malic enzyme, a homotetrameric protein, that catalyzes the oxidative decarboxylation of malate to pyruvate. It had previously been weakly linked to a syndrome known as Friedreich ataxia that has since been shown to be the result of mutation in a completely different gene. Certain single-nucleotide polymorphism haplotypes of this g... See more...

Aliases for ME2 Gene

Aliases for ME2 Gene

  • Malic Enzyme 2 2 3 4 5
  • NAD-Dependent Malic Enzyme, Mitochondrial 2 3 4
  • Malate Dehydrogenase (Oxaloacetate-Decarboxylating) 2 3
  • Malic Enzyme 2, NAD(+)-Dependent, Mitochondrial 2 3
  • NAD-ME 3 4
  • Pyruvic-Malic Carboxylase 3
  • EC 4
  • EC 1.1.1 50
  • ODS1 3
  • ME2 5

External Ids for ME2 Gene

Previous GeneCards Identifiers for ME2 Gene

  • GC18P048588
  • GC18P048341
  • GC18P046657
  • GC18P046659
  • GC18P048405
  • GC18P045260

Summaries for ME2 Gene

Entrez Gene Summary for ME2 Gene

  • This gene encodes a mitochondrial NAD-dependent malic enzyme, a homotetrameric protein, that catalyzes the oxidative decarboxylation of malate to pyruvate. It had previously been weakly linked to a syndrome known as Friedreich ataxia that has since been shown to be the result of mutation in a completely different gene. Certain single-nucleotide polymorphism haplotypes of this gene have been shown to increase the risk for idiopathic generalized epilepsy. Alternatively spliced transcript variants encoding different isoforms found for this gene. [provided by RefSeq, Dec 2009]

GeneCards Summary for ME2 Gene

ME2 (Malic Enzyme 2) is a Protein Coding gene. Diseases associated with ME2 include Epilepsy, Idiopathic Generalized and Epilepsy. Among its related pathways are Carbon metabolism and Glucose metabolism. Gene Ontology (GO) annotations related to this gene include electron transfer activity and malic enzyme activity. An important paralog of this gene is ME3.

Gene Wiki entry for ME2 Gene

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ME2 Gene

Genomics for ME2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ME2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH18J050877 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 270 +0.6 563 3.9 SP1 ZNF207 MYC ZNF600 POLR2A ZBTB10 CTCF CEBPB REST SMAD5 ME2 lnc-MRO-2 CXXC1 MBD1 SMAD4 RF00017-2415 ELAC1
GH18J051027 Promoter/Enhancer 1.6 Ensembl ENCODE CraniofacialAtlas 20 +151.7 151744 5.5 MYC ZNF600 KLF9 CEBPA POLR2A ZIC2 ZBTB10 YY1 MXD4 REST LOC105372117 NONHSAG023864.2 lnc-MEX3C-4 ME2 MRO RPL17P46 SMAD4 lnc-SMAD4-2 ENSG00000267699 MEX3C
GH18J050868 Enhancer 1.1 Ensembl ENCODE 18.5 -10.3 -10301 4.8 ZNF654 NCOR1 ZNF600 JUND ATF2 ZNF10 NFIC REST CEBPB HES1 ME2 RPL17P46 MRO piR-43106-103
GH18J050853 Enhancer 0.9 FANTOM5 ENCODE 21.4 -24.3 -24279 2.2 CEBPA YY1 CEBPB MAFF RXRA ZNF316 TCF7L2 JUND MAFK SPI1 piR-35674-234 ME2 MRO
GH18J050967 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 9.3 +89.4 89399 4.2 BCLAF1 ZNF207 MYC POLR2A ZNF223 ZBTB10 YY1 NONO ZNF592 SMAD5 ELAC1 ENSG00000267699 lnc-ME2-6 CXXC1 MBD1 MEX3C ME2 piR-48325-078 piR-36588-204 SMAD4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ME2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ME2

Top Transcription factor binding sites by QIAGEN in the ME2 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • Cart-1
  • FOXO1
  • FOXO1a
  • HSF2
  • POU2F1
  • POU2F1a
  • POU6F1 (c2)

Genomic Locations for ME2 Gene

Latest Assembly
75,556 bases
Plus strand

Previous Assembly
(GRCh37/hg19 by Entrez Gene)
75,140 bases
Plus strand

(GRCh37/hg19 by Ensembl)
69,273 bases
Plus strand

Genomic View for ME2 Gene

Genes around ME2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ME2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ME2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ME2 Gene

Proteins for ME2 Gene

  • Protein details for ME2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    NAD-dependent malic enzyme, mitochondrial
    Protein Accession:
    Secondary Accessions:
    • B2R8J2
    • Q9BWL6
    • Q9BYG1
    • Q9H4B2

    Protein attributes for ME2 Gene

    584 amino acids
    Molecular mass:
    65444 Da
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
    Quaternary structure:
    • Homotetramer.
    • This isoenzyme can also use NADP(+) but is more effective with NAD(+).

    Three dimensional structures from OCA and Proteopedia for ME2 Gene

    Alternative splice isoforms for ME2 Gene


neXtProt entry for ME2 Gene

Selected DME Specific Peptides for ME2 Gene


Post-translational modifications for ME2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibodies for research

  • Abcam antibodies for ME2
  • Santa Cruz Biotechnology (SCBT) Antibodies for ME2

Domains & Families for ME2 Gene

Gene Families for ME2 Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for ME2 Gene

Suggested Antigen Peptide Sequences for ME2 Gene

GenScript: Design optimal peptide antigens:
  • Malic enzyme 2 (MAOM_HUMAN)
  • Cadherin (O15200_HUMAN)
  • Malic enzyme (Q9BWL6_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the malic enzymes family.
  • Belongs to the malic enzymes family.
genes like me logo Genes that share domains with ME2: view

Function for ME2 Gene

Molecular function for ME2 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(S)-malate + NAD(+) = CO2 + NADH + pyruvate; Xref=Rhea:RHEA:12653, ChEBI:CHEBI:15361, ChEBI:CHEBI:15589, ChEBI:CHEBI:16526, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H(+) + oxaloacetate = CO2 + pyruvate; Xref=Rhea:RHEA:15641, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16452, ChEBI:CHEBI:16526; EC=;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Subject to allosteric activation by fumarate.
GENATLAS Biochemistry:
malic enzyme 2,mitochondrial

Enzyme Numbers (IUBMB) for ME2 Gene

Phenotypes From GWAS Catalog for ME2 Gene

Gene Ontology (GO) - Molecular Function for ME2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0004470 malic enzyme activity IEA,IMP 23334421
GO:0004471 malate dehydrogenase (decarboxylating) (NAD+) activity IEA --
GO:0004473 malate dehydrogenase (decarboxylating) (NADP+) activity IBA 21873635
GO:0008948 oxaloacetate decarboxylase activity IEA --
genes like me logo Genes that share ontologies with ME2: view
genes like me logo Genes that share phenotypes with ME2: view

Animal Models for ME2 Gene

MGI Knock Outs for ME2:
  • Me2 Me2<tm1b(EUCOMM)Hmgu>

Animal Models for research

  • Taconic Biosciences Mouse Models for ME2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ME2

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ME2 Gene

Localization for ME2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ME2 Gene

Mitochondrion matrix.

Subcellular locations from

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 ME2 gene
Compartment Confidence
mitochondrion 5
cytosol 3
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
nucleus 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for ME2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA --
GO:0005759 mitochondrial matrix TAS --
GO:0043231 intracellular membrane-bounded organelle IDA --
genes like me logo Genes that share ontologies with ME2: view

Pathways & Interactions for ME2 Gene

genes like me logo Genes that share pathways with ME2: view

Pathways by source for ME2 Gene

2 KEGG pathways for ME2 Gene
1 Cell Signaling Technology pathway for ME2 Gene

Gene Ontology (GO) - Biological Process for ME2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006090 pyruvate metabolic process IBA 21873635
GO:0006099 tricarboxylic acid cycle TAS --
GO:0006108 malate metabolic process IBA 21873635
GO:0008152 metabolic process IEA --
GO:0022900 electron transport chain IEA --
genes like me logo Genes that share ontologies with ME2: view

No data available for SIGNOR curated interactions for ME2 Gene

Drugs & Compounds for ME2 Gene

(15) Drugs for ME2 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
NADH Approved Nutra Target 0
Magnesium Approved, Experimental, Investigational Pharma 0
Carbon dioxide Approved, Investigational, Vet_approved Pharma 0
Manganese Approved Nutra 65
Pyruvic acid Approved, Investigational Nutra 0

(7) Additional Compounds for ME2 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Hydrogen Ion
  • H+
  • H(+)
  • Hydron
  • Hydrogen cation
  • Proton
Hydroxypropanedioic acid
  • 2-Hydroxymalonate
  • 2-Hydroxymalonic acid
  • 2-Hydroxypropanedioic acid
  • 2-Tartronic acid
  • Tartronic acid
Oxalacetic acid
  • 2-Oxobutanedioic acid
  • 2-Oxosuccinic acid
  • 3-Carboxy-3-oxopropanoic acid
  • Keto-succinic acid
  • Ketosuccinic acid
genes like me logo Genes that share compounds with ME2: view

Transcripts for ME2 Gene

mRNA/cDNA for ME2 Gene

9 NCBI additional mRNA sequence :
19 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ME2

Alternative Splicing Database (ASD) splice patterns (SP) for ME2 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15 ^ 16a · 16b · 16c
SP1: -
SP2: - - -
SP4: -

Relevant External Links for ME2 Gene

GeneLoc Exon Structure for

Expression for ME2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ME2 Gene

Protein differential expression in normal tissues from HIPED for ME2 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (9.4) and Spleen (6.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ME2 Gene

Protein tissue co-expression partners for ME2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ME2

SOURCE GeneReport for Unigene cluster for ME2 Gene:


Evidence on tissue expression from TISSUES for ME2 Gene

  • Blood(4.3)
  • Liver(4.3)
  • Nervous system(3.3)
  • Muscle(3.1)
  • Kidney(3.1)
  • Lung(3)
  • Heart(2.9)
  • Adrenal gland(2.7)
  • Gall bladder(2.7)
  • Intestine(2.7)
  • Lymph node(2.7)
  • Spleen(2.7)
  • Stomach(2.7)
  • Thyroid gland(2.7)
  • Pancreas(2.6)
genes like me logo Genes that share expression patterns with ME2: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for ME2 Gene

Orthologs for ME2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for ME2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia ME2 29 30
  • 99.54 (n)
(Canis familiaris)
Mammalia ME2 29 30
  • 90.64 (n)
(Bos Taurus)
Mammalia ME2 29 30
  • 90.24 (n)
(Rattus norvegicus)
Mammalia Me2 29
  • 85.27 (n)
(Mus musculus)
Mammalia Me2 29 16 30
  • 85.22 (n)
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 85 (a)
-- 30
  • 70 (a)
(Monodelphis domestica)
Mammalia ME2 30
  • 83 (a)
(Anolis carolinensis)
Reptilia -- 30
  • 80 (a)
-- 30
  • 65 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia me2 29
  • 71.27 (n)
African clawed frog
(Xenopus laevis)
Amphibia me2 29
(Danio rerio)
Actinopterygii me2 29 30 30
  • 66.21 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta Mdh 31
  • 54 (a)
Men-b 30
  • 48 (a)
Menl-1 31
  • 45 (a)
Menl-2 31
  • 42 (a)
Men 30 31
  • 37 (a)
CG7848 30 31
  • 32 (a)
(Caenorhabditis elegans)
Secernentea Y48B6A.12 31
  • 50 (a)
men-1 30
  • 46 (a)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MAE1 30
  • 30 (a)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons NADP-ME3 29
  • 56.55 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.3190 29
(Oryza sativa)
Liliopsida Os01g0723400 29
  • 55.78 (n)
Species where no ortholog for ME2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • 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)
  • 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 Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for ME2 Gene

Gene Tree for ME2 (if available)
Gene Tree for ME2 (if available)
Evolutionary constrained regions (ECRs) for ME2: view image
Alliance of Genome Resources:
Additional Orthologs for ME2

Paralogs for ME2 Gene

Paralogs for ME2 Gene Pseudogenes for ME2 Gene

genes like me logo Genes that share paralogs with ME2: view

Variants for ME2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ME2 Gene

SNP ID Clinical significance and condition Chr 18 pos Variation AA Info Type
rs142847061 Benign: not specified 50,932,347(+) T/A
NM_002396.5(ME2):c.1404T>A (p.Val468=)
rs142990108 Uncertain Significance: not specified 50,917,507(+) T/C
NM_002396.5(ME2):c.629T>C (p.Ile210Thr)
rs147002611 Likely Benign: not provided 50,917,475(+) G/A
NM_002396.5(ME2):c.597G>A (p.Leu199=)
rs370952608 Uncertain Significance: not specified 50,916,184(+) A/G
NM_002396.5(ME2):c.409A>G (p.Ile137Val)
rs765995662 Uncertain Significance: not specified 50,947,065(+) C/A
NM_002396.5(ME2):c.1636C>A (p.Pro546Thr)

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for ME2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for ME2 Gene

Variant ID Type Subtype PubMed ID
esv3642520 CNV loss 21293372
esv3893102 CNV loss 25118596
nsv1113927 CNV deletion 24896259
nsv527714 CNV gain 19592680
nsv576892 CNV gain 21841781
nsv9630 CNV loss 18304495

Variation tolerance for ME2 Gene

Residual Variation Intolerance Score: 50.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.32; 70.61% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ME2 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for
Leiden Open Variation Database (LOVD)

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ME2 Gene

Disorders for ME2 Gene

MalaCards: The human disease database

(6) MalaCards diseases for ME2 Gene - From: COP and GCD

- elite association - COSMIC cancer census association via MalaCards
Search ME2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ME2

Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with ME2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ME2 Gene

Publications for ME2 Gene

  1. Association analysis of malic enzyme 2 gene polymorphisms with idiopathic generalized epilepsy. (PMID: 16190936) Lenzen KP … Sander T (Epilepsia 2005) 3 22 40
  2. Physical and transcriptional map of a 311-kb segment of chromosome 18q21, a candidate lung tumor suppressor locus. (PMID: 11401430) Yanaihara N … Yokota J (Genomics 2001) 3 4 22
  3. Human NAD(+)-dependent mitochondrial malic enzyme. cDNA cloning, primary structure, and expression in Escherichia coli. (PMID: 1993674) Loeber G … Dworkin MB (The Journal of biological chemistry 1991) 2 3 4
  4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 40
  5. Mitochondrial malic enzyme (ME2) in pancreatic islets of the human, rat and mouse and clonal insulinoma cells. (PMID: 19691144) MacDonald MJ … Kendrick MA (Archives of biochemistry and biophysics 2009) 3 22

Products for ME2 Gene

Sources for ME2 Gene