Malic enzyme catalyzes the oxidative decarboxylation of malate to pyruvate using either NAD+ or NADP+ as a cofactor. Mammalian tissues contain 3 distinct isoforms of malic enzyme: a cytosolic NADP(+)-dependent isoform, a mitochondrial NADP(+)-dependent isoform, and a mitochondrial NAD(+)-dependent isoform. This gene encodes a mitochondrial NADP(+)-dependent isoform. Multiple al... See more...

Aliases for ME3 Gene

Aliases for ME3 Gene

  • Malic Enzyme 3 2 3 4 5
  • Malate Dehydrogenase (Oxaloacetate-Decarboxylating) (NADP(+)) 2 3
  • Malic Enzyme 3, NADP(+)-Dependent, Mitochondrial 2 3
  • NADP-Dependent Malic Enzyme, Mitochondrial 3 4
  • EC 4 50
  • NADP-ME 3 4
  • Mitochondrial NADP(+)-Dependent Malic Enzyme 3 3
  • Malic Enzyme, NADP+-Dependent, Mitochondrial 3
  • Pyruvic-Malic Carboxylase 3
  • EC 1.1.1 50
  • ME3 5

External Ids for ME3 Gene

Previous GeneCards Identifiers for ME3 Gene

  • GC11M088478
  • GC11M087691
  • GC11M086374
  • GC11M085878
  • GC11M085829
  • GC11M086152
  • GC11M082440

Summaries for ME3 Gene

Entrez Gene Summary for ME3 Gene

  • Malic enzyme catalyzes the oxidative decarboxylation of malate to pyruvate using either NAD+ or NADP+ as a cofactor. Mammalian tissues contain 3 distinct isoforms of malic enzyme: a cytosolic NADP(+)-dependent isoform, a mitochondrial NADP(+)-dependent isoform, and a mitochondrial NAD(+)-dependent isoform. This gene encodes a mitochondrial NADP(+)-dependent isoform. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

GeneCards Summary for ME3 Gene

ME3 (Malic Enzyme 3) is a Protein Coding gene. Diseases associated with ME3 include Polycystic Lipomembranous Osteodysplasia With Sclerosing Leukoencephalopathy 1. Among its related pathways are Carbon metabolism and PPAR signaling pathway. Gene Ontology (GO) annotations related to this gene include NAD binding and malic enzyme activity. An important paralog of this gene is ME1.

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ME3 Gene

Genomics for ME3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ME3 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 ME3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ME3

Top Transcription factor binding sites by QIAGEN in the ME3 gene promoter:
  • E47
  • IRF-2
  • POU3F2
  • POU3F2 (N-Oct-5a)
  • Tal-1

Genomic Locations for ME3 Gene

Latest Assembly
233,639 bases
Minus strand

Previous Assembly
(GRCh37/hg19 by Entrez Gene)
231,320 bases
Minus strand

(GRCh37/hg19 by Ensembl)
231,529 bases
Minus strand

Genomic View for ME3 Gene

Genes around ME3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ME3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ME3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ME3 Gene

Proteins for ME3 Gene

  • Protein details for ME3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    NADP-dependent malic enzyme, mitochondrial
    Protein Accession:
    Secondary Accessions:
    • B7Z6V0
    • Q8TBJ0

    Protein attributes for ME3 Gene

    604 amino acids
    Molecular mass:
    67068 Da
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for ME3 Gene


neXtProt entry for ME3 Gene

Selected DME Specific Peptides for ME3 Gene


Post-translational modifications for ME3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for ME3 Gene

Gene Families for ME3 Gene

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

Protein Domains for ME3 Gene

Suggested Antigen Peptide Sequences for ME3 Gene

GenScript: Design optimal peptide antigens:
  • Malic enzyme (B7Z6V0_HUMAN)
  • Malic enzyme (E9PMB9_HUMAN)
  • Malic enzyme (E9PNN2_HUMAN)
  • Malic enzyme 3 (MAON_HUMAN)
  • Cadherin (O15201_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 ME3: view

Function for ME3 Gene

Molecular function for ME3 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(S)-malate + NADP(+) = CO2 + NADPH + pyruvate; Xref=Rhea:RHEA:18253, ChEBI:CHEBI:15361, ChEBI:CHEBI:15589, ChEBI:CHEBI:16526, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; 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=;.
GENATLAS Biochemistry:
malic enzyme 3, NADP(+)-dependent, mitochondrial,predominantly expressed in tissues with a low division rate,catalyzing the decarboxylation of malate to pyruvate

Enzyme Numbers (IUBMB) for ME3 Gene

Phenotypes From GWAS Catalog for ME3 Gene

Gene Ontology (GO) - Molecular Function for ME3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004470 malic enzyme activity IEA,IDA 7818469
GO:0004471 malate dehydrogenase (decarboxylating) (NAD+) activity IEA --
GO:0004473 malate dehydrogenase (decarboxylating) (NADP+) activity IEA,IDA 7818469
GO:0008948 oxaloacetate decarboxylase activity IEA --
GO:0016491 oxidoreductase activity IEA --
genes like me logo Genes that share ontologies with ME3: view
genes like me logo Genes that share phenotypes with ME3: view

Animal Models for ME3 Gene

MGI Knock Outs for ME3:
  • Me3 Me3<tm1b(KOMP)Wtsi>

miRNA for ME3 Gene

miRTarBase miRNAs that target ME3

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ME3 Gene

Localization for ME3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ME3 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 ME3 gene
Compartment Confidence
mitochondrion 5
cytosol 3
peroxisome 2
nucleus 2
plasma membrane 1
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for ME3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IBA,TAS 7818469
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with ME3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for ME3 Gene

Pathways & Interactions for ME3 Gene

genes like me logo Genes that share pathways with ME3: view

Pathways by source for ME3 Gene

Gene Ontology (GO) - Biological Process for ME3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006090 pyruvate metabolic process IDA 7818469
GO:0006099 tricarboxylic acid cycle TAS --
GO:0006108 malate metabolic process IDA 7818469
GO:0009060 aerobic respiration TAS 7818469
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with ME3: view

No data available for SIGNOR curated interactions for ME3 Gene

Drugs & Compounds for ME3 Gene

(10) Drugs for ME3 Gene - From: DrugBank and HMDB

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

(3) Additional Compounds for ME3 Gene - From: 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 ME3: view

Transcripts for ME3 Gene

mRNA/cDNA for ME3 Gene

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

Alternative Splicing Database (ASD) splice patterns (SP) for ME3 Gene

No ASD Table

Relevant External Links for ME3 Gene

GeneLoc Exon Structure for

Expression for ME3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ME3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for ME3 Gene

This gene is overexpressed in Brain (25.2), Liver (14.8), and Frontal cortex (7.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ME3 Gene

Protein tissue co-expression partners for ME3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ME3

SOURCE GeneReport for Unigene cluster for ME3 Gene:


mRNA Expression by UniProt/SwissProt for ME3 Gene:

Tissue specificity: Expressed predominantly in organs with a low-division rate.

Evidence on tissue expression from TISSUES for ME3 Gene

  • Nervous system(4.8)
  • Intestine(4.3)
  • Heart(2.1)
  • Liver(2.1)
  • Muscle(2)
genes like me logo Genes that share expression patterns with ME3: view

Primer products for research

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for ME3 Gene

Orthologs for ME3 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for ME3 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia ME3 29 30
  • 99.72 (n)
(Canis familiaris)
Mammalia ME3 29 30
  • 92.05 (n)
(Bos Taurus)
Mammalia ME3 29 30
  • 91.23 (n)
(Mus musculus)
Mammalia Me3 29 16 30
  • 89.29 (n)
(Rattus norvegicus)
Mammalia Me3 29
  • 86.82 (n)
(Monodelphis domestica)
Mammalia ME3 30
  • 85 (a)
(Ornithorhynchus anatinus)
Mammalia ME3 30
  • 79 (a)
(Gallus gallus)
Aves ME3 29 30
  • 74.3 (n)
(Anolis carolinensis)
Reptilia ME3 30
  • 77 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia me3 29
  • 71.5 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.6324 29
(Danio rerio)
Actinopterygii me3 29 30
  • 72.33 (n)
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.326 29
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004159 29
  • 61.42 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta Men-b 29 30
  • 58.38 (n)
Mdh 31
  • 56 (a)
Menl-1 31
  • 45 (a)
Menl-2 31
  • 42 (a)
Men 30 31
  • 39 (a)
CG7848 30 31
  • 30 (a)
(Caenorhabditis elegans)
Secernentea men-1 29 30
  • 58.3 (n)
Y48B6A.12 31
  • 54 (a)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MAE1 30
  • 29 (a)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons NADP-ME1 29
  • 52.56 (n)
(Oryza sativa)
Liliopsida Os01g0743500 29
  • 54.69 (n)
(Triticum aestivum)
Liliopsida Ta.14421 29
Species where no ortholog for ME3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • 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)

Evolution for ME3 Gene

Gene Tree for ME3 (if available)
Gene Tree for ME3 (if available)
Evolutionary constrained regions (ECRs) for ME3: view image
Alliance of Genome Resources:
Additional Orthologs for ME3

Paralogs for ME3 Gene

Paralogs for ME3 Gene

(42) SIMAP similar genes for ME3 Gene using alignment to 10 proteins:

  • B7Z6V0_HUMAN
  • O15201_HUMAN
genes like me logo Genes that share paralogs with ME3: view

Variants for ME3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ME3 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs115220216 Benign: not provided 86,497,986(-) G/A
NM_001014811.1(ME3):c.682C>T (p.Leu228=)
rs1042780 -- p.Lys324Asn
rs17856661 -- p.Ser85Gly

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for ME3 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 ME3 Gene

Variant ID Type Subtype PubMed ID
dgv2046n54 CNV loss 21841781
dgv2047n54 CNV loss 21841781
dgv2048n54 CNV loss 21841781
dgv2049n54 CNV loss 21841781
dgv2050n54 CNV loss 21841781
dgv2051n54 CNV loss 21841781
dgv2052n54 CNV loss 21841781
dgv2053n54 CNV loss 21841781
dgv2054n54 CNV loss 21841781
dgv2055n54 CNV loss 21841781
dgv230e199 CNV deletion 23128226
dgv231n67 CNV loss 20364138
dgv232n67 CNV loss 20364138
dgv683n106 CNV deletion 24896259
esv2662437 CNV deletion 23128226
esv26643 CNV loss 19812545
esv2668174 CNV deletion 23128226
esv2672841 CNV deletion 23128226
esv2678915 CNV deletion 23128226
esv2744855 CNV deletion 23290073
esv2744856 CNV deletion 23290073
esv274960 CNV gain+loss 21479260
esv29418 CNV loss 19812545
esv3303304 CNV mobile element insertion 20981092
esv3398000 CNV insertion 20981092
esv3405888 CNV insertion 20981092
esv3548094 CNV deletion 23714750
esv3548095 CNV deletion 23714750
esv3627088 CNV gain 21293372
esv3627090 CNV loss 21293372
esv3627092 CNV loss 21293372
esv3627093 CNV loss 21293372
esv3627094 CNV loss 21293372
esv3627095 CNV gain 21293372
esv3627096 CNV loss 21293372
esv3627097 CNV loss 21293372
esv3627099 CNV gain 21293372
esv4749 CNV loss 18987735
nsv1119421 CNV insertion 24896259
nsv428263 CNV loss 18775914
nsv471753 CNV loss 16327809
nsv471754 CNV loss 16327809
nsv475811 CNV novel sequence insertion 20440878
nsv510265 OTHER sequence alteration 20534489
nsv520466 CNV loss 19592680
nsv522178 CNV loss 19592680
nsv522823 CNV loss 19592680
nsv528182 CNV loss 19592680
nsv555665 CNV loss 21841781
nsv555671 CNV loss 21841781
nsv555678 CNV loss 21841781
nsv555685 CNV loss 21841781
nsv555703 CNV loss 21841781
nsv555704 CNV loss 21841781
nsv819492 CNV loss 19587683
nsv826020 CNV loss 20364138
nsv8852 CNV loss 18304495

Variation tolerance for ME3 Gene

Residual Variation Intolerance Score: 10.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.59; 89.02% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ME3 Gene

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 ME3 Gene

Disorders for ME3 Gene

MalaCards: The human disease database

(1) MalaCards diseases for ME3 Gene - From: COP

- elite association - COSMIC cancer census association via MalaCards
Search ME3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ME3

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 ME3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ME3 Gene

Publications for ME3 Gene

  1. Purification, cDNA cloning and heterologous expression of the human mitochondrial NADP(+)-dependent malic enzyme. (PMID: 7818469) Loeber G … Schwendenwein R (The Biochemical journal 1994) 2 3 4
  2. Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study. (PMID: 20800603) Flachsbart F … Nebel A (Mutation research 2010) 3 40
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 40
  4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 40
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4

Products for ME3 Gene

Sources for ME3 Gene