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Aliases for MDH2 Gene

Aliases for MDH2 Gene

  • Malate Dehydrogenase 2 2 3 5
  • Malate Dehydrogenase 2, NAD (Mitochondrial) 2 3
  • EC 4 58
  • Malate Dehydrogenase, Mitochondrial 3
  • Testicular Tissue Protein Li 120 3
  • MGC:3559 3
  • EC 1.1.1 58
  • EIEE51 3
  • M-MDH 3
  • MOR1 3
  • MDH 3

External Ids for MDH2 Gene

Previous GeneCards Identifiers for MDH2 Gene

  • GC07P074212
  • GC07P075275
  • GC07P075289
  • GC07P075322
  • GC07P075515
  • GC07P075677
  • GC07P070763

Summaries for MDH2 Gene

Entrez Gene Summary for MDH2 Gene

  • Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the mitochondria and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

GeneCards Summary for MDH2 Gene

MDH2 (Malate Dehydrogenase 2) is a Protein Coding gene. Diseases associated with MDH2 include Epileptic Encephalopathy, Early Infantile, 51 and Hereditary Paraganglioma-Pheochromocytoma Syndromes. Among its related pathways are Metabolism and Glucose metabolism. GO annotations related to this gene include poly(A) RNA binding and oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor.

Gene Wiki entry for MDH2 Gene

Additional gene information for MDH2 Gene

No data available for CIViC summary , UniProtKB/Swiss-Prot , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MDH2 Gene

Genomics for MDH2 Gene

Regulatory Elements for MDH2 Gene

Enhancers for MDH2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH07H076104 1.2 Ensembl ENCODE 27.8 +59.5 59494 5.1 FOXA2 ARID4B SIN3A YY1 FOS SP5 REST KAT8 SREBF1 NFIL3 STYXL1 MDH2 ENSG00000230882 SRRM3 CCL26 RHBDD2 ENSG00000213549 RNU6-863P
GH07H076068 1.1 Ensembl ENCODE 24.4 +21.5 21473 1.5 CTCF PKNOX1 RB1 NFIB TBL1XR1 SIN3A NFXL1 RAD21 GATA3 CTBP1 STYXL1 MDH2 CCL24 ENSG00000230882 PMS2P3 STAG3L1 NSUN5P1 GTF2IRD2B SRRM3 LOC541473
GH07H076162 1.8 FANTOM5 Ensembl ENCODE 12.6 +117.1 117119 4.9 HDGF PKNOX1 FOXA2 ARNT ARID4B SIN3A ZNF2 YY1 SLC30A9 FOS STYXL1 ENSG00000230882 MDH2 UPK3B POR RHBDD2 SRRM3 GTF2IP7
GH07H076008 1.2 Ensembl ENCODE dbSUPER 18.7 -37.4 -37369 4.6 CBFB EBF1 BATF RELA ZNF316 EED SCRT2 IKZF1 ETV6 MLLT1 STYXL1 MDH2 ENSG00000230882 SNORA14A POR RHBDD2 CCL24 SRRM3 UPK3B TMEM120A
GH07H076070 0.8 Ensembl ENCODE 24.2 +23.4 23399 1 RING1 CBX1 L3MBTL2 ZFX STYXL1 MDH2 LOC100133091 PMS2P3 NSUN5P1 SPDYE18 SRRM3 CCL24 TRIM73 STAG3L1
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around MDH2 on UCSC Golden Path with GeneCards custom track

Promoters for MDH2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

Genomic Locations for MDH2 Gene

Genomic Locations for MDH2 Gene
19,490 bases
Plus strand

Genomic View for MDH2 Gene

Genes around MDH2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MDH2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MDH2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MDH2 Gene

Proteins for MDH2 Gene

  • Protein details for MDH2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Malate dehydrogenase, mitochondrial
    Protein Accession:
    Secondary Accessions:
    • A8K414
    • B2RE78
    • B4DE44
    • E9PDB2
    • O43682

    Protein attributes for MDH2 Gene

    338 amino acids
    Molecular mass:
    35503 Da
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for MDH2 Gene

    Alternative splice isoforms for MDH2 Gene


neXtProt entry for MDH2 Gene

Selected DME Specific Peptides for MDH2 Gene


Post-translational modifications for MDH2 Gene

  • Acetylation is enhanced by up to 67% after treatment either with trichostin A (TSA) or with nicotinamide (NAM) with the appearance of tri- and tetraacetylations. Glucose also increases acetylation by about 60%.
  • Ubiquitination at Lys78 and Lys301
  • Glycosylation at Ser33
  • Modification sites at PhosphoSitePlus

Other Protein References for MDH2 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for MDH2 (MDH2)
  • Santa Cruz Biotechnology (SCBT) Antibodies for MDH2

Domains & Families for MDH2 Gene

Gene Families for MDH2 Gene

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

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the LDH/MDH superfamily. MDH type 1 family.
  • Belongs to the LDH/MDH superfamily. MDH type 1 family.
genes like me logo Genes that share domains with MDH2: view

Function for MDH2 Gene

Molecular function for MDH2 Gene

GENATLAS Biochemistry:
malate dehydrogenase,NAD,mitochondrial,catalyzing the eight step of citric acid cycle
UniProtKB/Swiss-Prot CatalyticActivity:
(S)-malate + NAD(+) = oxaloacetate + NADH.
UniProtKB/Swiss-Prot EnzymeRegulation:
Enzyme activity is enhanced by acetylation.

Enzyme Numbers (IUBMB) for MDH2 Gene

Phenotypes From GWAS Catalog for MDH2 Gene

Gene Ontology (GO) - Molecular Function for MDH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding IDA 22658674
GO:0003824 catalytic activity IEA --
GO:0016491 oxidoreductase activity IEA --
GO:0016615 malate dehydrogenase activity IEA --
GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor IEA --
genes like me logo Genes that share ontologies with MDH2: view
genes like me logo Genes that share phenotypes with MDH2: view

Animal Model Products

Clone Products

  • Addgene plasmids for MDH2

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for MDH2 Gene

Localization for MDH2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MDH2 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 MDH2 gene
Compartment Confidence
extracellular 5
mitochondrion 5
nucleus 5
plasma membrane 2
cytosol 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for MDH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 21630459
GO:0005739 mitochondrion IDA,IEA 16740313
GO:0005743 mitochondrial inner membrane IEA --
GO:0005759 mitochondrial matrix TAS --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with MDH2: view

Pathways & Interactions for MDH2 Gene

genes like me logo Genes that share pathways with MDH2: view

Gene Ontology (GO) - Biological Process for MDH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005975 carbohydrate metabolic process IEA --
GO:0006094 gluconeogenesis TAS --
GO:0006099 tricarboxylic acid cycle TAS --
GO:0006107 oxaloacetate metabolic process IEA --
GO:0006108 malate metabolic process IMP 6576816
genes like me logo Genes that share ontologies with MDH2: view

No data available for SIGNOR curated interactions for MDH2 Gene

Drugs & Compounds for MDH2 Gene

(25) Drugs for MDH2 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
malic acid Investigational Pharma Agonist, Activator 0
Citric Acid Vet_approved Nutra Agonist, Activator, Target 1200
NADH Nutra Target 0
NAD Pharma Full agonist, Agonist 0

(35) Additional Compounds for MDH2 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Hydrogen Ion
  • Hydrogen cation
  • Hydron
  • Proton
L-Malic acid
  • (-)-(S)-Malate
  • (-)-(S)-Malic acid
  • (-)-Hydroxysuccinate
  • (-)-Hydroxysuccinic acid
  • (-)-L-Malic acid
Oxalacetic acid
  • 2-Ketosuccinate
  • 2-Ketosuccinic acid
  • 2-Oxobutanedioate
  • 2-Oxobutanedioic acid
  • 2-Oxosuccinate
genes like me logo Genes that share compounds with MDH2: view

Transcripts for MDH2 Gene

Unigene Clusters for MDH2 Gene

Malate dehydrogenase 2, NAD (mitochondrial):
Representative Sequences:

Clone Products

  • Addgene plasmids for MDH2

Alternative Splicing Database (ASD) splice patterns (SP) for MDH2 Gene

No ASD Table

Relevant External Links for MDH2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for MDH2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MDH2 Gene

mRNA differential expression in normal tissues according to GTEx for MDH2 Gene

This gene is overexpressed in Muscle - Skeletal (x5.5).

Protein differential expression in normal tissues from HIPED for MDH2 Gene

This gene is overexpressed in Liver, secretome (7.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for MDH2 Gene

Protein tissue co-expression partners for MDH2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of MDH2 Gene:


SOURCE GeneReport for Unigene cluster for MDH2 Gene:


Evidence on tissue expression from TISSUES for MDH2 Gene

  • Lung(4.8)
  • Nervous system(4.8)
  • Kidney(4.7)
  • Liver(4.7)
  • Muscle(3.9)
  • Skin(3.9)
  • Intestine(3.8)
  • Heart(3.5)
  • Pancreas(3.2)
  • Eye(2.6)
  • Stomach(2.6)
  • Blood(2.2)
genes like me logo Genes that share expression patterns with MDH2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for MDH2 Gene

Orthologs for MDH2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MDH2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia MDH2 33 34
  • 99.51 (n)
(Monodelphis domestica)
Mammalia MDH2 34
  • 92 (a)
(Canis familiaris)
Mammalia MDH2 33 34
  • 87.87 (n)
(Rattus norvegicus)
Mammalia Mdh2 33
  • 85.4 (n)
(Mus musculus)
Mammalia Mdh2 33 16 34
  • 85.21 (n)
(Ornithorhynchus anatinus)
Mammalia MDH2 34
  • 79 (a)
(Bos Taurus)
Mammalia MDH2 34
  • 73 (a)
(Gallus gallus)
Aves MDH2 33 34
  • 78.93 (n)
(Anolis carolinensis)
Reptilia MDH2 34
  • 80 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia mdh2 33
  • 74.46 (n)
Str.1699 33
African clawed frog
(Xenopus laevis)
Amphibia Xl.26083 33
(Danio rerio)
Actinopterygii mdh2 33 34
  • 76.46 (n)
Dr.25868 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.5113 33
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001903 33
  • 65.57 (n)
fruit fly
(Drosophila melanogaster)
Insecta Mdh2 33 34
  • 62.76 (n)
CG7998 35
  • 59 (a)
CG10749 35 34
  • 51 (a)
CG10748 35 34
  • 45 (a)
(Caenorhabditis elegans)
Secernentea mdh-1 35
  • 59 (a)
mdh-2 33 34
  • 58.59 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ADR152C 33
  • 57.22 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F25960g 33
  • 54.37 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MDH1 33 34 36
  • 53.5 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons mMDH1 33
  • 58.76 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.82 33
(Oryza sativa)
Liliopsida Os01g0649100 33
  • 58.86 (n)
Os.26206 33
(Hordeum vulgare)
Liliopsida Hv.702 33
(Triticum aestivum)
Liliopsida Ta.1039 33
(Zea mays)
Liliopsida Zm.2061 33
bread mold
(Neurospora crassa)
Ascomycetes NCU04899 33
  • 60.47 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPCC306.08c 33
  • 54.61 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.4030 34
  • 54 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.4779 33
Species where no ortholog for MDH2 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • 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 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 MDH2 Gene

Gene Tree for MDH2 (if available)
Gene Tree for MDH2 (if available)

Paralogs for MDH2 Gene

No data available for Paralogs for MDH2 Gene

Variants for MDH2 Gene

Sequence variations from dbSNP and Humsavar for MDH2 Gene

SNP ID Clin Chr 07 pos Sequence Context AA Info Type
rs375002796 Pathogenic, Epileptic encephalopathy, early infantile, 51 (EIEE51) [MIM:617339] 76,058,047(+) CTGCC(C/T)GGAAG reference, missense
rs782308462 Pathogenic, Epileptic encephalopathy, early infantile, 51 (EIEE51) [MIM:617339] 76,054,872(+) GCATC(A/G)GGCAG intron-variant, reference, missense
VAR_078003 Epileptic encephalopathy, early infantile, 51 (EIEE51) [MIM:617339]
rs1057519566 Pathogenic 76,063,579(+) CATCC(C/T)CCTGA reference, missense
rs1057519567 Pathogenic 76,063,555(+) TGGTG(-/G)CCATG reference, frameshift-variant

Structural Variations from Database of Genomic Variants (DGV) for MDH2 Gene

Variant ID Type Subtype PubMed ID
nsv528969 CNV gain 19592680
nsv428173 CNV gain 18775914
nsv1033450 CNV loss 25217958
esv3613754 CNV gain 21293372
dgv120n16 CNV deletion 17901297
dgv11459n54 CNV loss 21841781

Variation tolerance for MDH2 Gene

Residual Variation Intolerance Score: 53.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.12; 51.24% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MDH2 Gene

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

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MDH2 Gene

Disorders for MDH2 Gene

MalaCards: The human disease database

(7) MalaCards diseases for MDH2 Gene - From: HGMD, OMIM, ClinVar, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
epileptic encephalopathy, early infantile, 51
  • eiee51
hereditary paraganglioma-pheochromocytoma syndromes
  • paragangliomas 4
  • cholera morbus
l-2-hydroxyglutaric aciduria
  • combined d-2- and l-2-hydroxyglutaric aciduria
x-linked sideroblastic anemia with ataxia
  • anemia sideroblastic and spinocerebellar ataxia
- elite association - COSMIC cancer census association via MalaCards
Search MDH2 in MalaCards View complete list of genes associated with diseases


  • Epileptic encephalopathy, early infantile, 51 (EIEE51) [MIM:617339]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE51 is an autosomal recessive form characterized by onset of intractable seizures and hypotonia in the first days or weeks of life, and severely delayed psychomotor development. {ECO:0000269 PubMed:27989324}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for MDH2

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with MDH2: view

No data available for Genatlas for MDH2 Gene

Publications for MDH2 Gene

  1. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy. (PMID: 27989324) Ait-El-Mkadem S … Paquis-Flucklinger V (American journal of human genetics 2017) 3 4 60
  2. Regulation of cellular metabolism by protein lysine acetylation. (PMID: 20167786) Zhao S … Guan KL (Science (New York, N.Y.) 2010) 3 4 60
  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 45 60
  4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 45 60
  5. L-2-hydroxyglutaric aciduria, a defect of metabolite repair. (PMID: 17603759) Rzem R … Veiga-da-Cunha M (Journal of inherited metabolic disease 2007) 3 22 60

Products for MDH2 Gene

Sources for MDH2 Gene

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