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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
  • Malate Dehydrogenase, Mitochondrial 3
  • Testicular Tissue Protein Li 120 3
  • EC 4
  • MGC:3559 3
  • 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 Citrate cycle (TCA cycle). Gene Ontology (GO) annotations related to this gene include 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

GeneHancer (GH) Regulatory Elements for MDH2 Gene

Promoters and enhancers for MDH2 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
GH07J076046 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 667 +0.3 294 2.9 HDGF PKNOX1 CLOCK SMAD1 FOXA2 MLX ARNT ZFP64 ARID4B SIN3A STYXL1 MDH2 ENSG00000230882 PMS2P9 STAG3L1 PMS2P3 SRRM3 DTX2P1 PIR37432 GC07P076055
GH07J075877 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 16.9 -169.0 -168953 3.1 HDGF ARNT ARID4B SIN3A YBX1 DMAP1 ZNF2 YY1 SLC30A9 POLR2B RHBDD2 STAG3L1 PMS2P3 NSUN5P1 MDH2 SPDYE5 ENSG00000214243 CCL24 STYXL1 POR
GH07J076104 Enhancer 1.1 Ensembl ENCODE 27.8 +59.5 59493 5.1 FOXA2 ARID4B SIN3A ZNF48 FOS NFKBIZ RXRA SP5 REST KAT8 STYXL1 MDH2 PMS2P3 SPDYE5 STAG3L1 ENSG00000230882 NSUN5P1 SPDYE17 SPDYE18 SRRM3
GH07J076068 Enhancer 1 Ensembl ENCODE 24.4 +21.5 21473 1.5 PKNOX1 RB1 NFIB SIN3A NFXL1 RAD21 ZNF143 RCOR1 SMARCA5 ZNF263 STYXL1 PMS2P3 STAG3L1 MDH2 NSUN5P1 LOC100133091 CCL24 ENSG00000230882 GTF2IRD2B SPDYE18
GH07J076162 Enhancer 1.6 FANTOM5 Ensembl ENCODE 12.6 +117.1 117118 4.9 HDGF PKNOX1 SMAD1 FOXA2 ARNT ARID4B SIN3A ZNF2 YY1 SLC30A9 SRRM3 GTF2IP7 STYXL1 ENSG00000230882 MDH2 UPK3B POR RHBDD2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MDH2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MDH2 gene promoter:
  • Pax-4a
  • POU2F1c
  • POU2F1b
  • POU2F1a
  • POU2F1
  • Pax-2
  • Pax-2a
  • SREBP-1c
  • SREBP-1b
  • SREBP-1a

Genomic Locations for MDH2 Gene

Genomic Locations for MDH2 Gene
19,490 bases
Plus strand
19,458 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

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 isoforms=2301 and posLast=7878
  • Glycosylation at posLast=3333
  • Modification sites at PhosphoSitePlus

Other Protein References for MDH2 Gene

No data available for DME Specific Peptides for MDH2 Gene

Domains & Families for MDH2 Gene

Gene Families for MDH2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • 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

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

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 HDA 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

Human Phenotype Ontology for MDH2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

  • Taconic Biosciences Mouse Models for MDH2

Clone Products

  • Addgene plasmids for MDH2

No data available for 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 HDA 21630459
GO:0005739 mitochondrion IEA,IDA 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

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Citric Acid Approved, Vet_approved Nutra Agonist, Activator, Target 1243
NADH Approved Nutra Target 0
Cupric Chloride Approved, Investigational Pharma Enzyme 0
Nitrofurazone Approved, Investigational, Vet_approved Pharma Target, inhibitor 2
Xanthinol Approved, Withdrawn Pharma Target, cofactor 0

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Hydrogen Ion
  • H+
  • H(+)
  • Hydrogen cation
  • Hydron
  • Proton
L-Malic acid
  • (-)-L-Malic acid
  • (S)-(-)-Hydroxysuccinic acid
  • L-2-Hydroxybutanedioic acid
  • L-Apple acid
  • Malate
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 MDH2: view

Transcripts for MDH2 Gene

mRNA/cDNA 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, 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)
  • Intestine(3.9)
  • Muscle(3.9)
  • Skin(3.9)
  • Heart(3.5)
  • Pancreas(3.2)
  • Eye(2.6)
  • Stomach(2.6)
  • Blood(2.5)
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 34 33
  • 99.51 (n)
(Monodelphis domestica)
Mammalia MDH2 34
  • 92 (a)
(Canis familiaris)
Mammalia MDH2 34 33
  • 87.87 (n)
(Rattus norvegicus)
Mammalia Mdh2 33
  • 85.4 (n)
(Mus musculus)
Mammalia Mdh2 16 34 33
  • 85.21 (n)
(Ornithorhynchus anatinus)
Mammalia MDH2 34
  • 79 (a)
(Bos Taurus)
Mammalia MDH2 34
  • 73 (a)
(Gallus gallus)
Aves MDH2 34 33
  • 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 34 33
  • 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 34 33
  • 62.76 (n)
CG7998 35
  • 59 (a)
CG10749 34 35
  • 46 (a)
CG10748 34 35
  • 43 (a)
(Caenorhabditis elegans)
Secernentea mdh-1 35
  • 59 (a)
mdh-2 34 33
  • 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 36 34 33
  • 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)
Cin.4779 33
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)
Evolutionary constrained regions (ECRs) for MDH2: view image

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 Variation AA Info Type
rs1057519566 encephalopathy, early infantile, 51 (EIEE51) [MIM:617339], pathogenic, Epileptic encephalopathy, early infantile, 51, Infantile encephalopathy 76,063,579(+) C/T coding_sequence_variant, genic_downstream_transcript_variant, missense_variant
rs1057519567 pathogenic, Epileptic encephalopathy, early infantile, 51, Infantile encephalopathy 76,063,554(+) GG/G coding_sequence_variant, frameshift, genic_downstream_transcript_variant
rs375002796 pathogenic, Infantile encephalopathy, Epileptic encephalopathy, early infantile, 51, Epileptic encephalopathy, early infantile, 51 (EIEE51) [MIM:617339] 76,058,047(+) C/T coding_sequence_variant, genic_downstream_transcript_variant, missense_variant
rs782308462 pathogenic, Infantile encephalopathy, Epileptic encephalopathy, early infantile, 51, Epileptic encephalopathy, early infantile, 51 (EIEE51) [MIM:617339] 76,054,872(+) G/A coding_sequence_variant, genic_downstream_transcript_variant, intron_variant, missense_variant
rs189383313 likely-benign, not provided 76,048,243(+) G/A intron_variant

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

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

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)

Additional Variant Information for MDH2 Gene

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

SNP Genotyping and Copy Number Assay Products

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, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- 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.

Additional Disease Information for MDH2

Genetic Association Database
Human Genome Epidemiology 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 58
  2. 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 44 58
  3. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 44 58
  4. Regulation of cellular metabolism by protein lysine acetylation. (PMID: 20167786) Zhao S … Guan KL (Science (New York, N.Y.) 2010) 3 4 58
  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 58

Products for MDH2 Gene

Sources for MDH2 Gene

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