This gene encodes an enzyme that catalyzes the NAD/NADH-dependent, reversible oxidation of malate to oxaloacetate in many metabolic pathways, including the citric acid cycle. Two main isozymes are known to exist in eukaryotic cells: one is found in the mitochondrial matrix and the other in the cytoplasm. This gene encodes the cytosolic isozyme, which plays a key role in the mal... See more...

Aliases for MDH1 Gene

Aliases for MDH1 Gene

  • Malate Dehydrogenase 1 2 3 5
  • Malate Dehydrogenase 1, NAD (Soluble) 2 3
  • Malate Dehydrogenase, Cytoplasmic 3 4
  • Cytosolic Malate Dehydrogenase 3 4
  • Diiodophenylpyruvate Reductase 3 4
  • EC 4 51
  • MDHA 3 4
  • Epididymis Secretory Protein Li 32 3
  • Malate Dehydrogenase, Peroxisomal 3
  • Soluble Malate Dehydrogenase 3
  • EC 4
  • HEL-S-32 3
  • MGC:1375 3
  • MDH-S 3
  • MOR2 3
  • MDH1 5

External Ids for MDH1 Gene

Previous GeneCards Identifiers for MDH1 Gene

  • GC02P063944
  • GC02P063773
  • GC02P063790
  • GC02P063727
  • GC02P063669

Summaries for MDH1 Gene

Entrez Gene Summary for MDH1 Gene

  • This gene encodes an enzyme that catalyzes the NAD/NADH-dependent, reversible oxidation of malate to oxaloacetate in many metabolic pathways, including the citric acid cycle. Two main isozymes are known to exist in eukaryotic cells: one is found in the mitochondrial matrix and the other in the cytoplasm. This gene encodes the cytosolic isozyme, which plays a key role in the malate-aspartate shuttle that allows malate to pass through the mitochondrial membrane to be transformed into oxaloacetate for further cellular processes. Alternatively spliced transcript variants have been found for this gene. A recent study showed that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is localized in the peroxisomes. Pseudogenes have been identified on chromosomes X and 6. [provided by RefSeq, Feb 2016]

GeneCards Summary for MDH1 Gene

MDH1 (Malate Dehydrogenase 1) is a Protein Coding gene. Diseases associated with MDH1 include Cyclosporiasis and Gordon Holmes Syndrome. Among its related pathways are Glucose metabolism and Citrate cycle (TCA cycle). Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. An important paralog of this gene is MDH1B.

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MDH1 Gene

Genomics for MDH1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MDH1 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
GH02J063587 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 645.7 +0.8 767 6.4 CEBPG SP1 CREB1 GATAD2A PRDM10 ZNF629 TFE3 RFX1 SIX5 IKZF1 MDH1 WDPCP lnc-VPS54-7 VPS54 AFTPH piR-53440-003 lnc-WDPCP-3
GH02J063612 Enhancer 1.2 FANTOM5 ENCODE dbSUPER 42 +25.7 25747 4.7 BRCA1 TEAD4 PRDM1 POLR2A SOX6 CEBPA ATF7 SOX13 CTBP1 FOXA2 MDH1 WDPCP UGP2 piR-53440-003 lnc-VPS54-6 lnc-WDPCP-3
GH02J063665 Enhancer 0.7 Ensembl ENCODE 44 +78.7 78692 3.8 ATF7 SP1 YY1 ZBTB33 JUND RAD21 HNF4A RXRA MAX ATF2 MDH1 WDPCP lnc-VPS54-6 RPS4XP5 lnc-WDPCP-3
GH02J063662 Enhancer 0.6 Ensembl ENCODE 41.1 +74.3 74299 1.4 GABPA SP1 YY1 HNF4A RXRA HLF MDH1 RPS4XP5 lnc-VPS54-6 WDPCP lnc-WDPCP-3
GH02J063661 Enhancer 0.6 Ensembl ENCODE 43.2 +72.6 72592 1.6 CEBPB SPI1 HNF4A HNF4G MDH1 RPS4XP5 lnc-VPS54-6 WDPCP lnc-WDPCP-3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MDH1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MDH1

Top Transcription factor binding sites by QIAGEN in the MDH1 gene promoter:
  • CUTL1
  • FOXJ2
  • FOXJ2 (long isoform)
  • FOXO4
  • HNF-3beta
  • POU2F1
  • POU2F1a
  • SRY

Genomic Locations for MDH1 Gene

Genomic Locations for MDH1 Gene
18,589 bases
Plus strand
18,589 bases
Plus strand

Genomic View for MDH1 Gene

Genes around MDH1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MDH1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MDH1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MDH1 Gene

Proteins for MDH1 Gene

  • Protein details for MDH1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Malate dehydrogenase, cytoplasmic
    Protein Accession:
    Secondary Accessions:
    • B2R5V5
    • B4DUN2
    • B7Z3I7
    • F5H098
    • Q6I9V0

    Protein attributes for MDH1 Gene

    334 amino acids
    Molecular mass:
    36426 Da
    Quaternary structure:
    • Homodimer.

    Alternative splice isoforms for MDH1 Gene


neXtProt entry for MDH1 Gene

Selected DME Specific Peptides for MDH1 Gene


Post-translational modifications for MDH1 Gene

  • ISGylated.
  • Acetylation at Lys-118 dramatically enhances enzymatic activity and promotes adipogenic differentiation.
  • Ubiquitination at Lys118, Lys125, Lys142, Lys164, Lys205, Lys214, Lys298, and Lys318
  • Modification sites at PhosphoSitePlus

Domains & Families for MDH1 Gene

Gene Families for MDH1 Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for MDH1 Gene

Suggested Antigen Peptide Sequences for MDH1 Gene

GenScript: Design optimal peptide antigens:
  • Malate dehydrogenase (B4DUN2_HUMAN)
  • Malate dehydrogenase (C9JF79_HUMAN)
  • Malate dehydrogenase (F5H098_HUMAN)
  • Cytosolic malate dehydrogenase (MDHC_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the LDH/MDH superfamily. MDH type 2 family.
  • Belongs to the LDH/MDH superfamily. MDH type 2 family.
genes like me logo Genes that share domains with MDH1: view

Function for MDH1 Gene

Molecular function for MDH1 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(S)-malate + NAD(+) = H(+) + NADH + oxaloacetate; Xref=Rhea:RHEA:21432, ChEBI:CHEBI:15378, ChEBI:CHEBI:15589, ChEBI:CHEBI:16452, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=; Evidence={ECO:0000269|PubMed:3052244};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=3-(3,5-diiodo-4-hydroxyphenyl)lactate + NAD(+) = 3-(3,5-diiodo-4-hydroxyphenyl)pyruvate + H(+) + NADH; Xref=Rhea:RHEA:20293, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57647, ChEBI:CHEBI:57945, ChEBI:CHEBI:58023; EC=; Evidence={ECO:0000269|PubMed:3052244};.
GENATLAS Biochemistry:
malate dehydrogenase,NAD,soluble,same as KETAR (keto acid reductase,alpha-1)

Enzyme Numbers (IUBMB) for MDH1 Gene

Phenotypes From GWAS Catalog for MDH1 Gene

Gene Ontology (GO) - Molecular Function for MDH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0004470 malic enzyme activity TAS 8786100
GO:0005515 protein binding IPI 21044950
GO:0016491 oxidoreductase activity IEA --
GO:0016615 malate dehydrogenase activity IEA --
genes like me logo Genes that share ontologies with MDH1: view
genes like me logo Genes that share phenotypes with MDH1: view

Animal Model Products

CRISPR Products

miRNA for MDH1 Gene

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MDH1

Clone Products

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for MDH1 Gene

Localization for MDH1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MDH1 Gene


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 MDH1 gene
Compartment Confidence
cytosol 5
extracellular 4
cytoskeleton 3
mitochondrion 3
plasma membrane 2
peroxisome 2
nucleus 2
endoplasmic reticulum 2
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Centrosome (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MDH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space HDA 22664934
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0070062 extracellular exosome HDA 19056867
genes like me logo Genes that share ontologies with MDH1: view

Pathways & Interactions for MDH1 Gene

genes like me logo Genes that share pathways with MDH1: view

Pathways by source for MDH1 Gene

Gene Ontology (GO) - Biological Process for MDH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005975 carbohydrate metabolic process IEA --
GO:0006094 gluconeogenesis TAS --
GO:0006099 tricarboxylic acid cycle IBA 21873635
GO:0006107 oxaloacetate metabolic process IBA 21873635
GO:0006108 malate metabolic process IBA 21873635
genes like me logo Genes that share ontologies with MDH1: view

No data available for SIGNOR curated interactions for MDH1 Gene

Drugs & Compounds for MDH1 Gene

(7) Drugs for MDH1 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
NADH Approved Nutra Target 0
Dihydroartemisinin Experimental, Investigational Pharma Target, ligand 115
NADP Experimental Pharma Target 0
NAD Experimental Pharma Agonist, Full agonist, Activator 0
Malic acid Investigational Pharma Activator, Agonist 0

(10) Additional Compounds for MDH1 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • 3-(3,5-diiodo-4-Hydroxyphenyl)lactate
  • 3-(3,5-diiodo-4-Hydroxyphenyl)lactic acid
  • 3-(4-Hydroxy-3,5-diiodophenyl)lactate
  • 3,5-diiodo-4-Hydroxyphenylpyruvate
  • 3-(3,5-diiodo-4-Hydroxyphenyl)pyruvate
  • beta-(3,5-diiodo-4-Hydroxyphenyl)pyruvate
  • 3,5-diiodo-4-Hydroxyphenylpyruvic acid
  • (3,5-diiodo-4-Hydroxyphenyl)pyruvate
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 MDH1: view

Transcripts for MDH1 Gene

mRNA/cDNA for MDH1 Gene

11 NCBI additional mRNA sequence :
16 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 MDH1

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MDH1 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b · 7c · 7d ^ 8a · 8b · 8c ^ 9 ^ 10a · 10b ^ 11a · 11b ^ 12 ^ 13a · 13b · 13c
SP1: - - - - - -
SP2: - - - - -
SP3: - - - -
SP4: - - - - - - - -
SP5: - - - - - - - - - - -
SP6: - - - - - - - - - - - - - -
SP7: - - -
SP8: - - - -
SP9: - - - - - - - - -
SP10: - - - - -
SP11: - - -

Relevant External Links for MDH1 Gene

GeneLoc Exon Structure for

Expression for MDH1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MDH1 Gene

mRNA differential expression in normal tissues according to GTEx for MDH1 Gene

This gene is overexpressed in Heart - Left Ventricle (x6.9) and Heart - Atrial Appendage (x4.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MDH1 Gene

Protein tissue co-expression partners for MDH1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MDH1

SOURCE GeneReport for Unigene cluster for MDH1 Gene:


Evidence on tissue expression from TISSUES for MDH1 Gene

  • Nervous system(5)
  • Heart(5)
  • Liver(4.7)
  • Blood(4.6)
  • Skin(4.4)
  • Muscle(4.3)
  • Lung(4.1)
  • Kidney(3.8)
  • Eye(3.7)
  • Pancreas(3.7)
  • Intestine(3.3)
  • Thyroid gland(2.7)
  • Adrenal gland(2.6)
  • Stomach(2.6)
  • Lymph node(2.3)
  • Spleen(2.2)
  • Bone marrow(2.1)
genes like me logo Genes that share expression patterns with MDH1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for MDH1 Gene

Orthologs for MDH1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MDH1 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia MDH1 30 31
  • 99.72 (n)
(Bos Taurus)
Mammalia MDH1 30 31
  • 93.69 (n)
(Canis familiaris)
Mammalia MDH1 30 31
  • 93.59 (n)
(Monodelphis domestica)
Mammalia MDH1 31
  • 91 (a)
(Ornithorhynchus anatinus)
Mammalia MDH1 31
  • 91 (a)
(Mus musculus)
Mammalia Mdh1 30 17 31
  • 90.29 (n)
(Rattus norvegicus)
Mammalia Mdh1 30
  • 89.19 (n)
(Gallus gallus)
Aves MDH1 30 31
  • 81.83 (n)
(Anolis carolinensis)
Reptilia MDH1 31
  • 88 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia mdh1 30
  • 79.09 (n)
Str.84 30
African clawed frog
(Xenopus laevis)
Amphibia MGC68659 30
(Danio rerio)
Actinopterygii mdh1aa 31
  • 78 (a)
mdh1b 30
  • 73.43 (n)
wufk59d03 30
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.3779 30
Fruit Fly
(Drosophila melanogaster)
Insecta CG5362 32
  • 64 (a)
Mdh1 30 31
  • 62.44 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009510 30
  • 60.56 (n)
(Caenorhabditis elegans)
Secernentea mdh-1 30 31
  • 59.43 (n)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT1G04410 30
  • 60.69 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.7946 30
(Oryza sativa)
Liliopsida Os10g0478200 30
  • 60.99 (n)
(Hordeum vulgare)
Liliopsida Hv.746 30
(Triticum aestivum)
Liliopsida Ta.24987 30
(Zea mays)
Liliopsida Zm.5727 30
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.8282 31
  • 64 (a)
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.4600 30
Species where no ortholog for MDH1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • 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 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 MDH1 Gene

Gene Tree for MDH1 (if available)
Gene Tree for MDH1 (if available)
Evolutionary constrained regions (ECRs) for MDH1: view image

Paralogs for MDH1 Gene

Paralogs for MDH1 Gene

(1) SIMAP similar genes for MDH1 Gene using alignment to 8 proteins:

  • B8ZZ51_HUMAN
  • B9A041_HUMAN
  • C9JF79_HUMAN
  • F8WFC2_HUMAN Pseudogenes for MDH1 Gene

genes like me logo Genes that share paralogs with MDH1: view

Variants for MDH1 Gene

Additional dbSNP identifiers (rs#s) for MDH1 Gene

Structural Variations from Database of Genomic Variants (DGV) for MDH1 Gene

Variant ID Type Subtype PubMed ID
nsv582126 CNV gain 21841781
nsv7313 OTHER inversion 18451855

Variation tolerance for MDH1 Gene

Residual Variation Intolerance Score: 25.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.10; 22.45% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MDH1 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 and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MDH1 Gene

Disorders for MDH1 Gene

MalaCards: The human disease database

(5) MalaCards diseases for MDH1 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
  • cyclospora infection
gordon holmes syndrome
  • gdhs
retinitis pigmentosa
  • retinitis pigmentosa 1
  • sczd
amyotrophic lateral sclerosis 1
  • als1
- elite association - COSMIC cancer census association via MalaCards
Search MDH1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for MDH1

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with MDH1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MDH1 Gene

Publications for MDH1 Gene

  1. Molecular cloning and mapping of a human cDNA for cytosolic malate dehydrogenase (MDH1). (PMID: 8786100) Tanaka T … Nakamura Y (Genomics 1996) 3 4 23
  2. Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation via activating its enzymatic activity. (PMID: 22693256) Kim EY … Bae KH (Journal of lipid research 2012) 3 4
  3. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 41
  4. Physiogenomic analysis of statin-treated patients: domain-specific counter effects within the ACACB gene on low-density lipoprotein cholesterol? (PMID: 20602615) Ruaño G … Wu AH (Pharmacogenomics 2010) 3 41
  5. Physiogenomic comparison of edema and BMI in patients receiving rosiglitazone or pioglitazone. (PMID: 18996102) Ruaño G … Hanks S (Clinica chimica acta; international journal of clinical chemistry 2009) 3 41

Products for MDH1 Gene

Sources for MDH1 Gene