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MDH1 malate dehydrogenase 1 [ Homo sapiens (human) ]

Gene ID: 4190, updated on 3-Nov-2024

Summary

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Official Symbol
MDH1provided by HGNC
Official Full Name
malate dehydrogenase 1provided by HGNC
Primary source
HGNC:HGNC:6970
See related
Ensembl:ENSG00000014641 MIM:154200; AllianceGenome:HGNC:6970
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
KAR; MDHA; MOR2; DEE88; MDH-s; EIEE88; HEL-S-32; MGC:1375
Summary
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]
Expression
Broad expression in heart (RPKM 313.6), fat (RPKM 131.4) and 24 other tissues See more
Orthologs
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Genomic context

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See MDH1 in Genome Data Viewer
Location:
2p15
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (63588963..63607197)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (63596617..63614818)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (63816097..63834331)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene WD repeat containing planar cell polarity effector Neighboring gene uncharacterized LOC107985769 Neighboring gene MPRA-validated peak3728 silencer Neighboring gene MTFR2 pseudogene 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:63550648-63551224 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:63551225-63551800 Neighboring gene NANOG hESC enhancer GRCh37_chr2:63562934-63563435 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15875 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15876 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:63814776-63815296 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15877 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:63841564-63842426 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:63842427-63843289 Neighboring gene PRELID1 pseudogene 6 Neighboring gene ribosomal protein S4X pseudogene 5

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The reduction of aromatic alpha-keto acids by cytoplasmic malate dehydrogenase and lactate dehydrogenase. Friedrich CA, et al. Biochem Genet, 1987 Oct. PMID 2449162
  2. Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients. Zerr I, et al. Biomolecules, 2019 Nov 28. PMID 31795176, Free PMC Article
  3. MDH1 deficiency is a metabolic disorder of the malate-aspartate shuttle associated with early onset severe encephalopathy. Broeks MH, et al. Hum Genet, 2019 Dec. PMID 31538237
  4. Ultra high throughput sequencing excludes MDH1 as candidate gene for RP28-linked retinitis pigmentosa. Rio Frio T, et al. Mol Vis, 2009 Dec 8. PMID 20011630, Free PMC Article
  5. Developmental regulation and cellular distribution of human cytosolic malate dehydrogenase (MDH1). Lo AS, et al. J Cell Biochem, 2005 Mar 1. PMID 15565635

See all (112) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients.
    Title: Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients.
  2. MDH1 deficiency is a new metabolic defect in the malate-aspartate shuttle and is associated with a severe neurodevelopmental phenotype.
    Title: MDH1 deficiency is a metabolic disorder of the malate-aspartate shuttle associated with early onset severe encephalopathy.
  3. expression of miR-126-5p suppresses the enzymatic activity of MDH1, mitochondrial respiration and caused cell death in non-small cell lung carcinoma cell lines.
    Title: miR-126-5p targets Malate Dehydrogenase 1 in non-small cell lung carcinomas.
  4. Data show that in the endogenous readthrough of the human MDH1 stop codon, the stop codon can encode tryptophan and arginine, and is tissue-specific.
    Title: The functional readthrough extension of malate dehydrogenase reveals a modification of the genetic code.
  5. Proliferating cells rely on both MDH1 and LDH to replenish cytosolic NAD.
    Title: Cytosolic malate dehydrogenase activity helps support glycolysis in actively proliferating cells and cancer.
  6. Arginine methylation of MDH1 by CARM1 regulates cellular redox homeostasis and suppresses glutamine metabolism of pancreatic cancer.
    Title: Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic Cancer.
  7. adipogenic differentiation may be regulated by the acetylation of MDH1
    Title: Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation via activating its enzymatic activity.
  8. A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration.
    Title: Proteomic analysis identifies dysfunction in cellular transport, energy, and protein metabolism in different brain regions of atypical frontotemporal lobar degeneration.
  9. Observational study of gene-disease association. (HuGE Navigator)
    Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
  10. The MDH1 gene is not the cause of RP28-linked autosomal recessive retinitis pigmentosa.
    Title: Ultra high throughput sequencing excludes MDH1 as candidate gene for RP28-linked retinitis pigmentosa.
Submit: New GeneRIF Correction See all GeneRIFs (14)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Developmental and epileptic encephalopathy, 88
MedGen: C5394553 OMIM: 618959 GeneReviews: Not available
not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables L-malate dehydrogenase (NAD+) activity EXP
Inferred from Experiment
more info
 PubMed 
enables L-malate dehydrogenase (NAD+) activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables diiodophenylpyruvate reductase activity IEA
Inferred from Electronic Annotation
more info
  
enables hydroxyphenylpyruvate reductase activity IEA
Inferred from Electronic Annotation
more info
  
enables malic enzyme activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in NADH metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in NADH metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in NADP metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in malate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in malate-aspartate shuttle TAS
Traceable Author Statement
more info
  
involved_in oxaloacetate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in tricarboxylic acid cycle IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in centrosome IDA
Inferred from Direct Assay
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular space HDA PubMed 

General protein information

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Preferred Names
malate dehydrogenase, cytoplasmic; malate dehydrogenase, peroxisomal
Names
aromatic alpha-keto acid reductase
cytosolic malate dehydrogenase
diiodophenylpyruvate reductase
epididymis secretory protein Li 32
malate dehydrogenase 1, NAD (soluble)
soluble malate dehydrogenase
NP_001186040.1
NP_001186041.1
NP_001303303.1
NP_005908.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001199111.2 → NP_001186040.1  malate dehydrogenase, cytoplasmic isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains a different 5' terminal exon, which results in translation initiation from an alternate start codon compared to variant 1. The encoded isoform (2) is longer with a distinct N-terminus compared to isoform MDH1.
    Source sequence(s)
    AC016734, AK295931, BC001484, BI667299
    Consensus CDS
    CCDS56121.1
    UniProtKB/Swiss-Prot
    P40925
    Related
    ENSP00000410073.2, ENST00000432309.6
    Conserved Domains (2) summary
    TIGR01759
    Location:20 → 345
    MalateDH-SF1; malate dehydrogenase
    cd01336
    Location:21 → 346
    MDH_cytoplasmic_cytosolic; Cytoplasmic and cytosolic Malate dehydrogenases

  2. NM_001199112.2 → NP_001186041.1  malate dehydrogenase, cytoplasmic isoform 3

    See identical proteins and their annotated locations for NP_001186041.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an exon in the 5' region, which results in translation initiation from an in-frame downstream start codon compared to variant 1. The encoded isoform (3) has a shorter N-terminus compared to isoform MDH1.
    Source sequence(s)
    AC016734, AK300719, BC001484, BI667299
    UniProtKB/TrEMBL
    B9A041
    Related
    ENSP00000386719.1, ENST00000409476.5
    Conserved Domains (1) summary
    cl21454
    Location:1 → 239
    NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

  3. NM_001316374.2 → NP_001303303.1  malate dehydrogenase, peroxisomal isoform MDH1x

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript and encodes two isoforms, which result from the use of alternative in-frame translation termination codons. The shorter isoform (MDH1) results from translation termination at the upstream UGA stop codon, while the longer isoform (MDH1x) results from UGA stop codon readthrough to the downstream UGA termination codon. This RefSeq represents the longer, C-terminally extended isoform (MDH1x), which is localized in the peroxisomes. As the UGA stop codon has been reported to specify several alternative amino acids (tryptophan, cysteine, arginine and serine), its location in the longer isoform is denoted by an 'X'.
    Source sequence(s)
    BC001484, CB266998
    Consensus CDS
    CCDS92766.1
    UniProtKB/TrEMBL
    A0A5K1VW95
    Related
    ENSP00000438144.3, ENST00000539945.7
    Conserved Domains (2) summary
    TIGR01759
    Location:2 → 327
    MalateDH-SF1; malate dehydrogenase
    cd01336
    Location:3 → 328
    MDH_cytoplasmic_cytosolic; Cytoplasmic and cytosolic Malate dehydrogenases

  4. NM_005917.4 → NP_005908.1  malate dehydrogenase, cytoplasmic isoform MDH1

    See identical proteins and their annotated locations for NP_005908.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript and encodes two isoforms, which result from the use of alternative in-frame translation termination codons. The shorter isoform (MDH1) results from translation termination at the upstream UGA stop codon, while the longer isoform (MDH1x) results from UGA stop codon readthrough to the downstream UGA termination codon. This RefSeq represents the shorter isoform (MDH1), which is localized in the cytosol.
    Source sequence(s)
    BC001484, CB266998
    Consensus CDS
    CCDS1874.1
    UniProtKB/Swiss-Prot
    B2R5V5, B4DUN2, B7Z3I7, F5H098, P40925, Q6I9V0
    UniProtKB/TrEMBL
    V9HWF2
    Related
    ENSP00000233114.8, ENST00000233114.13
    Conserved Domains (1) summary
    cd01336
    Location:3 → 328
    MDH_cytoplasmic_cytosolic; Cytoplasmic and cytosolic Malate dehydrogenases

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    63588963..63607197
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    63596617..63614818
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P40925.4 GenPept UniProtKB/Swiss-Prot:P40925

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