MDH1 malate dehydrogenase 1 [Homo sapiens (human)] - Gene

Summary

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: mouse all
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Genomic context

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_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
adipogenic differentiation may be regulated by the acetylation of MDH1
Title: Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation via activating its enzymatic activity.
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.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-31543 (e-PCR)
- UniSTS:46188

D2S1567E (e-PCR)
- UniSTS:150651

RH16368 (e-PCR)
- UniSTS:13478

G59582 (e-PCR)
- UniSTS:136886

MDH1 (e-PCR)
- UniSTS:278730

WIAF-2167 (e-PCR)
- UniSTS:23026

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	IMP Inferred from Mutant Phenotype more info	PubMed
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 more info	PubMed
located_in extracellular space	HDA more info	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

EC 1.1.1.37

EC 1.1.1.96

NP_001186041.1

EC 1.1.1.37

EC 1.1.1.96

NP_001303303.1

EC 1.1.1.37

EC 1.1.1.96

NP_005908.1

EC 1.1.1.37

EC 1.1.1.96

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)

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
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
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
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