MDH2 malate dehydrogenase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MDH2provided by HGNC
Official Full Name: malate dehydrogenase 2provided by HGNC
Primary source: HGNC:HGNC:6971
See related: Ensembl:ENSG00000146701 MIM:154100; AllianceGenome:HGNC:6971
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: MDH; MOR1; DEE51; M-MDH; EIEE51; MGC:3559
Summary: 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]
Expression: Ubiquitous expression in heart (RPKM 76.5), duodenum (RPKM 46.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q11.23

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (76048106..76067508)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (77335642..77355027)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (75677424..75696826)

Chromosome 7 - NC_000007.14 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Structural Comparison of hMDH2 Complexed with Natural Substrates and Cofactors: The Importance of Phosphate Binding for Active Conformation and Catalysis.
Title: Structural Comparison of hMDH2 Complexed with Natural Substrates and Cofactors: The Importance of Phosphate Binding for Active Conformation and Catalysis.
Integrated genomic, transcriptomic and metabolomic analysis reveals MDH2 mutation-induced metabolic disorder in recurrent focal segmental glomerulosclerosis.
Title: Integrated genomic, transcriptomic and metabolomic analysis reveals MDH2 mutation-induced metabolic disorder in recurrent focal segmental glomerulosclerosis.
Bi-allelic variants in MDH2: Expanding the clinical phenotype.
Title: Bi-allelic variants in MDH2: Expanding the clinical phenotype.
Gain of Function of Malate Dehydrogenase 2 and Familial Hyperglycemia.
Title: Gain of Function of Malate Dehydrogenase 2 and Familial Hyperglycemia.
Urinary malate dehydrogenase 2 is a new biomarker for early detection of non-small-cell lung cancer.
Title: Urinary malate dehydrogenase 2 is a new biomarker for early detection of non-small-cell lung cancer.
his study suggests that MDH2 pathogenic variants may play a role in pheochromocytoma/paraganglioma (PPGL) susceptibility and that they might be responsible for less than 1% of PPGLs in patients without pathogenic variants in other major PPGL driver genes, a prevalence similar to the one recently described for other PPGL genes
Title: Role of MDH2 pathogenic variant in pheochromocytoma and paraganglioma patients.
these data suggest that MDH2, functioning as an RNA-binding protein, is involved in the posttranscriptional downregulation of SCN1A expression under seizure condition.
Title: MDH2 is an RNA binding protein involved in downregulation of sodium channel Scn1a expression under seizure condition.
loss-of-function mutations in MDH2 are also associated with severe neurological clinical presentations in children
Title: Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy.
Data indicate that acetyl-CoA acetyltransferase (ACAT1) and malate dehydrogenase (MDH2) are involved in various drug-resistance-forming mechanisms.
Title: Mitochondrial proteomics with siRNA knockdown to reveal ACAT1 and MDH2 in the development of doxorubicin-resistant uterine cancer.
Segregation of the mutation with disease and absence of MDH2 in mutated tumors revealed MDH2 as a novel pheochromocytoma/paraganglioma susceptibility gene.
Title: Whole-exome sequencing identifies MDH2 as a new familial paraganglioma gene.

Submit: New GeneRIF Correction See all GeneRIFs (13)

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, 51 MedGen: C4479208 OMIM: 617339 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of malate dehydrogenase 2 (MDH2) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed
retropepsin	gag-pol	Positional proteomics analysis identifies the cleavage of human malate dehydrogenase 2, NAD, mitochondrial (MDH2) at amino acid residues 94-95 by the HIV-1 protease	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH78279 (e-PCR)
- UniSTS:80716

G19751 (e-PCR)
- UniSTS:32845

A001X26 (e-PCR)
- UniSTS:32846

RH12763 (e-PCR)
- UniSTS:25686

SHGC-56100 (e-PCR)
- UniSTS:31853

A002I38 (e-PCR)
- UniSTS:48514

D7S553E (e-PCR)
- UniSTS:31388

D7S2059E (e-PCR)
- UniSTS:46761

SHGC-81711 (e-PCR)
- UniSTS:103893

GDB:4584955 (e-PCR)
- UniSTS:78590

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 L-malate dehydrogenase (NAD+) activity	IDA Inferred from Direct Assay more info	PubMed
enables L-malate dehydrogenase (NAD+) activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables L-malate dehydrogenase (NADP+) activity	IEA Inferred from Electronic Annotation more info
enables RNA binding	HDA more info	PubMed
enables identical protein binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in NADH metabolic process	IEA Inferred from Electronic Annotation more info
involved_in aerobic respiration	IDA Inferred from Direct Assay more info	PubMed
involved_in gluconeogenesis	IEA Inferred from Electronic Annotation more info
involved_in malate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in malate metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
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 tricarboxylic acid cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in tricarboxylic acid cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tricarboxylic acid cycle	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular exosome	HDA more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HDA more info	PubMed
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	HDA more info	PubMed

General protein information

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Preferred Names: malate dehydrogenase, mitochondrial

Names: malate dehydrogenase 2, NAD (mitochondrial); testicular tissue protein Li 120

NP_001269332.1

EC 1.1.1.37

NP_001269333.1

EC 1.1.1.37

NP_005909.2

EC 1.1.1.37

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.

Genomic

NG_052976.2 RefSeqGene

Range

5002..24404

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001282403.2 → NP_001269332.1 malate dehydrogenase, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AC005077, AC006330

Consensus CDS

CCDS64691.1

UniProtKB/TrEMBL

Q6FHZ0

Related

ENSP00000408649.2, ENST00000432020.2

Conserved Domains (2) summary

TIGR01772
Location:26 → 294

MDH_euk_gproteo; malate dehydrogenase, NAD-dependent

cd01337
Location:26 → 292

MDH_glyoxysomal_mitochondrial; Glyoxysomal and mitochondrial malate dehydrogenases
NM_001282404.2 → NP_001269333.1 malate dehydrogenase, mitochondrial isoform 3

See identical proteins and their annotated locations for NP_001269333.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate exon compared to variant 1, that causes translation to begin at a downstream AUG. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AC005077, AC006330

Consensus CDS

CCDS75622.1

UniProtKB/TrEMBL

B3KTM1, G3XAL0

Related

ENSP00000416929.1, ENST00000443006.5

Conserved Domains (1) summary

cd01337
Location:1 → 227

MDH_glyoxysomal_mitochondrial; Glyoxysomal and mitochondrial malate dehydrogenases
NM_005918.4 → NP_005909.2 malate dehydrogenase, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_005909.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC005077, AC006330

Consensus CDS

CCDS5581.1

UniProtKB/Swiss-Prot

A8K414, B2RE78, B4DE44, E9PDB2, O43682, P40926

UniProtKB/TrEMBL

A0A024R4K3, Q6FHZ0

Related

ENSP00000327070.5, ENST00000315758.10

Conserved Domains (1) summary

cd01337
Location:26 → 334

MDH_glyoxysomal_mitochondrial; Glyoxysomal and mitochondrial malate dehydrogenases

RNA

NR_104165.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) shares only the first exon and then has a unique exon compared to variant 1. This variant is represented as non-coding because it lacks most of the coding region compared to variant 1.

Source sequence(s)

AC006330

Related

ENST00000461263.2