MDH1 (malate dehydrogenase 1)

Gene

• Entrez ID: 4190
• Gene name: Malate dehydrogenase 1
• Gene symbol: MDH1
• Synonyms (NCBI Gene): DEE88, EIEE88, HEL-S-32, KAR, MDH-s, MDHA, MGC:1375, MOR2
• Chromosome: 2
• Chromosome location: 2p15
• 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 mi

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT028752	hsa-miR-26b-5p	Microarray	19088304
MIRT046497	hsa-miR-15b-5p	CLASH	23622248
MIRT045287	hsa-miR-186-5p	CLASH	23622248
MIRT1138602	hsa-miR-3662	CLIP-seq
MIRT1138603	hsa-miR-4719	CLIP-seq
MIRT1138604	hsa-miR-486-5p	CLIP-seq
MIRT1138605	hsa-miR-513b	CLIP-seq
MIRT1138606	hsa-miR-616	CLIP-seq
MIRT1138607	hsa-miR-649	CLIP-seq
MIRT1138608	hsa-miR-548g	CLIP-seq
MIRT1138602	hsa-miR-3662	CLIP-seq
MIRT1138603	hsa-miR-4719	CLIP-seq
MIRT1138609	hsa-miR-4760-5p	CLIP-seq
MIRT1138604	hsa-miR-486-5p	CLIP-seq
MIRT1138605	hsa-miR-513b	CLIP-seq
MIRT1138608	hsa-miR-548g	CLIP-seq
MIRT1138606	hsa-miR-616	CLIP-seq
MIRT1138610	hsa-miR-627	CLIP-seq
MIRT1138607	hsa-miR-649	CLIP-seq
MIRT2039329	hsa-miR-1263	CLIP-seq
MIRT1138610	hsa-miR-627	CLIP-seq
MIRT2269403	hsa-miR-127-5p	CLIP-seq
MIRT1138603	hsa-miR-4719	CLIP-seq
MIRT1138609	hsa-miR-4760-5p	CLIP-seq
MIRT1138604	hsa-miR-486-5p	CLIP-seq
MIRT1138605	hsa-miR-513b	CLIP-seq
MIRT1138608	hsa-miR-548g	CLIP-seq
MIRT1138606	hsa-miR-616	CLIP-seq
MIRT1138607	hsa-miR-649	CLIP-seq
MIRT2269404	hsa-miR-802	CLIP-seq
MIRT2568589	hsa-miR-1179	CLIP-seq
MIRT2039329	hsa-miR-1263	CLIP-seq
MIRT2269403	hsa-miR-127-5p	CLIP-seq
MIRT1138602	hsa-miR-3662	CLIP-seq
MIRT2568590	hsa-miR-4457	CLIP-seq
MIRT1138603	hsa-miR-4719	CLIP-seq
MIRT1138609	hsa-miR-4760-5p	CLIP-seq
MIRT2568591	hsa-miR-4795-3p	CLIP-seq
MIRT1138604	hsa-miR-486-5p	CLIP-seq
MIRT2568592	hsa-miR-5096	CLIP-seq
MIRT1138605	hsa-miR-513b	CLIP-seq
MIRT1138606	hsa-miR-616	CLIP-seq
MIRT1138610	hsa-miR-627	CLIP-seq
MIRT1138607	hsa-miR-649	CLIP-seq
MIRT2269404	hsa-miR-802	CLIP-seq
MIRT2568589	hsa-miR-1179	CLIP-seq
MIRT2039329	hsa-miR-1263	CLIP-seq
MIRT2269403	hsa-miR-127-5p	CLIP-seq
MIRT1138602	hsa-miR-3662	CLIP-seq
MIRT2568590	hsa-miR-4457	CLIP-seq
MIRT1138603	hsa-miR-4719	CLIP-seq
MIRT1138609	hsa-miR-4760-5p	CLIP-seq
MIRT2568591	hsa-miR-4795-3p	CLIP-seq
MIRT1138604	hsa-miR-486-5p	CLIP-seq
MIRT2568592	hsa-miR-5096	CLIP-seq
MIRT1138605	hsa-miR-513b	CLIP-seq
MIRT1138606	hsa-miR-616	CLIP-seq
MIRT1138610	hsa-miR-627	CLIP-seq
MIRT1138607	hsa-miR-649	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003824	Function	Catalytic activity	IEA
GO:0004470	Function	Malic enzyme activity	TAS	8786100
GO:0005515	Function	Protein binding	IPI	21044950
GO:0005615	Component	Extracellular space	HDA	22664934
GO:0005737	Component	Cytoplasm	IDA	34547241
GO:0005737	Component	Cytoplasm	IEA
GO:0005813	Component	Centrosome	IDA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS	8786100
GO:0006099	Process	Tricarboxylic acid cycle	IBA
GO:0006099	Process	Tricarboxylic acid cycle	IEA
GO:0006107	Process	Oxaloacetate metabolic process	IBA
GO:0006108	Process	Malate metabolic process	IBA
GO:0006108	Process	Malate metabolic process	IEA
GO:0006739	Process	NADP+ metabolic process	IDA	34547241
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016615	Function	Malate dehydrogenase activity	IEA
GO:0016616	Function	Oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	IEA
GO:0019674	Process	NAD+ metabolic process	IBA
GO:0019674	Process	NAD+ metabolic process	IDA	34547241
GO:0019674	Process	NAD+ metabolic process	IEA
GO:0019752	Process	Carboxylic acid metabolic process	IEA
GO:0030060	Function	L-malate dehydrogenase (NAD+) activity	EXP	3052244
GO:0030060	Function	L-malate dehydrogenase (NAD+) activity	IBA
GO:0030060	Function	L-malate dehydrogenase (NAD+) activity	IEA
GO:0043490	Process	Malate-aspartate shuttle	IEA
GO:0043490	Process	Malate-aspartate shuttle	IMP	37647199
GO:0043490	Process	Malate-aspartate shuttle	TAS
GO:0047860	Function	Diiodophenylpyruvate reductase (NAD+) activity	IEA
GO:0047995	Function	(2R)-hydroxyphenylpyruvate reductase [NAD(P)H] activity	IEA
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145

Other IDs

• MIM: 154200
• HGNC: 6970
• e!Ensembl: ENSG00000014641

Protein

• UniProt ID: P40925
• Protein name: Malate dehydrogenase, cytoplasmic (EC 1.1.1.37) (Aromatic alpha-keto acid reductase) (KAR) (EC 1.1.1.96) (Cytosolic malate dehydrogenase)
• Protein function: Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH (PubMed:2449162, PubMed:3052244). Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxi
• PDB: 7RM9, 7RRL
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00056	Ldh_1_N	5 → 153	lactate/malate dehydrogenase, NAD binding domain	Family
  PF02866	Ldh_1_C	156 → 331	lactate/malate dehydrogenase, alpha/beta C-terminal domain	Domain

• Sequence:

  MSEPIRVLVTGAAGQIAYSLLYSIGNGSVFGKDQPIILVLLDITPMMGVLDGVLMELQDC
  ALPLLKDVIATDKEDVAFKDLDVAILVGSMPRREGMERKDLLKANVKIFKSQGAALDKYA
  KKSVKVIVVGNPANTNCLTASKSAPSIPKENFSCLTRLDHNRAKAQIALKLGVTANDVKN
  VIIWGNHSSTQYPDVNHAKVKLQGKEVGVYEALKDDSWLKGEFVTTVQQRGAAVIKARKL
  SSAMSAAKAICDHVRDIWFGTPEGEFVSMGVISDGNSYGVPDDLLYSFPVVIKNKTWKFV
  EGLPINDFSREKMDLTAKELTEEKESAFEFLSSA

• Sequence length: 334

Pathways

KEGG:

Citrate cycle (TCA cycle)
Cysteine and methionine metabolism
Pyruvate metabolism
Glyoxylate and dicarboxylate metabolism
Metabolic pathways
Carbon metabolism
Proximal tubule bicarbonate reclamation

Reactome:

Gluconeogenesis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Developmental and epileptic encephalopathy, 88	Pathogenic	rs1709340590	RCV001250130	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 88	—	Disgenet, HPO Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSIVE DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER FAILURE, ACUTE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	26627638	Stimulate	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	31984950	Associate	★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	18652897		★☆☆☆☆ Found in Text Mining only
ANOPHTHALMIA AND PULMONARY HYPOPLASIA	Syndromic microphthalmia	BEFREE	27840030, 30765601		★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	27840030, 30765601	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	34044809	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Dilated	Cardiomyopathy	BEFREE	15565635		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Familial Idiopathic	Cardiomyopathy	BEFREE	15565635		★☆☆☆☆ Found in Text Mining only
Creutzfeldt-Jakob Disease, Sporadic	Creutzfeldt-Jakob disease	BEFREE	31795176		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	37977948	Associate	★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	31538237		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	36079864, 37977948	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophageal neoplasm	Pubtator	28937628	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	37402485	Associate	★☆☆☆☆ Found in Text Mining only
Fatal Familial Insomnia	Fatal Insomnia	BEFREE	31795176		★☆☆☆☆ Found in Text Mining only
Gerstmann-Straussler-Scheinker Disease	Gerstmann-Straussler-Scheinker syndrome	BEFREE	31795176		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	21655185	Associate	★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	CTD_human_DG	22228705		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Insomnia Fatal Familial	Insomnia	Pubtator	31795176	Stimulate	★☆☆☆☆ Found in Text Mining only
Lewy Body Disease	Lewy body disease	Pubtator	26627638	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	27840030		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	28263970, 28991459, 29970880		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	31538237		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	37977948	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	29452638	Associate	★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial infarction	Pubtator	32736138	Associate	★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	37151882	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	17308960, 28263970, 28819410		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	28819410, 29574159		★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	27840030		★☆☆☆☆ Found in Text Mining only
Pancreatic Ductal Adenocarcinoma	Pancreatic adenocarcinoma	BEFREE	30765601		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	27840030, 30765601	Associate	★☆☆☆☆ Found in Text Mining only
Prion Diseases	Prion disease	Pubtator	31795176	Associate	★☆☆☆☆ Found in Text Mining only
Respiratory Distress Syndrome, Adult	Respiratory Distress Syndrome	CTD_human_DG	25070658		★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis pigmentosa	Pubtator	15215745	Associate	★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis Pigmentosa	BEFREE	20011630		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	15176481		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	PSYGENET_DG	15176481		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	LHGDN	19110265		★★☆☆☆ Found in Text Mining + Unknown/Other Associations