ALDH2 (aldehyde dehydrogenase 2 family (mitochondrial))

2001-09-01   Vasilis Vasiliou , Nickolas Sophos 

Molecular Toxicology University of Colorado Health Sciences Center (UCHSC) Dept. of Pharmaceutical Sciences, C-238 4200 East Ninth Avenue Denver, CO 80262, USA

Identity

HGNC
LOCATION
12q24.12
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
ALDH-E2,ALDHI,ALDM
FUSION GENES

DNA/RNA

Description

ALDH2 gene spans 46031 base pairs (bp), consists of 13 exons and 12 introns and is located on the (+) DNA strand.

Transcription

The ALDH2 mRNA consists of 1989 base

Proteins

Description

The ALDH2 protein is 517 amino acid long, has a molecular weight of 56 Kd, and forms a homotetramer.

Expression

ALDH2 is expressed in several human tissues with the highest levels found in liver. Screening of human cDNA libraries has revealed that ALDH2 transcripts are present in human liver, kidney, heart, stomach, colon, muscle, ovary, pancreas, lung, prostate, ear, eye, marrow, gall bladder, testis, thyroid, retina, adipose, adrenal gland, blood, brain, breast, placenta, uterus, B-cells, fetal brain, tonsil, foreskin, nervous normal and also in lung tumor, bladder tumor, nervous tumor.

Localisation

Mitochondrial matrix

Function

Conversion of aldehydes to acids via the reaction: ALDEHYDE + NAD + H2O = ACID + NADH

Homology

Mutations

Germinal

One of the most studied polymorphism is a single base-pair mutation (1510 GA) in exon 12 of ALDH2 gene that causes an E487K substitution (ALDH2*2 allele), which results in catalytic inactivation of the enzyme. The ALDH2*2 allele is dominant negative and is responsible for acute alcohol intoxication due to accumulation of acetaldehyde. Facial flushing, nausea, dizziness and tachycardia characterize this alcohol intoxication. The ALDH2*2 allele is frequent in, but confined to Asian individuals, and it appears to be a determinant against alcoholism. On the other hand, alcohol-drinking individuals having the ALDH2*2 genotype are at substantially high risk of developing esophageal and upper aerodigestive tract cancers, head and neck cancers, colorectal cancer.

Implicated in

Entity name
Uterine leiomyoma (uterine fibroids) --> HMGIC-ALDH2
Disease
Benign mesenchymal tumors
Prognosis
Good
Hybrid gene
The HMGIC-ALDH2 aberrant transcript contains complete exons 1-3 of HMGI-C and the epitopic sequence that includes complete exon 13 of the ALDH2 gene and part of the 3 untrasnlated region of this gene.
Fusion protein
The ALDH2 contributes 10 amino acids to the fusion HMGIC-ALDH2 protein.
Oncogenesis
HMGIC-ALDH2: it has been suggested that the truncation of HMGIC, rather than fusion may be responsible for tumorigenesis. The fusion of the 3 untranslated region of the ALDH2 may contribute to the stabilization of HMGIC mRNA.

Bibliography

Pubmed IDLast YearTitleAuthors
89862251996Investigation of genetic risk factors associated with alcoholism.Harada S et al
85213891995Description of a novel fusion transcript between HMGI-C, a gene encoding for a member of the high mobility group proteins, and the mitochondrial aldehyde dehydrogenase gene.Kazmierczak B et al
104702821999Genotype difference of aldehyde dehydrogenase 2 gene in alcohol drinkers influences the incidence of Japanese colorectal cancer patients.Murata M et al
108969182000Association of aldehyde dehydrogenase 2 gene polymorphism with multiple oesophageal dysplasia in head and neck cancer patients.Muto M et al
105088431999Effects of worldwide population subdivision on ALDH2 linkage disequilibrium.Peterson RJ et al
109712052000Polymorphisms of human aldehyde dehydrogenases. Consequences for drug metabolism and disease.Vasiliou V et al
40158231985Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases.Yoshida A et al

Other Information

Locus ID:

NCBI: 217
MIM: 100650
HGNC: 404
Ensembl: ENSG00000111275

Variants:

dbSNP: 217
ClinVar: 217
TCGA: ENSG00000111275
COSMIC: ALDH2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000111275ENST00000261733P05091
ENSG00000111275ENST00000261733A0A384NPN7
ENSG00000111275ENST00000416293P05091
ENSG00000111275ENST00000548536F8VSB0
ENSG00000111275ENST00000549106S4R3S4

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
Glycolysis / GluconeogenesisKEGGko00010
Ascorbate and aldarate metabolismKEGGko00053
Fatty acid degradationKEGGko00071
Valine, leucine and isoleucine degradationKEGGko00280
Lysine degradationKEGGko00310
Arginine and proline metabolismKEGGko00330
Histidine metabolismKEGGko00340
Tryptophan metabolismKEGGko00380
beta-Alanine metabolismKEGGko00410
Glycerolipid metabolismKEGGko00561
Pyruvate metabolismKEGGko00620
Glycolysis / GluconeogenesisKEGGhsa00010
Ascorbate and aldarate metabolismKEGGhsa00053
Fatty acid degradationKEGGhsa00071
Valine, leucine and isoleucine degradationKEGGhsa00280
Lysine degradationKEGGhsa00310
Arginine and proline metabolismKEGGhsa00330
Histidine metabolismKEGGhsa00340
Tryptophan metabolismKEGGhsa00380
beta-Alanine metabolismKEGGhsa00410
Glycerolipid metabolismKEGGhsa00561
Pyruvate metabolismKEGGhsa00620
Metabolic pathwaysKEGGhsa01100
GABA biosynthesis, eukaryotes, putrescine => GABAKEGGhsa_M00135
GABA biosynthesis, eukaryotes, putrescine => GABAKEGGM00135
Neuronal SystemREACTOMER-HSA-112316
Transmission across Chemical SynapsesREACTOMER-HSA-112315
Neurotransmitter Clearance In The Synaptic CleftREACTOMER-HSA-112311
Serotonin clearance from the synaptic cleftREACTOMER-HSA-380615
Metabolism of serotoninREACTOMER-HSA-380612
MetabolismREACTOMER-HSA-1430728
Biological oxidationsREACTOMER-HSA-211859
Phase 1 - Functionalization of compoundsREACTOMER-HSA-211945
Ethanol oxidationREACTOMER-HSA-71384

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA166186245acetaldehydeChemicalClinicalAnnotationassociatedPK31002879
PA443309AlcoholismDiseaseClinicalAnnotationassociatedPD15902904, 16679777
PA444460Heroin DependenceDiseaseClinicalAnnotationassociated21723677
PA448073ethanolChemicalClinicalAnnotationassociatedPKPD15902904, 16679777, 31002879
PA452619heroinChemicalClinicalAnnotationassociated21723677

References

Pubmed IDYearTitleCitations
243828822014Targeting aldehyde dehydrogenase 2: new therapeutic opportunities.117
196987172009Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk.107
183185972008Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach.105
229609992012Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.102
198745742009Genetical genomic determinants of alcohol consumption in rats and humans.93
189969232009Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis.89
189969232009Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis.89
193324622009Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction.89
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
168221692006Meta-analyses of ALDH2 and ADH1B with alcohol dependence in Asians.80

Citation

Vasilis Vasiliou ; Nickolas Sophos

ALDH2 (aldehyde dehydrogenase 2 family (mitochondrial))

Atlas Genet Cytogenet Oncol Haematol. 2001-09-01

Online version: http://atlasgeneticsoncology.org/gene/250/aldh2-(aldehyde-dehydrogenase-2-family-(mitochondrial))