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ALDH2 (aldehyde dehydrogenase 2 family (mitochondrial))

Identity

HGNC (Hugo) ALDH2
LocusID (NCBI) 217
Location 12q24.12
Location_base_pair Starts at 112204691 and ends at 112247789 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

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

Protein

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 ALDH2 belongs to the aldehyde dehydrogenase gene superfamily .

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 Uterine leiomyoma (uterine fibroids) --> HMGIC-ALDH2
Disease Benign mesenchymal tumors
Prognosis Good
Hybrid/Mutated 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.
Abnormal 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.
  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945

External links

Nomenclature
HGNC (Hugo)ALDH2   404
Cards
AtlasALDH2ID250
Entrez_Gene (NCBI)ALDH2  217  aldehyde dehydrogenase 2 family (mitochondrial)
GeneCards (Weizmann)ALDH2
Ensembl hg19 (Hinxton)ENSG00000111275 [Gene_View]  chr12:112204691-112247789 [Contig_View]  ALDH2 [Vega]
Ensembl hg38 (Hinxton)ENSG00000111275 [Gene_View]  chr12:112204691-112247789 [Contig_View]  ALDH2 [Vega]
ICGC DataPortalENSG00000111275
cBioPortalALDH2
AceView (NCBI)ALDH2
Genatlas (Paris)ALDH2
WikiGenes217
SOURCE (Princeton)ALDH2
Genomic and cartography
GoldenPath hg19 (UCSC)ALDH2  -     chr12:112204691-112247789 +  12q24.12   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)ALDH2  -     12q24.12   [Description]    (hg38-Dec_2013)
EnsemblALDH2 - 12q24.12 [CytoView hg19]  ALDH2 - 12q24.12 [CytoView hg38]
Mapping of homologs : NCBIALDH2 [Mapview hg19]  ALDH2 [Mapview hg38]
OMIM100650   610251   
Gene and transcription
Genbank (Entrez)AK223373 AK301375 AK314856 AY621070 BC002967
RefSeq transcript (Entrez)NM_000690 NM_001204889
RefSeq genomic (Entrez)AC_000144 NC_000012 NC_018923 NG_012250 NT_029419 NW_001838063 NW_004929385
Consensus coding sequences : CCDS (NCBI)ALDH2
Cluster EST : UnigeneHs.604551 [ NCBI ]
CGAP (NCI)Hs.604551
Alternative Splicing : Fast-db (Paris)GSHG0007010
Alternative Splicing GalleryENSG00000111275
Gene ExpressionALDH2 [ NCBI-GEO ]     ALDH2 [ SEEK ]   ALDH2 [ MEM ]
SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP05091 (Uniprot)
NextProtP05091  [Medical]
With graphics : InterProP05091
Splice isoforms : SwissVarP05091 (Swissvar)
Catalytic activity : Enzyme1.2.1.3 [ Enzyme-Expasy ]   1.2.1.31.2.1.3 [ IntEnz-EBI ]   1.2.1.3 [ BRENDA ]   1.2.1.3 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)ALDEHYDE_DEHYDR_CYS (PS00070)    ALDEHYDE_DEHYDR_GLU (PS00687)   
Domains : Interpro (EBI)Ald_DH/histidinol_DH    Ald_DH_C    Ald_DH_CS_CYS    Ald_DH_CS_GLU    Ald_DH_N    Aldehyde_DH_dom   
Related proteins : CluSTrP05091
Domain families : Pfam (Sanger)Aldedh (PF00171)   
Domain families : Pfam (NCBI)pfam00171   
DMDM Disease mutations217
Blocks (Seattle)P05091
PDB (SRS)1CW3    1NZW    1NZX    1NZZ    1O00    1O01    1O02    1O04    1O05    1ZUM    2ONM    2ONN    2ONO    2ONP    2VLE    3INJ    3INL    3N80    3N81    3N82    3N83    3SZ9    4FQF    4FR8    4KWF    4KWG   
PDB (PDBSum)1CW3    1NZW    1NZX    1NZZ    1O00    1O01    1O02    1O04    1O05    1ZUM    2ONM    2ONN    2ONO    2ONP    2VLE    3INJ    3INL    3N80    3N81    3N82    3N83    3SZ9    4FQF    4FR8    4KWF    4KWG   
PDB (IMB)1CW3    1NZW    1NZX    1NZZ    1O00    1O01    1O02    1O04    1O05    1ZUM    2ONM    2ONN    2ONO    2ONP    2VLE    3INJ    3INL    3N80    3N81    3N82    3N83    3SZ9    4FQF    4FR8    4KWF    4KWG   
PDB (RSDB)1CW3    1NZW    1NZX    1NZZ    1O00    1O01    1O02    1O04    1O05    1ZUM    2ONM    2ONN    2ONO    2ONP    2VLE    3INJ    3INL    3N80    3N81    3N82    3N83    3SZ9    4FQF    4FR8    4KWF    4KWG   
Human Protein AtlasENSG00000111275
Peptide AtlasP05091
HPRD00003
IPIIPI00006663   IPI01021497   IPI01022501   IPI01022431   IPI00792207   
Protein Interaction databases
DIP (DOE-UCLA)P05091
IntAct (EBI)P05091
FunCoupENSG00000111275
BioGRIDALDH2
IntegromeDBALDH2
STRING (EMBL)ALDH2
Ontologies - Pathways
QuickGOP05091
Ontology : AmiGOaldehyde dehydrogenase (NAD) activity  aldehyde dehydrogenase [NAD(P)+] activity  mitochondrial matrix  carbohydrate metabolic process  alcohol metabolic process  ethanol catabolic process  ethanol oxidation  xenobiotic metabolic process  synaptic transmission  electron carrier activity  neurotransmitter biosynthetic process  small molecule metabolic process  extracellular vesicular exosome  
Ontology : EGO-EBIaldehyde dehydrogenase (NAD) activity  aldehyde dehydrogenase [NAD(P)+] activity  mitochondrial matrix  carbohydrate metabolic process  alcohol metabolic process  ethanol catabolic process  ethanol oxidation  xenobiotic metabolic process  synaptic transmission  electron carrier activity  neurotransmitter biosynthetic process  small molecule metabolic process  extracellular vesicular exosome  
Pathways : KEGGGlycolysis / Gluconeogenesis    Pentose and glucuronate interconversions    Ascorbate and aldarate metabolism    Fatty acid degradation    Valine, leucine and isoleucine degradation    Lysine degradation    Arginine and proline metabolism    Histidine metabolism    Tryptophan metabolism    beta-Alanine metabolism    Glycerolipid metabolism    Pyruvate metabolism    Propanoate metabolism   
REACTOMEP05091 [protein]
REACTOME PathwaysREACT_111217 Metabolism [pathway]
REACTOME PathwaysREACT_13685 Neuronal System [pathway]
Protein Interaction DatabaseALDH2
DoCM (Curated mutations)ALDH2
Wikipedia pathwaysALDH2
Gene fusion - rearrangements
Rearrangement : COSMICHMGA2 [12q14.3]  -  ALDH2 [12q24.12]
Polymorphisms : SNP, variants
NCBI Variation ViewerALDH2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ALDH2
dbVarALDH2
ClinVarALDH2
1000_GenomesALDH2 
Exome Variant ServerALDH2
SNP (GeneSNP Utah)ALDH2
SNP : HGBaseALDH2
Genetic variants : HAPMAPALDH2
Genomic VariantsALDH2  ALDH2 [DGVbeta]
Mutations
ICGC Data PortalENSG00000111275 
Cancer Gene: CensusALDH2 
Somatic Mutations in Cancer : COSMICALDH2 
CONAN: Copy Number AnalysisALDH2 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)12:112204691-112247789
Mutations and Diseases : HGMDALDH2
OMIM100650    610251   
MedgenALDH2
NextProtP05091 [Medical]
GENETestsALDH2
Disease Genetic AssociationALDH2
Huge Navigator ALDH2 [HugePedia]  ALDH2 [HugeCancerGEM]
snp3D : Map Gene to Disease217
DGIdb (Drug Gene Interaction db)ALDH2
General knowledge
Homologs : HomoloGeneALDH2
Homology/Alignments : Family Browser (UCSC)ALDH2
Phylogenetic Trees/Animal Genes : TreeFamALDH2
Chemical/Protein Interactions : CTD217
Chemical/Pharm GKB GenePA24696
Clinical trialALDH2
Cancer Resource (Charite)ENSG00000111275
Other databases
Probes
ProbeCancer Cytogenetics (Bari)
Litterature
PubMed448 Pubmed reference(s) in Entrez
CoreMineALDH2
GoPubMedALDH2
iHOPALDH2

Bibliography

Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases.
Yoshida A, Ikawa M, Hsu LC, Tani K
Alcohol (Fayetteville, N.Y.). 1985 ; 2 (1) : 103-106.
PMID 4015823
 
Description 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, Hennig Y, Wanschura S, Rogalla P, Bartnitzke S, Van de Ven W, Bullerdiek J
Cancer research. 1995 ; 55 (24) : 6038-6039.
PMID 8521389
 
Investigation of genetic risk factors associated with alcoholism.
Harada S, Okubo T, Tsutsumi M, Takase S, Muramatsu T
Alcoholism, clinical and experimental research. 1996 ; 20 (9 Suppl) : 293A-296A.
PMID 8986225
 
Description 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, Hennig Y, Wanschura S, Rogalla P, Bartnitzke S, Van de Ven W, Bullerdiek J
Cancer research. 1995 ; 55 (24) : 6038-6039.
PMID 8521389
 
Effects of worldwide population subdivision on ALDH2 linkage disequilibrium.
Peterson RJ, Goldman D, Long JC
Genome research. 1999 ; 9 (9) : 844-852.
PMID 10508843
 
Genotype difference of aldehyde dehydrogenase 2 gene in alcohol drinkers influences the incidence of Japanese colorectal cancer patients.
Murata M, Tagawa M, Watanabe S, Kimura H, Takeshita T, Morimoto K
Japanese journal of cancer research : Gann. 1999 ; 90 (7) : 711-719.
PMID 10470282
 
Association of aldehyde dehydrogenase 2 gene polymorphism with multiple oesophageal dysplasia in head and neck cancer patients.
Muto M, Hitomi Y, Ohtsu A, Ebihara S, Yoshida S, Esumi H
Gut. 2000 ; 47 (2) : 256-261.
PMID 10896918
 
Polymorphisms of human aldehyde dehydrogenases. Consequences for drug metabolism and disease.
Vasiliou V, Pappa A
Pharmacology. 2000 ; 61 (3) : 192-198.
PMID 10971205
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written09-2001Vasilis 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

Citation

This paper should be referenced as such :
Vasiliou, V ; Sophos, N
ALDH2 (aldehyde dehydrogenase 2 family (mitochondrial))
Atlas Genet Cytogenet Oncol Haematol. 2002;5(1):1-2.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/ALDH2ID250.html

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indexed on : Sat Dec 20 15:19:53 CET 2014

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