ALDH2

Identity

HGNC	ALDH2
Location	12q24.2
Location_base_pair	Starts at 110688729 and ends at 110732167 bp from pter ( according to hg18-Mar_2006).

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 GÆA) 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.

External links

	Nomenclature
HGNC	ALDH2   404
Entrez_Gene	ALDH2  217  aldehyde dehydrogenase 2 family (mitochondrial)
	Cards
Atlas	ALDH2ID250
GeneCards	ALDH2
Ensembl	ENSG00000111275 [Gene_View]  ALDH2 [Vega]
Genatlas	ALDH2
	Genomic and cartography
GoldenPath	ALDH2  -  12q24.2   chr12:110688729-110732167 +  12q24.12   [Description]    (hg18-Mar_2006)
Ensembl	ALDH2 - 12q24.12 [CytoView]
NCBI	Mapview
OMIM	100650 Disease map [OMIM]
HomoloGene	ALDH2
	Gene and transcription
Genbank	AK223373 [ ENTREZ ]
Genbank	AK301375 [ ENTREZ ]
Genbank	AK314856 [ ENTREZ ]
Genbank	AY621070 [ ENTREZ ]
Genbank	BC002967 [ ENTREZ ]
RefSeq	NM_000690 [ SRS ]    NM_000690 [ ENTREZ ]
RefSeq	AC_000055 [ SRS ]    AC_000055 [ ENTREZ ]
RefSeq	AC_000144 [ SRS ]    AC_000144 [ ENTREZ ]
RefSeq	NC_000012 [ SRS ]    NC_000012 [ ENTREZ ]
RefSeq	NT_009775 [ SRS ]    NT_009775 [ ENTREZ ]
RefSeq	NW_001838063 [ SRS ]    NW_001838063 [ ENTREZ ]
RefSeq	NW_925395 [ SRS ]    NW_925395 [ ENTREZ ]
CCDS	ALDH2 CCDS - NCBI
AceView	ALDH2 AceView - NCBI
Unigene	Hs.632733 [ SRS ]    Hs.632733 [ NCBI ]
Fast-db	13453 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P05091 [ SRS]    P05091 [ EXPASY ]     P05091 [ INTERPRO ]     P05091 [ UNIPROT ] P05091 [ VarSplice FASTA ]
Prosite	PS00070 ALDEHYDE_DEHYDR_CYS [ SRS ]    PS00070 ALDEHYDE_DEHYDR_CYS [ Expasy ]
Prosite	PS00687 ALDEHYDE_DEHYDR_GLU [ SRS ]    PS00687 ALDEHYDE_DEHYDR_GLU [ Expasy ]
Interpro	IPR016160 Ald_DHase_CS [ SRS ]    IPR016160 Ald_DHase_CS [ EBI ]
Interpro	IPR016162 Ald_DHase_N [ SRS ]    IPR016162 Ald_DHase_N [ EBI ]
Interpro	IPR015590 Aldehyde_DHase [ SRS ]    IPR015590 Aldehyde_DHase [ EBI ]
CluSTr	P05091
Pfam	PF00171 Aldedh [ SRS ]    PF00171 Aldedh [ Sanger ]    pfam00171 [ NCBI-CDD ]
Blocks	P05091
PDB	1CW3 [ SRS ]    1CW3 [ PdbSum ],   1CW3 [ IMB ]   1CW3 [ RSDB ]
PDB	1NZW [ SRS ]    1NZW [ PdbSum ],   1NZW [ IMB ]   1NZW [ RSDB ]
PDB	1NZX [ SRS ]    1NZX [ PdbSum ],   1NZX [ IMB ]   1NZX [ RSDB ]
PDB	1NZZ [ SRS ]    1NZZ [ PdbSum ],   1NZZ [ IMB ]   1NZZ [ RSDB ]
PDB	1O00 [ SRS ]    1O00 [ PdbSum ],   1O00 [ IMB ]   1O00 [ RSDB ]
PDB	1O01 [ SRS ]    1O01 [ PdbSum ],   1O01 [ IMB ]   1O01 [ RSDB ]
PDB	1O02 [ SRS ]    1O02 [ PdbSum ],   1O02 [ IMB ]   1O02 [ RSDB ]
PDB	1O04 [ SRS ]    1O04 [ PdbSum ],   1O04 [ IMB ]   1O04 [ RSDB ]
PDB	1O05 [ SRS ]    1O05 [ PdbSum ],   1O05 [ IMB ]   1O05 [ RSDB ]
PDB	1OF7 [ SRS ]    1OF7 [ PdbSum ],   1OF7 [ IMB ]   1OF7 [ RSDB ]
PDB	1ZUM [ SRS ]    1ZUM [ PdbSum ],   1ZUM [ IMB ]   1ZUM [ RSDB ]
PDB	2ONM [ SRS ]    2ONM [ PdbSum ],   2ONM [ IMB ]   2ONM [ RSDB ]
PDB	2ONN [ SRS ]    2ONN [ PdbSum ],   2ONN [ IMB ]   2ONN [ RSDB ]
PDB	2ONO [ SRS ]    2ONO [ PdbSum ],   2ONO [ IMB ]   2ONO [ RSDB ]
PDB	2ONP [ SRS ]    2ONP [ PdbSum ],   2ONP [ IMB ]   2ONP [ RSDB ]
HPRD	00003
	Protein Interaction databases
DIP	P05091
IntAct	P05091
	Polymorphism : SNP, mutations, diseases
OMIM	100650    [ map ]
GENETests	100650
SNP	ALDH2 [dbSNP-NCBI]
SNP	NM_000690 [SNP-NCI]
SNP	ALDH2 [GeneSNPs - Utah]  ALDH2] [HGBASE - SRS]
HAPMAP	ALDH2 [HAPMAP]
COSMIC	ALDH2 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	ALDH2
Genetic Association	ALDH2
CDC HuGE	ALDH2
	General knowledge
Family Browser	ALDH2 [UCSC Family Browser]
SOURCE	NM_000690
SMD	Hs.632733
SAGE	Hs.632733
Enzyme	1.2.1.3 [ Enzyme-Expasy ]   1.2.1.3 [ Enzyme-SRS ]   1.2.1.3 [ IntEnz-EBI ]   1.2.1.3 [ BRENDA ]   1.2.1.3 [ KEGG ]
GO	aldehyde dehydrogenase (NAD) activity [Amigo]  aldehyde dehydrogenase (NAD) activity
GO	aldehyde dehydrogenase [NAD(P)+] activity [Amigo]  aldehyde dehydrogenase [NAD(P)+] activity
GO	neuropeptide hormone activity [Amigo]  neuropeptide hormone activity
GO	mitochondrion [Amigo]  mitochondrion
GO	mitochondrial matrix [Amigo]  mitochondrial matrix
GO	carbohydrate metabolic process [Amigo]  carbohydrate metabolic process
GO	alcohol metabolic process [Amigo]  alcohol metabolic process
GO	neuropeptide signaling pathway [Amigo]  neuropeptide signaling pathway
GO	electron carrier activity [Amigo]  electron carrier activity
GO	oxidoreductase activity [Amigo]  oxidoreductase activity
GO	oxidation reduction [Amigo]  oxidation reduction
KEGG	Glycolysis / Gluconeogenesis
KEGG	Ascorbate and aldarate metabolism
KEGG	Fatty acid metabolism
KEGG	Bile acid biosynthesis
KEGG	Valine, leucine and isoleucine degradation
KEGG	Lysine degradation
KEGG	Arginine and proline metabolism
KEGG	Histidine metabolism
KEGG	Tryptophan metabolism
KEGG	beta-Alanine metabolism
KEGG	Glycerolipid metabolism
KEGG	Pyruvate metabolism
KEGG	Propanoate metabolism
KEGG	Butanoate metabolism
KEGG	Limonene and pinene degradation
PubGene	ALDH2
TreeFam	ALDH2
CTD	217 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	Cancer Cytogenetics (Bari)
Probe	ALDH2 Related clones (RZPD - Berlin)
	PubMed
PubMed	231 Pubmed reference(s) in Entrez

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 articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	09-2001	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

Citation

This paper should be referenced as such :

Vasiliou V, Sophos N . ALDH2. Atlas Genet Cytogenet Oncol Haematol. September 2001 . URL : http://AtlasGeneticsOncology.org/Genes/ALDH2ID250.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Thu Nov 27 13:19:20 2008