PharmGKB: The Pharmacogenomics Knowledge Base

Gene:
ADH1A
alcohol dehydrogenase 1A (class I), alpha polypeptide

Overview

Alternate Names: ADH, alpha subunit; alcohol dehydrogenase 1; alcohol dehydrogenase 1 (class I), alpha polypeptide; aldehyde reductase; class I alcohol dehydrogenase, alpha subunit
Alternate Symbols: ADH1
PharmGKB Accession Id: PA24570

Details

Cytogenetic Location: chr4 : q23
GP mRNA Boundary†: chr4 : 100416547 - 100431165
GP Gene Boundary†: chr4 : 100413547 - 100441165
Strand: minus
Product Name: ADH, alpha subunit, alcohol dehydrogenase 1 (class I), alpha polypeptide, aldehyde reductase, class I alcohol dehydrogenase, alpha subunit
† The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

Introduction

View Full VIP Annotation

ADH1A is one of three Class I alcohol dehydrogenases expressed in humans [17204375], with the other two being the similar enzymes ADH1B and ADH1C. The Class I alcohol dehydrogenases all have high expression in human liver [15449945]. Studying the specific roles of these individual enzymes in alcohol dependence using model organisms such as mouse and rat can be difficult since these rodents have only one Class I alcohol dehydrogenase [10424757]. These genes likely came about as gene duplication events, and they are all located on the same chromosome in humans [17204375]. The amino acid composition of the resulting proteins is very similar between the three enzymes, and the catalyzed reactions are similar, although differences in the active site have led to the development of an isozyme-specific inhibitor for ADH1A [15449945]. The Class I isozymes have been identified as both homodimers and heterodimers [15449945]. The Class I alcohol dehydrogenases are differentially expressed during development, with each isozyme becoming the predominat alcohol dehydrogenase expressed at different times [12489990]. ADH1A is initially the predominant isoform expressed in fetal liver [12489990]. In adult tissues, this isoform has the highest expression of any Class I alcohol dehydrogenase in the kidney [16571603].

Each Class I ADH is able to catalyze the conversion of alcohol to acetaldehyde, a metabolite that is associated with some of the toxicities associated with alcohol [17718399]. Acetaldehyde is detoxified via further metabolism by aldehyde dehydrogenase genes ALDH1A1 and ALDH2 [17590985]. Variants of all the Class I alcohol dehydrogenase genes have been described [17273965], and many have been associated with a predisposition towards Alcoholism [17185388 16685648], or have been associated with a protective effect of alcohol [17273965]. The structure of ADH1A has been solved, and the active domain appears to be more "closed" than other known alcohol dehydrogenase structures [11274460]. ADH1A has also been shown to have the highest activity of any Class I alcohol dehydrogenase towards secondary alcohols [11274460]. Despite these discoveries, ADH1A remains the least well characterized of the Class I alcohol dehydrogenases, with only a handful of variants described in the literature, and its contribution towards Alcoholism likely pales in comparison to that of ADH1B.

In-Depth Annotations (In-Depth Annotation)

  1. rs975833 at chr4:100420762 in ADH1A
    This SNP is located in intron 7 of ADH1A. ADH1A^SNP11 was the only SNP examined in ADH1A that showed a tendency towards an association with alcohol dependence in the African American sample.
    Variant Name:
    ADH1A^SNP11
    Related Drugs:
    ethanol
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

Non-Curated Information

A list of non-curated publications that mention this gene along with other genes is available.

Curated Information

The following drugs are in curated knowledge about this gene.

  Drug Relationship Evidence
Phenotype data available No genotype data Literature annotations available Not annotated
ethanol
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants

Non-Curated Information

A list of non-curated publications that mention this gene along with other drugs is available.

Curated Information

The following diseases are in curated knowledge about this gene.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Alcohol-Related Disorders
  • CO
  • PD
  • PK
  •   
  • GN
Publications

Non-Curated Information

A list of non-curated publications that mention this gene along with other diseases is available.

Downloads

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LinkOuts

Entrez Gene ID:
124
OMIM Accession:
103700
UCSC Genome Browser ID:
NM_000667
Ref Seq NM Accession:
NM_000667
Ref Seq NP Accession:
AAA51590
AAA51591
AAA52276
AAA68131
AAH74738
AAI17443
AAI26307
AAV38615
AAX20115
BAF83247
EAX06093
EAX06094
NP_000658
P07327
Ref Seq NT Accession:
AC_000047
AC_000136
NC_000004
NT_016354
NW_001838915
NW_922162
UniProtKB Accesssion:
ADH1A_HUMAN (P07327)
Ensembl ID:
ENSG00000187758
GenAtlas ID:
ADH1A
GeneCard ID:
ADH1A
SOURCE ID:
ADH1A
MutDB ID:
ADH1A
PromoLign ID:
ortho_1906
ALFRED ID:
LO000422I
HuGE ID:
ADH1A
Comparative Toxicogenomics Acc ID:
124
ModBase:
P07327

Common Searches

Non-Curated Publications

A list of non-curated publications that mention this gene is available.

The PharmGKB is financially supported by the NIH/ NIGMS and is managed at Stanford University (U01GM61374).
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