Annotated PGx Gene Information for ADH1A
Submitted by: Ryan Owen (PharmGKB)
Reviewed by: Under Review
Submitted date: Feb 21, 2008
| Gene HGNC Name: | ADH1A |
|---|---|
| Gene Common Name: | ADH1, alcohol dehydrogenase |
| Introductory Information: | 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. |
| Key PubMed IDs: | 17204375 15449945 17185388 16685648 11274460 |
| Key Pathways: | N/A |
| Drugs/Substrates: | alcohol |
| Phenotypes/Diseases: | Alcoholism |
| Important Variants: | ADH1A^SNP11 |
| Important Haplotypes: | ADH1A diplotypes |