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

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB has no annotated drug labels with pharmacogenomic information for this . If you know of a drug label with PGx, send us a message.

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Related Drugs?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs1229967 100207578G>C, 100207578G>T, 24755299G>C, 24755299G>T, 259+429C>A, 259+429C>G, 3790-374G>C, 3790-374G>T
G > C
G > T
Intronic
No VIP available No Clinical Annotations available VA
rs1229976 100202078C>T, 24749799C>T, 3790-5874C>T, 829-642G>A
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs1826909 100217743C>T, 24765464C>T, 4161-3713C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs2276332 100203447A>C, 24751168A>C, 3790-4505A>C, 828+56T>G
A > C
Intronic
No VIP available No Clinical Annotations available VA
rs6811453 100194977G>A, 24742698G>A, 3790-12975G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs931635 100210847A>G, 18+1207T>C, 24758568A>G, 4148+905A>G
A > G
Intronic
VIP No Clinical Annotations available No Variant Annotations available
rs975833 100201739G>C, 24749460G>C, 3790-6213G>C, 829-303C>G, ADH1A^SNP11
G > C
Intronic
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  None
Alternate Symbols:  None
PharmGKB Accession Id: PA24570

Details

Cytogenetic Location: chr4 : q23 - q23
GP mRNA Boundary: chr4 : 100197523 - 100212185
GP Gene Boundary: chr4 : 100194523 - 100222185
Strand: minus
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.

ADH1A is one of three Class I alcohol dehydrogenases expressed in humans [Article:17204375], with the other two being the similar enzymes ADH1B and ADH1C. The Class I alcohol dehydrogenases all have high expression in human liver [Article: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 [Article:10424757]. These genes likely came about as gene duplication events, and they are all located on the same chromosome in humans [Article: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 [Article:15449945]. The Class I isozymes have been identified as both homodimers and heterodimers [Article:15449945]. The Class I alcohol dehydrogenases are differentially expressed during development, with each isozyme becoming the predominat alcohol dehydrogenase expressed at different times [Article:12489990]. ADH1A is initially the predominant isoform expressed in fetal liver [Article:12489990]. In adult tissues, this isoform has the highest expression of any Class I alcohol dehydrogenase in the kidney [Article: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 [Article:17718399]. Acetaldehyde is detoxified via further metabolism by aldehyde dehydrogenase genes ALDH1A1 and ALDH2 [Article:17590985]. Variants of all the Class I alcohol dehydrogenase genes have been described [Article:17273965], and many have been associated with a predisposition towards Alcoholism [Article:17185388 16685648], or have been associated with a protective effect of alcohol [Article:17273965]. The structure of ADH1A has been solved, and the active domain appears to be more "closed" than other known alcohol dehydrogenase structures [Article:11274460]. ADH1A has also been shown to have the highest activity of any Class I alcohol dehydrogenase towards secondary alcohols [Article: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.

Citation
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
History

Submitted by Ryan Owen

Variant Summaries rs975833
Drugs
Drug (1)
Diseases

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Abacavir Pathway, Pharmacokinetics/Pharmacodynamics
    Schematic representation of abacavir metabolism and mechanism of action. The potential mechanism of an abacavir hypersensitivity reaction is also shown.
  1. Cyclophosphamide Pathway, Pharmacodynamics
    Model non-tissue-specific cancer cell displaying genes which may be involved in the cyclophosphamide pathway.
  1. Ifosfamide Pathway, Pharmacodynamics
    Model non-tissue specific cancer cell displaying genes which may be involved in the ifosfamide pathway.

External Pathways

Links to non-PharmGKB pathways.

  1. Ethanol is oxidized by NAD+ to form acetaldehyde, NADH, and H+ - (Reactome via Pathway Interaction Database)
No related genes are available

Curated Information ?

Curated Information ?

Publications related to ADH1A: 5

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Profiling of drug-metabolizing enzymes/transporters in CD33+ acute myeloid leukemia patients treated with Gemtuzumab-Ozogamicin and Fludarabine, Cytarabine and Idarubicin. The pharmacogenomics journal. 2012. Iacobucci I, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
ADH single nucleotide polymorphism associations with alcohol metabolism in vivo. Human molecular genetics. 2009. Birley Andrew J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans. Human molecular genetics. 2007. Luo Xingguang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Diplotype trend regression analysis of the ADH gene cluster and the ALDH2 gene: multiple significant associations with alcohol dependence. American journal of human genetics. 2006. Luo Xingguang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Three-dimensional structures of the three human class I alcohol dehydrogenases. Protein science : a publication of the Protein Society. 2001. Niederhut M S, et al. PubMed

LinkOuts

Entrez Gene:
124
OMIM:
103700
UCSC Genome Browser:
NM_000667
RefSeq RNA:
NM_000667
RefSeq Protein:
NP_000658
MutDB:
ADH1A
ALFRED:
LO000422I
HuGE:
ADH1A
Comparative Toxicogenomics Database:
124
ModBase:
P07327
HGNC:
249

Common Searches