aldehyde dehydrogenase 1 family, member A1

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

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

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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.

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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.

List of all variant annotations for ALDH1A1

Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
No VIP available No Clinical Annotations available VA
rs168351 NC_000009.11:g.75517311A>G, NC_000009.12:g.72902395A>G, NG_012249.1:g.55659T>C, NM_000689.4:c.1434-1115T>C, XM_005251800.1:c.1434-1115T>C, XM_005251801.1:c.1374-1115T>C, rs2183402, rs635555
A > G
No VIP available No Clinical Annotations available VA
rs3764435 NC_000009.11:g.75516876A>C, NC_000009.12:g.72901960A>C, NG_012249.1:g.56094T>G, NM_000689.4:c.1434-680T>G, XM_005251800.1:c.1434-680T>G, XM_005251801.1:c.1374-680T>G
A > C
rs6151031 NC_000009.11:g.75568383_75568384insCTGGTGAGGAGAGAACC, NC_000009.12:g.72953467_72953468insCTGGTGAGGAGAGAACC, NG_012249.1:g.4586_4587insGGTTCTCTCCTCACCAG, NM_000689.4:c.-468_-467insGGTTCTCTCCTCACCAG, XM_005251800.1:c.-14-454_-14-453insGGTTCTCTCCTCACCAG, rs142856037
No VIP available No Clinical Annotations available VA
rs63319 NC_000009.11:g.75524784G>T, NC_000009.12:g.72909868G>T, NG_012249.1:g.48186C>A, NM_000689.4:c.1201-109C>A, XM_005251800.1:c.1201-109C>A, XM_005251801.1:c.1141-109C>A, rs386602334, rs604561, rs726191
G > T
VIP No Clinical Annotations available No Variant Annotations available
rs72554629 NC_000009.11:g.75568477_75568478insGTA, NC_000009.11:g.75568477_75568478insTAC, NC_000009.12:g.72953561_72953562insGTA, NC_000009.12:g.72953561_72953562insTAC, NG_012249.1:g.4492_4493insGTA, NG_012249.1:g.4492_4493insTAC, NM_000689.4:c.-562_-561insGTA, NM_000689.4:c.-562_-561insTAC, XM_005251800.1:c.-14-548_-14-547insGTA, XM_005251800.1:c.-14-548_-14-547insTAC
- > GTA
- > TAC
No VIP available No Clinical Annotations available VA
rs8187996 NC_000009.11:g.75516495C>T, NC_000009.12:g.72901579C>T, NG_012249.1:g.56475G>A, NM_000689.4:c.1434-299G>A, XM_005251800.1:c.1434-299G>A, XM_005251801.1:c.1374-299G>A, rs17647529
C > T
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147


Alternate Names:  ALDH1; PUMB1; retinaldehyde dehydrogenase 1
Alternate Symbols:  RALDH1
PharmGKB Accession Id: PA24692


Cytogenetic Location: chr9 : q21.13 - q21.13
GP mRNA Boundary: chr9 : 75515578 - 75653633
GP Gene Boundary: chr9 : 75512578 - 75663633
Strand: minus


UCSC has a Genome Browser that you can use to view PharmGKB annotations for this gene in context with many other sources of information.

View on UCSC Browser
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.

ALDH1A1 is one member of a family of aldehyde dehydrogenases, and is also known as the cytosolic aldehyde dehydrogenase. The human ortholog of this enzyme was first purified in 1979 [Article:224930], and the genomic structure and protein length (501 amino acids) were described ten years later [Article:2591967]. ALDH1A1 shows strong tissue expression in the liver, but is also constitutively expressed in other tissues, including erythrocytes, eye, and brain [Article:10971205]. Aldehyde dehydrogenases are of interest due to their important and diverse physiological roles, which often include the detoxification of metabolic intermediates from an aldehyde form to a carboxylic acid form.

ALDH1A1 has been shown to play a role in alcohol metabolism [Article:17718394]. The alcohol metabolism process is essentially a two step process: first alcohol is converted to acetaldehyde by an alcohol dehydrogenase family member, and then the acetaldehyde is converted to acetate by an aldehyde dehydrogenase (ALDH1A1 or ALDH2) [Article:17718394]. The intermediate metabolite, acetaldehyde, is thought to be toxic at high levels, and it may be responsible for some of the adverse reactions associated with alcohol such as facial flushing, nausea, and an increased heart rate [Article:17718394]. An accumulation of acetaldehyde can occur either due to a hyperactive alcohol dehydrogenase enzyme, or an impaired aldehyde dehydrogenase enzyme [Article:17718394]. Although some genetic variation has been described for ALDH1A1 (see variant pages), it appears that genetic variation in ALDH2 plays a more important role in determining predisposition towards alcoholism [Article:17718394].

ALDH1A1 is also involved in the retinol (vitamin A) metabolic pathway [Article:12851412]. The retinol pathway and the ethanol pathway share considerable overlap, and ALDH1A1 is involved in the conversion of retinaldehyde to retanoic acid (RA) [Article:12851412]. Vitamin A (retinol) can be converted to retinal by alcohol dehydrogenase enzymes, and then further converted to RA by ALDH1A1 or other aldehyde dehydrogenases [Article:10880953]. Retinoic Acid is involved in a number of physiological processes including cell growth and differentiation [Article:10971205, 10880953]. RA exerts its effect on the transcriptional level, by binding to retinoid receptors RAR and/or RXR, which often form a heterodimer [Article:10880953]. The RAR/RXR heterodimer is then able to transcriptionally regulate several genes. There may be some interactions between retinol and ethanol metabolic pathways, which could potentially play a role in fetal alcohol syndrome [Article:9802541].

ALDH1A1 has also been shown to be involved in the resistance to the chemotherapeutic agent cyclophosphamide (CP) and its derivatives [Article:15237855]. CP is used in the treatment of several types of cancer [Article:15237855]. CP is converted to 4-hydroxycyclophosphamide by several different CYP enzymes, and the 4-hydroxy-CP which can intraconvert with aldophosphamide [Article:15237855]. Aldophosphamide can undergo several metabolic fates, including the formation of acrolein and phosphoramide mustard, both of which are cytotoxic alkylating agents [Article:15237855]. Alternatively, aldophosphamide can be metabolized by ALDH1A1 (or other aldehyde dehydrogenases) to carboxyphosphamide [Article:15237855]. This is considered to be a detoxification step, as carboxyphosphamide is not cytotoxic [Article:10469894]. An increase in expression of ALDH1A1 has been shown to be correlated with CP-resistant cancers in patients [Article:16918308], and in vitro evidence suggests that tranfection with ALDH1A1 can be sufficient to confer resistance to CP-induced cytotoxicity [Article:10469894].

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

Submitted by Ryan Owen (Feb 21, 2008)

Variant Summaries rs6151031, rs72554629

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  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.
  1. Ifosfamide Pathway, Pharmacokinetics
    Model human liver cell showing genes involved in the metabolism of ifosfamide.
No related genes are available

Curated Information ?

Curated Information ?

Publications related to ALDH1A1: 7

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: ifosfamide pathways, pharmacokinetics and pharmacodynamics. Pharmacogenetics and genomics. 2014. Lowenberg Daniella, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Germline genetic variants in ABCB1, ABCC1 and ALDH1A1, and risk of hematological and gastrointestinal toxicities in a SWOG Phase III trial S0221 for breast cancer. The pharmacogenomics journal. 2013. Yao S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Aldehyde dehydrogenase 1A1 confers intrinsic and acquired resistance to gemcitabine in human pancreatic adenocarcinoma MIA PaCa-2 cells. International journal of oncology. 2012. Duong Hong-Quan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Human aldehyde dehydrogenase genes: alternatively spliced transcriptional variants and their suggested nomenclature. Pharmacogenetics and genomics. 2009. Black William J, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Relations between polymorphisms in drug-metabolising enzymes and toxicity of chemotherapy with cyclophosphamide, thiotepa and carboplatin. Pharmacogenetics and genomics. 2008. Ekhart Corine, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Influence of polymorphisms of drug metabolizing enzymes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1) on the pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide. Pharmacogenetics and genomics. 2008. Ekhart Corine, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Molecular pharmacology. 2002. Maglich Jodi M, et al. PubMed


NCBI Gene:
UCSC Genome Browser:
RefSeq RNA:
RefSeq Protein:
RefSeq DNA:
AL1A1_HUMAN (P00352)
Comparative Toxicogenomics Database:
HumanCyc Gene:

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