Gene:
ALOX5
arachidonate 5-lipoxygenase

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

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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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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.

List of all ALOX5 variant annotations

Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
VIP No Clinical Annotations available No Variant Annotations available
chr10:45869552
rs2115819 246472A>G, 3546154A>G, 36461A>G, 432-6550A>G, 45901089A>G, rs2115819
A > G
Intronic
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142

Overview

Alternate Names:  None
Alternate Symbols:  5-LOX
PharmGKB Accession Id: PA46

Details

Cytogenetic Location: chr10 : q11.21 - q11.21
GP mRNA Boundary: chr10 : 45869629 - 45941565
GP Gene Boundary: chr10 : 45859629 - 45944565
Strand: plus
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.

ALOX5 encodes arachidonate 5-lipoxygenase, a cystolic enzyme that catalyzes the two-step conversion of arachidonic acid to leukotriene A4 (LTA4). The gene was originally cloned in 1988 by both Matsumoto et al., from human lung and placenta and by Dixon et al., from human neutrophils [Articles:2829172, 3422434]. The gene was mapped to chromosome 10 by Funk et al. using a human-hamster somatic hybrid DNA panel [Article:2565035]. ALOX5 is specifically located on chromosome 10q11.2. The gene consists of 14 exons encompassing 2493 nucleotides which encode a 674 amino-acid protein. The product 5-lipoxygenase is expressed exclusively in bone-marrow-derived cells, including macrophages, monocytes and primarily neutrophils. 5-lipoxygenase products are acted upon by several downstream enzymes, resulting in the formation of several leukotriene products. Together, these enzymes form the leukotriene pathway which is known to play a significant role in the inflammatory process. Furthermore, this pathway has been implicated in the pathogenesis of inflammatory diseases such as asthma and atherosclerosis.

ALOX5 has one widely-studied polymorphism. The alleles of this polymorphism are formed by 3-8 tandem repeats of the nucleotide sequence 5'GGGCGG3' located in the ALOX5 promoter region. The most common (wild-type) allele has 5 repeats and all others are considered variants. These variants are associated with decreased ALOX5 promoter activity in in vitro reporter-gene models [Articles:9062372, 16364163]. Phenotypically, variants in ALOX5 are associated with inflammatory disease, including asthma [Article:15876305], atherosclerosis [Article:14702425], and colon cancer. In particular, the ALOX5 promoter variants are associated with diminished response to leukotriene-inhibitor treatment, although these results are conflicting and these studies have not evaluated similar outcomes [Articles:16293801, 12107604, 10369259]. In addition, a link between ALOX5 promoter variants and the development and progression of atherosclerosis has been established [Articles:14702425, 15933245].

In addition, several other polymorphisms in ALOX5 have been reported although there is less evidence associating these variants with their phenotypes. Most prominent is a newly-identified intronic single nucleotide polymorphism (SNP) reported by Lima et al. ([rs2115819]), which is positively associated with increased FEV 1 response to montelukast therapy. This SNP is also part of a 4-SNP haplotype associated with increased numbers of asthma exacerbations during 6 months of montelukast treatment relative to placebo [Article:16293801] (see Phenotype Dataset). Further, Goodman et al. reported a significant association between 2 SNPs in the negative regulatory region of the ALOX5 promoter and a reduced risk of colon cancer, although this association was seen only in Caucasians. A haplotype which included these SNPs is also associated with reduced colon cancer risk [Article:15308583].

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 Anzeela M. Schentrup, John J. Lima, Julie A. Johnson (PEAR and PAM) (April 17, 2006)

Variant Summaries chr10:45869552, rs2115819
Drugs
Drug (1)
Diseases

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

External Pathways

Links to non-PharmGKB pathways.

  1. eicosanoid metabolism - (BioCarta via Pathway Interaction Database)
  2. Leukotriene synthesis - (Reactome via Pathway Interaction Database)
No related genes are available

Curated Information ?

Evidence Drug
montelukast
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available PW
zileuton

Curated Information ?

Publications related to ALOX5: 23

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Integrative systems biology approaches in asthma pharmacogenomics. Pharmacogenomics. 2012. Dahlin Amber, 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
The pharmacogenetics and pharmacogenomics of asthma therapy. The pharmacogenomics journal. 2011. Tse S M, 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
Role of cyclooxygenase-2 and 5-lipoxygenase polymorphisms in Alzheimer's disease in a population from northern Italy: implication for pharmacogenomics. Journal of Alzheimer's disease : JAD. 2010. Listì Florinda, 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
Genetics and pharmacogenetics of the leukotriene pathway. The Journal of allergy and clinical immunology. 2009. Tantisira Kelan G, 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
Leukotriene pathway genetics and pharmacogenetics in allergy. Allergy. 2009. Duroudier N P, 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
5-lipoxygenase pharmacogenetics in asthma: overlap with Cys-leukotriene receptor antagonist loci. Pharmacogenetics and genomics. 2009. Tantisira Kelan G, 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
Asthma pharmacogenetic study using finite mixture models to handle drug-response heterogeneity. Pharmacogenomics. 2009. York Timothy P, 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
Pharmacogenetics of asthma. Current opinion in pulmonary medicine. 2009. Lima John J, et al. PubMed
Influence of leukotriene pathway polymorphisms on response to montelukast in asthma. American journal of respiratory and critical care medicine. 2006. Lima John J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
ALOX5 promoter genotype, asthma severity and LTC production by eosinophils. Allergy. 2006. Kalayci O, 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
Overview of the pharmacogenetics of asthma treatment. The pharmacogenomics journal. 2006. Weiss S T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Association between 5-lipoxygenase expression and plaque instability in humans. Arteriosclerosis, thrombosis, and vascular biology. 2005. Cipollone Francesco, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Polymorphism of tandem repeat in promoter of 5-lipoxygenase in ASA-intolerant asthma: a positive association with airway hyperresponsiveness. Allergy. 2005. Kim S-H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. The New England journal of medicine. 2004. Dwyer James H, 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
Classification of pediatric acute lymphoblastic leukemia by gene expression profiling. Blood. 2003. Ross Mary E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
5-Lipoxygenase polymorphism and in-vivo response to leukotriene receptor antagonists. European journal of clinical pharmacology. 2002. Fowler Stephen J, 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
Cloning and functional analysis of the mouse 5-lipoxygenase promoter. American journal of respiratory cell and molecular biology. 2002. Silverman Eric 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
Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer cell. 2002. Yeoh Eng-Juh, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nature genetics. 1999. Drazen J M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription. The Journal of clinical investigation. 1997. In K H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Characterization of the human 5-lipoxygenase gene. Proceedings of the National Academy of Sciences of the United States of America. 1989. Funk C D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Cloning of the cDNA for human 5-lipoxygenase. Proceedings of the National Academy of Sciences of the United States of America. 1988. Dixon R A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Molecular cloning and amino acid sequence of human 5-lipoxygenase. Proceedings of the National Academy of Sciences of the United States of America. 1988. Matsumoto T, et al. PubMed

LinkOuts

Entrez Gene:
240
OMIM:
152390
600807
UCSC Genome Browser:
NM_000698
RefSeq RNA:
NM_000698
RefSeq Protein:
NP_000689
RefSeq DNA:
AC_000053
AC_000142
NC_000010
NG_011437
NT_033985
NW_001837940
NW_003315935
NW_921506
NW_924606
UniProtKB:
LOX5_HUMAN (P09917)
Ensembl:
ENSG00000012779
GenAtlas:
ALOX5
GeneCard:
ALOX5
MutDB:
ALOX5
ALFRED:
LO037847D
HuGE:
ALOX5
Comparative Toxicogenomics Database:
240
ModBase:
P09917
HumanCyc Gene:
HS00336
HGNC:
435

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