Gene:
AHR
aryl hydrocarbon receptor

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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.

Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
rs2066853 1661G>A, 17369110G>A, 17379110G>A, AHR:554R>K, AHR:R554K, Arg554Lys
G > A
Missense
Arg554Lys
No VIP available No Clinical Annotations available VA
rs4410790 17274577T>C, 17284577T>C
T > C
Not Available
No VIP available No Clinical Annotations available VA
rs75519181
A > G
Missense
Asn487Asp
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  None
Alternate Symbols:  bHLHe76
PharmGKB Accession Id: PA24641

Details

Cytogenetic Location: chr7 : p21.1 - p21.1
GP mRNA Boundary: chr7 : 17338276 - 17385775
GP Gene Boundary: chr7 : 17328276 - 17388775
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.

The human aryl hydrocarbon receptor (AHR) was cloned in 1993 [Article:8246913]. AHR was found to be 848 amino acids long [Article:8246913], and to show some regional conservation to the murine AHR [Article:8408082]. The AHR protein contains several structurally-recognized motifs including: a basic helix-loop-helix (bHLH) sequence, a nuclear localization sequence, a Per-ARNT-Sim (PAS) domain, a nuclear export signal (NES), and a transactivation domain (TAD) [Articles:15581594, 16153594, 17481570]. AHR was originally of interest due to its role in inducing the transcription of genes involved in xenobiotic metabolism, although recent work, particularly in model organisms, has suggested that AHR may have endogenous roles as well [Article:17535977].

The inactive form of AHR is associated with a protein complex in the cytoplasm [Articles:16780804, 17266942, 17535977]. The protein complex consists of inactive AHR, two Hsp90 subunits, p23, and ARA9 [Article:16780804]. This complex is activated by the binding of a xenobiotic ligand to AHR. The activated complex then migrates out of the cytoplasm and into the nucleus [Articles:16780804, 17266942, 17535977]. Once the complex has relocated to the nucleus, AHR dissociates from the complex and forms a heterodimer with ARNT [Articles:16780804, 17266942, 17535977]. Together, these two proteins form a complex that recognizes a Xenobiotic Response Element (XRE), also called a Dioxin Response Element (DRE) [Articles:16780804, 17266942, 17535977]. The consensus sequence of this response element is TNGCGTG [Article:16780804]. The complex binds the response element and drives the transcription of its target genes. Genes that are under transcriptional regulation from the AHR/ARNT heterodimer include: CYP1A1, CYP1A2, CYP1B1, NQO1, GSTA2, UGT1A1, UGT1A6, and Nrf2 (NFE2L2) [Articles:16780804, 17481570].

AHR recognizes the presence of xenobiotics in the cytoplasm, and then acts to induce metabolic genes to facilitate the elimination of the foreign compounds [Article:17481570]. AHR recognizes planar aromatic hydrocarbons as its substrates [Article:12213382]. Frequently used model compounds include 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene (MC) [Article:17481570]. Chemicals that activate AHR can be found in various consumable vegetables such as cabbage, broccoli, and cauliflower [Article:16780804].

The role of AHR in regulating genes for xenobiotic metabolism is considered to be an adaptive function. Studies in model organisms suggest that orthologs of AHR are involved in growth and development [Articles:950178, 9573046, 8589437, 17535977]. Several different laboratories have generated AHR knockout mice [Articles:7732381, 9427285, 8692887]. Although these mice are viable, they do have some abnormalities including a decreased liver size, lower fecundity, and portal fibrosis; this further supports a role for AHR beyond xenobiotic metabolism [Articles:7732381, 9427285, 8692887, 17353977]. Additionally, AHR knockout mice are resistant to TCDD toxicities [Articles:7732381, 9427285, 8692887, 17353977]. The physiological role of AHR in humans has not been well studied, and is to this point poorly understood.

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 rs2066853

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

PharmGKB contains no curated pathways for this gene. If you would like to volunteer to work on a pathway, please let us know.

External Pathways

Links to non-PharmGKB pathways.

  1. ahr signal transduction pathway - (BioCarta via Pathway Interaction Database)
No related genes are available

Curated Information ?

Evidence Drug
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
olanzapine
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
omeprazole
Evidence Drug Class
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
xenobiotics

Curated Information ?

Publications related to AHR: 22

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
An atlas of genetic influences on human blood metabolites. Nature genetics. 2014. Shin So-Youn, 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 olanzapine metabolism. Pharmacogenomics. 2013. Söderberg Mao Mao, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Influence of CYP1A1/CYP1A2 and AHR polymorphisms on systemic olanzapine exposure. Pharmacogenetics and genomics. 2013. Söderberg Mao 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
PharmGKB summary: caffeine pathway. Pharmacogenetics and genomics. 2012. Thorn Caroline F, 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
Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption. Human molecular genetics. 2011. Sulem Patrick, 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
Genome-Wide Meta-Analysis Identifies Regions on 7p21 (AHR) and 15q24 (CYP1A2) As Determinants of Habitual Caffeine Consumption. PLoS genetics. 2011. Cornelis Marilyn C, 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
Genetic variation in the bioactivation pathway for polycyclic hydrocarbons and heterocyclic amines in relation to risk of colorectal neoplasia. Carcinogenesis. 2011. Wang Hansong, 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 human AHR: identification of single nucleotide polymorphisms from six ethnic populations. Pharmacogenetics and genomics. 2010. Rowlands Craig 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
Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity. Clinical pharmacology and therapeutics. 2010. Mathias A A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Meat intake, heterocyclic amine exposure, and metabolizing enzyme polymorphisms in relation to colorectal polyp risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2008. Shin Aesun, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The aryl hydrocarbon receptor sans xenobiotics: endogenous function in genetic model systems. Molecular pharmacology. 2007. McMillan Brian J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Coordinate regulation of Phase I and II xenobiotic metabolisms by the Ah receptor and Nrf2. Biochemical pharmacology. 2007. Köhle Christoph, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Activation of coupled Ah receptor and Nrf2 gene batteries by dietary phytochemicals in relation to chemoprevention. Biochemical pharmacology. 2006. Köhle Christoph, 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 CYP3A4 in the regulation of the aryl hydrocarbon receptor by omeprazole sulphide. Cellular signalling. 2006. Gerbal-Chaloin Sabine, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Functional analysis of six human aryl hydrocarbon receptor variants in a Japanese population. Drug metabolism and disposition: the biological fate of chemicals. 2005. Koyano Satoru, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Polymorphism of alpha-estrogen receptor and aryl hydrocarbon receptor genes in dementia patients in Shanghai suburb. Acta pharmacologica Sinica. 2003. Lin Guo-Fang, 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
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Nonassociation of aryl hydrocarbon receptor genotypes with susceptibility to bladder cancer in Shanghai population. Acta pharmacologica Sinica. 2002. Zhang Dong-Sheng, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
CYP1A1 levels in lung tissue of tobacco smokers and polymorphisms of CYP1A1 and aromatic hydrocarbon receptor. Pharmacogenetics. 2001. Anttila S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Ethnic variability in the allelic distribution of human aryl hydrocarbon receptor codon 554 and assessment of variant receptor function in vitro. Pharmacogenetics. 2001. Wong J M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Variation in induced CYP1A1 levels: relationship to CYP1A1, Ah receptor and GSTM1 polymorphisms. Pharmacogenetics. 2000. Smart J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Polymorphisms of human Ah receptor gene are not involved in lung cancer. Pharmacogenetics. 1995. Kawajiri K, et al. PubMed

LinkOuts

Entrez Gene:
196
OMIM:
600253
UCSC Genome Browser:
NM_001621
RefSeq RNA:
NM_001621
RefSeq Protein:
NP_001612
RefSeq DNA:
AC_000050
AC_000068
AC_000139
NC_000007
NT_007819
NT_079592
NW_001839003
NW_923240
UniProtKB:
AHR_HUMAN (P35869)
Ensembl:
ENSG00000106546
GenAtlas:
AHR
GeneCard:
AHR
MutDB:
AHR
ALFRED:
LO000300D
HuGE:
AHR
Comparative Toxicogenomics Database:
196
ModBase:
P35869
HumanCyc Gene:
HS02922
HGNC:
348

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