Drug/Small Molecule:
etanercept

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

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.



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 page.

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.

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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 Gene?

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.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs1043879 12250169T>C, 25570081T>C, 716A>G, Glu239Gly
T > C
Missense
Glu239Gly
No VIP available No Clinical Annotations available VA
rs10499194 138002637C>T, 42172094C>T
C > T
Not Available
No VIP available No Clinical Annotations available VA
rs10903129 12449025A>G, 25768937A>G, 81-4316A>G
A > G
Intronic
No VIP available CA VA
rs10919563 1382-304G>A, 1865-304G>A, 198700442G>A, 50189084G>A, 97218G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs11586238 117263138C>G, 87235056C>G
C > G
Not Available
No VIP available No Clinical Annotations available VA
rs13031237 395-7883G>T, 39958016G>T, 61136129G>T
G > T
Intronic
No VIP available CA No Variant Annotations available
rs1799724 *1012C>T, -1037C>T, 2828023C>T, 2836120C>T, 2873283C>T, 2885366C>T, 2922188C>T, 3052098C>T, 31482482C>T, 31542482C>T, 4133C>T, 7607C>T, TNF:-850C-T, TNF:-857 C/T
C > T
5' Flanking
No VIP available No Clinical Annotations available VA
rs1800471 14127094C>G, 16203G>C, 41858876C>G, 5956G>C, 74G>C, Arg25Pro, TGFB1:914G>C, TGFB1:Arg25Pro, TGFB1:Ex1-282G>C, TGFB1:G915C, TGFB1:GC915
C > G
Missense
Arg25Pro
No VIP available CA VA
rs1800629 -308, -308G>A, -488G>A, 2828572G>A, 2836669G>A, 2873832G>A, 2885915G>A, 2922737G>A, 3052647A>A, 31483031G>A, 31543031G>A, 4682G>A, 8156G>A, TNF alpha -308G/A, TNF2, TNF:, TNF:-308 G/A, TNF:-308G/A
G > A
5' Flanking
No VIP available No Clinical Annotations available VA
rs1800795 -237C>G, 22756645C>G, 22766645C>G, 4880C>G, 50-321G>C
C > G
Intronic
No VIP available No Clinical Annotations available VA
rs1801274 12968387A>G, 161479745A>G, 497A>G, 500A>G, 9541A>G, FCGR2A:His131Arg
A > G
Missense
His167Arg
No VIP available No Clinical Annotations available VA
rs1980422 204610396C>T, 54819814C>T
C > T
Not Available
No VIP available No Clinical Annotations available VA
rs20575 10917470C>G, 23059324C>G, 28357G>C, 626G>C, Arg209Thr
C > G
Missense
Arg209Thr
No VIP available No Clinical Annotations available VA
rs2104286 10228A>G, 6039045T>C, 6099045T>C, 64+5006A>G
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs2228145 1066+4514A>C, 1066+4514A>T, 1073A>C, 1073A>T, 154426970A>C, 154426970A>T, 54302A>C, 54302A>T, 5915612A>C, 5915612A>T, Asp358Ala, Asp358Val
A > T
A > C
Intronic
Asp358Ala
No VIP available No Clinical Annotations available VA
rs2476601 114377568A>A, 114377568A>G, 1693C>C, 1693C>T, 1858C>C, 1858C>T, 41808C>C, 41808C>T, 84349486A>A, 84349486A>G, Arg565=, Arg620=
A > G
Missense
Arg620Trp
No VIP available No Clinical Annotations available VA
rs2736340 11343973C>T, 3819324C>T
C > T
Not Available
No VIP available No Clinical Annotations available VA
rs2812378 -197C>T, 34700260G>A, 34710260G>A
G > A
5' Flanking
No VIP available No Clinical Annotations available VA
rs3087243 *1384G>A, *1421G>A, 11411G>A, 204738919G>A, 54948337G>A
G > A
3' Flanking
No VIP available No Clinical Annotations available VA
rs3218253 -34+1055C>T, 16935379G>A, 37544810G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs3761847 -1638C>T, -366+1153C>T, 123690239G>A, 52854771G>A, 6213C>T
G > A
5' Flanking
No VIP available CA VA
rs3794271 13620217G>A, 20860093G>A, 404+1078G>A, 50+1078G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs394581 159482521C>T, 63651978C>T
C > T
Not Available
No VIP available No Clinical Annotations available VA
rs396991 10872T>G, 13003184A>C, 158V/F, 161514542A>C, 176F/V, 523T>G, 526T>G, 631T>G, 634T>G, A559C, FCGR3A: V158F, Phe175Val, Phe176Val, Phe211Val, Phe212Val, T559G
A > C
Missense
Phe175Val
No VIP available No Clinical Annotations available VA
rs4750316 6333260C>G, 6393260C>G, 978C>G
C > G
3' Flanking
No VIP available No Clinical Annotations available VA
rs4810485 14944039T>G, 44747947T>G, 51+914T>G, 6042T>G
T > G
Intronic
No VIP available No Clinical Annotations available VA
rs548234 106568034C>T, 10737491C>T
C > T
Not Available
No VIP available CA VA
rs6427528 *1738T>C, *1808T>C, 12004950A>G, 160516308A>G
A > G
3' UTR
No VIP available No Clinical Annotations available VA
rs6691117 118459A>G, 1300710A>G, 207782931A>G, 4843A>G, 6193A>G, Ile1615Val, Ile2065Val
A > G
Missense
Ile2065Val
No VIP available No Clinical Annotations available VA
rs6822844 123509421G>T, 48057142G>T
G > T
Not Available
No VIP available No Clinical Annotations available VA
rs6920220 138006504G>A, 42175961G>A
G > A
Not Available
No VIP available No Clinical Annotations available VA
rs7527798 1143-244T>C, 1390069T>C, 207872290T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs7574865 191964633T>G, 274-23582A>C, 42174051T>G, 56293A>C
T > G
Intronic
No VIP available CA VA
rs767455 36A>G, 5317A>G, 6390945T>C, 6450945T>C, Pro12=
T > C
Synonymous
Pro12Pro
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • CD120b
  • TNF-R2
  • Tumor necrosis factor receptor 2
  • Tumor necrosis factor receptor superfamily member 1B precursor
  • Tumor necrosis factor receptor type II
  • etanercept
  • p75
  • p80 TNF-alpha receptor
Trade Names
  • Enbrel
  • Enbrel (Immunex Corp)
  • Enbrel Sureclick
Brand Mixture Names

PharmGKB Accession Id:
PA449515

Description

Dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton (p75) tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1. The Fc component of etanercept contains the CH2 domain, the CH3 domain and hinge region, but not the CH1 domain of IgG1. Etanercept is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian cell expression system. It consists of 934 amino acids

Source: Drug Bank

Indication

For treatment of severe active rheumatoid arthritis in adults, severe juvenile idiopathic arthritis, ankylosing spondylitis, and severe plaque psoriasis.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

There are two distinct receptors for TNF (TNFRs), a 55 kilodalton protein (p55) and a 75 kilodalton protein (p75). The biological activity of TNF is dependent upon binding to either cell surface receptor (p75 or p55). Etanercept is a dimeric soluble form of the p75 TNF receptor that can bind to two TNF molecules, thereby effectively removing them from circulation.

Source: Drug Bank

Pharmacology

Tumor necrosis factor TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels of TNF are found in tissues and fluids of patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (AS), and plaque psoriasis. Etanercept binds specifically to tumor necrosis factor (TNF) and blocks its interaction with cell surface TNF receptors.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Half-Life

102 +/- 30 hrs

Source: Drug Bank

Clearance

Source: Drug Bank

Chemical Properties

Chemical Formula

C2224H3475N621O698S36

Source: Drug Bank

Canonical SMILES

Not Available

Source: Drug Bank

Average Molecular Weight

51234.9000

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
C1QA (source: Drug Bank)
C1QB (source: Drug Bank)
C1QC (source: Drug Bank)
C1R (source: Drug Bank)
C1S (source: Drug Bank)
FCGR1A (source: Drug Bank)
FCGR2A (source: Drug Bank)
FCGR2B (source: Drug Bank)
FCGR2C (source: Drug Bank)
FCGR3A (source: Drug Bank)
FCGR3B (source: Drug Bank)
LTA (source: Drug Bank)
TNF (source: Drug Bank)
TNFRSF1B (source: Drug Bank)

Drug Interactions

Drug Description
etanercept Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to etanercept: 29

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Confirmation of -174G/C interleukin-6 gene promoter polymorphism as a genetic marker predicting antitumor necrosis factor treatment outcome. Pharmacogenetics and genomics. 2013. Dávila-Fajardo Cristina L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Association of TNF-alpha polymorphism with prediction of response to TNF blockers in spondyloarthritis and inflammatory bowel disease: a meta-analysis. Pharmacogenomics. 2013. Tong Qiang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
The role of Fcgamma receptor polymorphisms in the response to anti-tumor necrosis factor therapy in psoriasis A pharmacogenetic study. JAMA dermatology (Chicago, Ill.). 2013. Julià Marc, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Association of a complement receptor 1 gene variant with baseline erythrocyte sedimentation rate levels in patients starting anti-TNF therapy in a UK rheumatoid arthritis cohort: results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort. The pharmacogenomics journal. 2013. Bluett J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Association between tumor necrosis factor-alpha (TNF-alpha) promoter -308 G/A and response to TNF-alpha blockers in rheumatoid arthritis: a meta-analysis. Modern rheumatology / the Japan Rheumatism Association. 2013. Zeng Zhen, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
GWAS replication study confirms the association of PDE3A-SLCO1C1 with anti-TNF therapy response in rheumatoid arthritis. Pharmacogenomics. 2013. Acosta-Colman Isabel, 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
Biologic therapies in the treatment of psoriasis: a comprehensive evidence-based basic science and clinical review and a practical guide to tuberculosis monitoring. Clinical reviews in allergy & immunology. 2013. Sivamani Raja K, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis. PLoS genetics. 2013. Cui Jing, 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 disease-modifying antirheumatic drugs in rheumatoid arthritis: towards personalized medicine. Pharmacogenomics. 2013. Umićević Mirkov Maša, 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
Gene polymorphisms that can predict response to anti-TNF therapy in patients with psoriasis and related autoimmune diseases. The pharmacogenomics journal. 2013. Prieto-Pérez R, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effects of polymorphisms in TRAILR1 and TNFR1A on the response to anti-TNF therapies in patients with rheumatoid and psoriatic arthritis. Joint, bone, spine : revue du rhumatisme. 2012. Morales-Lara María José, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
TGF beta1 polymorphisms are candidate predictors of the clinical response to rituximab in rheumatoid arthritis. Joint, bone, spine : revue du rhumatisme. 2012. Daïen Claire Immediato, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association of Rheumatoid Arthritis Risk Alleles with Response to Anti-TNF Biologics: Results from the CORRONA Registry and Meta-analysis. Inflammation. 2012. Pappas Dimitrios A, 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 and genomic predictors of anti-TNF response. Pharmacogenomics. 2011. Prajapati Rita, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy. Arthritis and rheumatism. 2010. Cui Jing, 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
Polymorphisms spanning the TNFR2 and TACE genes do not contribute towards variable anti-TNF treatment response. Pharmacogenetics and genomics. 2010. Potter Catherine, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Genotype at the sIL-6R A358C polymorphism does not influence response to anti-TNF therapy in patients with rheumatoid arthritis. Rheumatology (Oxford, England). 2010. Hassan Batool, 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 TNF superfamily in 2009: new pathways, new indications, and new drugs. Drug discovery today. 2009. Tansey Malú 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
Serum osteopontin as a predictive marker of responsiveness to methotrexate in juvenile idiopathic arthritis. The Journal of rheumatology. 2009. Masi Laura, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
TNF-alpha-308 G/A polymorphism and responsiveness to TNF-alpha blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis. The pharmacogenomics journal. 2009. O'Rielly D D, 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
Perispinal etanercept for neuroinflammatory disorders. Drug discovery today. 2009. Tobinick Edward. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Association of the tumour necrosis factor-308 variant with differential response to anti-TNF agents in the treatment of rheumatoid arthritis. Human molecular genetics. 2008. Maxwell James R, 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 etanercept in rheumatoid arthritis. Pharmacogenomics. 2008. Danila Maria I, 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
Etanercept treatment for children and adolescents with plaque psoriasis. The New England journal of medicine. 2008. Paller Amy 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
Pharmacogenetics of anti-TNF treatment in patients with rheumatoid arthritis. Pharmacogenomics. 2007. Coenen Marieke J 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
Potential role of pharmacogenetics in anti-TNF treatment of rheumatoid arthritis and Crohn's disease. Drug discovery today. 2007. Kooloos Wouter 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
The -308 tumour necrosis factor-alpha gene polymorphism predicts therapeutic response to TNFalpha-blockers in rheumatoid arthritis and spondyloarthritis patients. Rheumatology (Oxford, England). 2007. Seitz M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association of TNF-alpha -308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis. Rheumatology international. 2006. Lee Young Ho, 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 influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Arthritis and rheumatism. 2004. Criswell Lindsey A, et al. PubMed

LinkOuts

GenBank:
M32315
Web Resource:
Wikipedia
UniProtKB:
TNR1B_HUMAN (P20333)
National Drug Code Directory:
58406-455-04
DrugBank:
DB00005
KEGG Compound:
C07897
KEGG Drug:
D00742
PubChem Substance:
10099
Drugs Product Database (DPD):
2242903
Therapeutic Targets Database:
DNC000605
FDA Drug Label at DailyMed:
a002b40c-097d-47a5-957f-7a7b1807af7f

Clinical Trials

These are trials that mention etanercept and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.