PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
etanercept

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)
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 adult and juvenille rheumatoid arthritis (source: Drug Bank)

ATC Therapeutic Category

  • L04AA:Selective immunosuppressants

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

Used in the treatment of rheumatoid arthritis and the reduction of the adverse effects of tumor necrosis factor (TNF). 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)

Curated Annotations (Curated Annotation)

  1. rs983332 at chr1:87904968
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000005; OR: 10.2 (2.6, 59.2)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  2. rs928655 at chr1:89622162 in GBP6
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.00003; OR: 5.5 (1.8, 20.2)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  3. rs13393173 at chr2:169097337 in LASS6
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000004; OR: 6.8 (1.7, 40.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  4. rs437943 at chr4:35048493
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000004; OR: 4.6 (1.8, 12.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  5. rs1800629 at chr6:31651010 in LTA, TNF
    The TNF:(-308)G>A polymorphism is a weak marker for response to anti-TNF treatment, with A-allele carriers being significantly less likely to respond than patients with the GG genotype.
    Variant Name:
    TNF:(-308)G>A; -308G>A
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:17638513
  6. rs10945919 at chr6:164106667
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000003; OR: 4.6 (1.8, 12.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  7. rs854547 at chr7:94761792 in PPP1R9A
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000006; OR: 3.6 (1.5, 9.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  8. rs854548 at chr7:94763756 in PON1, PPP1R9A
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000003; OR: 8.5 (2.6, 36.5)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  9. rs854555 at chr7:94768327 in PON1
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000002; OR: 4.6 (1.8, 12.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  10. rs868856 at chr9:27479251 in MOBKL2B
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000005; OR: 4.9 (1.8, 14.0)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  11. rs7046653 at chr9:27480967 in MOBKL2B
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000005; OR: 4.9 (1.8, 14.0)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  12. rs2814707 at chr9:27526397 in MOBKL2B
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000002; OR: 5.2 (1.8, 16.7)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  13. rs3849942 at chr9:27533281
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000005; OR: 5.0 (1.7, 15.8)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  14. rs774359 at chr9:27551049 in C9orf72
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000006; OR: 5.4 (1.9, 17.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  15. rs6138150 at chr20:23795009
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000003; OR: 11.1 (2.5, 103.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  16. rs6028945 at chr20:38254219
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000002; OR: 11.2 (2.3, 108.1)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
  17. rs6071980 at chr20:38301990
    This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000003; OR: 7.6 (1.9, 44.6)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.
    Related Drugs:
    adalimumab, etanercept, infliximab
    Related Diseases:
    Arthritis, Rheumatoid
    Evidence:
    PMID:18615156
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data No genotype data No literature annotations Not annotated
C9orf72
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data No literature annotations Not annotated
GBP6
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data No literature annotations Not annotated
LASS6
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
LTA
  • CO
  • PD
  •   
  •   
  •   
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
MOBKL2B
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
PON1
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data No literature annotations Not annotated
PPP1R9A
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data Literature annotations available Not annotated
SPP1
  • CO
  •   
  •   
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
TNF
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
TNFRSF14
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
TNFRSF1A
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
TNFRSF1B
  •   
  • PD
  •   
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

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

A list of non-curated publications that mention this drug along with other drugs is available.

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Alzheimer Disease
  • CO
  •   
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Arthritis
  • CO
  •   
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Arthritis, Juvenile Rheumatoid
  • CO
  •   
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Arthritis, Rheumatoid
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Crohn Disease
  • CO
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Psoriasis
  • CO
  •   
  •   
  •   
  •   
Publications

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00005
KEGG Compound ID:
C07897
KEGG Drug ID:
D00742
PubChem Substance ID:
10099

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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