Gene:
F2
coagulation factor II (thrombin)

PharmGKB contains no dosing guidelines for this . 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.


last updated 01/16/2014

FDA Label for tamoxifen and ESR1, ESR2, F2, F5

This label is on the FDA Biomarker List
Actionable PGx

Summary

Tamoxifen is an anti-estrogen used in the treatment and prevention of breast neoplasms particularly those with estrogen receptor positive breast cancer.

Annotation

Tamoxifen is an anti-estrogen used in the treatment and prevention of breast neoplasms particularly those with estrogen receptor positive breast cancer.

Excerpts from the tamoxifen (Nolvadex) drug label:

Available evidence indicates that patients whose tumors are estrogen receptor positive are more likely to benefit from NOLVADEX therapy.

The estrogen and progesterone receptor values may help to predict whether adjuvant NOLVADEX therapy is likely to be beneficial. NOLVADEX reduces the occurrence of contralateral breast cancer in patients receiving adjuvant NOLVADEX therapy for breast cancer.

The FDA also highlight factor V Leiden and Prothrombin mutations in their "Table of Pharmacogenomic Biomarkers in Drug Labels", however in the trial mentioned within the drug label there was no benefit of screening for these factors:

When NOLVADEX is coadminstered with chemotherapy, there may be a further increase in the incidence of thromboembolic effects. For treatment of breast cancer, the risks and benefits of NOLVADEX should be carefully considered in women with a history of thromboembolic events. In a subsmall study (N=81) of the NSABP P-1 trial, there appeared to be no benefit to screening women for Factor V Leiden and Prothrombin mutations G20210A as a means to identify those who may not be appropriate candidates for NOLVADEX therapy.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the tamoxifen drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Breast Neoplasms
    • Indications & usage section, Contraindications section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Death
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Depression
    • Adverse reactions section
    • source: PHONT
  • Hot Flashes
    • Adverse reactions section
    • source: PHONT
  • Neoplasms
    • Indications & usage section, Contraindications section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Pain
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • ESR1
    • Indications & usage section, Precautions section, efficacy
    • source: FDA Label
  • ESR2
    • Indications & usage section, Precautions section, efficacy
    • source: FDA Label
  • F2
    • Warnings section, toxicity
    • source: FDA Label
  • F5
    • Warnings section, toxicity
    • source: FDA Label

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.

? = Mouse-over for quick help

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
No VIP available No Clinical Annotations available VA
rs1799963 *97G>A, 25313G>A, 46701055G>A, 46761055G>A
G > A
3' UTR
No VIP available No Clinical Annotations available VA
rs5896 46685003C>T, 46745003C>T, 494C>T, 9261C>T, Thr165Met
C > T
Missense
Thr165Met
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  prepro-coagulation factor II
Alternate Symbols:  None
PharmGKB Accession Id: PA157

Details

Cytogenetic Location: chr11 : p11.2 - p11.2
GP mRNA Boundary: chr11 : 46740743 - 46761056
GP Gene Boundary: chr11 : 46730743 - 46764056
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.

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Platelet Aggregation Inhibitor Pathway, Pharmacodynamics
    Effects of antiplatelet drugs on platelet aggregation pathway.
  1. Warfarin Pathway, Pharmacodynamics
    Simplified diagram of the target of warfarin action and downstream genes and effects.

External Pathways

Links to non-PharmGKB pathways.

  1. Angiopoietin receptor Tie2-mediated signaling - (Pathway Interaction Database NCI-Nature Curated)
  2. aspirin blocks signaling pathway involved in platelet activation - (BioCarta via Pathway Interaction Database)
  3. Cell surface interactions at the vascular wall - (Reactome via Pathway Interaction Database)
  4. Common Pathway - (Reactome via Pathway Interaction Database)
  5. extrinsic prothrombin activation pathway - (BioCarta via Pathway Interaction Database)
  6. fibrinolysis pathway - (BioCarta via Pathway Interaction Database)
  7. FOXA2 and FOXA3 transcription factor networks - (Pathway Interaction Database NCI-Nature Curated)
  8. Gamma-carboxylation of protein precursors - (Reactome via Pathway Interaction Database)
  9. Intrinsic Pathway - (Reactome via Pathway Interaction Database)
  10. intrinsic prothrombin activation pathway - (BioCarta via Pathway Interaction Database)
  11. Peptide ligand-binding receptors - (Reactome via Pathway Interaction Database)
  12. platelet amyloid precursor protein pathway - (BioCarta via Pathway Interaction Database)
  13. Regulation of IGF Activity by IGFBP - (Reactome via Pathway Interaction Database)
  14. Removal of aminoterminal propeptides from gamma-carboxylated proteins - (Reactome via Pathway Interaction Database)
  15. Syndecan-4-mediated signaling events - (Pathway Interaction Database NCI-Nature Curated)
  16. thrombin signaling and protease-activated receptors - (BioCarta via Pathway Interaction Database)
  17. Thrombin-mediated activation of PARs - (Reactome via Pathway Interaction Database)
  18. transcriptional activation of dbpb from mrna - (BioCarta via Pathway Interaction Database)
  19. Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus - (Reactome via Pathway Interaction Database)
No related genes are available

Curated Information ?

Evidence Drug
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
tamoxifen
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
warfarin

Curated Information ?

Publications related to F2: 13

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Influence of genetic, biological and pharmacological factors on warfarin dose in a Southern Brazilian population of European ancestry. British journal of clinical pharmacology. 2011. Botton Mariana Rodrigues, 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
Predictive role of coagulation-balance gene polymorphisms in the efficacy of photodynamic therapy with verteporfin for classic choroidal neovascularization secondary to age-related macular degeneration. Pharmacogenetics and genomics. 2007. Parmeggiani Francesco, 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 the dual FII/FX inhibitor BIBT 986 in endotoxin-induced coagulation. Clinical pharmacology and therapeutics. 2007. Leitner J M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Oral contraceptive use, thrombophilia and their interaction in young women with ischemic stroke. Haematologica. 2006. Martinelli Ida, 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
Site-directed mutagenesis of coumarin-type anticoagulant-sensitive VKORC1: evidence that highly conserved amino acids define structural requirements for enzymatic activity and inhibition by warfarin. Thrombosis and haemostasis. 2005. Rost Simone, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Polymorphisms in factor II and factor VII genes modulate oral anticoagulation with warfarin. Haematologica. 2004. D'Ambrosio Rosa Lucia, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Venous thromboembolic disease in users of low-estrogen combined estrogen-progestin oral contraceptives. Contraception. 2004. Sidney Stephen, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and gamma-glutamyl carboxylase) gene variants with warfarin sensitivity. Blood. 2004. Shikata Eriko, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Venous thromboembolism in young women; role of thrombophilic mutations and oral contraceptive use. European heart journal. 2002. Legnani 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
Hormone replacement therapy, prothrombotic mutations, and the risk of incident nonfatal myocardial infarction in postmenopausal women. JAMA : the journal of the American Medical Association. 2001. Psaty B 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
Structure-activity and crystallographic analysis of a new class of non-amide-based thrombin inhibitor. Bioorganic & medicinal chemistry letters. 2000. Lu T, 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
Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arteriosclerosis, thrombosis, and vascular biology. 1999. Martinelli 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
High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives. The New England journal of medicine. 1998. Martinelli I, et al. PubMed

LinkOuts

Entrez Gene:
2147
OMIM:
176930
UCSC Genome Browser:
NM_000506
RefSeq RNA:
NM_000506
RefSeq Protein:
NP_000497
RefSeq DNA:
AC_000054
AC_000143
NC_000011
NG_008953
NT_009237
NW_001838022
NW_925006
UniProtKB:
THRB_HUMAN (P00734)
Ensembl:
ENSG00000180210
GenAtlas:
F2
GeneCard:
F2
MutDB:
F2
ALFRED:
LO000605L
HuGE:
F2
Comparative Toxicogenomics Database:
2147
ModBase:
P00734
HumanCyc Gene:
HS11470
HGNC:
3535

Common Searches