Gene:
BCR
breakpoint cluster region

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


Annotated Labels

  1. FDA Label for blinatumomab and ABL1,BCR
  2. FDA Label for bosutinib and ABL1,BCR
  3. FDA Label for busulfan and ABL1,BCR
  4. FDA Label for dasatinib and ABL1,BCR
  5. FDA Label for homoharringtonine and ABL1,BCR
  6. FDA Label for imatinib and ABL1,BCR,KIT
  7. FDA Label for nilotinib and ABL1,BCR
  8. FDA Label for ponatinib and ABL1,BCR
  9. EMA Label for bosutinib and ABL1,BCR
  10. EMA Label for dasatinib and ABL1,BCR
  11. EMA Label for imatinib and ABL1,BCR,FIP1L1,KIT,PDGFRB
  12. EMA Label for nilotinib and ABL1,BCR
  13. EMA Label for ponatinib and ABL1,BCR
  14. PMDA Label for dasatinib and ABL1,BCR
  15. PMDA Label for imatinib and ABL1,BCR,FIP1L1,KIT,PDGFRA
  16. HCSC Label for bosutinib and ABL1,BCR
  17. HCSC Label for dasatinib and ABI1,BCR
  18. HCSC Label for imatinib and ABI1,BCR,FIP1L1,KIT,PDGFRA,PDGFRB
  19. HCSC Label for nilotinib and ABI1,BCR
  20. HCSC Label for ponatinib and ABI1,BCR





















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

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

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 variant annotations for BCR

Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs140504 NC_000022.10:g.23627369A>G, NC_000022.11:g.23285182A>G, NG_009244.1:g.109818A>G, NM_004327.3:c.2387A>G, NM_021574.2:c.2387A>G, NP_004318.3:p.Asn796Ser, NP_067585.2:p.Asn796Ser, XR_244382.1:n.3133A>G, rs1126848, rs2227941, rs56986372
A > G
SNP
N796S
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Alternate Names:  BCR1; D22S11
Alternate Symbols:  ALL; CML; D22S662; PHL
PharmGKB Accession Id: PA25321

Details

Cytogenetic Location: chr22 : q11.23 - q11.23
GP mRNA Boundary: chr22 : 23522402 - 23660224
GP Gene Boundary: chr22 : 23512402 - 23663224
Strand: plus

Visualization

UCSC has a Genome Browser that you can use to view PharmGKB annotations for this gene in context with many other sources of information.

View on UCSC Browser
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 BCR gene is an important cancer PGx diagnostic pharmacogene as part of the BCR-ABL fusion protein (see drug label annotations for bosutinib, busulfan, dasatinib, homoharringtonine, imatinib, nilotinib, ponatinib).

BCR is part of the Philadelphia chromosome (Ph+), translocation event that is characteristic of chronic myelocytic leukaemia, CML [Article:6960256]. The fusion of BCR and ABL1 results in the tyrosine kinase domain of the ABL protein becoming dysregulated and over-activated [Article:2676087]. There is heterogeneity in the size of the BCR-ABL fusion proteins generated due to different breakpoints of the translocation. The breakpoints in the ABL gene on chromosome 9 occur usually at exon a2, the breakpoints in BCR on chromosome 22 are between exons e12-e16 (also known as b1-b5) [Article:25949834]. Some of the breakages too small to be seen by karyotype, ie classified as Ph-, but still harbor the BCR-ABL fusion protein [Article:25949834].

There are several drugs that target the BCR-ABL fusion protein (imatinib, nilotinib, dasatinib, rebastinib, bosutinib, ponatinib); they are all directed against the ABL tyrosine kinase part of the protein [Article:25132497].

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 Caroline F Thorn

Key Publications
  1. Optimal Molecular Methods in Detecting p190 (BCR-ABL) Fusion Variants in Hematologic Malignancies: A Case Report and Review of the Literature. Case reports in hematology. 2015. Sonu Rebecca J, Jonas Brian A, Dwyre Denis M, Gregg Jeffrey P, Rashidi Hooman H. PubMed
  2. BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. Cancer cell. 2014. Zabriskie Matthew S, Eide Christopher A, Tantravahi Srinivas K, Vellore Nadeem A, Estrada Johanna, Nicolini Franck E, Khoury Hanna J, Larson Richard A, Konopleva Marina, Cortes Jorge E, Kantarjian Hagop, Jabbour Elias J, Kornblau Steven M, Lipton Jeffrey H, Rea Delphine, Stenke Leif, Barbany Gisela, Lange Thoralf, Hernández-Boluda Juan-Carlos, Ossenkoppele Gert J, Press Richard D, Chuah Charles, Goldberg Stuart L, Wetzler Meir, Mahon Francois-Xavier, Etienne Gabriel, Baccarani Michele, Soverini Simona, Rosti Gianantonio, Rousselot Philippe, Friedman Ran, Deininger Marie, Reynolds Kimberly R, Heaton William L, Eiring Anna M, Pomicter Anthony D, Khorashad Jamshid S, Kelley Todd W, Baron Riccardo, Druker Brian J, Deininger Michael W, O'Hare Thomas. PubMed
  3. The molecular biology of CML: a review. Cancer investigation. 1989. Leibowitz D, Young K S. PubMed
Diseases
Pathways

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

No related genes are available

Curated Information ?

Curated Information ?

Publications related to BCR: 18

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Expanding the computational toolbox for interrogating cancer kinomes. Pharmacogenomics. 2016. Tan Aik Choon, 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
Pharmacogenomic agreement between two cancer cell line data sets. Nature. 2015. Cancer Cell Line Encyclopedia Consortium, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Optimal Molecular Methods in Detecting p190 (BCR-ABL) Fusion Variants in Hematologic Malignancies: A Case Report and Review of the Literature. Case reports in hematology. 2015. Sonu Rebecca J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. Cancer cell. 2014. Zabriskie Matthew 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 childhood acute lymphoblastic leukemia. Pharmacogenomics. 2014. Lopez-Lopez Elixabet, 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
EMA Initiatives and Perspectives on Pharmacogenomics. British journal of clinical pharmacology. 2014. Ehmann Falk, 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
Phase 2 study of subcutaneous omacetaxine mepesuccinate for chronic-phase chronic myeloid leukemia patients resistant to or intolerant of tyrosine kinase inhibitors. American journal of hematology. 2013. Cortes 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
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, 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
Off-target effects of BCR-ABL1 inhibitors and their potential long-term implications in patients with chronic myeloid leukemia. Leukemia & lymphoma. 2012. Steegmann Juan Luis, 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 Novel BCR-ABL and FLT3 Inhibitor Ponatinib Is a Potent Inhibitor of the MDR-Associated ATP-Binding Cassette Transporter ABCG2. Molecular cancer therapeutics. 2012. Sen Rupashree, 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
Rho Kinase Regulates the Survival and Transformation of Cells Bearing Oncogenic Forms of KIT, FLT3, and BCR-ABL. Cancer cell. 2011. Mali Raghuveer Singh, 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
Chemotherapeutic agents circumvent emergence of dasatinib-resistant BCR-ABL kinase mutations in a precise mouse model of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011. Boulos Nidal, 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
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Pharmacogenetics of lithium response in bipolar disorder. Pharmacogenomics. 2010. McCarthy Michael 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
The cancer biomarker problem. Nature. 2008. Sawyers Charles L. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Overriding imatinib resistance with a novel ABL kinase inhibitor. Science (New York, N.Y.). 2004. Shah Neil 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
The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood. 1997. Deininger M W, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The molecular biology of CML: a review. Cancer investigation. 1989. Leibowitz D, et al. PubMed

LinkOuts

NCBI Gene:
613
OMIM:
151410
608232
613065
UCSC Genome Browser:
NM_004327
RefSeq RNA:
NM_004327
NM_021574
RefSeq Protein:
NP_004318
NP_067585
RefSeq DNA:
NG_009244
NT_011520
UniProtKB:
BCR_HUMAN (P11274)
Ensembl:
ENSG00000186716
GenAtlas:
BCR
GeneCard:
BCR
MutDB:
BCR
ALFRED:
LO015393V
HuGE:
BCR
Comparative Toxicogenomics Database:
613
ModBase:
P11274
HumanCyc Gene:
HS09933
HGNC:
1014

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