Human Gene BCR (uc010gtx.1)
  Description: Homo sapiens breakpoint cluster region (BCR), transcript variant 2, mRNA.
RefSeq Summary (NM_021574): A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein which is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint. Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The unregulated tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukaemic cells. The BCR protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac and other kinases. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2020].
Transcript (Including UTRs)
   Position: hg19 chr22:23,595,986-23,627,388 Size: 31,403 Total Exon Count: 8 Strand: +
Coding Region
   Position: hg19 chr22:23,603,167-23,627,388 Size: 24,222 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr22:23,595,986-23,627,388)mRNA (may differ from genome)Protein (269 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblExonPrimerGeneCardsGeneNetworkH-INV
HGNCLynxMalacardsMGIPubMedTreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: H0Y554_HUMAN
DESCRIPTION: SubName: Full=Breakpoint cluster region protein; Flags: Fragment;
SIMILARITY: Contains 1 DH (DBL-homology) domain.
CAUTION: The sequence shown here is derived from an Ensembl automatic analysis pipeline and should be considered as preliminary data.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): BCR
CDC HuGE Published Literature: BCR
Positive Disease Associations: Blood Vessels , Body Height , depressive disorder, major; bipolar disorder , height , Hip
Related Studies:
  1. Blood Vessels
    Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics. [PubMed 17903301]
    In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
  2. Body Height
    Daniel F Gudbjartsson et al. Nature genetics 2008, Many sequence variants affecting diversity of adult human height., Nature genetics. [PubMed 18391951]
  3. depressive disorder, major; bipolar disorder
    Hashimoto, R. et al. 2005, The Breakpoint Cluster Region Gene on Chromosome 22q11 is Associated with Bipolar Disorder, Biological psychiatry. 2005 May;57(10):1097-102. [PubMed 15866548]
    Our results suggest that genetic variations in the BCR gene could confer susceptibility to bipolar disorder and major depressive disorder.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: BCR
Diseases sorted by gene-association score: leukemia, chronic myeloid, somatic* (880), leukemia, acute lymphoblastic* (315), leukemia, acute lymphoblastic 3* (126), chronic myelocytic leukemia* (118), precursor t-cell acute lymphoblastic leukemia* (97), philadelphia-negative chronic myeloid leukemia (18), myeloid leukemia (13), chromosome 22q11.2 deletion syndrome, distal* (12), leukemia (10), chronic leukemia (9), acute lymphocytic leukemia (8), xeroderma pigmentosum, group b (7), bone marrow cancer (7), cryoglobulinemia, familial mixed (6), lymphoid leukemia (6), myeloproliferative neoplasm (6), amyotrophic lateral sclerosis 3 (6), richter's syndrome (6), chromosome 22q11.2 microduplication syndrome (5), denture stomatitis (5), 8p11 myeloproliferative syndrome (5), chronic lymphocytic leukemia (5), lymphoblastic leukemia (5), amyotrophic lateral sclerosis 9 (5), amyotrophic lateral sclerosis 7 (4), burkitt lymphoma (4), hematologic cancer (3), b-cell expansion with nfkb and t-cell anergy (3), essential thrombocythemia (2), myelofibrosis with myeloid metaplasia, somatic (2), amyotrophic lateral sclerosis 1 (1), lymphoma, non-hodgkin (1), leukemia, acute myeloid (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D004390 Chlorpyrifos
  • C488369 dasatinib
  • C097613 imatinib
  • C085911 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • C498826 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
  • C545373 AP24534
  • D000255 Adenosine Triphosphate
  • D001564 Benzo(a)pyrene
  • D019327 Copper Sulfate
  • D003907 Dexamethasone
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 28.33 RPKM in Brain - Nucleus accumbens (basal ganglia)
Total median expression: 494.79 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -80.10212-0.378 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000219 - DH-domain
IPR001331 - GDS_CDC24_CS
IPR011993 - PH_like_dom

Pfam Domains:
PF00621 - RhoGEF domain

SCOP Domains:
48065 - DBL homology domain (DH-domain)
50729 - PH domain-like

ModBase Predicted Comparative 3D Structure on H0Y554
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005085 guanyl-nucleotide exchange factor activity
GO:0005089 Rho guanyl-nucleotide exchange factor activity
GO:0005096 GTPase activator activity

Biological Process:
GO:0035023 regulation of Rho protein signal transduction
GO:0035556 intracellular signal transduction
GO:0043547 positive regulation of GTPase activity

Cellular Component:
GO:0005622 intracellular


-  Descriptions from all associated GenBank mRNAs
  Y00661 - Human bcr mRNA (break point cluster gene).
X02596 - Human mRNA for bcr (breakpoint cluster region) gene in Philadelphia chromosome.
BC066122 - Homo sapiens breakpoint cluster region, mRNA (cDNA clone IMAGE:30341883).
AB209991 - Homo sapiens mRNA for BCR variant protein, clone: aj01345.
AB384354 - Synthetic construct DNA, clone: pF1KSDB0005, Homo sapiens BCR gene for breakpoint cluster region protein, complete cds, without stop codon, in Flexi system.
EU216070 - Homo sapiens BCR/ABL fusion protein isoform Y4 (BCR/ABL fusion) mRNA, complete cds.
EU216064 - Homo sapiens BCR/ABL fusion protein isoform X7 (BCR/ABL fusion) mRNA, complete cds.
EU216062 - Homo sapiens BCR/ABL fusion protein isoform X5 (BCR/ABL fusion) mRNA, complete cds.
EU216059 - Homo sapiens BCR/ABL fusion protein isoform X2 (BCR/ABL fusion) mRNA, complete cds.
EU216061 - Homo sapiens BCR/ABL fusion protein isoform X4 (BCR/ABL fusion) mRNA, complete cds.
EU216068 - Homo sapiens BCR/ABL fusion protein isoform Y2 (BCR/ABL fusion) mRNA, complete cds.
EU216067 - Homo sapiens BCR/ABL fusion protein isoform Y1 (BCR/ABL fusion) mRNA, complete cds.
AM491362 - Homo sapiens partial mRNA for bcr-abl1 e6a2 chimeric protein.
X14676 - Human bcr-abl mRNA fragment (clone 10b).
AJ298916 - Homo sapiens partial mRNA for BCR/FGFR1 chimaeric fusion protein.
HQ622706 - Homo sapiens BCR-ABL1 e8a2 variant (BCR-ABL1) mRNA, partial cds.
M17542 - Human bcr/abl protein gene (product of translocation t(22q11; 9q34)), exons 1 and 2.
X14677 - Human bcr-abl mRNA 5' fragment (clone 8a).
X14675 - Human bcr-abl mRNA 5' fragment (clone 3c).
AK303241 - Homo sapiens cDNA FLJ58654 complete cds, highly similar to Breakpoint cluster region protein (EC 2.7.11.1).
AK128501 - Homo sapiens cDNA FLJ46653 fis, clone TRACH3005173.
AB742170 - Homo sapiens mRNA for BCR/FGFR1 chimera protein, partial cds.
AY536245 - Homo sapiens isolate BCRcml2L1I072001 breakpoint cluster region protein (BCR) mRNA, partial cds.
AY536247 - Homo sapiens isolate BCRcml2k10I072001 breakpoint cluster region protein (BCR) mRNA, partial cds.
AY536248 - Homo sapiens isolate BCRall115I012001 breakpoint cluster region protein (BCR) mRNA, partial cds.
AY536250 - Homo sapiens isolate BCRallcl2frB012001 breakpoint cluster region protein (BCR) mRNA, partial cds.
AY533677 - Homo sapiens BCR mRNA, partial cds.
AY536246 - Homo sapiens isolate BCRCML2K191I072001 breakpoint cluster region protein (BCR) mRNA, partial cds.
AK024483 - Homo sapiens mRNA for FLJ00077 protein, partial cds.
BC169208 - Synthetic construct Homo sapiens clone IMAGE:9093269 breakpoint cluster region isoform 1 (BCR) gene, partial cds.
KU234180 - Homo sapiens BCR-ABL1 fusion protein mRNA, partial cds.
AB742171 - Homo sapiens mRNA for FGFR1/BCR chimera protein, partial cds.
AJ298917 - Homo sapiens partial mRNA for FGFR1/BCR chimaeric fusion peptide.
AB069693 - Homo sapiens mRNA for bcr/abl e8a2 fusion protein, partial cds.
EU154998 - Homo sapiens BCR/ABL e8a2 fusion protein mRNA, partial cds.
EU394717 - Homo sapiens BCR/ABL e8a2 fusion protein (BCR/ABL fusion) mRNA, exons 7, 8, a2 and partial cds.
AY536244 - Homo sapiens isolate BCRcml2K192I072001 breakpoint cluster region protein (BCR) mRNA, partial cds.
AY536249 - Homo sapiens isolate BCRcml2K23I072001 breakpoint cluster region protein (BCR) mRNA, partial cds.
E00984 - Probe detection of breakpoint cluster region.
M30829 - Human bcr/abl fusion protein mRNA, partial cds, clone K28.
M30832 - Human bcr/abl fusion protein, partial cds, clone E3.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa05200 - Pathways in cancer
hsa05220 - Chronic myeloid leukemia

BioCarta from NCI Cancer Genome Anatomy Project
h_gleevecpathway - Inhibition of Cellular Proliferation by Gleevec
h_integrinPathway - Integrin Signaling Pathway

-  Other Names for This Gene
  Alternate Gene Symbols: AY533677, H0Y554, H0Y554_HUMAN
UCSC ID: uc010gtx.1
RefSeq Accession: NM_021574
Protein: H0Y554

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: AY533677.1
exon count: 8CDS single in 3' UTR: no RNA size: 771
ORF size: 807CDS single in intron: no Alignment % ID: 99.87
txCdsPredict score: 1550.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: no retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.