BCR Gene: Breakpoint Cluster Region - Structure, Function, and Clinical Significance
A comprehensive guide to the BCR gene, its role in Philadelphia chromosome-positive leukemias, and its molecular characteristics.
Gene Information Card
| Symbol | BCR |
|---|---|
| Full Name | BCR (breakpoint cluster region) gene |
| Gene Type | Protein coding |
| Chromosomal Location | 22q11.23 (GRCh38) |
| NCBI Gene ID | 613 ncbi.nlm.nih.gov/gene/613 |
| Ensembl ID | ENSG00000186716 |
| UniProt ID | P11274 |
| OMIM ID | 151410 |
| HGNC ID | 1014 |
| Aliases | BCR1, CML, D22S11, FLJ16453, DKFZp686A19064 |
Description
The BCR gene encodes a serine/threonine kinase that functions as a Rho/Rac GTPase-activating protein (GAP) and is involved in multiple signaling pathways, including cell growth, differentiation, and adhesion. It is most famously known for its involvement in the Philadelphia chromosome translocation t(9;22)(q34;q11), which creates the BCR-ABL1 fusion gene, a hallmark of chronic myeloid leukemia (CML) and a subset of acute lymphoblastic leukemia (ALL). The BCR protein also contains a Dbl homology (DH) domain that acts as a guanine nucleotide exchange factor (GEF) for Rho GTPases, and a pleckstrin homology (PH) domain. Its normal function is critical for cellular homeostasis, and its dysregulation contributes to oncogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic Myeloid Leukemia (CML) | The t(9;22) translocation fuses BCR to ABL1, producing a constitutively active BCR-ABL1 tyrosine kinase that drives uncontrolled myeloid proliferation. | OMIM #608232; NCBI Gene; COSMIC |
| Acute Lymphoblastic Leukemia (ALL) | The BCR-ABL1 fusion (often with a smaller BCR breakpoint, p190) is present in ~25% of adult and ~5% of pediatric ALL cases, leading to aberrant kinase signaling and leukemogenesis. | OMIM #613065; NCBI Gene; COSMIC |
| Other Philadelphia-positive leukemias | BCR-ABL1 fusions are also found in rare cases of acute myeloid leukemia (AML) and mixed-phenotype acute leukemia, with similar oncogenic mechanisms. | COSMIC; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 12.2 | Medium |
| Bone Marrow | 10.5 | Medium |
| Spleen | 8.3 | Low |
| Lymph Node | 7.9 | Low |
| Brain | 4.1 | Low |
| Liver | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (CML) | 45.3 | High expression due to BCR-ABL1 fusion |
| HL-60 (AML) | 18.7 | Moderate expression |
| HeLa (cervical) | 6.2 | Low expression |
| A549 (lung) | 5.1 | Low expression |
| MCF7 (breast) | 4.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| BCR-ABL1 fusion (t(9;22)) | Chromosomal translocation | Present in >90% of CML cases | Constitutive kinase activation, oncogenic transformation |
| Missense mutations in DH domain | Point mutation | Rare (<1%) | Altered GEF activity, potential impact on Rho signaling |
| Deletions in BCR region | Deletion | Rare | Loss of GAP function, may contribute to genomic instability |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in BCR are rare and may impair its GAP activity, leading to dysregulated Rho/Rac signaling and potentially contributing to abnormal cell growth. However, such mutations are not well-characterized in cancer.
Gain of Function (GOF)
The BCR-ABL1 fusion is a classic gain-of-function mutation, where the BCR portion oligomerizes and activates the ABL1 kinase, resulting in constitutive tyrosine kinase activity that drives leukemogenesis.
Dominant Negative (DN)
No dominant-negative mutations have been described for BCR. The fusion protein acts as an oncogene rather than a dominant-negative inhibitor.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • Guanine nucleotide exchange factor activity |
| • Protein serine/threonine kinase activity | • Signal transduction |
| • Cell adhesion | • Regulation of Rho protein signal transduction |
| • Cytoskeleton organization | • Cellular response to DNA damage stimulus |
Pathways
• BCR-ABL1 signaling in CML
• Rho GTPase cycle
• Rac1 signaling
• ErbB signaling pathway
• Fc gamma R-mediated phagocytosis
Protein Summary
The BCR protein is a 1,271-amino-acid multidomain protein with serine/threonine kinase activity, a Dbl homology (DH) domain that acts as a GEF for Rho GTPases, a pleckstrin homology (PH) domain, and a RhoGAP domain. It is involved in regulating cell growth, cytoskeletal remodeling, and adhesion. In the BCR-ABL1 fusion, the N-terminal coiled-coil domain of BCR mediates dimerization, leading to constitutive activation of the ABL1 tyrosine kinase, which is the primary driver of Philadelphia-positive leukemias. The protein is ubiquitously expressed but shows higher levels in hematopoietic tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BCR Knockout HEK293 Cell Line | EDJ-KQ3805 | Human | 613 | Details Get a Quote |
| BCR Knockout A-549 Cell Line | EDJ-KQ25925 | Human | 613 | Details Get a Quote |
| BCR Knockout HCT 116 Cell Line | EDJ-KQ25926 | Human | 613 | Details Get a Quote |
| BCR Knockout HeLa Cell Line | EDJ-KQ25927 | Human | 613 | Details Get a Quote |
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