BCR
protein-codingBCR activator of RhoGEF and GTPase, the group of Pleckstrin homology domain containing|C2 domain containing|Dbl family Rho GEFs|My-T-BRC complex
Gene summary
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]
- D22S11
- BCR1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~138.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: General
Intervention: Pharmacogenomic
Rationale: Variants may confer resistance to certain medications (eg, dasatinib); Certain variants appear to confer STI571 resistance in CML treatment
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to BCR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004327.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 44 | 8 | 55 | ||
| missense | 199 | 9 | 3 | 211 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 205 | 54 | 11 | 270 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004318.3 | 23 | MANE Select | |
| Ensembl | ENSP00000303507.8 | 23 | MANE Select | |
| RefSeq | NP_067585.2 | 22 | Standard | |
| Ensembl | ENSP00000352535.3 | 22 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Chronic myeloid leukemia - Homo sapiens (human)
- Pathways in cancer - Homo sapiens (human)
- Imatinib Pathway, Pharmacokinetics/Pharmacodynamics
- Imatinib and Chronic Myeloid Leukemia
- Disease
Biological Process
- negative regulation of cellular extravasation
- renal system process
- protein phosphorylation
- signal transduction
- brain development
Molecular Function
- protein serine/threonine kinase activity
- protein tyrosine kinase activity
- Rho guanyl-nucleotide exchange factor activity
- GTPase activator activity
- protein binding
Cellular Component
- cytosol
- postsynaptic density
- membrane
- cell junction
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000305877
- Coding exons
- 23
- Length
- 138334
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125744
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.888 | 685 | 754 | 0.909 | 0.0000469 | 8218 |
| Missense (PolyPhen) | 120 | 179.41 | 0.66884 | 1860 | ||
| Synonymous | -1.91 | 370 | 326 | 1.13 | 0.0000221 | 2449 |
| Loss of Function | 5.79 | 10 | 57.4 | 0.174 | 0.00000263 | 679 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00036 | 0.00031 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000086 | 0.000046 | rare |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity. {ECO:0000269|PubMed:1657398, ECO:0000269|PubMed:1903516}.;
- Disease
- DISEASE: Leukemia, chronic myeloid (CML) [MIM:608232]: A clonal myeloproliferative disorder of a pluripotent stem cell with a specific cytogenetic abnormality, the Philadelphia chromosome (Ph), involving myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T-lymphoid cells, but not marrow fibroblasts. {ECO:0000269|PubMed:2407300, ECO:0000269|PubMed:3107980, ECO:0000269|PubMed:3540951}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Note=A chromosomal aberration involving BCR has been found in patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). {ECO:0000269|PubMed:3107980, ECO:0000269|PubMed:7665185}.;
Recessive Scores
- pRec
- 0.764
Intolerance Scores
- LoFtool
- 0.144
- RVIS EVS
- -1.25
- RVIS percentile EVS
- 5.36
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |