BCR

BCR activator of RhoGEF and GTPase, the group of Pleckstrin homology domain containing|C2 domain containing|Dbl family Rho GEFs|My-T-BRC complex

Basic information

Region (hg38): 22:23179704-23318037

Previous symbols: [ "D22S11", "BCR1" ]

Links

ENSG00000186716

∙ NCBI:613 ∙ OMIM:151410 ∙ HGNC:1014 ∙ Uniprot:P11274 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
CML treatment, response to	AD	Pharmacogenomic	Variants may confer resistance to certain medications (eg, dasatinib); Certain variants appear to confer STI571 resistance in CML treatment	General	11423618; 12654249; 14534339; 17684099

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BCR gene.

not_specified (164 variants)
not_provided (57 variants)
Chronic_myelogenous_leukemia,_BCR-ABL1_positive (8 variants)
Acute_lymphoid_leukemia (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BCR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004327.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	24 clinvar	10 clinvar	35
missense			165 clinvar	6 clinvar	4 clinvar	175
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	167	30	14

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BCR	protein_coding	protein_coding	ENST00000305877	23	138334

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.988	0.0124	125726	0	18	125744	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.888	685	754	0.909	0.0000469	8218
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000518	0.000460
Ashkenazi Jewish	0.000202	0.000198
East Asian	0.00	0.00
Finnish	0.0000865	0.0000462
European (Non-Finnish)	0.0000449	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

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}.;
Pathway: Chronic myeloid leukemia - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Imatinib Pathway, Pharmacokinetics/Pharmacodynamics;Imatinib and Chronic Myeloid Leukemia;Disease;Signal Transduction;inhibition of cellular proliferation by gleevec;integrin signaling pathway;bcr signaling pathway;ctcf: first multivalent nuclear factor;Rho GTPase cycle;Signaling by Rho GTPases;Regulation of RAC1 activity;Signaling by FGFR in disease;Signaling by cytosolic FGFR1 fusion mutants;FGFR1 mutant receptor activation;Signaling by FGFR1 in disease;Diseases of signal transduction;Regulation of RhoA activity (Consensus)

Recessive Scores

pRec: 0.764

Intolerance Scores

loftool: 0.144
rvis_EVS: -1.25
rvis_percentile_EVS: 5.36

Haploinsufficiency Scores

pHI: 0.279
hipred: Y
hipred_score: 0.816
ghis: 0.515

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: N
essential_gene_gene_trap: K
gene_indispensability_pred: E
gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Bcr
Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; immune system phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: negative regulation of cellular extravasation;renal system process;protein phosphorylation;signal transduction;brain development;peptidyl-tyrosine phosphorylation;actin cytoskeleton organization;regulation of Rho protein signal transduction;intracellular signal transduction;inner ear morphogenesis;regulation of vascular permeability;negative regulation of neutrophil degranulation;positive regulation of GTPase activity;protein autophosphorylation;platelet-derived growth factor receptor signaling pathway;homeostasis of number of cells;negative regulation of inflammatory response;positive regulation of phagocytosis;modulation of chemical synaptic transmission;neuromuscular process controlling balance;regulation of small GTPase mediated signal transduction;regulation of nitrogen compound metabolic process;regulation of cell cycle;definitive hemopoiesis;negative regulation of respiratory burst;negative regulation of blood vessel remodeling;intracellular protein transmembrane transport;cellular response to lipopolysaccharide;negative regulation of reactive oxygen species metabolic process
Cellular component: cytosol;postsynaptic density;membrane;cell junction;protein-containing complex;postsynaptic membrane;extracellular exosome;Schaffer collateral - CA1 synapse;glutamatergic synapse;postsynaptic density, intracellular component
Molecular function: protein serine/threonine kinase activity;protein tyrosine kinase activity;Rho guanyl-nucleotide exchange factor activity;GTPase activator activity;protein binding;ATP binding;kinase activity