BCR BCR activator of RhoGEF and GTPase [Homo sapiens (human)] - Gene

Summary

Official Symbol: BCRprovided by HGNC
Official Full Name: BCR activator of RhoGEF and GTPaseprovided by HGNC
Primary source: HGNC:HGNC:1014
See related: Ensembl:ENSG00000186716 MIM:151410; AllianceGenome:HGNC:1014
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ALL; CML; PHL; BCR1; D22S11; D22S662
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]
Expression: Ubiquitous expression in testis (RPKM 14.9), brain (RPKM 14.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q11.23

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (23180509..23318037)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (23603367..23740899)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (23522696..23660224)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Validation of a novel NGS based BCR::ABL1 kinase domain mutation detection assay in Indian cohort.
Title: Validation of a novel NGS based BCR::ABL1 kinase domain mutation detection assay in Indian cohort.
Developmental trajectories and cooperating genomic events define molecular subtypes of BCR::ABL1-positive ALL.
Title: Developmental trajectories and cooperating genomic events define molecular subtypes of BCR::ABL1-positive ALL.
Histone demethylase PHF8 facilitates the development of chronic myeloid leukaemia by directly targeting BCR::ABL1.
Title: Histone demethylase PHF8 facilitates the development of chronic myeloid leukaemia by directly targeting BCR::ABL1.
The interplay between telomeric complex members and BCR::ABL1 oncogenic tyrosine kinase in the maintenance of telomere length in chronic myeloid leukemia.
Title: The interplay between telomeric complex members and BCR::ABL1 oncogenic tyrosine kinase in the maintenance of telomere length in chronic myeloid leukemia.
Emergence of a BCR::ABL1 rearrangement following a uniquely complex clonal evolution pattern in a patient undergoing Fms-like tyrosine kinase 3 inhibitor therapy for acute myeloid leukemia.
Title: Emergence of a BCR::ABL1 rearrangement following a uniquely complex clonal evolution pattern in a patient undergoing Fms-like tyrosine kinase 3 inhibitor therapy for acute myeloid leukemia.
Deep sequencing reveals the spectrum of BCR-ABL1 mutations upon front-line therapy resistance in chronic myeloid leukemia: An Eastern-Indian cohort study.
Title: Deep sequencing reveals the spectrum of BCR-ABL1 mutations upon front-line therapy resistance in chronic myeloid leukemia: An Eastern-Indian cohort study.
Mutation Profile in BCR-ABL1-Negative Myeloproliferative Neoplasms: A Single-Center Experience From India.
Title: Mutation Profile in BCR-ABL1-Negative Myeloproliferative Neoplasms: A Single-Center Experience From India.
Identification of putative genetic variants in major depressive disorder patients in Pakistan.
Title: Identification of putative genetic variants in major depressive disorder patients in Pakistan.
Fluorescent and colorimetric RT-LAMP as a rapid and specific qualitative method for chronic myeloid leukemia diagnosis.
Title: Fluorescent and colorimetric RT-LAMP as a rapid and specific qualitative method for chronic myeloid leukemia diagnosis.
Prevalence of BCR-ABL T315I Mutation in Different Chronic Myeloid Leukemia patients Categories.
Title: Prevalence of BCR-ABL T315I Mutation in Different Chronic Myeloid Leukemia patients Categories.

Submit: New GeneRIF Correction See all GeneRIFs (301)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Acute lymphoid leukemia MedGen: C0023449 OMIM: 613065 GeneReviews: Not available	Compare labs
Chronic myelogenous leukemia, BCR-ABL1 positive MedGen: C0279543 OMIM: 608232 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2012-07-10) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2012-07-10) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Genome-wide association study of antibody response to smallpox vaccine. EBI GWAS Catalog EBI GWAS CatalogPubMed
Many sequence variants affecting diversity of adult human height. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of breakpoint cluster region (BCR) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH80432 (e-PCR)
- UniSTS:90373

STS-H69004 (e-PCR)
- UniSTS:30987

RH11197 (e-PCR)
- UniSTS:83988

RH27788 (e-PCR)
- UniSTS:90901

SHGC-170331 (e-PCR)
- UniSTS:183582

D11S2560 (e-PCR)
- UniSTS:37928

RH66855 (e-PCR)
- UniSTS:67886

G20484 (e-PCR)
- UniSTS:18482

A005T29 (e-PCR)
- UniSTS:18483

GDB:193184 (e-PCR)
- UniSTS:155741

SHGC-9196 (e-PCR)
- UniSTS:36972

D15S1477 (e-PCR)
- UniSTS:474482

GDB:181503 (e-PCR)
- UniSTS:155250

GDB:181505 (e-PCR)
- UniSTS:155251

BCR (e-PCR)
- UniSTS:504182

D22S257 (e-PCR), detects polymorphism
- UniSTS:13973

D22S257 (e-PCR), detects polymorphism
- UniSTS:13974

SHGC-85827 (e-PCR)
- UniSTS:103830

A009L29 (e-PCR)
- UniSTS:44967

G60279 (e-PCR)
- UniSTS:137384

D22S1027 (e-PCR)
- UniSTS:56750

BCR_4443 (e-PCR)
- UniSTS:462775

D22S1100E (e-PCR)
- UniSTS:147386

GDB:451800 (e-PCR)
- UniSTS:157371

GDB:177065 (e-PCR)
- UniSTS:154819

SHGC-30277 (e-PCR)
- UniSTS:21720

GDB:452640 (e-PCR)
- UniSTS:157404

GDB:631802 (e-PCR)
- UniSTS:158429

GDB:190907 (e-PCR)
- UniSTS:155631

G32654 (e-PCR)
- UniSTS:117236

RH70541 (e-PCR)
- UniSTS:28151

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables GTPase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
enables guanyl-nucleotide exchange factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables guanyl-nucleotide exchange factor activity	TAS Traceable Author Statement more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info	PubMed
enables protein tyrosine kinase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	IEA Inferred from Electronic Annotation more info
involved_in activation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in activation of GTPase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in brain development	IEA Inferred from Electronic Annotation more info
involved_in cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in definitive hemopoiesis	IEA Inferred from Electronic Annotation more info
involved_in focal adhesion assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in homeostasis of number of cells	IEA Inferred from Electronic Annotation more info
involved_in inner ear morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in intracellular protein transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in keratinocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in macrophage migration	IEA Inferred from Electronic Annotation more info
involved_in modulation of chemical synaptic transmission	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of blood vessel remodeling	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cellular extravasation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of macrophage migration	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neutrophil degranulation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of reactive oxygen species metabolic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of respiratory burst	IEA Inferred from Electronic Annotation more info
involved_in neuromuscular process controlling balance	IEA Inferred from Electronic Annotation more info
involved_in neutrophil degranulation	IEA Inferred from Electronic Annotation more info
involved_in phagocytosis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of phagocytosis	IEA Inferred from Electronic Annotation more info
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in regulation of Rho protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cell cycle	IEA Inferred from Electronic Annotation more info
involved_in regulation of small GTPase mediated signal transduction	TAS Traceable Author Statement more info
involved_in regulation of vascular permeability	IEA Inferred from Electronic Annotation more info
involved_in renal system process	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in small GTPase-mediated signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Schaffer collateral - CA1 synapse	ISS Inferred from Sequence or Structural Similarity more info
located_in axon	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in dendritic spine	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in glutamatergic synapse	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	HDA more info	PubMed
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in postsynaptic density	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: breakpoint cluster region protein

Names: BCR, RhoGEF and GTPase activating protein; BCR/FGFR1 chimera protein; FGFR1/BCR chimera protein; breakpoint cluster region; renal carcinoma antigen NY-REN-26

NP_004318.3

EC 2.7.11.1

NP_067585.2

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009244.2 RefSeqGene

Range

5145..142673

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1112

mRNA and Protein(s)

NM_004327.4 → NP_004318.3 breakpoint cluster region protein isoform 1

See identical proteins and their annotated locations for NP_004318.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

BC066122, BQ422888, U07000, X02596

Consensus CDS

CCDS13806.1

UniProtKB/Swiss-Prot

P11274, P78501, Q12842, Q4LE80, Q6NZI3

UniProtKB/TrEMBL

A0A2X0SFQ7

Related

ENSP00000303507.8, ENST00000305877.13

Conserved Domains (6) summary

cd08686
Location:913 → 1033

C2_ABR; C2 domain in the Active BCR (Breakpoint cluster region) Related protein

cd04387
Location:1052 → 1252

RhoGAP_Bcr; RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, ...

cd13367
Location:684 → 877

PH_BCR_vertebrate; Breakpoint Cluster Region-related pleckstrin homology (PH) domain

pfam00621
Location:502 → 690

RhoGEF; RhoGEF domain

pfam07001
Location:81 → 174

BAT2_N; BAT2 N-terminus

pfam09036
Location:3 → 75

Bcr-Abl_Oligo; Bcr-Abl oncoprotein oligomerization domain
NM_021574.3 → NP_067585.2 breakpoint cluster region protein isoform 2

See identical proteins and their annotated locations for NP_067585.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

BC066122, BQ422888, U07000, Y00661

Consensus CDS

CCDS13807.1

UniProtKB/TrEMBL

A0A2X0SFQ7

Related

ENSP00000352535.3, ENST00000359540.7

Conserved Domains (6) summary

cd04387
Location:1008 → 1208

RhoGAP_Bcr; RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, ...

cd13367
Location:684 → 877

PH_BCR_vertebrate; Breakpoint Cluster Region-related pleckstrin homology (PH) domain

pfam00621
Location:502 → 690

RhoGEF; RhoGEF domain

pfam07001
Location:81 → 174

BAT2_N; BAT2 N-terminus

pfam09036
Location:3 → 75

Bcr-Abl_Oligo; Bcr-Abl oncoprotein oligomerization domain

cl14603
Location:913 → 989

C2; C2 domain