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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:BCR-RET (FusionGDB2 ID:HG613TG5979)

Fusion Gene Summary for BCR-RET

check button Fusion gene summary
Fusion gene informationFusion gene name: BCR-RET
Fusion gene ID: hg613tg5979
HgeneTgene
Gene symbol

BCR

RET

Gene ID

613

5979

Gene nameBCR activator of RhoGEF and GTPaseret proto-oncogene
SynonymsALL|BCR1|CML|D22S11|D22S662|PHLCDHF12|CDHR16|HSCR1|MEN2A|MEN2B|MTC1|PTC|RET-ELE1
Cytomap('BCR')('RET')

22q11.23

10q11.21

Type of geneprotein-codingprotein-coding
Descriptionbreakpoint cluster region proteinBCR, RhoGEF and GTPase activating proteinBCR/FGFR1 chimera proteinFGFR1/BCR chimera proteinbreakpoint cluster regionrenal carcinoma antigen NY-REN-26proto-oncogene tyrosine-protein kinase receptor RetRET receptor tyrosine kinasecadherin family member 12cadherin-related family member 16proto-oncogene c-Retrearranged during transfectionret proto-oncogene (multiple endocrine neoplasia and medullary
Modification date2020031320200322
UniProtAcc

P11274

P07949

Ensembl transtripts involved in fusion geneENST00000305877, ENST00000359540, 
ENST00000398512, ENST00000436990, 
Fusion gene scores* DoF score22 X 142 X 16=4998432 X 31 X 11=10912
# samples 16348
** MAII scorelog2(163/49984*10)=-4.93852248902354
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(48/10912*10)=-4.50673733341565
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: BCR [Title/Abstract] AND RET [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint
Anticipated loss of major functional domain due to fusion event.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneBCR

GO:0090630

activation of GTPase activity

7479768

TgeneRET

GO:0030155

regulation of cell adhesion

21357690

TgeneRET

GO:0030335

positive regulation of cell migration

20702524

TgeneRET

GO:0033619

membrane protein proteolysis

21357690

TgeneRET

GO:0033630

positive regulation of cell adhesion mediated by integrin

20702524

TgeneRET

GO:0035860

glial cell-derived neurotrophic factor receptor signaling pathway

28953886

TgeneRET

GO:0043410

positive regulation of MAPK cascade

28846099



check button Fusion gene information
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerKB4..BCRchr22

23603541

+RETchr10

23603541

+


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Fusion Gene ORF analysis for BCR-RET

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
intron-intronENST00000305877ENST00000340058BCRchr22

23603541

+RETchr10

23603541

+
intron-intronENST00000305877ENST00000355710BCRchr22

23603541

+RETchr10

23603541

+
intron-intronENST00000359540ENST00000340058BCRchr22

23603541

+RETchr10

23603541

+
intron-intronENST00000359540ENST00000355710BCRchr22

23603541

+RETchr10

23603541

+
intron-intronENST00000398512ENST00000340058BCRchr22

23603541

+RETchr10

23603541

+
intron-intronENST00000398512ENST00000355710BCRchr22

23603541

+RETchr10

23603541

+
intron-intronENST00000436990ENST00000340058BCRchr22

23603541

+RETchr10

23603541

+
intron-intronENST00000436990ENST00000355710BCRchr22

23603541

+RETchr10

23603541

+

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score

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Fusion Genomic Features for BCR-RET


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)


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Fusion Protein Features for BCR-RET


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:/:)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
BCR

P11274

RET

P07949

FUNCTION: Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:7479768, PubMed:1903516, PubMed:17116687). The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:7479768, PubMed:23940119). The amino terminus contains an intrinsic kinase activity (PubMed:1657398). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687). Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (PubMed:23940119). {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:1657398, ECO:0000269|PubMed:17116687, ECO:0000269|PubMed:1903516, ECO:0000269|PubMed:23940119, ECO:0000269|PubMed:7479768}.FUNCTION: Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways (PubMed:28846097, PubMed:28953886, PubMed:28846099). Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL (PubMed:28846099). {ECO:0000269|PubMed:20064382, ECO:0000269|PubMed:20616503, ECO:0000269|PubMed:20702524, ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886}.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page


* Minus value of BPloci means that the break pointn is located before the CDS.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for BCR-RET


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for BCR-RET


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for BCR-RET


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status
HgeneBCRP11274DB00619ImatinibInhibitorSmall moleculeApproved
HgeneBCRP11274DB00619ImatinibInhibitorSmall moleculeApproved
HgeneBCRP11274DB00619ImatinibInhibitorSmall moleculeApproved
HgeneBCRP11274DB06616BosutinibInhibitorSmall moleculeApproved
HgeneBCRP11274DB06616BosutinibInhibitorSmall moleculeApproved
HgeneBCRP11274DB06616BosutinibInhibitorSmall moleculeApproved
HgeneBCRP11274DB01254DasatinibSmall moleculeApproved|Investigational
HgeneBCRP11274DB01254DasatinibSmall moleculeApproved|Investigational
HgeneBCRP11274DB01254DasatinibSmall moleculeApproved|Investigational
HgeneBCRP11274DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
HgeneBCRP11274DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
HgeneBCRP11274DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB05294VandetanibSmall moleculeApproved
TgeneRETP07949DB05294VandetanibSmall moleculeApproved
TgeneRETP07949DB05294VandetanibSmall moleculeApproved
TgeneRETP07949DB05294VandetanibSmall moleculeApproved
TgeneRETP07949DB05294VandetanibSmall moleculeApproved
TgeneRETP07949DB08896RegorafenibInhibitorSmall moleculeApproved
TgeneRETP07949DB08896RegorafenibInhibitorSmall moleculeApproved
TgeneRETP07949DB08896RegorafenibInhibitorSmall moleculeApproved
TgeneRETP07949DB08896RegorafenibInhibitorSmall moleculeApproved
TgeneRETP07949DB08896RegorafenibInhibitorSmall moleculeApproved
TgeneRETP07949DB00398SorafenibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB00398SorafenibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB00398SorafenibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB00398SorafenibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB00398SorafenibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB08875CabozantinibAntagonistSmall moleculeApproved|Investigational
TgeneRETP07949DB08875CabozantinibAntagonistSmall moleculeApproved|Investigational
TgeneRETP07949DB08875CabozantinibAntagonistSmall moleculeApproved|Investigational
TgeneRETP07949DB08875CabozantinibAntagonistSmall moleculeApproved|Investigational
TgeneRETP07949DB08875CabozantinibAntagonistSmall moleculeApproved|Investigational
TgeneRETP07949DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB08901PonatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB09078LenvatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB09078LenvatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB09078LenvatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB09078LenvatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB09078LenvatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15685SelpercatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15685SelpercatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15685SelpercatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15685SelpercatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15685SelpercatinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15822PralsetinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15822PralsetinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15822PralsetinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15822PralsetinibInhibitorSmall moleculeApproved|Investigational
TgeneRETP07949DB15822PralsetinibInhibitorSmall moleculeApproved|Investigational

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Related Diseases for BCR-RET


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneBCRC0005586Bipolar Disorder4PSYGENET
HgeneBCRC0023473Myeloid Leukemia, Chronic3CTD_human;ORPHANET
HgeneBCRC0005699Blast Phase1CTD_human
HgeneBCRC0006413Burkitt Lymphoma1ORPHANET
HgeneBCRC0023893Liver Cirrhosis, Experimental1CTD_human
HgeneBCRC0027022Myeloproliferative disease1CTD_human
HgeneBCRC0027540Necrosis1CTD_human
HgeneBCRC0027659Neoplasms, Experimental1CTD_human
HgeneBCRC0041696Unipolar Depression1PSYGENET
HgeneBCRC1269683Major Depressive Disorder1PSYGENET
HgeneBCRC1292769Precursor B-cell lymphoblastic leukemia1ORPHANET
TgeneC1833921Familial medullary thyroid carcinoma23CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneC3888239HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 116GENOMICS_ENGLAND;UNIPROT
TgeneC0025268Multiple Endocrine Neoplasia Type 2a15CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneC1708353Hereditary Paraganglioma-Pheochromocytoma Syndrome12CLINGEN
TgeneC0025269Multiple Endocrine Neoplasia Type 2b10CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneC0238463Papillary thyroid carcinoma3CTD_human;ORPHANET
TgeneC1275808Congenital central hypoventilation3CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneC1859049CCHS WITH HIRSCHSPRUNG DISEASE3CTD_human;ORPHANET
TgeneC0009402Colorectal Carcinoma2CTD_human;UNIPROT
TgeneC0009404Colorectal Neoplasms2CTD_human
TgeneC0019569Hirschsprung Disease2CTD_human
TgeneC0027662Multiple Endocrine Neoplasia2CTD_human;GENOMICS_ENGLAND
TgeneC0085758Aganglionosis, Colonic2CTD_human
TgeneC0266294Unilateral agenesis of kidney2ORPHANET
TgeneC1257840Aganglionosis, Rectosigmoid Colon2CTD_human
TgeneC3661523Congenital Intestinal Aganglionosis2CTD_human
TgeneC0006413Burkitt Lymphoma1CTD_human
TgeneC0031511Pheochromocytoma1CGI;CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneC0038220Status Epilepticus1CTD_human
TgeneC0040136Thyroid Neoplasm1CGI;CTD_human
TgeneC0151468Thyroid Gland Follicular Adenoma1CTD_human
TgeneC0206693Medullary carcinoma1CTD_human
TgeneC0238462Medullary carcinoma of thyroid1CGI;CTD_human
TgeneC0270823Petit mal status1CTD_human
TgeneC0311335Grand Mal Status Epilepticus1CTD_human
TgeneC0343640African Burkitt's lymphoma1CTD_human
TgeneC0393734Complex Partial Status Epilepticus1CTD_human
TgeneC0549473Thyroid carcinoma1CGI;CTD_human;UNIPROT
TgeneC0740340Amyloidosis, Familial1CTD_human
TgeneC0751522Status Epilepticus, Subclinical1CTD_human
TgeneC0751523Non-Convulsive Status Epilepticus1CTD_human
TgeneC0751524Simple Partial Status Epilepticus1CTD_human
TgeneC1257877Pheochromocytoma, Extra-Adrenal1CTD_human
TgeneC1609433Congenital absence of kidneys syndrome1CTD_human;GENOMICS_ENGLAND;ORPHANET
TgeneC3501843Nonmedullary Thyroid Carcinoma1CTD_human
TgeneC3501844Familial Nonmedullary Thyroid Cancer1CTD_human
TgeneC4721444Burkitt Leukemia1CTD_human