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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:CASP8-ERBB4 (FusionGDB2 ID:HG841TG2066)

Fusion Gene Summary for CASP8-ERBB4

check button Fusion gene summary
Fusion gene informationFusion gene name: CASP8-ERBB4
Fusion gene ID: hg841tg2066
HgeneTgene
Gene symbol

CASP8

ERBB4

Gene ID

841

2066

Gene namecaspase 8erb-b2 receptor tyrosine kinase 4
SynonymsALPS2B|CAP4|Casp-8|FLICE|MACH|MCH5ALS19|HER4|p180erbB4
Cytomap('CASP8')('ERBB4')

2q33.1

2q34

Type of geneprotein-codingprotein-coding
Descriptioncaspase-8FADD-homologous ICE/CED-3-like proteaseFADD-like ICEICE-like apoptotic protease 5MACH-alpha-1/2/3 proteinMACH-beta-1/2/3/4 proteinMORT1-associated ced-3 homologapoptotic cysteine proteaseapoptotic protease Mch-5caspase 8, apoptosis-relatreceptor tyrosine-protein kinase erbB-4avian erythroblastic leukemia viral (v-erb-b2) oncogene homolog 4human epidermal growth factor receptor 4proto-oncogene-like protein c-ErbB-4tyrosine kinase-type cell surface receptor HER4v-erb-a erythroblastic
Modification date2020032220200327
UniProtAcc.

Q15303

Ensembl transtripts involved in fusion geneENST00000264274, ENST00000264275, 
ENST00000323492, ENST00000358485, 
ENST00000392258, ENST00000392259, 
ENST00000392266, ENST00000432109, 
ENST00000490682, 
Fusion gene scores* DoF score10 X 7 X 10=70018 X 16 X 8=2304
# samples 1217
** MAII scorelog2(12/700*10)=-2.54432051622381
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(17/2304*10)=-3.76053406530461
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: CASP8 [Title/Abstract] AND ERBB4 [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
HgeneCASP8

GO:0006508

proteolysis

12888622

HgeneCASP8

GO:0036462

TRAIL-activated apoptotic signaling pathway

21785459

HgeneCASP8

GO:0045862

positive regulation of proteolysis

18387192

HgeneCASP8

GO:0097191

extrinsic apoptotic signaling pathway

21785459

HgeneCASP8

GO:0097202

activation of cysteine-type endopeptidase activity

18387192

TgeneERBB4

GO:0007165

signal transduction

10572067

TgeneERBB4

GO:0007169

transmembrane receptor protein tyrosine kinase signaling pathway

10353604|18334220

TgeneERBB4

GO:0016477

cell migration

9135143

TgeneERBB4

GO:0018108

peptidyl-tyrosine phosphorylation

18334220

TgeneERBB4

GO:0046777

protein autophosphorylation

18334220



check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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..CASP8chr2

202131183

+ERBB4chr2

202131183

-


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Fusion Gene ORF analysis for CASP8-ERBB4

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-intronENST00000264274ENST00000342788CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000264274ENST00000402597CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000264274ENST00000436443CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000264274ENST00000484474CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000264275ENST00000342788CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000264275ENST00000402597CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000264275ENST00000436443CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000264275ENST00000484474CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000323492ENST00000342788CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000323492ENST00000402597CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000323492ENST00000436443CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000323492ENST00000484474CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000358485ENST00000342788CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000358485ENST00000402597CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000358485ENST00000436443CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000358485ENST00000484474CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000392258ENST00000342788CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000392258ENST00000402597CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000392258ENST00000436443CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000392258ENST00000484474CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000392259ENST00000342788CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000392259ENST00000402597CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000392259ENST00000436443CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000392259ENST00000484474CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000392266ENST00000342788CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000392266ENST00000402597CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000392266ENST00000436443CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000392266ENST00000484474CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000432109ENST00000342788CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000432109ENST00000402597CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000432109ENST00000436443CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000432109ENST00000484474CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000490682ENST00000342788CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000490682ENST00000402597CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000490682ENST00000436443CASP8chr2

202131183

+ERBB4chr2

202131183

-
intron-intronENST00000490682ENST00000484474CASP8chr2

202131183

+ERBB4chr2

202131183

-

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 CASP8-ERBB4


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 CASP8-ERBB4


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
.ERBB4

Q15303

FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.FUNCTION: Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis. {ECO:0000269|PubMed:10348342, ECO:0000269|PubMed:10353604, ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:10722704, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:11178955, ECO:0000269|PubMed:11390655, ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:15534001, ECO:0000269|PubMed:15746097, ECO:0000269|PubMed:16251361, ECO:0000269|PubMed:16778220, ECO:0000269|PubMed:16837552, ECO:0000269|PubMed:17486069, ECO:0000269|PubMed:17638867, ECO:0000269|PubMed:19098003, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:8617750, ECO:0000269|PubMed:9135143, ECO:0000269|PubMed:9168115, ECO:0000269|PubMed:9334263}.

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 CASP8-ERBB4


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 CASP8-ERBB4


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 CASP8-ERBB4


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status
TgeneERBB4Q15303DB08916AfatinibInhibitorSmall moleculeApproved
TgeneERBB4Q15303DB08916AfatinibInhibitorSmall moleculeApproved
TgeneERBB4Q15303DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneERBB4Q15303DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneERBB4Q15303DB12267BrigatinibInhibitorSmall moleculeApproved|Investigational
TgeneERBB4Q15303DB12267BrigatinibInhibitorSmall moleculeApproved|Investigational
TgeneERBB4Q15303DB15035ZanubrutinibInhibitorSmall moleculeApproved|Investigational
TgeneERBB4Q15303DB15035ZanubrutinibInhibitorSmall moleculeApproved|Investigational

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Related Diseases for CASP8-ERBB4


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneCASP8C0006142Malignant neoplasm of breast4CGI;CTD_human
HgeneCASP8C0678222Breast Carcinoma4CGI;CTD_human
HgeneCASP8C1257931Mammary Neoplasms, Human4CTD_human
HgeneCASP8C1458155Mammary Neoplasms4CTD_human
HgeneCASP8C4704874Mammary Carcinoma, Human4CTD_human
HgeneCASP8C1846545Autoimmune Lymphoproliferative Syndrome Type 2B3CTD_human;ORPHANET;UNIPROT
HgeneCASP8C0014859Esophageal Neoplasms2CTD_human
HgeneCASP8C0025202melanoma2CTD_human
HgeneCASP8C0546837Malignant neoplasm of esophagus2CTD_human
HgeneCASP8C0001418Adenocarcinoma1CTD_human
HgeneCASP8C0005586Bipolar Disorder1PSYGENET
HgeneCASP8C0007114Malignant neoplasm of skin1CTD_human
HgeneCASP8C0007131Non-Small Cell Lung Carcinoma1CTD_human
HgeneCASP8C0007873Uterine Cervical Neoplasm1CTD_human
HgeneCASP8C0009402Colorectal Carcinoma1CTD_human
HgeneCASP8C0009404Colorectal Neoplasms1CTD_human
HgeneCASP8C0011616Contact Dermatitis1CTD_human
HgeneCASP8C0011860Diabetes Mellitus, Non-Insulin-Dependent1CTD_human
HgeneCASP8C0013604Edema1CTD_human
HgeneCASP8C0023452Childhood Acute Lymphoblastic Leukemia1CTD_human
HgeneCASP8C0023453L2 Acute Lymphoblastic Leukemia1CTD_human
HgeneCASP8C0024121Lung Neoplasms1CTD_human
HgeneCASP8C0024623Malignant neoplasm of stomach1CTD_human
HgeneCASP8C0027055Myocardial Reperfusion Injury1CTD_human
HgeneCASP8C0035126Reperfusion Injury1CTD_human
HgeneCASP8C0037286Skin Neoplasms1CTD_human
HgeneCASP8C0038220Status Epilepticus1CTD_human
HgeneCASP8C0038356Stomach Neoplasms1CTD_human
HgeneCASP8C0151603Anasarca1CTD_human
HgeneCASP8C0162351Contact hypersensitivity1CTD_human
HgeneCASP8C0162820Dermatitis, Allergic Contact1CTD_human
HgeneCASP8C0205641Adenocarcinoma, Basal Cell1CTD_human
HgeneCASP8C0205642Adenocarcinoma, Oxyphilic1CTD_human
HgeneCASP8C0205643Carcinoma, Cribriform1CTD_human
HgeneCASP8C0205644Carcinoma, Granular Cell1CTD_human
HgeneCASP8C0205645Adenocarcinoma, Tubular1CTD_human
HgeneCASP8C0242379Malignant neoplasm of lung1CTD_human
HgeneCASP8C0270823Petit mal status1CTD_human
HgeneCASP8C0279607Adult Hepatocellular Carcinoma1ORPHANET
HgeneCASP8C0311335Grand Mal Status Epilepticus1CTD_human
HgeneCASP8C0343641Human papilloma virus infection1CTD_human
HgeneCASP8C0393734Complex Partial Status Epilepticus1CTD_human
HgeneCASP8C0751522Status Epilepticus, Subclinical1CTD_human
HgeneCASP8C0751523Non-Convulsive Status Epilepticus1CTD_human
HgeneCASP8C0751524Simple Partial Status Epilepticus1CTD_human
HgeneCASP8C1168401Squamous cell carcinoma of the head and neck1CTD_human
HgeneCASP8C1708349Hereditary Diffuse Gastric Cancer1CTD_human
HgeneCASP8C1961102Precursor Cell Lymphoblastic Leukemia Lymphoma1CTD_human
HgeneCASP8C2931456Prostate cancer, familial1CTD_human
HgeneCASP8C2937358Cerebral Hemorrhage1CTD_human
HgeneCASP8C4048328cervical cancer1CTD_human
HgeneCASP8C4722327PROSTATE CANCER, HEREDITARY, 11CTD_human
TgeneC0005586Bipolar Disorder5PSYGENET
TgeneC0036341Schizophrenia4PSYGENET
TgeneC0004238Atrial Fibrillation2CTD_human
TgeneC0235480Paroxysmal atrial fibrillation2CTD_human
TgeneC2585653Persistent atrial fibrillation2CTD_human
TgeneC3468561familial atrial fibrillation2CTD_human
TgeneC0002736Amyotrophic Lateral Sclerosis1ORPHANET
TgeneC0007114Malignant neoplasm of skin1CTD_human
TgeneC0016978gallbladder neoplasm1CTD_human
TgeneC0025202melanoma1CGI;CTD_human
TgeneC0037286Skin Neoplasms1CTD_human
TgeneC0153452Malignant neoplasm of gallbladder1CTD_human
TgeneC3715155AMYOTROPHIC LATERAL SCLEROSIS 191CTD_human;GENOMICS_ENGLAND;UNIPROT