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Center for Computational Systems Medicine
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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:TENM4-NRG1 (FusionGDB2 ID:89460)

Fusion Gene Summary for TENM4-NRG1

check button Fusion gene summary
Fusion gene informationFusion gene name: TENM4-NRG1
Fusion gene ID: 89460
HgeneTgene
Gene symbol

TENM4

NRG1

Gene ID

26011

3084

Gene nameteneurin transmembrane protein 4neuregulin 1
SynonymsDoc4|ETM5|ODZ4|TEN4|TNM4|Ten-M4|ten-4ARIA|GGF|GGF2|HGL|HRG|HRG1|HRGA|MST131|MSTP131|NDF|NRG1-IT2|SMDF
Cytomap

11q14.1

8p12

Type of geneprotein-codingprotein-coding
Descriptionteneurin-4odz, odd Oz/ten-m homolog 4protein Odd Oz/ten-m homolog 4tenascin-M4pro-neuregulin-1, membrane-bound isoformacetylcholine receptor-inducing activityglial growth factor 2heregulin, alpha (45kD, ERBB2 p185-activator)neu differentiation factorpro-NRG1sensory and motor neuron derived factor
Modification date2020031320200320
UniProtAcc.

Q02297

Ensembl transtripts involved in fusion geneENST00000278550, ENST00000533038, 
ENST00000519301, ENST00000520407, 
ENST00000523079, ENST00000338921, 
ENST00000356819, ENST00000287845, 
ENST00000341377, ENST00000287842, 
ENST00000521670, ENST00000405005, 
ENST00000520502, ENST00000539990, 
ENST00000523681, 
Fusion gene scores* DoF score13 X 13 X 7=118325 X 17 X 14=5950
# samples 1327
** MAII scorelog2(13/1183*10)=-3.18586654531133
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(27/5950*10)=-4.46185835603184
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: TENM4 [Title/Abstract] AND NRG1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointTENM4(78926957)-NRG1(32453345), # samples:1
TENM4(78565149)-NRG1(32453345), # samples:1
Anticipated loss of major functional domain due to fusion event.TENM4-NRG1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
TENM4-NRG1 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
* 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
TgeneNRG1

GO:0003222

ventricular trabecula myocardium morphogenesis

17336907

TgeneNRG1

GO:0031334

positive regulation of protein complex assembly

10559227

TgeneNRG1

GO:0038127

ERBB signaling pathway

11389077

TgeneNRG1

GO:0038129

ERBB3 signaling pathway

27353365

TgeneNRG1

GO:0045892

negative regulation of transcription, DNA-templated

15073182

TgeneNRG1

GO:0051048

negative regulation of secretion

10559227

TgeneNRG1

GO:0060379

cardiac muscle cell myoblast differentiation

17336907

TgeneNRG1

GO:0060956

endocardial cell differentiation

17336907


check buttonFusion gene breakpoints across TENM4 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonFusion gene breakpoints across NRG1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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
ChimerDB4breast cancerAF009227TENM4chr11

78926957

NRG1chr8

32453345

ChiTaRS5.0N/AAF009227TENM4chr11

78565149

-NRG1chr8

32453345

+


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Fusion Gene ORF analysis for TENM4-NRG1

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-3CDSENST00000278550ENST00000519301TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000278550ENST00000520407TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000278550ENST00000523079TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000278550ENST00000338921TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000278550ENST00000356819TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000278550ENST00000287845TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000278550ENST00000341377TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000278550ENST00000287842TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000278550ENST00000521670TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000278550ENST00000405005TENM4chr11

78926957

NRG1chr8

32453345

intron-intronENST00000278550ENST00000520502TENM4chr11

78926957

NRG1chr8

32453345

intron-intronENST00000278550ENST00000539990TENM4chr11

78926957

NRG1chr8

32453345

intron-intronENST00000278550ENST00000523681TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000533038ENST00000519301TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000533038ENST00000520407TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000533038ENST00000523079TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000533038ENST00000338921TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000533038ENST00000356819TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000533038ENST00000287845TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000533038ENST00000341377TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000533038ENST00000287842TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000533038ENST00000521670TENM4chr11

78926957

NRG1chr8

32453345

intron-3CDSENST00000533038ENST00000405005TENM4chr11

78926957

NRG1chr8

32453345

intron-intronENST00000533038ENST00000520502TENM4chr11

78926957

NRG1chr8

32453345

intron-intronENST00000533038ENST00000539990TENM4chr11

78926957

NRG1chr8

32453345

intron-intronENST00000533038ENST00000523681TENM4chr11

78926957

NRG1chr8

32453345

Frame-shiftENST00000278550ENST00000519301TENM4chr11

78565149

-NRG1chr8

32453345

+
Frame-shiftENST00000278550ENST00000520407TENM4chr11

78565149

-NRG1chr8

32453345

+
Frame-shiftENST00000278550ENST00000523079TENM4chr11

78565149

-NRG1chr8

32453345

+
Frame-shiftENST00000278550ENST00000338921TENM4chr11

78565149

-NRG1chr8

32453345

+
Frame-shiftENST00000278550ENST00000356819TENM4chr11

78565149

-NRG1chr8

32453345

+
Frame-shiftENST00000278550ENST00000287845TENM4chr11

78565149

-NRG1chr8

32453345

+
Frame-shiftENST00000278550ENST00000341377TENM4chr11

78565149

-NRG1chr8

32453345

+
Frame-shiftENST00000278550ENST00000287842TENM4chr11

78565149

-NRG1chr8

32453345

+
Frame-shiftENST00000278550ENST00000521670TENM4chr11

78565149

-NRG1chr8

32453345

+
Frame-shiftENST00000278550ENST00000405005TENM4chr11

78565149

-NRG1chr8

32453345

+
5CDS-intronENST00000278550ENST00000520502TENM4chr11

78565149

-NRG1chr8

32453345

+
5CDS-intronENST00000278550ENST00000539990TENM4chr11

78565149

-NRG1chr8

32453345

+
5CDS-intronENST00000278550ENST00000523681TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-3CDSENST00000533038ENST00000519301TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-3CDSENST00000533038ENST00000520407TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-3CDSENST00000533038ENST00000523079TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-3CDSENST00000533038ENST00000338921TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-3CDSENST00000533038ENST00000356819TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-3CDSENST00000533038ENST00000287845TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-3CDSENST00000533038ENST00000341377TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-3CDSENST00000533038ENST00000287842TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-3CDSENST00000533038ENST00000521670TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-3CDSENST00000533038ENST00000405005TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-intronENST00000533038ENST00000520502TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-intronENST00000533038ENST00000539990TENM4chr11

78565149

-NRG1chr8

32453345

+
intron-intronENST00000533038ENST00000523681TENM4chr11

78565149

-NRG1chr8

32453345

+

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 TENM4-NRG1


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)
TENM4chr1178565148-NRG1chr832453345+0.132833660.86716634
TENM4chr1178565148-NRG1chr832453345+0.132833660.86716634

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for TENM4-NRG1


check button Go to

FGviewer for the breakpoints of :-:

.
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
.NRG1

Q02297

FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.FUNCTION: Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development. Binds to ERBB4 (PubMed:10867024, PubMed:7902537). Binds to ERBB3 (PubMed:20682778). Acts as a ligand for integrins and binds (via EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling. Induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:20682778). Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons (By similarity). {ECO:0000250|UniProtKB:P43322, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:1348215, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:7902537}.

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 TENM4-NRG1


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 TENM4-NRG1


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 TENM4-NRG1


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for TENM4-NRG1


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneTENM4C0005586Bipolar Disorder1CTD_human
HgeneTENM4C0005587Depression, Bipolar1CTD_human
HgeneTENM4C0024713Manic Disorder1CTD_human
HgeneTENM4C0033975Psychotic Disorders1PSYGENET
HgeneTENM4C0036341Schizophrenia1PSYGENET
HgeneTENM4C0338831Manic1CTD_human
HgeneTENM4C0349204Nonorganic psychosis1PSYGENET
HgeneTENM4C4225223TREMOR, HEREDITARY ESSENTIAL, 51CTD_human;UNIPROT
TgeneNRG1C0036341Schizophrenia7CTD_human
TgeneNRG1C0005586Bipolar Disorder5PSYGENET
TgeneNRG1C0024809Marijuana Abuse3PSYGENET
TgeneNRG1C0011570Mental Depression2PSYGENET
TgeneNRG1C0011581Depressive disorder2PSYGENET
TgeneNRG1C0006142Malignant neoplasm of breast1CTD_human
TgeneNRG1C0006870Cannabis Dependence1PSYGENET
TgeneNRG1C0007621Neoplastic Cell Transformation1CTD_human
TgeneNRG1C0011616Contact Dermatitis1CTD_human
TgeneNRG1C0018801Heart failure1CTD_human
TgeneNRG1C0018802Congestive heart failure1CTD_human
TgeneNRG1C0019569Hirschsprung Disease1CTD_human
TgeneNRG1C0023212Left-Sided Heart Failure1CTD_human
TgeneNRG1C0023893Liver Cirrhosis, Experimental1CTD_human
TgeneNRG1C0024121Lung Neoplasms1CTD_human
TgeneNRG1C0026650Movement Disorders1CTD_human
TgeneNRG1C0027626Neoplasm Invasiveness1CTD_human
TgeneNRG1C0030193Pain1CTD_human
TgeneNRG1C0032460Polycystic Ovary Syndrome1CTD_human
TgeneNRG1C0038358Gastric ulcer1CTD_human
TgeneNRG1C0085758Aganglionosis, Colonic1CTD_human
TgeneNRG1C0087031Juvenile-Onset Still Disease1CTD_human
TgeneNRG1C0162351Contact hypersensitivity1CTD_human
TgeneNRG1C0234230Pain, Burning1CTD_human
TgeneNRG1C0234238Ache1CTD_human
TgeneNRG1C0234254Radiating pain1CTD_human
TgeneNRG1C0235527Heart Failure, Right-Sided1CTD_human
TgeneNRG1C0236733Amphetamine-Related Disorders1CTD_human
TgeneNRG1C0236804Amphetamine Addiction1CTD_human
TgeneNRG1C0236807Amphetamine Abuse1CTD_human
TgeneNRG1C0242379Malignant neoplasm of lung1CTD_human
TgeneNRG1C0266487Etat Marbre1CTD_human
TgeneNRG1C0458257Pain, Splitting1CTD_human
TgeneNRG1C0458259Pain, Crushing1CTD_human
TgeneNRG1C0678222Breast Carcinoma1CTD_human
TgeneNRG1C0751407Pain, Migratory1CTD_human
TgeneNRG1C0751408Suffering, Physical1CTD_human
TgeneNRG1C0876994Cardiotoxicity1CTD_human
TgeneNRG1C1136382Sclerocystic Ovaries1CTD_human
TgeneNRG1C1257840Aganglionosis, Rectosigmoid Colon1CTD_human
TgeneNRG1C1257931Mammary Neoplasms, Human1CTD_human
TgeneNRG1C1458155Mammary Neoplasms1CTD_human
TgeneNRG1C1959583Myocardial Failure1CTD_human
TgeneNRG1C1961112Heart Decompensation1CTD_human
TgeneNRG1C3495559Juvenile arthritis1CTD_human
TgeneNRG1C3661523Congenital Intestinal Aganglionosis1CTD_human
TgeneNRG1C3714758Juvenile psoriatic arthritis1CTD_human
TgeneNRG1C4552091Polyarthritis, Juvenile, Rheumatoid Factor Negative1CTD_human
TgeneNRG1C4704862Polyarthritis, Juvenile, Rheumatoid Factor Positive1CTD_human
TgeneNRG1C4704874Mammary Carcinoma, Human1CTD_human