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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:TENC1-ACVR1B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TENC1-ACVR1B
FusionPDB ID: 90039
FusionGDB2.0 ID: 92926
HgeneTgene
Gene symbol

TENC1

ACVR1B

Gene ID

23371

91

Gene nametensin 2activin A receptor type 1B
SynonymsC1-TEN|C1TEN|TENC1ACTRIB|ACVRLK4|ALK4|SKR2
Cytomap

12q13.13

12q13.13

Type of geneprotein-codingprotein-coding
Descriptiontensin-2C1 domain-containing phosphatase and tensin homologtensin like C1 domain containing phosphatase (tensin 2)tensin-like C1 domain-containing phosphataseactivin receptor type-1Bactivin A receptor, type IBactivin A receptor, type II-like kinase 4activin receptor-like kinase 4serine/threonine-protein kinase receptor R2
Modification date2020032020200313
UniProtAcc.

P36896

Main function of 5'-partner protein: FUNCTION: Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2. {ECO:0000269|PubMed:12364468, ECO:0000269|PubMed:12639945, ECO:0000269|PubMed:18039968, ECO:0000269|PubMed:20226172, ECO:0000269|PubMed:8196624, ECO:0000269|PubMed:9032295, ECO:0000269|PubMed:9892009}.
Ensembl transtripts involved in fusion geneENST idsENST00000314250, ENST00000314276, 
ENST00000451358, ENST00000546602, 
ENST00000549700, ENST00000552570, 
ENST00000379902, 
ENST00000563121, 
ENST00000257963, ENST00000415850, 
ENST00000426655, ENST00000541224, 
ENST00000542485, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score1 X 1 X 1=16 X 5 X 6=180
# samples 16
** MAII scorelog2(1/1*10)=3.32192809488736log2(6/180*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TENC1 [Title/Abstract] AND ACVR1B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TENC1 [Title/Abstract] AND ACVR1B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TENC1(53445747)-ACVR1B(52378976), # samples:2
Anticipated loss of major functional domain due to fusion event.TENC1-ACVR1B seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
TENC1-ACVR1B seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame 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
HgeneTENC1

GO:0035335

peptidyl-tyrosine dephosphorylation

23401856

HgeneTENC1

GO:0046627

negative regulation of insulin receptor signaling pathway

23401856

TgeneACVR1B

GO:0000082

G1/S transition of mitotic cell cycle

11117535

TgeneACVR1B

GO:0006355

regulation of transcription, DNA-templated

8622651|12665502

TgeneACVR1B

GO:0006468

protein phosphorylation

12065756

TgeneACVR1B

GO:0007165

signal transduction

8622651|12665502

TgeneACVR1B

GO:0018107

peptidyl-threonine phosphorylation

18039968

TgeneACVR1B

GO:0030308

negative regulation of cell growth

11117535

TgeneACVR1B

GO:0032924

activin receptor signaling pathway

9892009

TgeneACVR1B

GO:0032927

positive regulation of activin receptor signaling pathway

16720724

TgeneACVR1B

GO:0045648

positive regulation of erythrocyte differentiation

9032295

TgeneACVR1B

GO:0046777

protein autophosphorylation

18039968

TgeneACVR1B

GO:1901165

positive regulation of trophoblast cell migration

21356369



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/chr12:53445747/chr12:52378976)
- 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 buttonRetention analysis results 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, are available here.

check buttonFusion gene breakpoints across TENC1 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across ACVR1B (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000314276TENC1chr1253445747+ENST00000257963ACVR1Bchr1252378976+3916409141947268
ENST00000314276TENC1chr1253445747+ENST00000541224ACVR1Bchr1252378976+1055409141947268
ENST00000314276TENC1chr1253445747+ENST00000426655ACVR1Bchr1252378976+1170409141860239
ENST00000314276TENC1chr1253445747+ENST00000415850ACVR1Bchr1252378976+1095409141893250
ENST00000314276TENC1chr1253445747+ENST00000542485ACVR1Bchr1252378976+1763409141947268
ENST00000451358TENC1chr1253445747+ENST00000257963ACVR1Bchr1252378976+3981474531012319
ENST00000451358TENC1chr1253445747+ENST00000541224ACVR1Bchr1252378976+1120474531012319
ENST00000451358TENC1chr1253445747+ENST00000426655ACVR1Bchr1252378976+123547453925290
ENST00000451358TENC1chr1253445747+ENST00000415850ACVR1Bchr1252378976+116047453958301
ENST00000451358TENC1chr1253445747+ENST00000542485ACVR1Bchr1252378976+1828474531012319
ENST00000314250TENC1chr1253445747+ENST00000257963ACVR1Bchr1252378976+3981474531012319
ENST00000314250TENC1chr1253445747+ENST00000541224ACVR1Bchr1252378976+1120474531012319
ENST00000314250TENC1chr1253445747+ENST00000426655ACVR1Bchr1252378976+123547453925290
ENST00000314250TENC1chr1253445747+ENST00000415850ACVR1Bchr1252378976+116047453958301
ENST00000314250TENC1chr1253445747+ENST00000542485ACVR1Bchr1252378976+1828474531012319
ENST00000546602TENC1chr1253445747+ENST00000257963ACVR1Bchr1252378976+36911840722240
ENST00000546602TENC1chr1253445747+ENST00000541224ACVR1Bchr1252378976+8301840722240
ENST00000546602TENC1chr1253445747+ENST00000426655ACVR1Bchr1252378976+9451840635211
ENST00000546602TENC1chr1253445747+ENST00000415850ACVR1Bchr1252378976+8701840668222
ENST00000546602TENC1chr1253445747+ENST00000542485ACVR1Bchr1252378976+15381840722240
ENST00000552570TENC1chr1253445747+ENST00000257963ACVR1Bchr1252378976+36911840722240
ENST00000552570TENC1chr1253445747+ENST00000541224ACVR1Bchr1252378976+8301840722240
ENST00000552570TENC1chr1253445747+ENST00000426655ACVR1Bchr1252378976+9451840635211
ENST00000552570TENC1chr1253445747+ENST00000415850ACVR1Bchr1252378976+8701840668222
ENST00000552570TENC1chr1253445747+ENST00000542485ACVR1Bchr1252378976+15381840722240
ENST00000549700TENC1chr1253445747+ENST00000257963ACVR1Bchr1252378976+36911840722240
ENST00000549700TENC1chr1253445747+ENST00000541224ACVR1Bchr1252378976+8301840722240
ENST00000549700TENC1chr1253445747+ENST00000426655ACVR1Bchr1252378976+9451840635211
ENST00000549700TENC1chr1253445747+ENST00000415850ACVR1Bchr1252378976+8701840668222
ENST00000549700TENC1chr1253445747+ENST00000542485ACVR1Bchr1252378976+15381840722240

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
ENST00000314276ENST00000257963TENC1chr1253445747+ACVR1Bchr1252378976+0.0038162310.9961838
ENST00000314276ENST00000541224TENC1chr1253445747+ACVR1Bchr1252378976+0.0035018360.9964981
ENST00000314276ENST00000426655TENC1chr1253445747+ACVR1Bchr1252378976+0.0047019080.9952981
ENST00000314276ENST00000415850TENC1chr1253445747+ACVR1Bchr1252378976+0.0015667930.9984332
ENST00000314276ENST00000542485TENC1chr1253445747+ACVR1Bchr1252378976+0.0059673810.99403256
ENST00000451358ENST00000257963TENC1chr1253445747+ACVR1Bchr1252378976+0.0024016250.99759835
ENST00000451358ENST00000541224TENC1chr1253445747+ACVR1Bchr1252378976+0.0041431980.9958568
ENST00000451358ENST00000426655TENC1chr1253445747+ACVR1Bchr1252378976+0.0093148340.99068516
ENST00000451358ENST00000415850TENC1chr1253445747+ACVR1Bchr1252378976+0.0022040750.99779594
ENST00000451358ENST00000542485TENC1chr1253445747+ACVR1Bchr1252378976+0.0059673130.9940327
ENST00000314250ENST00000257963TENC1chr1253445747+ACVR1Bchr1252378976+0.0024016250.99759835
ENST00000314250ENST00000541224TENC1chr1253445747+ACVR1Bchr1252378976+0.0041431980.9958568
ENST00000314250ENST00000426655TENC1chr1253445747+ACVR1Bchr1252378976+0.0093148340.99068516
ENST00000314250ENST00000415850TENC1chr1253445747+ACVR1Bchr1252378976+0.0022040750.99779594
ENST00000314250ENST00000542485TENC1chr1253445747+ACVR1Bchr1252378976+0.0059673130.9940327
ENST00000546602ENST00000257963TENC1chr1253445747+ACVR1Bchr1252378976+0.0021030530.9978969
ENST00000546602ENST00000541224TENC1chr1253445747+ACVR1Bchr1252378976+0.0035475330.99645245
ENST00000546602ENST00000426655TENC1chr1253445747+ACVR1Bchr1252378976+0.0055113360.9944886
ENST00000546602ENST00000415850TENC1chr1253445747+ACVR1Bchr1252378976+0.0015660480.9984339
ENST00000546602ENST00000542485TENC1chr1253445747+ACVR1Bchr1252378976+0.0039553830.99604464
ENST00000552570ENST00000257963TENC1chr1253445747+ACVR1Bchr1252378976+0.0021030530.9978969
ENST00000552570ENST00000541224TENC1chr1253445747+ACVR1Bchr1252378976+0.0035475330.99645245
ENST00000552570ENST00000426655TENC1chr1253445747+ACVR1Bchr1252378976+0.0055113360.9944886
ENST00000552570ENST00000415850TENC1chr1253445747+ACVR1Bchr1252378976+0.0015660480.9984339
ENST00000552570ENST00000542485TENC1chr1253445747+ACVR1Bchr1252378976+0.0039553830.99604464
ENST00000549700ENST00000257963TENC1chr1253445747+ACVR1Bchr1252378976+0.0021030530.9978969
ENST00000549700ENST00000541224TENC1chr1253445747+ACVR1Bchr1252378976+0.0035475330.99645245
ENST00000549700ENST00000426655TENC1chr1253445747+ACVR1Bchr1252378976+0.0055113360.9944886
ENST00000549700ENST00000415850TENC1chr1253445747+ACVR1Bchr1252378976+0.0015660480.9984339
ENST00000549700ENST00000542485TENC1chr1253445747+ACVR1Bchr1252378976+0.0039553830.99604464

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for TENC1-ACVR1B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TENC1chr1253445747ACVR1Bchr125237897618461CKVTIDGTGVSCRGKPGIAHRDLKSK
TENC1chr1253445747ACVR1Bchr125237897640989CKVTIDGTGVSCRGKPGIAHRDLKSK
TENC1chr1253445747ACVR1Bchr1252378976474140CKVTIDGTGVSCRGKPGIAHRDLKSK

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Potential FusionNeoAntigen Information of TENC1-ACVR1B in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
TENC1-ACVR1B_53445747_52378976.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
TENC1-ACVR1Bchr1253445747chr1252378976474HLA-A30:08RGKPGIAHR0.9950.91291221
TENC1-ACVR1Bchr1253445747chr1252378976474HLA-A74:09RGKPGIAHR0.98840.88991221
TENC1-ACVR1Bchr1253445747chr1252378976474HLA-A74:03RGKPGIAHR0.98840.88991221
TENC1-ACVR1Bchr1253445747chr1252378976474HLA-A74:11RGKPGIAHR0.98840.88991221
TENC1-ACVR1Bchr1253445747chr1252378976474HLA-A31:02RGKPGIAHR0.94860.84981221
TENC1-ACVR1Bchr1253445747chr1252378976474HLA-A31:06RGKPGIAHR0.7460.79751221
TENC1-ACVR1Bchr1253445747chr1252378976474HLA-A31:01RGKPGIAHR0.98980.84761221
TENC1-ACVR1Bchr1253445747chr1252378976474HLA-A30:01RGKPGIAHR0.99550.96431221
TENC1-ACVR1Bchr1253445747chr1252378976474HLA-A74:01RGKPGIAHR0.98840.88991221

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Potential FusionNeoAntigen Information of TENC1-ACVR1B in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of TENC1-ACVR1B

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
3168GTGVSCRGKPGIAHTENC1ACVR1Bchr1253445747chr1252378976474

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TENC1-ACVR1B

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN3168GTGVSCRGKPGIAH-7.15543-7.26883
HLA-B14:023BVN3168GTGVSCRGKPGIAH-4.77435-5.80965
HLA-B52:013W393168GTGVSCRGKPGIAH-6.80875-6.92215
HLA-B52:013W393168GTGVSCRGKPGIAH-4.20386-5.23916
HLA-A11:014UQ23168GTGVSCRGKPGIAH-7.5194-8.5547
HLA-A11:014UQ23168GTGVSCRGKPGIAH-6.9601-7.0735
HLA-A24:025HGA3168GTGVSCRGKPGIAH-7.52403-7.63743
HLA-A24:025HGA3168GTGVSCRGKPGIAH-5.82433-6.85963
HLA-B27:056PYJ3168GTGVSCRGKPGIAH-3.28285-4.31815
HLA-B44:053DX83168GTGVSCRGKPGIAH-5.91172-6.94702
HLA-B44:053DX83168GTGVSCRGKPGIAH-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of TENC1-ACVR1B

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
TENC1-ACVR1Bchr1253445747chr12523789761221RGKPGIAHRGAGGGAAGCCTGGAATTGCTCATCGAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of TENC1-ACVR1B

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
BRCATENC1-ACVR1Bchr1253445747ENST00000314250chr1252378976ENST00000257963TCGA-C8-A12V-01A

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Potential target of CAR-T therapy development for TENC1-ACVR1B

check button Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to TENC1-ACVR1B

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to TENC1-ACVR1B

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource