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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:CREB3L2-MACC1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CREB3L2-MACC1
FusionPDB ID: 19327
FusionGDB2.0 ID: 19327
HgeneTgene
Gene symbol

CREB3L2

MACC1

Gene ID

64764

346389

Gene namecAMP responsive element binding protein 3 like 2MET transcriptional regulator MACC1
SynonymsBBF2H77A5|SH3BP4L
Cytomap

7q33

7p21.1

Type of geneprotein-codingprotein-coding
Descriptioncyclic AMP-responsive element-binding protein 3-like protein 2B-ZIB transcription factorBBF2 human homolog on chromosome 7FUS/BBF2H7 proteinTCAG_1951439basic transcription factor 2cAMP-responsive element-binding protein 3-like protein 2metastasis-associated in colon cancer protein 1MACC1, MET transcriptional regulatorSH3 domain-containing protein 7a5metastasis associated in colon cancer 1putative binding protein 7a5
Modification date2020031320200313
UniProtAcc

Q70SY1

Main function of 5'-partner protein: FUNCTION: Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes (By similarity). In a neuroblastoma cell line, protects cells from ER stress-induced death (PubMed:17178827). In vitro activates transcription of target genes via direct binding to the CRE site (PubMed:17178827). {ECO:0000250|UniProtKB:Q8BH52, ECO:0000269|PubMed:17178827}.

Q6ZN28

Main function of 5'-partner protein: FUNCTION: Acts as a transcription activator for MET and as a key regulator of HGF-MET signaling. Promotes cell motility, proliferation and hepatocyte growth factor (HGF)-dependent scattering in vitro and tumor growth and metastasis in vivo. {ECO:0000269|PubMed:19098908}.
Ensembl transtripts involved in fusion geneENST idsENST00000330387, ENST00000452463, 
ENST00000456390, ENST00000468127, 
ENST00000458726, 
ENST00000471019, 
ENST00000332878, ENST00000400331, 
ENST00000589011, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 16 X 7=16803 X 3 X 3=27
# samples 184
** MAII scorelog2(18/1680*10)=-3.22239242133645
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/27*10)=0.567040592723894
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: CREB3L2 [Title/Abstract] AND MACC1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CREB3L2 [Title/Abstract] AND MACC1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CREB3L2(137686350)-MACC1(20194004), # samples:1
Anticipated loss of major functional domain due to fusion event.CREB3L2-MACC1 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.
CREB3L2-MACC1 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
HgeneCREB3L2

GO:0045893

positive regulation of transcription, DNA-templated

17178827

TgeneMACC1

GO:0045944

positive regulation of transcription by RNA polymerase II

19098908



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/chr7:137686350/chr7:20194004)
- 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 CREB3L2 (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 MACC1 (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)
ENST00000330387CREB3L2chr7137686350-ENST00000400331MACC1chr720194004-7147454352855167
ENST00000330387CREB3L2chr7137686350-ENST00000332878MACC1chr720194004-1177454352855167
ENST00000330387CREB3L2chr7137686350-ENST00000589011MACC1chr720194004-885454352855167
ENST00000456390CREB3L2chr7137686350-ENST00000400331MACC1chr720194004-7157464362865167
ENST00000456390CREB3L2chr7137686350-ENST00000332878MACC1chr720194004-1187464362865167
ENST00000456390CREB3L2chr7137686350-ENST00000589011MACC1chr720194004-895464362865167
ENST00000452463CREB3L2chr7137686350-ENST00000400331MACC1chr720194004-7137444342845167
ENST00000452463CREB3L2chr7137686350-ENST00000332878MACC1chr720194004-1167444342845167
ENST00000452463CREB3L2chr7137686350-ENST00000589011MACC1chr720194004-875444342845167

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
ENST00000330387ENST00000400331CREB3L2chr7137686350-MACC1chr720194004-0.003225770.99677426
ENST00000330387ENST00000332878CREB3L2chr7137686350-MACC1chr720194004-0.0046102150.9953898
ENST00000330387ENST00000589011CREB3L2chr7137686350-MACC1chr720194004-0.0073263730.9926736
ENST00000456390ENST00000400331CREB3L2chr7137686350-MACC1chr720194004-0.0032243960.99677557
ENST00000456390ENST00000332878CREB3L2chr7137686350-MACC1chr720194004-0.0066336080.9933664
ENST00000456390ENST00000589011CREB3L2chr7137686350-MACC1chr720194004-0.0087653650.99123466
ENST00000452463ENST00000400331CREB3L2chr7137686350-MACC1chr720194004-0.0032222370.99677783
ENST00000452463ENST00000332878CREB3L2chr7137686350-MACC1chr720194004-0.0047326550.9952674
ENST00000452463ENST00000589011CREB3L2chr7137686350-MACC1chr720194004-0.0078459640.99215406

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 CREB3L2-MACC1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CREB3L2chr7137686350MACC1chr72019400444434SEPGDGEALMYHTALLKMDCQELVAR
CREB3L2chr7137686350MACC1chr72019400445434SEPGDGEALMYHTALLKMDCQELVAR
CREB3L2chr7137686350MACC1chr72019400446434SEPGDGEALMYHTALLKMDCQELVAR

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Potential FusionNeoAntigen Information of CREB3L2-MACC1 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.
CREB3L2-MACC1_137686350_20194004.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)
CREB3L2-MACC1chr7137686350chr720194004454HLA-B39:01YHTALLKM0.99940.6571018
CREB3L2-MACC1chr7137686350chr720194004454HLA-B38:02YHTALLKM0.99860.78611018
CREB3L2-MACC1chr7137686350chr720194004454HLA-B38:01YHTALLKM0.99850.78121018
CREB3L2-MACC1chr7137686350chr720194004454HLA-B08:01ALMYHTAL0.99350.8809715
CREB3L2-MACC1chr7137686350chr720194004454HLA-B45:01GEALMYHTA0.99850.757514
CREB3L2-MACC1chr7137686350chr720194004454HLA-B50:02GEALMYHTA0.99570.598514
CREB3L2-MACC1chr7137686350chr720194004454HLA-A30:08LMYHTALLK0.98380.5022817
CREB3L2-MACC1chr7137686350chr720194004454HLA-B08:01EALMYHTAL0.97780.7832615
CREB3L2-MACC1chr7137686350chr720194004454HLA-A02:13ALMYHTALL0.9710.5612716
CREB3L2-MACC1chr7137686350chr720194004454HLA-B08:09EALMYHTAL0.96960.7296615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B35:03EALMYHTAL0.93380.7204615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B35:04EALMYHTAL0.890.8479615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B35:02EALMYHTAL0.890.8479615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B41:01GEALMYHTA0.64170.9262514
CREB3L2-MACC1chr7137686350chr720194004454HLA-B50:01GEALMYHTA0.35310.6053514
CREB3L2-MACC1chr7137686350chr720194004454HLA-B39:12YHTALLKM0.99920.67151018
CREB3L2-MACC1chr7137686350chr720194004454HLA-B39:05YHTALLKM0.99820.60521018
CREB3L2-MACC1chr7137686350chr720194004454HLA-B40:06GEALMYHTA0.99660.5299514
CREB3L2-MACC1chr7137686350chr720194004454HLA-C03:19EALMYHTAL0.99650.9788615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B42:02EALMYHTAL0.98720.8006615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B35:12EALMYHTAL0.890.8479615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B14:03EALMYHTAL0.84910.6385615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B39:10EALMYHTAL0.73850.7782615
CREB3L2-MACC1chr7137686350chr720194004454HLA-C07:05MYHTALLKM0.47280.9322918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C07:27MYHTALLKM0.4520.918918
CREB3L2-MACC1chr7137686350chr720194004454HLA-B15:21MYHTALLKM0.44840.8685918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C07:80MYHTALLKM0.41890.8861918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C07:67MYHTALLKM0.41890.8861918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C07:10MYHTALLKM0.39280.9304918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C12:16MYHTALLKM0.36770.9431918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C07:46MYHTALLKM0.36470.7131918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C07:29MYHTALLKM0.32680.7875918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C07:13MYHTALLKM0.25230.8149918
CREB3L2-MACC1chr7137686350chr720194004454HLA-B38:05YHTALLKM0.99850.78121018
CREB3L2-MACC1chr7137686350chr720194004454HLA-B08:18ALMYHTAL0.99350.8809715
CREB3L2-MACC1chr7137686350chr720194004454HLA-B39:11YHTALLKM0.85650.60841018
CREB3L2-MACC1chr7137686350chr720194004454HLA-C03:04EALMYHTAL0.99830.972615
CREB3L2-MACC1chr7137686350chr720194004454HLA-C03:03EALMYHTAL0.99830.972615
CREB3L2-MACC1chr7137686350chr720194004454HLA-C03:05EALMYHTAL0.99590.8445615
CREB3L2-MACC1chr7137686350chr720194004454HLA-C03:17EALMYHTAL0.99560.9028615
CREB3L2-MACC1chr7137686350chr720194004454HLA-A02:03ALMYHTALL0.97930.5463716
CREB3L2-MACC1chr7137686350chr720194004454HLA-B08:18EALMYHTAL0.97780.7832615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B40:04GEALMYHTA0.94720.7308514
CREB3L2-MACC1chr7137686350chr720194004454HLA-B35:13EALMYHTAL0.93460.745615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B35:09EALMYHTAL0.890.8479615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B08:12EALMYHTAL0.85590.8543615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B35:24EALMYHTAL0.78980.6871615
CREB3L2-MACC1chr7137686350chr720194004454HLA-B15:73ALMYHTALL0.73140.8044716
CREB3L2-MACC1chr7137686350chr720194004454HLA-B15:30ALMYHTALL0.63840.86716
CREB3L2-MACC1chr7137686350chr720194004454HLA-B41:03GEALMYHTA0.58850.6103514
CREB3L2-MACC1chr7137686350chr720194004454HLA-C07:17MYHTALLKM0.45030.9331918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C07:02MYHTALLKM0.41890.8861918
CREB3L2-MACC1chr7137686350chr720194004454HLA-B50:04GEALMYHTA0.35310.6053514
CREB3L2-MACC1chr7137686350chr720194004454HLA-B50:05GEALMYHTA0.35310.6053514
CREB3L2-MACC1chr7137686350chr720194004454HLA-C03:67MYHTALLKM0.34740.9584918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C06:02MYHTALLKM0.21530.9806918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C06:17MYHTALLKM0.21530.9806918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C04:04MYHTALLKM0.07870.737918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C14:03MYHTALLKM0.04580.9489918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C14:02MYHTALLKM0.04580.9489918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C06:06MYHTALLKM0.0280.9756918
CREB3L2-MACC1chr7137686350chr720194004454HLA-C06:08MYHTALLKM0.0260.971918
CREB3L2-MACC1chr7137686350chr720194004454HLA-B40:04GEALMYHTAL0.99630.612515
CREB3L2-MACC1chr7137686350chr720194004454HLA-B41:03GEALMYHTAL0.86520.5831515

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Potential FusionNeoAntigen Information of CREB3L2-MACC1 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 CREB3L2-MACC1

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
1535EALMYHTALLKMDCCREB3L2MACC1chr7137686350chr720194004454

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CREB3L2-MACC1

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-B14:023BVN1535EALMYHTALLKMDC-7.9962-8.1096
HLA-B14:023BVN1535EALMYHTALLKMDC-5.70842-6.74372
HLA-B52:013W391535EALMYHTALLKMDC-6.83737-6.95077
HLA-B52:013W391535EALMYHTALLKMDC-4.4836-5.5189
HLA-A11:014UQ21535EALMYHTALLKMDC-10.0067-10.1201
HLA-A11:014UQ21535EALMYHTALLKMDC-9.03915-10.0745
HLA-A24:025HGA1535EALMYHTALLKMDC-6.56204-6.67544
HLA-A24:025HGA1535EALMYHTALLKMDC-5.42271-6.45801
HLA-B44:053DX81535EALMYHTALLKMDC-7.85648-8.89178
HLA-B44:053DX81535EALMYHTALLKMDC-5.3978-5.5112
HLA-A02:016TDR1535EALMYHTALLKMDC-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of CREB3L2-MACC1

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
CREB3L2-MACC1chr7137686350chr7201940041018YHTALLKMTACCACACGGCTCTTCTGAAAATG
CREB3L2-MACC1chr7137686350chr720194004514GEALMYHTAGGCGAGGCCCTCATGTACCACACGGCT
CREB3L2-MACC1chr7137686350chr720194004515GEALMYHTALGGCGAGGCCCTCATGTACCACACGGCTCTT
CREB3L2-MACC1chr7137686350chr720194004615EALMYHTALGAGGCCCTCATGTACCACACGGCTCTT
CREB3L2-MACC1chr7137686350chr720194004715ALMYHTALGCCCTCATGTACCACACGGCTCTT
CREB3L2-MACC1chr7137686350chr720194004716ALMYHTALLGCCCTCATGTACCACACGGCTCTTCTG
CREB3L2-MACC1chr7137686350chr720194004817LMYHTALLKCTCATGTACCACACGGCTCTTCTGAAA
CREB3L2-MACC1chr7137686350chr720194004918MYHTALLKMATGTACCACACGGCTCTTCTGAAAATG

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 CREB3L2-MACC1

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
Non-CancerCREB3L2-MACC1chr7137686350ENST00000330387chr720194004ENST00000332878TCGA-BR-6802-11A

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Potential target of CAR-T therapy development for CREB3L2-MACC1

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 CREB3L2-MACC1

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 CREB3L2-MACC1

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