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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:B4GALT1-RAF1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: B4GALT1-RAF1
FusionPDB ID: 8747
FusionGDB2.0 ID: 8747
HgeneTgene
Gene symbol

B4GALT1

RAF1

Gene ID

2683

6037

Gene namebeta-1,4-galactosyltransferase 1ribonuclease A family member 3
SynonymsB4GAL-T1|CDG2D|GGTB2|GT1|GTB|beta4Gal-T1ECP|RAF1|RNS3
Cytomap

9p21.1

14q11.2

Type of geneprotein-codingprotein-coding
Descriptionbeta-1,4-galactosyltransferase 1N-acetyllactosamine synthaseUDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 1UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 1UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 1beeosinophil cationic proteinRNase 3cytotoxic ribonucleaseribonuclease 3ribonuclease, RNase A family, 3
Modification date2020031320200313
UniProtAcc

P15291

Main function of 5'-partner protein: FUNCTION: [Beta-1,4-galactosyltransferase 1]: The Golgi complex form catalyzes the production of lactose in the lactating mammary gland and could also be responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids. {ECO:0000269|PubMed:16157350}.; FUNCTION: [Processed beta-1,4-galactosyltransferase 1]: The cell surface form functions as a recognition molecule during a variety of cell to cell and cell to matrix interactions, as those occurring during development and egg fertilization, by binding to specific oligosaccharide ligands on opposing cells or in the extracellular matrix. {ECO:0000269|PubMed:16157350}.

P04049

Main function of 5'-partner protein: FUNCTION: Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}.
Ensembl transtripts involved in fusion geneENST idsENST00000379731, ENST00000535206, 
ENST00000541851, 
ENST00000251849, 
ENST00000442415, ENST00000534997, 
ENST00000542177, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 9 X 8=108019 X 16 X 7=2128
# samples 2018
** MAII scorelog2(20/1080*10)=-2.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(18/2128*10)=-3.56342933917152
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: B4GALT1 [Title/Abstract] AND RAF1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: B4GALT1 [Title/Abstract] AND RAF1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)B4GALT1(33166756)-RAF1(12641914), # samples:2
Anticipated loss of major functional domain due to fusion event.B4GALT1-RAF1 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.
B4GALT1-RAF1 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.
B4GALT1-RAF1 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.
B4GALT1-RAF1 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
HgeneB4GALT1

GO:0006487

protein N-linked glycosylation

16157350

HgeneB4GALT1

GO:0009312

oligosaccharide biosynthetic process

2120039

TgeneRAF1

GO:0002227

innate immune response in mucosa

12860195

TgeneRAF1

GO:0019731

antibacterial humoral response

12860195

TgeneRAF1

GO:0043152

induction of bacterial agglutination

23992292

TgeneRAF1

GO:0045087

innate immune response

23992292

TgeneRAF1

GO:0050829

defense response to Gram-negative bacterium

23992292

TgeneRAF1

GO:0050830

defense response to Gram-positive bacterium

12860195|23992292

TgeneRAF1

GO:0061844

antimicrobial humoral immune response mediated by antimicrobial peptide

12860195



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/chr9:33166756/chr3:12641914)
- 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 B4GALT1 (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 RAF1 (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)
ENST00000535206B4GALT1chr933166756-ENST00000251849RAF1chr312641914-26255995781711377
ENST00000535206B4GALT1chr933166756-ENST00000442415RAF1chr312641914-24285995781711377
ENST00000535206B4GALT1chr933166756-ENST00000534997RAF1chr312641914-19595995781711377
ENST00000535206B4GALT1chr933166756-ENST00000542177RAF1chr312641914-18935995781711377
ENST00000379731B4GALT1chr933166756-ENST00000251849RAF1chr312641914-26255995781711377
ENST00000379731B4GALT1chr933166756-ENST00000442415RAF1chr312641914-24285995781711377
ENST00000379731B4GALT1chr933166756-ENST00000534997RAF1chr312641914-19595995781711377
ENST00000379731B4GALT1chr933166756-ENST00000542177RAF1chr312641914-18935995781711377
ENST00000535206B4GALT1chr933166755-ENST00000251849RAF1chr312641914-26255995781711377
ENST00000535206B4GALT1chr933166755-ENST00000442415RAF1chr312641914-24285995781711377
ENST00000535206B4GALT1chr933166755-ENST00000534997RAF1chr312641914-19595995781711377
ENST00000535206B4GALT1chr933166755-ENST00000542177RAF1chr312641914-18935995781711377
ENST00000379731B4GALT1chr933166755-ENST00000251849RAF1chr312641914-26255995781711377
ENST00000379731B4GALT1chr933166755-ENST00000442415RAF1chr312641914-24285995781711377
ENST00000379731B4GALT1chr933166755-ENST00000534997RAF1chr312641914-19595995781711377
ENST00000379731B4GALT1chr933166755-ENST00000542177RAF1chr312641914-18935995781711377

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
ENST00000535206ENST00000251849B4GALT1chr933166756-RAF1chr312641914-0.0059733920.99402654
ENST00000535206ENST00000442415B4GALT1chr933166756-RAF1chr312641914-0.0068555650.9931444
ENST00000535206ENST00000534997B4GALT1chr933166756-RAF1chr312641914-0.0082252770.9917747
ENST00000535206ENST00000542177B4GALT1chr933166756-RAF1chr312641914-0.0087651520.9912348
ENST00000379731ENST00000251849B4GALT1chr933166756-RAF1chr312641914-0.0059733920.99402654
ENST00000379731ENST00000442415B4GALT1chr933166756-RAF1chr312641914-0.0068555650.9931444
ENST00000379731ENST00000534997B4GALT1chr933166756-RAF1chr312641914-0.0082252770.9917747
ENST00000379731ENST00000542177B4GALT1chr933166756-RAF1chr312641914-0.0087651520.9912348
ENST00000535206ENST00000251849B4GALT1chr933166755-RAF1chr312641914-0.0059733920.99402654
ENST00000535206ENST00000442415B4GALT1chr933166755-RAF1chr312641914-0.0068555650.9931444
ENST00000535206ENST00000534997B4GALT1chr933166755-RAF1chr312641914-0.0082252770.9917747
ENST00000535206ENST00000542177B4GALT1chr933166755-RAF1chr312641914-0.0087651520.9912348
ENST00000379731ENST00000251849B4GALT1chr933166755-RAF1chr312641914-0.0059733920.99402654
ENST00000379731ENST00000442415B4GALT1chr933166755-RAF1chr312641914-0.0068555650.9931444
ENST00000379731ENST00000534997B4GALT1chr933166755-RAF1chr312641914-0.0082252770.9917747
ENST00000379731ENST00000542177B4GALT1chr933166755-RAF1chr312641914-0.0087651520.9912348

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 B4GALT1-RAF1

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

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Potential FusionNeoAntigen Information of B4GALT1-RAF1 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.

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)

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Potential FusionNeoAntigen Information of B4GALT1-RAF1 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 B4GALT1-RAF1

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of B4GALT1-RAF1

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

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Vaccine Design for the FusionNeoAntigens of B4GALT1-RAF1

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

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 B4GALT1-RAF1

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

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Potential target of CAR-T therapy development for B4GALT1-RAF1

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
HgeneB4GALT1chr9:33166755chr3:12641914ENST00000379731-1625_44137399.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneB4GALT1chr9:33166756chr3:12641914ENST00000379731-1625_44137399.0TransmembraneHelical%3B Signal-anchor for type II membrane protein

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 B4GALT1-RAF1

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 B4GALT1-RAF1

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
TgeneRAF1C0028326Noonan Syndrome10CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET
TgeneRAF1C0175704LEOPARD Syndrome7CLINGEN;CTD_human;GENOMICS_ENGLAND
TgeneRAF1C1969057Noonan Syndrome 54CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneRAF1C1969056LEOPARD SYNDROME 23CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneRAF1C0007194Hypertrophic Cardiomyopathy2CTD_human
TgeneRAF1C0041409Turner Syndrome, Male2CTD_human
TgeneRAF1C1519086Pilomyxoid astrocytoma2ORPHANET
TgeneRAF1C1527404Female Pseudo-Turner Syndrome2CTD_human
TgeneRAF1C4551472Hypertrophic obstructive cardiomyopathy2CTD_human
TgeneRAF1C4551602Noonan Syndrome 12CTD_human
TgeneRAF1C0006142Malignant neoplasm of breast1CTD_human
TgeneRAF1C0007131Non-Small Cell Lung Carcinoma1CTD_human
TgeneRAF1C0007193Cardiomyopathy, Dilated1CTD_human
TgeneRAF1C0017638Glioma1CTD_human
TgeneRAF1C0020429Hyperalgesia1CTD_human
TgeneRAF1C0022665Kidney Neoplasm1CTD_human
TgeneRAF1C0023903Liver neoplasms1CTD_human
TgeneRAF1C0024121Lung Neoplasms1CTD_human
TgeneRAF1C0242379Malignant neoplasm of lung1CTD_human
TgeneRAF1C0259783mixed gliomas1CTD_human
TgeneRAF1C0340427Familial dilated cardiomyopathy1ORPHANET
TgeneRAF1C0345904Malignant neoplasm of liver1CTD_human
TgeneRAF1C0345967Malignant mesothelioma1CTD_human
TgeneRAF1C0458247Allodynia1CTD_human
TgeneRAF1C0555198Malignant Glioma1CTD_human
TgeneRAF1C0587248Costello syndrome (disorder)1CLINGEN
TgeneRAF1C0678222Breast Carcinoma1CTD_human
TgeneRAF1C0740457Malignant neoplasm of kidney1CTD_human
TgeneRAF1C0751211Hyperalgesia, Primary1CTD_human
TgeneRAF1C0751212Hyperalgesia, Secondary1CTD_human
TgeneRAF1C0751213Tactile Allodynia1CTD_human
TgeneRAF1C0751214Hyperalgesia, Thermal1CTD_human
TgeneRAF1C1257931Mammary Neoplasms, Human1CTD_human
TgeneRAF1C1275081Cardio-facio-cutaneous syndrome1CLINGEN
TgeneRAF1C1449563Cardiomyopathy, Familial Idiopathic1CTD_human
TgeneRAF1C1458155Mammary Neoplasms1CTD_human
TgeneRAF1C2936719Mechanical Allodynia1CTD_human
TgeneRAF1C4014656CARDIOMYOPATHY, DILATED, 1NN1CTD_human;UNIPROT
TgeneRAF1C4551484Leopard Syndrome 11CTD_human;GENOMICS_ENGLAND
TgeneRAF1C4704874Mammary Carcinoma, Human1CTD_human
TgeneRAF1C4721610Carcinoma, Ovarian Epithelial1CTD_human