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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:ADAM17-SEC31A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ADAM17-SEC31A
FusionPDB ID: 1981
FusionGDB2.0 ID: 1981
HgeneTgene
Gene symbol

ADAM17

SEC31A

Gene ID

6868

22872

Gene nameADAM metallopeptidase domain 17SEC31 homolog A, COPII coat complex component
SynonymsADAM18|CD156B|CSVP|NISBD|NISBD1|TACEABP125|ABP130|HSPC275|HSPC334|NEDSOSB|SEC31L1
Cytomap

2p25.1

4q21.22

Type of geneprotein-codingprotein-coding
Descriptiondisintegrin and metalloproteinase domain-containing protein 17ADAM metallopeptidase domain 18TNF-alpha convertaseTNF-alpha converting enzymesnake venom-like proteasetumor necrosis factor, alpha, converting enzymeprotein transport protein Sec31ASEC31 homolog A, COPII coating complex componentSEC31-like protein 1SEC31-related protein Aweb1-like proteinyeast Sec31p homolog
Modification date2020032020200313
UniProtAcc

P78536

Main function of 5'-partner protein: FUNCTION: Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form (PubMed:9034191). Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein (PubMed:12441351). Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT) (PubMed:24226769). Plays a role in the proteolytic processing of ACE2 (PubMed:24227843). Plays a role in hemostasis through shedding of GP1BA, the platelet glycoprotein Ib alpha chain (By similarity). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). Mediates the proteolytic cleavage of IL6R, leading to the release of secreted form of IL6R (PubMed:26876177, PubMed:28060820). {ECO:0000250|UniProtKB:Q9Z0F8, ECO:0000269|PubMed:12441351, ECO:0000269|PubMed:20592283, ECO:0000269|PubMed:24226769, ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:26876177, ECO:0000269|PubMed:28060820, ECO:0000269|PubMed:9034191}.

O94979

Main function of 5'-partner protein: FUNCTION: Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER) (PubMed:10788476). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules (By similarity). {ECO:0000250|UniProtKB:Q9Z2Q1, ECO:0000269|PubMed:10788476}.
Ensembl transtripts involved in fusion geneENST idsENST00000310823, ENST00000497134, 
ENST00000436790, ENST00000264405, 
ENST00000311785, ENST00000326950, 
ENST00000348405, ENST00000355196, 
ENST00000395310, ENST00000432794, 
ENST00000443462, ENST00000448323, 
ENST00000500777, ENST00000505472, 
ENST00000505984, ENST00000508479, 
ENST00000508502, ENST00000509142, 
ENST00000513858, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 8 X 6=28827 X 19 X 11=5643
# samples 1128
** MAII scorelog2(11/288*10)=-1.38856528791765
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(28/5643*10)=-4.33296361729939
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ADAM17 [Title/Abstract] AND SEC31A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ADAM17 [Title/Abstract] AND SEC31A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADAM17(9634765)-SEC31A(83765662), # samples:1
Anticipated loss of major functional domain due to fusion event.ADAM17-SEC31A 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.
ADAM17-SEC31A 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.
ADAM17-SEC31A 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.
ADAM17-SEC31A 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
HgeneADAM17

GO:0001666

response to hypoxia

18276953

HgeneADAM17

GO:0006508

proteolysis

24227843

HgeneADAM17

GO:0006509

membrane protein ectodomain proteolysis

9034190|9574564|17786981|18676862

HgeneADAM17

GO:0007155

cell adhesion

14970227

HgeneADAM17

GO:0007173

epidermal growth factor receptor signaling pathway

12743035

HgeneADAM17

GO:0007220

Notch receptor processing

24226769

HgeneADAM17

GO:0032496

response to lipopolysaccharide

18383040

HgeneADAM17

GO:0033627

cell adhesion mediated by integrin

14970227

HgeneADAM17

GO:0043536

positive regulation of blood vessel endothelial cell migration

24813629

HgeneADAM17

GO:0045741

positive regulation of epidermal growth factor-activated receptor activity

18483258

HgeneADAM17

GO:0051088

PMA-inducible membrane protein ectodomain proteolysis

14625290|15691827|17010968

HgeneADAM17

GO:0071403

cellular response to high density lipoprotein particle stimulus

17786981

HgeneADAM17

GO:1905564

positive regulation of vascular endothelial cell proliferation

24813629

TgeneSEC31A

GO:0051592

response to calcium ion

17196169

TgeneSEC31A

GO:0090110

cargo loading into COPII-coated vesicle

17499046|18843296



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/chr2:9634765/chr4:83765662)
- 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 ADAM17 (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 SEC31A (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)
ENST00000310823ADAM17chr29634765-ENST00000348405SEC31Achr483765662-3671209718332571024
ENST00000310823ADAM17chr29634765-ENST00000513858SEC31Achr483765662-332920971832915910
ENST00000310823ADAM17chr29634765-ENST00000395310SEC31Achr483765662-3671209718332571024
ENST00000310823ADAM17chr29634765-ENST00000443462SEC31Achr483765662-3625209718332121009
ENST00000310823ADAM17chr29634765-ENST00000509142SEC31Achr483765662-332820971832915910
ENST00000310823ADAM17chr29634765-ENST00000326950SEC31Achr483765662-3670209718332571024
ENST00000310823ADAM17chr29634765-ENST00000432794SEC31Achr483765662-3709209718332961037
ENST00000310823ADAM17chr29634765-ENST00000311785SEC31Achr483765662-332820971832915910
ENST00000310823ADAM17chr29634765-ENST00000448323SEC31Achr483765662-3670209718332571024
ENST00000310823ADAM17chr29634765-ENST00000505472SEC31Achr483765662-3660209718332571024
ENST00000310823ADAM17chr29634765-ENST00000500777SEC31Achr483765662-331820971832915910
ENST00000310823ADAM17chr29634765-ENST00000508502SEC31Achr483765662-3276209718332121009
ENST00000310823ADAM17chr29634765-ENST00000355196SEC31Achr483765662-3321209718332571024
ENST00000310823ADAM17chr29634765-ENST00000264405SEC31Achr483765662-3265209718332121009
ENST00000310823ADAM17chr29634765-ENST00000505984SEC31Achr483765662-3243209718332121009
ENST00000310823ADAM17chr29634765-ENST00000508479SEC31Achr483765662-292220971832228681

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
ENST00000310823ENST00000348405ADAM17chr29634765-SEC31Achr483765662-0.0003837990.99961615
ENST00000310823ENST00000513858ADAM17chr29634765-SEC31Achr483765662-0.0004556550.9995443
ENST00000310823ENST00000395310ADAM17chr29634765-SEC31Achr483765662-0.0003837990.99961615
ENST00000310823ENST00000443462ADAM17chr29634765-SEC31Achr483765662-0.0003970120.999603
ENST00000310823ENST00000509142ADAM17chr29634765-SEC31Achr483765662-0.0004568080.9995432
ENST00000310823ENST00000326950ADAM17chr29634765-SEC31Achr483765662-0.0003839470.999616
ENST00000310823ENST00000432794ADAM17chr29634765-SEC31Achr483765662-0.0004572060.99954283
ENST00000310823ENST00000311785ADAM17chr29634765-SEC31Achr483765662-0.0004568080.9995432
ENST00000310823ENST00000448323ADAM17chr29634765-SEC31Achr483765662-0.0003839470.999616
ENST00000310823ENST00000505472ADAM17chr29634765-SEC31Achr483765662-0.0004038340.9995962
ENST00000310823ENST00000500777ADAM17chr29634765-SEC31Achr483765662-0.0004818110.99951816
ENST00000310823ENST00000508502ADAM17chr29634765-SEC31Achr483765662-0.0004619020.99953806
ENST00000310823ENST00000355196ADAM17chr29634765-SEC31Achr483765662-0.0004441520.9995559
ENST00000310823ENST00000264405ADAM17chr29634765-SEC31Achr483765662-0.0005093040.9994906
ENST00000310823ENST00000505984ADAM17chr29634765-SEC31Achr483765662-0.0005172990.99948263
ENST00000310823ENST00000508479ADAM17chr29634765-SEC31Achr483765662-0.0004114180.99958855

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 ADAM17-SEC31A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ADAM17chr29634765SEC31Achr4837656622097638KGKPCTVGFCDMNGENPPPPGFIMHG

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Potential FusionNeoAntigen Information of ADAM17-SEC31A 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.
ADAM17-SEC31A_9634765_83765662.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)
ADAM17-SEC31Achr29634765chr4837656622097HLA-B47:01NGENPPPPGF0.74920.59121222
ADAM17-SEC31Achr29634765chr4837656622097HLA-B44:03NGENPPPPGF0.67160.95521222
ADAM17-SEC31Achr29634765chr4837656622097HLA-B18:01NGENPPPPGF0.34010.98161222
ADAM17-SEC31Achr29634765chr4837656622097HLA-B47:01MNGENPPPPGF0.99010.5751122
ADAM17-SEC31Achr29634765chr4837656622097HLA-B44:03MNGENPPPPGF0.97310.95481122
ADAM17-SEC31Achr29634765chr4837656622097HLA-B44:07NGENPPPPGF0.67160.95521222
ADAM17-SEC31Achr29634765chr4837656622097HLA-B44:13NGENPPPPGF0.67160.95521222
ADAM17-SEC31Achr29634765chr4837656622097HLA-B44:26NGENPPPPGF0.67160.95521222
ADAM17-SEC31Achr29634765chr4837656622097HLA-B18:11NGENPPPPGF0.56560.94241222
ADAM17-SEC31Achr29634765chr4837656622097HLA-B18:03NGENPPPPGF0.34210.98021222
ADAM17-SEC31Achr29634765chr4837656622097HLA-B18:05NGENPPPPGF0.34010.98161222
ADAM17-SEC31Achr29634765chr4837656622097HLA-B44:13MNGENPPPPGF0.97310.95481122
ADAM17-SEC31Achr29634765chr4837656622097HLA-B44:26MNGENPPPPGF0.97310.95481122
ADAM17-SEC31Achr29634765chr4837656622097HLA-B44:07MNGENPPPPGF0.97310.95481122

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Potential FusionNeoAntigen Information of ADAM17-SEC31A 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 ADAM17-SEC31A

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
9946VGFCDMNGENPPPPADAM17SEC31Achr29634765chr4837656622097

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ADAM17-SEC31A

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-B14:023BVN9946VGFCDMNGENPPPP-7.9962-8.1096
HLA-B14:023BVN9946VGFCDMNGENPPPP-5.70842-6.74372
HLA-B52:013W399946VGFCDMNGENPPPP-6.83737-6.95077
HLA-B52:013W399946VGFCDMNGENPPPP-4.4836-5.5189
HLA-A11:014UQ29946VGFCDMNGENPPPP-10.0067-10.1201
HLA-A11:014UQ29946VGFCDMNGENPPPP-9.03915-10.0745
HLA-A24:025HGA9946VGFCDMNGENPPPP-6.56204-6.67544
HLA-A24:025HGA9946VGFCDMNGENPPPP-5.42271-6.45801
HLA-B44:053DX89946VGFCDMNGENPPPP-7.85648-8.89178
HLA-B44:053DX89946VGFCDMNGENPPPP-5.3978-5.5112
HLA-A02:016TDR9946VGFCDMNGENPPPP-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ADAM17-SEC31A

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
ADAM17-SEC31Achr29634765chr4837656621122MNGENPPPPGFATGAATGGAGAAAATCCTCCACCTCCGGGTTTC
ADAM17-SEC31Achr29634765chr4837656621222NGENPPPPGFAATGGAGAAAATCCTCCACCTCCGGGTTTC

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 ADAM17-SEC31A

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
ESCAADAM17-SEC31Achr29634765ENST00000310823chr483765662ENST00000264405TCGA-VR-A8EU

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Potential target of CAR-T therapy development for ADAM17-SEC31A

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 ADAM17-SEC31A

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 ADAM17-SEC31A

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
TgeneSEC31AC0079744Diffuse Large B-Cell Lymphoma1CTD_human