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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:C3-HP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: C3-HP
FusionPDB ID: 11694
FusionGDB2.0 ID: 11694
HgeneTgene
Gene symbol

C3

HP

Gene ID

718

10395

Gene namecomplement C3DLC1 Rho GTPase activating protein
SynonymsAHUS5|ARMD9|ASP|C3a|C3b|CPAMD1|HEL-S-62pARHGAP7|HP|STARD12|p122-RhoGAP
Cytomap

19p13.3

8p22

Type of geneprotein-codingprotein-coding
Descriptioncomplement C3C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1C3a anaphylatoxinacylation-stimulating protein cleavage productcomplement component 3complement component C3acomplement component C3bepididymis secretory sperm binding prrho GTPase-activating protein 7Rho-GTPase-activating protein 7START domain-containing protein 12StAR-related lipid transfer (START) domain containing 12deleted in liver cancer 1 proteindeleted in liver cancer 1 variant 2deleted in liver cancer varia
Modification date2020032720200313
UniProtAcc

A6NLC5

Main function of 5'-partner protein: FUNCTION: May play a role in neuronal and neurobehavioral development. {ECO:0000250|UniProtKB:Q1LY84}.

P02790

Main function of 5'-partner protein: FUNCTION: Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation.
Ensembl transtripts involved in fusion geneENST idsENST00000245907, ENST00000599668, 
ENST00000565574, ENST00000569639, 
ENST00000355906, ENST00000357763, 
ENST00000398131, ENST00000562526, 
ENST00000570083, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score28 X 24 X 14=940814 X 11 X 3=462
# samples 3313
** MAII scorelog2(33/9408*10)=-4.83335013059055
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/462*10)=-1.8293812283876
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: C3 [Title/Abstract] AND HP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: C3 [Title/Abstract] AND HP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)C3(6694442)-HP(72093016), # samples:1
HP(72094660)-C3(6677988), # samples:1
HP(72110851)-C3(6677988), # samples:1
HP(72094669)-C3(6677979), # samples:1
Anticipated loss of major functional domain due to fusion event.C3-HP 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.
C3-HP 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.
C3-HP 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.
C3-HP 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.
HP-C3 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.
HP-C3 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.
C3-HP seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
HP-C3 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneC3

GO:0001934

positive regulation of protein phosphorylation

15833747

HgeneC3

GO:0010575

positive regulation of vascular endothelial growth factor production

16452172

HgeneC3

GO:0010828

positive regulation of glucose transmembrane transport

9059512|15833747

HgeneC3

GO:0010866

regulation of triglyceride biosynthetic process

10432298

HgeneC3

GO:0010884

positive regulation of lipid storage

9555951

HgeneC3

GO:0045745

positive regulation of G protein-coupled receptor signaling pathway

15833747

TgeneHP

GO:0006915

apoptotic process

17292327

TgeneHP

GO:0006919

activation of cysteine-type endopeptidase activity involved in apoptotic process

17888903

TgeneHP

GO:0008285

negative regulation of cell proliferation

12545165|17932950

TgeneHP

GO:0030336

negative regulation of cell migration

17932950|19158340

TgeneHP

GO:0035307

positive regulation of protein dephosphorylation

17292327

TgeneHP

GO:0051497

negative regulation of stress fiber assembly

17932950

TgeneHP

GO:0051895

negative regulation of focal adhesion assembly

19158340

TgeneHP

GO:1900119

positive regulation of execution phase of apoptosis

17888903



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/chr19:6694442/chr16:72093016)
- 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 C3 (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 HP (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)
ENST00000245907C3chr196694442-ENST00000570083HPchr1672093016+426632476941001343
ENST00000245907C3chr196694442-ENST00000355906HPchr1672093016+426532476941001343
ENST00000245907C3chr196694442-ENST00000398131HPchr1672093016+426532476941001343
ENST00000245907C3chr196694442-ENST00000357763HPchr1672093016+422732476941001343
ENST00000245907C3chr196694442-ENST00000562526HPchr1672093016+371532476933351088

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
ENST00000245907ENST00000570083C3chr196694442-HPchr1672093016+0.0012709720.99872905
ENST00000245907ENST00000355906C3chr196694442-HPchr1672093016+0.0012843620.99871564
ENST00000245907ENST00000398131C3chr196694442-HPchr1672093016+0.0012843620.99871564
ENST00000245907ENST00000357763C3chr196694442-HPchr1672093016+0.0013033940.9986966
ENST00000245907ENST00000562526C3chr196694442-HPchr1672093016+0.0022165740.9977835

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 C3-HP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
C3chr196694442HPchr167209301632471059LEKRQGALELIKKGVYTLNNEKQWIN

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Potential FusionNeoAntigen Information of C3-HP 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.
C3-HP_6694442_72093016.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)
C3-HPchr196694442chr16720930163247HLA-B18:01LELIKKGVY0.99150.5086716
C3-HPchr196694442chr16720930163247HLA-A32:13LIKKGVYTL0.49740.8231918
C3-HPchr196694442chr16720930163247HLA-B15:04LIKKGVYTL0.97490.6755918
C3-HPchr196694442chr16720930163247HLA-B18:05LELIKKGVY0.99150.5086716
C3-HPchr196694442chr16720930163247HLA-B18:06LELIKKGVY0.99020.5029716
C3-HPchr196694442chr16720930163247HLA-C03:05LIKKGVYTL0.92440.7654918
C3-HPchr196694442chr16720930163247HLA-B15:73LIKKGVYTL0.91070.6045918
C3-HPchr196694442chr16720930163247HLA-B15:30LIKKGVYTL0.81510.5619918
C3-HPchr196694442chr16720930163247HLA-A32:01LIKKGVYTL0.6140.8966918
C3-HPchr196694442chr16720930163247HLA-B08:12ELIKKGVYTL0.92680.5409818

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Potential FusionNeoAntigen Information of C3-HP 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.
C3-HP_6694442_72093016.msa

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)
C3-HPchr196694442chr16720930163247DRB1-0413KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0413IKKGVYTLNNEKQWI1025
C3-HPchr196694442chr16720930163247DRB1-0415KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0436KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0440KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0440IKKGVYTLNNEKQWI1025
C3-HPchr196694442chr16720930163247DRB1-0442KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0442IKKGVYTLNNEKQWI1025
C3-HPchr196694442chr16720930163247DRB1-0442LIKKGVYTLNNEKQW924
C3-HPchr196694442chr16720930163247DRB1-0444KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0450KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0451KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0453KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0453IKKGVYTLNNEKQWI1025
C3-HPchr196694442chr16720930163247DRB1-0455KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0456KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0456IKKGVYTLNNEKQWI1025
C3-HPchr196694442chr16720930163247DRB1-0458KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0459KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0468KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0468IKKGVYTLNNEKQWI1025
C3-HPchr196694442chr16720930163247DRB1-0470KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0470IKKGVYTLNNEKQWI1025
C3-HPchr196694442chr16720930163247DRB1-0473KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-0479KKGVYTLNNEKQWIN1126
C3-HPchr196694442chr16720930163247DRB1-1113QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1118QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1134QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1142QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1157QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1192QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1201QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1204QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1204RQGALELIKKGVYTL318
C3-HPchr196694442chr16720930163247DRB1-1205QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1206QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1207QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1208QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1208RQGALELIKKGVYTL318
C3-HPchr196694442chr16720930163247DRB1-1209QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1209RQGALELIKKGVYTL318
C3-HPchr196694442chr16720930163247DRB1-1210QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1211QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1214QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1217QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1306QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1343QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1343RQGALELIKKGVYTL318
C3-HPchr196694442chr16720930163247DRB1-1344QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1354QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1377QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1377RQGALELIKKGVYTL318
C3-HPchr196694442chr16720930163247DRB1-1377KRQGALELIKKGVYT217
C3-HPchr196694442chr16720930163247DRB1-1417QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1428QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1433QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1435QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1464QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1465QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1465RQGALELIKKGVYTL318
C3-HPchr196694442chr16720930163247DRB1-1472QGALELIKKGVYTLN419
C3-HPchr196694442chr16720930163247DRB1-1478QGALELIKKGVYTLN419

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Fusion breakpoint peptide structures of C3-HP

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
353ALELIKKGVYTLNNC3HPchr196694442chr16720930163247

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of C3-HP

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-B14:023BVN353ALELIKKGVYTLNN-7.15543-7.26883
HLA-B14:023BVN353ALELIKKGVYTLNN-4.77435-5.80965
HLA-B52:013W39353ALELIKKGVYTLNN-6.80875-6.92215
HLA-B52:013W39353ALELIKKGVYTLNN-4.20386-5.23916
HLA-A11:014UQ2353ALELIKKGVYTLNN-7.5194-8.5547
HLA-A11:014UQ2353ALELIKKGVYTLNN-6.9601-7.0735
HLA-A24:025HGA353ALELIKKGVYTLNN-7.52403-7.63743
HLA-A24:025HGA353ALELIKKGVYTLNN-5.82433-6.85963
HLA-B27:056PYJ353ALELIKKGVYTLNN-3.28285-4.31815
HLA-B44:053DX8353ALELIKKGVYTLNN-5.91172-6.94702
HLA-B44:053DX8353ALELIKKGVYTLNN-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of C3-HP

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
C3-HPchr196694442chr1672093016716LELIKKGVYTGGAGCTCATCAAGAAGGGAGTGTACA
C3-HPchr196694442chr1672093016818ELIKKGVYTLAGCTCATCAAGAAGGGAGTGTACACCTTAA
C3-HPchr196694442chr1672093016918LIKKGVYTLTCATCAAGAAGGGAGTGTACACCTTAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
C3-HPchr196694442chr16720930161025IKKGVYTLNNEKQWITCAAGAAGGGAGTGTACACCTTAAACAATGAGAAGCAGTGGATAA
C3-HPchr196694442chr16720930161126KKGVYTLNNEKQWINAGAAGGGAGTGTACACCTTAAACAATGAGAAGCAGTGGATAAATA
C3-HPchr196694442chr1672093016217KRQGALELIKKGVYTAGCGGCAGGGGGCCTTGGAGCTCATCAAGAAGGGAGTGTACACCT
C3-HPchr196694442chr1672093016318RQGALELIKKGVYTLGGCAGGGGGCCTTGGAGCTCATCAAGAAGGGAGTGTACACCTTAA
C3-HPchr196694442chr1672093016419QGALELIKKGVYTLNAGGGGGCCTTGGAGCTCATCAAGAAGGGAGTGTACACCTTAAACA
C3-HPchr196694442chr1672093016924LIKKGVYTLNNEKQWTCATCAAGAAGGGAGTGTACACCTTAAACAATGAGAAGCAGTGGA

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Information of the samples that have these potential fusion neoantigens of C3-HP

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
LIHCC3-HPchr196694442ENST00000245907chr1672093016ENST00000355906TCGA-EP-A2KC-01A

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Potential target of CAR-T therapy development for C3-HP

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 C3-HP

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 C3-HP

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