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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:HCN1-SPEF2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HCN1-SPEF2
FusionPDB ID: 35780
FusionGDB2.0 ID: 35780
HgeneTgene
Gene symbol

HCN1

SPEF2

Gene ID

348980

79925

Gene namehyperpolarization activated cyclic nucleotide gated potassium channel 1sperm flagellar 2
SynonymsBCNG-1|BCNG1|EIEE24|GEFSP10|HAC-2CT122|KPL2|SPGF43
Cytomap

5p12

5p13.2

Type of geneprotein-codingprotein-coding
Descriptionpotassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1brain cyclic nucleotide-gated channel 1sperm flagellar protein 2cancer/testis antigen 122testis tissue sperm-binding protein Li 47a
Modification date2020031320200313
UniProtAcc

O60741

Main function of 5'-partner protein: FUNCTION: Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions (PubMed:28086084). Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). May mediate responses to sour stimuli. {ECO:0000269|PubMed:15351778, ECO:0000269|PubMed:28086084, ECO:0000269|PubMed:29936235, ECO:0000269|PubMed:30351409}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000303230, ENST00000303129, 
ENST00000282469, ENST00000356031, 
ENST00000440995, ENST00000509059, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=88 X 10 X 12=960
# samples 216
** MAII scorelog2(2/8*10)=1.32192809488736log2(16/960*10)=-2.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: HCN1 [Title/Abstract] AND SPEF2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: HCN1 [Title/Abstract] AND SPEF2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HCN1(45645287)-SPEF2(35667174), # samples:2
Anticipated loss of major functional domain due to fusion event.HCN1-SPEF2 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.
HCN1-SPEF2 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.
HCN1-SPEF2 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.
HCN1-SPEF2 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
HgeneHCN1

GO:0051289

protein homotetramerization

28086084

HgeneHCN1

GO:0071320

cellular response to cAMP

22748890



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/chr5:45645287/chr5:35667174)
- 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 HCN1 (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 SPEF2 (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)
ENST00000303230HCN1chr545645287-ENST00000282469SPEF2chr535667174+2612907581284408
ENST00000303230HCN1chr545645287-ENST00000509059SPEF2chr535667174+4293907582571837
ENST00000303230HCN1chr545645287-ENST00000356031SPEF2chr535667174+52679075852081716
ENST00000303230HCN1chr545645287-ENST00000440995SPEF2chr535667174+57049075851961712

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
ENST00000303230ENST00000282469HCN1chr545645287-SPEF2chr535667174+0.0002238720.9997762
ENST00000303230ENST00000509059HCN1chr545645287-SPEF2chr535667174+0.0007081080.9992919
ENST00000303230ENST00000356031HCN1chr545645287-SPEF2chr535667174+0.0004777830.9995222
ENST00000303230ENST00000440995HCN1chr545645287-SPEF2chr535667174+0.0005543140.9994456

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 HCN1-SPEF2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
HCN1chr545645287SPEF2chr535667174907283LSRLIRYIHQWEEALAKQAKIDFEEQ

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Potential FusionNeoAntigen Information of HCN1-SPEF2 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.
HCN1-SPEF2_45645287_35667174.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)
HCN1-SPEF2chr545645287chr535667174907HLA-B50:02EEALAKQA0.99970.79441119
HCN1-SPEF2chr545645287chr535667174907HLA-B45:01EEALAKQA0.99950.95061119
HCN1-SPEF2chr545645287chr535667174907HLA-B39:24IHQWEEAL0.99940.7091715
HCN1-SPEF2chr545645287chr535667174907HLA-B39:01IHQWEEAL0.99910.9811715
HCN1-SPEF2chr545645287chr535667174907HLA-B15:10IHQWEEAL0.99340.7278715
HCN1-SPEF2chr545645287chr535667174907HLA-B45:01WEEALAKQA0.9930.98861019
HCN1-SPEF2chr545645287chr535667174907HLA-B39:06IHQWEEALA0.98670.9055716
HCN1-SPEF2chr545645287chr535667174907HLA-B50:02WEEALAKQA0.96790.86311019
HCN1-SPEF2chr545645287chr535667174907HLA-A02:22YIHQWEEAL0.87690.569615
HCN1-SPEF2chr545645287chr535667174907HLA-B35:03YIHQWEEAL0.81070.9528615
HCN1-SPEF2chr545645287chr535667174907HLA-A02:04YIHQWEEAL0.80830.8305615
HCN1-SPEF2chr545645287chr535667174907HLA-A02:17YIHQWEEAL0.78850.5397615
HCN1-SPEF2chr545645287chr535667174907HLA-B35:04YIHQWEEAL0.57310.9788615
HCN1-SPEF2chr545645287chr535667174907HLA-B35:02YIHQWEEAL0.57310.9788615
HCN1-SPEF2chr545645287chr535667174907HLA-B50:01WEEALAKQA0.53310.96071019
HCN1-SPEF2chr545645287chr535667174907HLA-B47:01HQWEEALAK0.42960.7091817
HCN1-SPEF2chr545645287chr535667174907HLA-B41:01WEEALAKQA0.33750.99011019
HCN1-SPEF2chr545645287chr535667174907HLA-B45:01QWEEALAKQA0.91390.9936919
HCN1-SPEF2chr545645287chr535667174907HLA-B27:07IRYIHQWEEAL10.7062415
HCN1-SPEF2chr545645287chr535667174907HLA-B39:05IHQWEEAL0.99820.9777715
HCN1-SPEF2chr545645287chr535667174907HLA-C03:08YIHQWEEAL0.99560.9293615
HCN1-SPEF2chr545645287chr535667174907HLA-B40:06WEEALAKQA0.99550.85891019
HCN1-SPEF2chr545645287chr535667174907HLA-B51:07EALAKQAKI0.9930.89841221
HCN1-SPEF2chr545645287chr535667174907HLA-C03:19YIHQWEEAL0.99240.994615
HCN1-SPEF2chr545645287chr535667174907HLA-C03:07YIHQWEEAL0.99210.9864615
HCN1-SPEF2chr545645287chr535667174907HLA-C08:04YIHQWEEAL0.95380.9767615
HCN1-SPEF2chr545645287chr535667174907HLA-C08:13YIHQWEEAL0.95380.9767615
HCN1-SPEF2chr545645287chr535667174907HLA-C08:03YIHQWEEAL0.81250.9846615
HCN1-SPEF2chr545645287chr535667174907HLA-B35:12YIHQWEEAL0.57310.9788615
HCN1-SPEF2chr545645287chr535667174907HLA-B73:01IRYIHQWEEA0.99650.9173414
HCN1-SPEF2chr545645287chr535667174907HLA-B15:09IHQWEEAL0.9920.9586715
HCN1-SPEF2chr545645287chr535667174907HLA-B39:11IHQWEEAL0.92380.9417715
HCN1-SPEF2chr545645287chr535667174907HLA-C03:04YIHQWEEAL0.99770.9937615
HCN1-SPEF2chr545645287chr535667174907HLA-C03:03YIHQWEEAL0.99770.9937615
HCN1-SPEF2chr545645287chr535667174907HLA-C03:05YIHQWEEAL0.99110.9622615
HCN1-SPEF2chr545645287chr535667174907HLA-C03:06YIHQWEEAL0.96330.9942615
HCN1-SPEF2chr545645287chr535667174907HLA-B15:73YIHQWEEAL0.89790.9741615
HCN1-SPEF2chr545645287chr535667174907HLA-B15:30YIHQWEEAL0.86210.945615
HCN1-SPEF2chr545645287chr535667174907HLA-A02:14YIHQWEEAL0.85290.6975615
HCN1-SPEF2chr545645287chr535667174907HLA-C08:01YIHQWEEAL0.81250.9846615
HCN1-SPEF2chr545645287chr535667174907HLA-B35:13YIHQWEEAL0.76270.9551615
HCN1-SPEF2chr545645287chr535667174907HLA-B35:22YIHQWEEAL0.57920.5605615
HCN1-SPEF2chr545645287chr535667174907HLA-B35:09YIHQWEEAL0.57310.9788615
HCN1-SPEF2chr545645287chr535667174907HLA-B50:05WEEALAKQA0.53310.96071019
HCN1-SPEF2chr545645287chr535667174907HLA-B50:04WEEALAKQA0.53310.96071019
HCN1-SPEF2chr545645287chr535667174907HLA-B27:06IRYIHQWEEAL10.9031415
HCN1-SPEF2chr545645287chr535667174907HLA-B27:09IRYIHQWEEAL10.9098415

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Potential FusionNeoAntigen Information of HCN1-SPEF2 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.
HCN1-SPEF2_45645287_35667174.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)
HCN1-SPEF2chr545645287chr535667174907DRB1-0902IHQWEEALAKQAKID722
HCN1-SPEF2chr545645287chr535667174907DRB1-1220EEALAKQAKIDFEEQ1126
HCN1-SPEF2chr545645287chr535667174907DRB1-1503IRYIHQWEEALAKQA419
HCN1-SPEF2chr545645287chr535667174907DRB1-1503LIRYIHQWEEALAKQ318
HCN1-SPEF2chr545645287chr535667174907DRB1-1503RYIHQWEEALAKQAK520
HCN1-SPEF2chr545645287chr535667174907DRB1-1503RLIRYIHQWEEALAK217
HCN1-SPEF2chr545645287chr535667174907DRB1-1504IRYIHQWEEALAKQA419
HCN1-SPEF2chr545645287chr535667174907DRB1-1510IRYIHQWEEALAKQA419
HCN1-SPEF2chr545645287chr535667174907DRB1-1521IRYIHQWEEALAKQA419
HCN1-SPEF2chr545645287chr535667174907DRB1-1523IRYIHQWEEALAKQA419
HCN1-SPEF2chr545645287chr535667174907DRB1-1523LIRYIHQWEEALAKQ318
HCN1-SPEF2chr545645287chr535667174907DRB1-1523RYIHQWEEALAKQAK520

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Fusion breakpoint peptide structures of HCN1-SPEF2

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
10674YIHQWEEALAKQAKHCN1SPEF2chr545645287chr535667174907

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HCN1-SPEF2

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-B14:023BVN10674YIHQWEEALAKQAK-7.15543-7.26883
HLA-B14:023BVN10674YIHQWEEALAKQAK-4.77435-5.80965
HLA-B52:013W3910674YIHQWEEALAKQAK-6.80875-6.92215
HLA-B52:013W3910674YIHQWEEALAKQAK-4.20386-5.23916
HLA-A11:014UQ210674YIHQWEEALAKQAK-7.5194-8.5547
HLA-A11:014UQ210674YIHQWEEALAKQAK-6.9601-7.0735
HLA-A24:025HGA10674YIHQWEEALAKQAK-7.52403-7.63743
HLA-A24:025HGA10674YIHQWEEALAKQAK-5.82433-6.85963
HLA-B27:056PYJ10674YIHQWEEALAKQAK-3.28285-4.31815
HLA-B44:053DX810674YIHQWEEALAKQAK-5.91172-6.94702
HLA-B44:053DX810674YIHQWEEALAKQAK-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of HCN1-SPEF2

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
HCN1-SPEF2chr545645287chr5356671741019WEEALAKQATGGGAAGAGGCTTTGGCAAAACAAGCC
HCN1-SPEF2chr545645287chr5356671741119EEALAKQAGAAGAGGCTTTGGCAAAACAAGCC
HCN1-SPEF2chr545645287chr5356671741221EALAKQAKIGAGGCTTTGGCAAAACAAGCCAAGATT
HCN1-SPEF2chr545645287chr535667174414IRYIHQWEEAATTAGATACATACATCAATGGGAAGAGGCT
HCN1-SPEF2chr545645287chr535667174415IRYIHQWEEALATTAGATACATACATCAATGGGAAGAGGCTTTG
HCN1-SPEF2chr545645287chr535667174615YIHQWEEALTACATACATCAATGGGAAGAGGCTTTG
HCN1-SPEF2chr545645287chr535667174715IHQWEEALATACATCAATGGGAAGAGGCTTTG
HCN1-SPEF2chr545645287chr535667174716IHQWEEALAATACATCAATGGGAAGAGGCTTTGGCA
HCN1-SPEF2chr545645287chr535667174817HQWEEALAKCATCAATGGGAAGAGGCTTTGGCAAAA
HCN1-SPEF2chr545645287chr535667174919QWEEALAKQACAATGGGAAGAGGCTTTGGCAAAACAAGCC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
HCN1-SPEF2chr545645287chr5356671741126EEALAKQAKIDFEEQGAAGAGGCTTTGGCAAAACAAGCCAAGATTGACTTTGAAGAACAA
HCN1-SPEF2chr545645287chr535667174217RLIRYIHQWEEALAKAGGTTAATTAGATACATACATCAATGGGAAGAGGCTTTGGCAAAA
HCN1-SPEF2chr545645287chr535667174318LIRYIHQWEEALAKQTTAATTAGATACATACATCAATGGGAAGAGGCTTTGGCAAAACAA
HCN1-SPEF2chr545645287chr535667174419IRYIHQWEEALAKQAATTAGATACATACATCAATGGGAAGAGGCTTTGGCAAAACAAGCC
HCN1-SPEF2chr545645287chr535667174520RYIHQWEEALAKQAKAGATACATACATCAATGGGAAGAGGCTTTGGCAAAACAAGCCAAG
HCN1-SPEF2chr545645287chr535667174722IHQWEEALAKQAKIDATACATCAATGGGAAGAGGCTTTGGCAAAACAAGCCAAGATTGAC

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Information of the samples that have these potential fusion neoantigens of HCN1-SPEF2

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
SKCMHCN1-SPEF2chr545645287ENST00000303230chr535667174ENST00000282469TCGA-D3-A1Q3-06A

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Potential target of CAR-T therapy development for HCN1-SPEF2

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
HgeneHCN1chr5:45645287chr5:35667174ENST00000303230-28143_164283891.0TransmembraneHelical%3B Name%3DSegment S1
HgeneHCN1chr5:45645287chr5:35667174ENST00000303230-28174_194283891.0TransmembraneHelical%3B Name%3DSegment S2
HgeneHCN1chr5:45645287chr5:35667174ENST00000303230-28216_236283891.0TransmembraneHelical%3B Name%3DSegment S3
HgeneHCN1chr5:45645287chr5:35667174ENST00000303230-28261_281283891.0TransmembraneHelical%3B Voltage-sensor%3B Name%3DSegment S4

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 HCN1-SPEF2

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 HCN1-SPEF2

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