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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:TTC1-CAMK2A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TTC1-CAMK2A
FusionPDB ID: 94930
FusionGDB2.0 ID: 94930
HgeneTgene
Gene symbol

TTC1

CAMK2A

Gene ID

7265

815

Gene nametetratricopeptide repeat domain 1calcium/calmodulin dependent protein kinase II alpha
SynonymsTPR1CAMKA|CaMKIINalpha|CaMKIIalpha|MRD53|MRT63
Cytomap

5q33.3

5q32

Type of geneprotein-codingprotein-coding
Descriptiontetratricopeptide repeat protein 1TPR repeat protein 1calcium/calmodulin-dependent protein kinase type II subunit alphaCaM kinase II alpha subunitCaM-kinase II alpha chainCaMK-II alpha subunitcaM kinase II subunit alphacaMK-II subunit alphacalcium/calmodulin-dependent protein kinase (CaM kinase) II alp
Modification date2020031320200327
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000520274, ENST00000231238, 
ENST00000522793, 
ENST00000348628, 
ENST00000351010, ENST00000398376, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 7 X 3=1477 X 7 X 6=294
# samples 87
** MAII scorelog2(8/147*10)=-0.877744249949002
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/294*10)=-2.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TTC1 [Title/Abstract] AND CAMK2A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TTC1 [Title/Abstract] AND CAMK2A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TTC1(159470176)-CAMK2A(149602780), # samples:1
Anticipated loss of major functional domain due to fusion event.TTC1-CAMK2A 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.
TTC1-CAMK2A 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
TgeneCAMK2A

GO:0006468

protein phosphorylation

17052756

TgeneCAMK2A

GO:0038166

angiotensin-activated signaling pathway

20584908



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/chr5:159470176/chr5:149602780)
- 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 TTC1 (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 CAMK2A (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)
ENST00000522793TTC1chr5159470176+ENST00000348628CAMK2Achr5149602780-410064898880260
ENST00000231238TTC1chr5159470176+ENST00000348628CAMK2Achr5149602780-4103651101883260

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
ENST00000522793ENST00000348628TTC1chr5159470176+CAMK2Achr5149602780-0.0013539880.9986461
ENST00000231238ENST00000348628TTC1chr5159470176+CAMK2Achr5149602780-0.0013254020.99867463

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 TTC1-CAMK2A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TTC1chr5159470176CAMK2Achr5149602780648183QDKKEMAINDCSKVWSRNSKPVHTTI
TTC1chr5159470176CAMK2Achr5149602780651183QDKKEMAINDCSKVWSRNSKPVHTTI

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Potential FusionNeoAntigen Information of TTC1-CAMK2A 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.
TTC1-CAMK2A_159470176_149602780.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)
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B58:02AINDCSKVW0.96550.923615
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B57:01MAINDCSKVW0.99980.9321515
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B58:01MAINDCSKVW0.99920.8718515
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B58:02MAINDCSKVW0.99920.8854515
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B57:03MAINDCSKVW0.99670.9573515
TTC1-CAMK2Achr5159470176chr5149602780651HLA-A31:02AINDCSKVWSR0.99080.8953617
TTC1-CAMK2Achr5159470176chr5149602780651HLA-A31:06AINDCSKVWSR0.98920.8532617
TTC1-CAMK2Achr5159470176chr5149602780651HLA-A74:09AINDCSKVWSR0.98720.9121617
TTC1-CAMK2Achr5159470176chr5149602780651HLA-A74:03AINDCSKVWSR0.98720.9121617
TTC1-CAMK2Achr5159470176chr5149602780651HLA-A74:11AINDCSKVWSR0.98720.9121617
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B44:08AINDCSKVW0.06720.5566615
TTC1-CAMK2Achr5159470176chr5149602780651HLA-A31:01AINDCSKVWSR0.99170.8856617
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B57:04AINDCSKVW0.99320.8632615
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B58:06AINDCSKVW0.980.8978615
TTC1-CAMK2Achr5159470176chr5149602780651HLA-A32:01AINDCSKVW0.95940.9489615
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B15:24AINDCSKVW0.93110.9348615
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B57:10MAINDCSKVW0.99980.9321515
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B57:04MAINDCSKVW0.99970.7426515
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B58:06MAINDCSKVW0.99840.8258515
TTC1-CAMK2Achr5159470176chr5149602780651HLA-B57:02MAINDCSKVW0.99810.9329515
TTC1-CAMK2Achr5159470176chr5149602780651HLA-A74:01AINDCSKVWSR0.98720.9121617

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Potential FusionNeoAntigen Information of TTC1-CAMK2A 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.
TTC1-CAMK2A_159470176_149602780.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)
TTC1-CAMK2Achr5159470176chr5149602780651DRB3-0201KKEMAINDCSKVWSR217
TTC1-CAMK2Achr5159470176chr5149602780651DRB3-0214KKEMAINDCSKVWSR217
TTC1-CAMK2Achr5159470176chr5149602780651DRB3-0224KKEMAINDCSKVWSR217
TTC1-CAMK2Achr5159470176chr5149602780651DRB3-0301KKEMAINDCSKVWSR217

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Fusion breakpoint peptide structures of TTC1-CAMK2A

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
287AINDCSKVWSRNSKTTC1CAMK2Achr5159470176chr5149602780651

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TTC1-CAMK2A

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-B14:023BVN287AINDCSKVWSRNSK-7.9962-8.1096
HLA-B14:023BVN287AINDCSKVWSRNSK-5.70842-6.74372
HLA-B52:013W39287AINDCSKVWSRNSK-6.83737-6.95077
HLA-B52:013W39287AINDCSKVWSRNSK-4.4836-5.5189
HLA-A11:014UQ2287AINDCSKVWSRNSK-10.0067-10.1201
HLA-A11:014UQ2287AINDCSKVWSRNSK-9.03915-10.0745
HLA-A24:025HGA287AINDCSKVWSRNSK-6.56204-6.67544
HLA-A24:025HGA287AINDCSKVWSRNSK-5.42271-6.45801
HLA-B44:053DX8287AINDCSKVWSRNSK-7.85648-8.89178
HLA-B44:053DX8287AINDCSKVWSRNSK-5.3978-5.5112
HLA-A02:016TDR287AINDCSKVWSRNSK-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of TTC1-CAMK2A

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
TTC1-CAMK2Achr5159470176chr5149602780515MAINDCSKVWTGGCCATCAATGACTGCAGCAAAGTGTGGT
TTC1-CAMK2Achr5159470176chr5149602780615AINDCSKVWCCATCAATGACTGCAGCAAAGTGTGGT
TTC1-CAMK2Achr5159470176chr5149602780617AINDCSKVWSRCCATCAATGACTGCAGCAAAGTGTGGTCCCGGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TTC1-CAMK2Achr5159470176chr5149602780217KKEMAINDCSKVWSRAGAAAGAAATGGCCATCAATGACTGCAGCAAAGTGTGGTCCCGGA

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Information of the samples that have these potential fusion neoantigens of TTC1-CAMK2A

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
STADTTC1-CAMK2Achr5159470176ENST00000231238chr5149602780ENST00000348628TCGA-HU-A4GN-01A

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Potential target of CAR-T therapy development for TTC1-CAMK2A

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 TTC1-CAMK2A

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 TTC1-CAMK2A

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