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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:TCP1-HIF1A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TCP1-HIF1A
FusionPDB ID: 89879
FusionGDB2.0 ID: 89879
HgeneTgene
Gene symbol

TCP1

HIF1A

Gene ID

6950

3091

Gene namet-complex 1hypoxia inducible factor 1 subunit alpha
SynonymsCCT-alpha|CCT1|CCTa|D6S230E|TCP-1-alphaHIF-1-alpha|HIF-1A|HIF-1alpha|HIF1|HIF1-ALPHA|MOP1|PASD8|bHLHe78
Cytomap

6q25.3

14q23.2

Type of geneprotein-codingprotein-coding
DescriptionT-complex protein 1 subunit alphaT-complex protein 1, alpha subunitt-complex 1 proteintailless complex polypeptide 1hypoxia-inducible factor 1-alphaARNT interacting proteinPAS domain-containing protein 8basic-helix-loop-helix-PAS protein MOP1class E basic helix-loop-helix protein 78hypoxia inducible factor 1 alpha subunithypoxia inducible factor 1, alpha subunit
Modification date2020031320200329
UniProtAcc.

Q9NWT6

Main function of 5'-partner protein: FUNCTION: Hydroxylates HIF-1 alpha at 'Asn-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation. {ECO:0000269|PubMed:12042299, ECO:0000269|PubMed:12080085, ECO:0000269|PubMed:17003112, ECO:0000269|PubMed:17573339, ECO:0000269|PubMed:18299578, ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:21177872, ECO:0000269|PubMed:21251231}.
Ensembl transtripts involved in fusion geneENST idsENST00000321394, ENST00000420894, 
ENST00000392168, ENST00000544255, 
ENST00000546023, 
ENST00000557206, 
ENST00000323441, ENST00000337138, 
ENST00000394997, ENST00000539097, 
ENST00000557538, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 5 X 2=507 X 7 X 3=147
# samples 57
** MAII scorelog2(5/50*10)=0log2(7/147*10)=-1.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TCP1 [Title/Abstract] AND HIF1A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TCP1 [Title/Abstract] AND HIF1A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TCP1(160210436)-HIF1A(62213651), # samples:1
Anticipated loss of major functional domain due to fusion event.TCP1-HIF1A 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.
TCP1-HIF1A 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.
TCP1-HIF1A 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.
TCP1-HIF1A 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.
TCP1-HIF1A seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
TCP1-HIF1A seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
TCP1-HIF1A seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
TCP1-HIF1A seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
TCP1-HIF1A seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF.
TCP1-HIF1A seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
TgeneHIF1A

GO:0001666

response to hypoxia

8756616|9887100|11782478|15261140|18419598

TgeneHIF1A

GO:0006355

regulation of transcription, DNA-templated

11782478|15261140

TgeneHIF1A

GO:0010468

regulation of gene expression

18419598

TgeneHIF1A

GO:0010573

vascular endothelial growth factor production

12958148

TgeneHIF1A

GO:0010575

positive regulation of vascular endothelial growth factor production

8756616

TgeneHIF1A

GO:0010628

positive regulation of gene expression

15459207|24244340

TgeneHIF1A

GO:0032364

oxygen homeostasis

16956324

TgeneHIF1A

GO:0043619

regulation of transcription from RNA polymerase II promoter in response to oxidative stress

8089148|8387214

TgeneHIF1A

GO:0045893

positive regulation of transcription, DNA-templated

8089148|9887100|25043030

TgeneHIF1A

GO:0045944

positive regulation of transcription by RNA polymerase II

11573933

TgeneHIF1A

GO:0046886

positive regulation of hormone biosynthetic process

1448077

TgeneHIF1A

GO:0061419

positive regulation of transcription from RNA polymerase II promoter in response to hypoxia

22735262

TgeneHIF1A

GO:0071456

cellular response to hypoxia

11573933|19528298|20889502

TgeneHIF1A

GO:1902895

positive regulation of pri-miRNA transcription by RNA polymerase II

19782034

TgeneHIF1A

GO:1903377

negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway

24899725



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/chr6:160210436/chr14:62213651)
- 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 TCP1 (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 HIF1A (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)
ENST00000321394TCP1chr6160210436-ENST00000394997HIF1Achr1462213651+16703454051135
ENST00000321394TCP1chr6160210436-ENST00000337138HIF1Achr1462213651+16703454051135
ENST00000420894TCP1chr6160210436-ENST00000394997HIF1Achr1462213651+1493168228176
ENST00000420894TCP1chr6160210436-ENST00000337138HIF1Achr1462213651+1493168228176

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
ENST00000321394ENST00000394997TCP1chr6160210436-HIF1Achr1462213651+0.76175020.23824982
ENST00000321394ENST00000337138TCP1chr6160210436-HIF1Achr1462213651+0.76175020.23824982
ENST00000420894ENST00000394997TCP1chr6160210436-HIF1Achr1462213651+0.286438260.7135618
ENST00000420894ENST00000337138TCP1chr6160210436-HIF1Achr1462213651+0.286438260.7135618

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 TCP1-HIF1A

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 TCP1-HIF1A 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 TCP1-HIF1A 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 TCP1-HIF1A

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 TCP1-HIF1A

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 TCP1-HIF1A

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 TCP1-HIF1A

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 TCP1-HIF1A

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 TCP1-HIF1A

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 TCP1-HIF1A

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