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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:COL12A1-TDRD3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: COL12A1-TDRD3
FusionPDB ID: 18062
FusionGDB2.0 ID: 18062
HgeneTgene
Gene symbol

COL12A1

TDRD3

Gene ID

1303

81550

Gene namecollagen type XII alpha 1 chaintudor domain containing 3
SynonymsBA209D8.1|BTHLM2|COL12A1L|DJ234P15.1|EDSMYP|UCMD2-
Cytomap

6q13-q14.1

13q21.2

Type of geneprotein-codingprotein-coding
Descriptioncollagen alpha-1(XII) chaincollagen type XII proteoglycancollagen, type XII, alpha 1tudor domain-containing protein 3
Modification date2020031320200313
UniProtAcc

Q99715

Main function of 5'-partner protein: FUNCTION: Type XII collagen interacts with type I collagen-containing fibrils, the COL1 domain could be associated with the surface of the fibrils, and the COL2 and NC3 domains may be localized in the perifibrillar matrix. {ECO:0000250}.		.
Ensembl transtripts involved in fusion geneENST idsENST00000322507, ENST00000345356, 
ENST00000416123, ENST00000483888, 
ENST00000511023, 		ENST00000463109, 
ENST00000196169, ENST00000377881, 
ENST00000377894, ENST00000535286, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 9 X 4=21610 X 10 X 5=500
# samples 911
** MAII scorelog2(9/216*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(11/500*10)=-2.18442457113743
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: COL12A1 [Title/Abstract] AND TDRD3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: COL12A1 [Title/Abstract] AND TDRD3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)COL12A1(75801206)-TDRD3(61141659), # samples:1
Anticipated loss of major functional domain due to fusion event.COL12A1-TDRD3 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.
COL12A1-TDRD3 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.
COL12A1-TDRD3 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.
COL12A1-TDRD3 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


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/chr6:75801206/chr13:61141659)
- 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 COL12A1 (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 TDRD3 (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)
ENST00000322507COL12A1chr675801206-ENST00000196169TDRD3chr1361141659+9387899531091112933
ENST00000322507COL12A1chr675801206-ENST00000377894TDRD3chr1361141659+9383899531091112933
ENST00000322507COL12A1chr675801206-ENST00000535286TDRD3chr1361141659+9384899531091112933
ENST00000322507COL12A1chr675801206-ENST00000377881TDRD3chr1361141659+9378899531091112933
ENST00000345356COL12A1chr675801206-ENST00000196169TDRD3chr1361141659+5695530311054191769
ENST00000345356COL12A1chr675801206-ENST00000377894TDRD3chr1361141659+5691530311054191769
ENST00000345356COL12A1chr675801206-ENST00000535286TDRD3chr1361141659+5692530311054191769
ENST00000345356COL12A1chr675801206-ENST00000377881TDRD3chr1361141659+5686530311054191769
ENST00000416123COL12A1chr675801206-ENST00000196169TDRD3chr1361141659+88498457085732857
ENST00000416123COL12A1chr675801206-ENST00000377894TDRD3chr1361141659+88458457085732857
ENST00000416123COL12A1chr675801206-ENST00000535286TDRD3chr1361141659+88468457085732857
ENST00000416123COL12A1chr675801206-ENST00000377881TDRD3chr1361141659+88408457085732857
ENST00000483888COL12A1chr675801206-ENST00000196169TDRD3chr1361141659+914687548188702929
ENST00000483888COL12A1chr675801206-ENST00000377894TDRD3chr1361141659+914287548188702929
ENST00000483888COL12A1chr675801206-ENST00000535286TDRD3chr1361141659+914387548188702929
ENST00000483888COL12A1chr675801206-ENST00000377881TDRD3chr1361141659+913787548188702929

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
ENST00000322507ENST00000196169COL12A1chr675801206-TDRD3chr1361141659+0.0002792150.99972075
ENST00000322507ENST00000377894COL12A1chr675801206-TDRD3chr1361141659+0.0002777650.9997222
ENST00000322507ENST00000535286COL12A1chr675801206-TDRD3chr1361141659+0.000277490.99972254
ENST00000322507ENST00000377881COL12A1chr675801206-TDRD3chr1361141659+0.000279720.9997203
ENST00000345356ENST00000196169COL12A1chr675801206-TDRD3chr1361141659+0.0002341970.9997658
ENST00000345356ENST00000377894COL12A1chr675801206-TDRD3chr1361141659+0.0002329940.999767
ENST00000345356ENST00000535286COL12A1chr675801206-TDRD3chr1361141659+0.0002328440.9997671
ENST00000345356ENST00000377881COL12A1chr675801206-TDRD3chr1361141659+0.0002357370.99976426
ENST00000416123ENST00000196169COL12A1chr675801206-TDRD3chr1361141659+8.25E-050.9999175
ENST00000416123ENST00000377894COL12A1chr675801206-TDRD3chr1361141659+8.21E-050.99991786
ENST00000416123ENST00000535286COL12A1chr675801206-TDRD3chr1361141659+8.20E-050.999918
ENST00000416123ENST00000377881COL12A1chr675801206-TDRD3chr1361141659+8.28E-050.99991715
ENST00000483888ENST00000196169COL12A1chr675801206-TDRD3chr1361141659+0.0002757160.9997242
ENST00000483888ENST00000377894COL12A1chr675801206-TDRD3chr1361141659+0.0002748410.99972516
ENST00000483888ENST00000535286COL12A1chr675801206-TDRD3chr1361141659+0.0002746230.9997254
ENST00000483888ENST00000377881COL12A1chr675801206-TDRD3chr1361141659+0.0002769880.999723

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 COL12A1-TDRD3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
COL12A1chr675801206TDRD3chr136114165953031731PGPSGLKGEKGDREEEGTYDQTLEFR
COL12A1chr675801206TDRD3chr136114165984572819PGPSGLKGEKGDREEEGTYDQTLEFR
COL12A1chr675801206TDRD3chr136114165987542891PGPSGLKGEKGDREEEGTYDQTLEFR
COL12A1chr675801206TDRD3chr136114165989952895PGPSGLKGEKGDREEEGTYDQTLEFR

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Potential FusionNeoAntigen Information of COL12A1-TDRD3 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.
COL12A1-TDRD3_75801206_61141659.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)
COL12A1-TDRD3chr675801206chr13611416598995HLA-B39:13REEEGTYDQTL0.99280.90291223
COL12A1-TDRD3chr675801206chr13611416598995HLA-B41:01REEEGTYDQTL0.96740.84471223
COL12A1-TDRD3chr675801206chr13611416598995HLA-B39:08REEEGTYDQTL0.99830.80981223
COL12A1-TDRD3chr675801206chr13611416598995HLA-B40:04REEEGTYDQTL0.99980.70371223
COL12A1-TDRD3chr675801206chr13611416598995HLA-B39:11REEEGTYDQTL0.99820.69471223
COL12A1-TDRD3chr675801206chr13611416598995HLA-B39:02REEEGTYDQTL0.99430.90291223
COL12A1-TDRD3chr675801206chr13611416598995HLA-B41:03REEEGTYDQTL0.98310.59461223

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Potential FusionNeoAntigen Information of COL12A1-TDRD3 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 COL12A1-TDRD3

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
4250KGEKGDREEEGTYDCOL12A1TDRD3chr675801206chr13611416598995

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of COL12A1-TDRD3

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-B14:023BVN4250KGEKGDREEEGTYD-7.9962-8.1096
HLA-B14:023BVN4250KGEKGDREEEGTYD-5.70842-6.74372
HLA-B52:013W394250KGEKGDREEEGTYD-6.83737-6.95077
HLA-B52:013W394250KGEKGDREEEGTYD-4.4836-5.5189
HLA-A11:014UQ24250KGEKGDREEEGTYD-10.0067-10.1201
HLA-A11:014UQ24250KGEKGDREEEGTYD-9.03915-10.0745
HLA-A24:025HGA4250KGEKGDREEEGTYD-6.56204-6.67544
HLA-A24:025HGA4250KGEKGDREEEGTYD-5.42271-6.45801
HLA-B44:053DX84250KGEKGDREEEGTYD-7.85648-8.89178
HLA-B44:053DX84250KGEKGDREEEGTYD-5.3978-5.5112
HLA-A02:016TDR4250KGEKGDREEEGTYD-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of COL12A1-TDRD3

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
COL12A1-TDRD3chr675801206chr13611416591223REEEGTYDQTLAGGGAGGAAGAAGGCACCTACGATCAAACTCTG

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 COL12A1-TDRD3

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
PRADCOL12A1-TDRD3chr675801206ENST00000322507chr1361141659ENST00000196169TCGA-EJ-A65G-01A

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Potential target of CAR-T therapy development for COL12A1-TDRD3

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 COL12A1-TDRD3

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 COL12A1-TDRD3

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