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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:TANC2-ARHGEF12

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TANC2-ARHGEF12
FusionPDB ID: 88929
FusionGDB2.0 ID: 88929
HgeneTgene
Gene symbol

TANC2

ARHGEF12

Gene ID

26115

23365

Gene nametetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2Rho guanine nucleotide exchange factor 12
SynonymsROLSA|rolsLARG|PRO2792
Cytomap

17q23.2-q23.3

11q23.3

Type of geneprotein-codingprotein-coding
Descriptionprotein TANC2putative ankyrin-repeat containing proteinrolling pebbles homolog Btetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 2rho guanine nucleotide exchange factor 12Rho guanine nucleotide exchange factor (GEF) 12leukemia-associated RhoGEFleukemia-associated rho guanine nucleotide exchange factor
Modification date2020031320200313
UniProtAcc.

Q9NZN5

Main function of 5'-partner protein: FUNCTION: May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. {ECO:0000269|PubMed:11094164}.
Ensembl transtripts involved in fusion geneENST idsENST00000389520, ENST00000424789, 
ENST00000356641, ENST00000397843, 
ENST00000532993, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score39 X 25 X 15=146257 X 8 X 5=280
# samples 457
** MAII scorelog2(45/14625*10)=-5.02236781302845
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/280*10)=-2
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TANC2 [Title/Abstract] AND ARHGEF12 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TANC2 [Title/Abstract] AND ARHGEF12 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TANC2(61151375)-ARHGEF12(120317112), # samples:3
Anticipated loss of major functional domain due to fusion event.TANC2-ARHGEF12 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.
TANC2-ARHGEF12 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.
TANC2-ARHGEF12 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.
TANC2-ARHGEF12 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
TgeneARHGEF12

GO:0007186

G protein-coupled receptor signaling pathway

15755723



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/chr17:61151375/chr11:120317112)
- 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 TANC2 (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 ARHGEF12 (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)
ENST00000424789TANC2chr1761151375+ENST00000397843ARHGEF12chr11120317112+8292143434321142
ENST00000424789TANC2chr1761151375+ENST00000356641ARHGEF12chr11120317112+8292143434321142
ENST00000424789TANC2chr1761151375+ENST00000532993ARHGEF12chr11120317112+7390143434321142
ENST00000389520TANC2chr1761151375+ENST00000397843ARHGEF12chr11120317112+8288139034281142
ENST00000389520TANC2chr1761151375+ENST00000356641ARHGEF12chr11120317112+8288139034281142
ENST00000389520TANC2chr1761151375+ENST00000532993ARHGEF12chr11120317112+7386139034281142

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
ENST00000424789ENST00000397843TANC2chr1761151375+ARHGEF12chr11120317112+8.01E-050.9999199
ENST00000424789ENST00000356641TANC2chr1761151375+ARHGEF12chr11120317112+8.01E-050.9999199
ENST00000424789ENST00000532993TANC2chr1761151375+ARHGEF12chr11120317112+9.95E-050.99990046
ENST00000389520ENST00000397843TANC2chr1761151375+ARHGEF12chr11120317112+7.95E-050.9999205
ENST00000389520ENST00000356641TANC2chr1761151375+ARHGEF12chr11120317112+7.95E-050.9999205
ENST00000389520ENST00000532993TANC2chr1761151375+ARHGEF12chr11120317112+9.86E-050.9999014

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 TANC2-ARHGEF12

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TANC2chr1761151375ARHGEF12chr1112031711213946QSSVDSRQSRSGQEKRRPELIPEDLH
TANC2chr1761151375ARHGEF12chr1112031711214346QSSVDSRQSRSGQEKRRPELIPEDLH

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Potential FusionNeoAntigen Information of TANC2-ARHGEF12 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.
TANC2-ARHGEF12_61151375_120317112.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)
TANC2-ARHGEF12chr1761151375chr11120317112139HLA-B48:01GQEKRRPEL0.99710.63361120
TANC2-ARHGEF12chr1761151375chr11120317112139HLA-B39:13GQEKRRPEL0.85910.9661120
TANC2-ARHGEF12chr1761151375chr11120317112139HLA-B48:03GQEKRRPEL0.98170.53241120
TANC2-ARHGEF12chr1761151375chr11120317112139HLA-B39:08GQEKRRPEL0.91320.86251120
TANC2-ARHGEF12chr1761151375chr11120317112139HLA-B14:03GQEKRRPEL0.81990.81131120
TANC2-ARHGEF12chr1761151375chr11120317112139HLA-B40:12GQEKRRPEL0.98170.53241120
TANC2-ARHGEF12chr1761151375chr11120317112139HLA-A30:01RQSRSGQEK0.96930.7675615
TANC2-ARHGEF12chr1761151375chr11120317112139HLA-B39:02GQEKRRPEL0.91630.96221120
TANC2-ARHGEF12chr1761151375chr11120317112139HLA-B40:21GQEKRRPEL0.80540.60611120
TANC2-ARHGEF12chr1761151375chr11120317112139HLA-B15:73GQEKRRPEL0.55320.96731120
TANC2-ARHGEF12chr1761151375chr11120317112139HLA-B15:30GQEKRRPEL0.45420.94681120

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Potential FusionNeoAntigen Information of TANC2-ARHGEF12 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 TANC2-ARHGEF12

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
8137RQSRSGQEKRRPELTANC2ARHGEF12chr1761151375chr11120317112139

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TANC2-ARHGEF12

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-B14:023BVN8137RQSRSGQEKRRPEL-5.97758-6.09098
HLA-B14:023BVN8137RQSRSGQEKRRPEL-5.15013-6.18543
HLA-B52:013W398137RQSRSGQEKRRPEL-6.29935-6.41275
HLA-B52:013W398137RQSRSGQEKRRPEL-6.07479-7.11009
HLA-A24:025HGA8137RQSRSGQEKRRPEL-7.25246-8.28776
HLA-A24:025HGA8137RQSRSGQEKRRPEL-6.23064-6.34404
HLA-B44:053DX88137RQSRSGQEKRRPEL-4.66421-5.69951
HLA-B44:053DX88137RQSRSGQEKRRPEL-4.52141-4.63481
HLA-A02:016TDR8137RQSRSGQEKRRPEL-7.72945-7.84285

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Vaccine Design for the FusionNeoAntigens of TANC2-ARHGEF12

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
TANC2-ARHGEF12chr1761151375chr111203171121120GQEKRRPELGGCAAGAAAAGAGAAGACCTGAGCTCA
TANC2-ARHGEF12chr1761151375chr11120317112615RQSRSGQEKGCCAAAGCCGCTCTGGGCAAGAAAAGA

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 TANC2-ARHGEF12

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
SARCTANC2-ARHGEF12chr1761151375ENST00000389520chr11120317112ENST00000356641TCGA-FX-A2QS-01A

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Potential target of CAR-T therapy development for TANC2-ARHGEF12

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 TANC2-ARHGEF12

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 TANC2-ARHGEF12

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
TgeneARHGEF12C0043094Weight Gain1CTD_human