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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:GNA12-ADSS

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GNA12-ADSS
FusionPDB ID: 33523
FusionGDB2.0 ID: 33523
HgeneTgene
Gene symbol

GNA12

ADSS

Gene ID

2768

159

Gene nameG protein subunit alpha 12adenylosuccinate synthase 2
SynonymsNNX3|RMP|gepADEH|ADSS|ADSS 2
Cytomap

7p22.3-p22.2

1q44

Type of geneprotein-codingprotein-coding
Descriptionguanine nucleotide-binding protein subunit alpha-12WUGSC:H_GS165O14.2g alpha-12guanine nucleotide binding protein (G protein) alpha 12adenylosuccinate synthetase isozyme 2AMPSase 2IMP--aspartate ligase 2L-type adenylosuccinate synthetaseadSS 2adenylosuccinate synthetase (Ade(-)H-complementing)adenylosuccinate synthetase, acidic isozymeadenylosuccinate synthetase, liver isozymeep
Modification date2020031320200313
UniProtAcc

Q03113

Main function of 5'-partner protein: FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems (PubMed:22609986, PubMed:15525651, PubMed:15240885, PubMed:17565996, PubMed:12515866, PubMed:16787920, PubMed:16705036, PubMed:23762476, PubMed:27084452). Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF12/LARG) (PubMed:15240885, PubMed:12515866, PubMed:16202387). GNA12-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1) (By similarity). GNA12-dependent Rho signaling also regulates protein phosphatese 2A activation causing dephosphorylation of its target proteins (PubMed:15525651, PubMed:17565996). Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway and up-regulating proinflammatory cytokine production (PubMed:23762476, PubMed:16787920, PubMed:16705036, PubMed:27084452). Inhibits CDH1-mediated cell adhesion in process independent from Rho activation (PubMed:11976333, PubMed:16787920). Together with NAPA promotes CDH5 localization to plasma membrane (PubMed:15980433). May play a role in the control of cell migration through the TOR signaling cascade (PubMed:22609986). {ECO:0000250|UniProtKB:P27600, ECO:0000269|PubMed:11976333, ECO:0000269|PubMed:12515866, ECO:0000269|PubMed:15240885, ECO:0000269|PubMed:15525651, ECO:0000269|PubMed:15980433, ECO:0000269|PubMed:16705036, ECO:0000269|PubMed:16787920, ECO:0000269|PubMed:17565996, ECO:0000269|PubMed:22609986, ECO:0000269|PubMed:23762476, ECO:0000269|PubMed:27084452}.

P30520

Main function of 5'-partner protein: FUNCTION: Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP. {ECO:0000250|UniProtKB:P46664}.
Ensembl transtripts involved in fusion geneENST idsENST00000275364, ENST00000407904, 
ENST00000544127, ENST00000396960, 
ENST00000407653, ENST00000491117, 
ENST00000462358, ENST00000366535, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 4 X 7=30810 X 5 X 6=300
# samples 1412
** MAII scorelog2(14/308*10)=-1.13750352374993
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/300*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: GNA12 [Title/Abstract] AND ADSS [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GNA12 [Title/Abstract] AND ADSS [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GNA12(2834562)-ADSS(244601070), # samples:3
Anticipated loss of major functional domain due to fusion event.GNA12-ADSS 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.
GNA12-ADSS 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.
GNA12-ADSS 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.
GNA12-ADSS 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
TgeneADSS

GO:0006167

AMP biosynthetic process

2004783



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/chr7:2834562/chr1:244601070)
- 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 GNA12 (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 ADSS (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)
ENST00000275364GNA12chr72834562-ENST00000366535ADSSchr1244601070-29686881631875570
ENST00000544127GNA12chr72834562-ENST00000366535ADSSchr1244601070-2660380231567514
ENST00000407904GNA12chr72834562-ENST00000366535ADSSchr1244601070-29576773291864511
ENST00000275364GNA12chr72834561-ENST00000366535ADSSchr1244601070-29686881631875570
ENST00000544127GNA12chr72834561-ENST00000366535ADSSchr1244601070-2660380231567514
ENST00000407904GNA12chr72834561-ENST00000366535ADSSchr1244601070-29576773291864511

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
ENST00000275364ENST00000366535GNA12chr72834562-ADSSchr1244601070-0.000347040.999653
ENST00000544127ENST00000366535GNA12chr72834562-ADSSchr1244601070-0.0001131640.9998869
ENST00000407904ENST00000366535GNA12chr72834562-ADSSchr1244601070-0.0002884140.9997116
ENST00000275364ENST00000366535GNA12chr72834561-ADSSchr1244601070-0.000347040.999653
ENST00000544127ENST00000366535GNA12chr72834561-ADSSchr1244601070-0.0001131640.9998869
ENST00000407904ENST00000366535GNA12chr72834561-ADSSchr1244601070-0.0002884140.9997116

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 GNA12-ADSS

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GNA12chr72834561ADSSchr1244601070380119IREAFSRRSEFQLGGNNAGHTVVVDS
GNA12chr72834561ADSSchr1244601070677116IREAFSRRSEFQLGGNNAGHTVVVDS
GNA12chr72834561ADSSchr1244601070688175IREAFSRRSEFQLGGNNAGHTVVVDS
GNA12chr72834562ADSSchr1244601070380119IREAFSRRSEFQLGGNNAGHTVVVDS
GNA12chr72834562ADSSchr1244601070677116IREAFSRRSEFQLGGNNAGHTVVVDS
GNA12chr72834562ADSSchr1244601070688175IREAFSRRSEFQLGGNNAGHTVVVDS

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Potential FusionNeoAntigen Information of GNA12-ADSS 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.
GNA12-ADSS_2834561_244601070.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)
GNA12-ADSSchr72834561chr1244601070688HLA-B45:01SEFQLGGNNA0.99470.966818
GNA12-ADSSchr72834561chr1244601070688HLA-B50:02SEFQLGGNNA0.9890.8073818
GNA12-ADSSchr72834561chr1244601070688HLA-B50:01SEFQLGGNNA0.80830.8652818
GNA12-ADSSchr72834561chr1244601070688HLA-B41:01SEFQLGGNNA0.79190.9921818
GNA12-ADSSchr72834561chr1244601070688HLA-B27:14RRSEFQLGG0.97450.6206615
GNA12-ADSSchr72834561chr1244601070688HLA-B40:06SEFQLGGNNA0.99590.8614818
GNA12-ADSSchr72834561chr1244601070688HLA-B50:05SEFQLGGNNA0.80830.8652818
GNA12-ADSSchr72834561chr1244601070688HLA-B50:04SEFQLGGNNA0.80830.8652818

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Potential FusionNeoAntigen Information of GNA12-ADSS 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.
GNA12-ADSS_2834561_244601070.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)
GNA12-ADSSchr72834561chr1244601070688DRB1-0401RSEFQLGGNNAGHTV722
GNA12-ADSSchr72834561chr1244601070688DRB1-0401RRSEFQLGGNNAGHT621
GNA12-ADSSchr72834561chr1244601070688DRB1-0433RSEFQLGGNNAGHTV722
GNA12-ADSSchr72834561chr1244601070688DRB1-0433RRSEFQLGGNNAGHT621
GNA12-ADSSchr72834561chr1244601070688DRB1-0435RSEFQLGGNNAGHTV722
GNA12-ADSSchr72834561chr1244601070688DRB1-0438RSEFQLGGNNAGHTV722
GNA12-ADSSchr72834561chr1244601070688DRB1-0438RRSEFQLGGNNAGHT621
GNA12-ADSSchr72834561chr1244601070688DRB1-0463RSEFQLGGNNAGHTV722
GNA12-ADSSchr72834561chr1244601070688DRB1-0463RRSEFQLGGNNAGHT621
GNA12-ADSSchr72834561chr1244601070688DRB1-0464RSEFQLGGNNAGHTV722
GNA12-ADSSchr72834561chr1244601070688DRB1-0472RSEFQLGGNNAGHTV722
GNA12-ADSSchr72834561chr1244601070688DRB1-0474RSEFQLGGNNAGHTV722
GNA12-ADSSchr72834561chr1244601070688DRB1-0474RRSEFQLGGNNAGHT621
GNA12-ADSSchr72834561chr1244601070688DRB1-0475RSEFQLGGNNAGHTV722
GNA12-ADSSchr72834561chr1244601070688DRB1-0475RRSEFQLGGNNAGHT621
GNA12-ADSSchr72834561chr1244601070688DRB1-0476RSEFQLGGNNAGHTV722
GNA12-ADSSchr72834561chr1244601070688DRB1-0476RRSEFQLGGNNAGHT621

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Fusion breakpoint peptide structures of GNA12-ADSS

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
8196RRSEFQLGGNNAGHGNA12ADSSchr72834561chr1244601070688

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GNA12-ADSS

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-B53:011A1O8196RRSEFQLGGNNAGH-3.20963-4.24493
HLA-B51:011E288196RRSEFQLGGNNAGH-4.71049-4.82389
HLA-B51:011E288196RRSEFQLGGNNAGH-2.41218-3.44748
HLA-B57:032BVO8196RRSEFQLGGNNAGH-1.15793-2.19323
HLA-A03:012XPG8196RRSEFQLGGNNAGH-2.82905-3.86435
HLA-B14:023BVN8196RRSEFQLGGNNAGH-6.01624-6.12964
HLA-B14:023BVN8196RRSEFQLGGNNAGH-3.0101-4.0454
HLA-B44:033DX78196RRSEFQLGGNNAGH0.0456146-0.989685
HLA-B52:013W398196RRSEFQLGGNNAGH-5.58746-5.70086
HLA-B52:013W398196RRSEFQLGGNNAGH-3.59213-4.62743
HLA-B18:014JQV8196RRSEFQLGGNNAGH-3.3293-3.4427
HLA-B18:014JQV8196RRSEFQLGGNNAGH-0.305763-1.34106
HLA-A11:014UQ28196RRSEFQLGGNNAGH-8.33749-8.45089
HLA-A11:014UQ28196RRSEFQLGGNNAGH-6.15985-7.19515
HLA-A24:025HGA8196RRSEFQLGGNNAGH-5.17069-6.20599
HLA-A24:025HGA8196RRSEFQLGGNNAGH-4.18377-4.29717
HLA-B57:015VUD8196RRSEFQLGGNNAGH-1.89423-2.92953
HLA-B27:056PYJ8196RRSEFQLGGNNAGH-2.66447-3.69977
HLA-B27:056PYJ8196RRSEFQLGGNNAGH-2.44586-2.55926
HLA-B27:036PZ58196RRSEFQLGGNNAGH-5.44487-5.55827
HLA-B27:036PZ58196RRSEFQLGGNNAGH-3.87227-4.90757
HLA-B44:053DX88196RRSEFQLGGNNAGH-5.01764-5.13104
HLA-B44:053DX88196RRSEFQLGGNNAGH-2.6392-3.6745
HLA-B44:021M6O8196RRSEFQLGGNNAGH-6.36013-6.47353
HLA-B44:021M6O8196RRSEFQLGGNNAGH-4.88756-5.92286
HLA-B07:025EO08196RRSEFQLGGNNAGH-4.6629-4.7763
HLA-B07:025EO08196RRSEFQLGGNNAGH-4.00587-5.04117
HLA-A02:016TDR8196RRSEFQLGGNNAGH-4.04667-4.16007
HLA-A02:016TDR8196RRSEFQLGGNNAGH-1.46854-2.50384

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Vaccine Design for the FusionNeoAntigens of GNA12-ADSS

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
GNA12-ADSSchr72834561chr1244601070615RRSEFQLGGCGGAGAAGCGAGTTTCAGCTGGGAGGA
GNA12-ADSSchr72834561chr1244601070818SEFQLGGNNAAGCGAGTTTCAGCTGGGAGGAAATAATGCT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
GNA12-ADSSchr72834561chr1244601070621RRSEFQLGGNNAGHTCGGAGAAGCGAGTTTCAGCTGGGAGGAAATAATGCTGGCCATACA
GNA12-ADSSchr72834561chr1244601070722RSEFQLGGNNAGHTVAGAAGCGAGTTTCAGCTGGGAGGAAATAATGCTGGCCATACAGTT

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Information of the samples that have these potential fusion neoantigens of GNA12-ADSS

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
BRCAGNA12-ADSSchr72834561ENST00000275364chr1244601070ENST00000366535TCGA-E9-A1N6

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Potential target of CAR-T therapy development for GNA12-ADSS

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 GNA12-ADSS

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 GNA12-ADSS

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