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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:SLC25A12-ITGA6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SLC25A12-ITGA6
FusionPDB ID: 82541
FusionGDB2.0 ID: 82541
HgeneTgene
Gene symbol

SLC25A12

ITGA6

Gene ID

8604

3655

Gene namesolute carrier family 25 member 12integrin subunit alpha 6
SynonymsAGC1|ARALAR|EIEE39CD49f|ITGA6B|VLA-6
Cytomap

2q31.1

2q31.1

Type of geneprotein-codingprotein-coding
Descriptioncalcium-binding mitochondrial carrier protein Aralar1araceli hiperlargacalcium binding mitochondrial carrier superfamily member Aralar1mitochondrial aspartate glutamate carrier 1solute carrier family 25 (aspartate/glutamate carrier), member 12solute integrin alpha-6CD49 antigen-like family member Fintegrin alpha6Bintegrin, alpha 6
Modification date2020031320200329
UniProtAcc.

P23229

Main function of 5'-partner protein: FUNCTION: Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets (By similarity). Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (By similarity). Integrin alpha-6/beta-4 (ITGA6:ITGB4) is a receptor for laminin in epithelial cells and it plays a critical structural role in the hemidesmosome (By similarity). ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). {ECO:0000250|UniProtKB:Q61739, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}.
Ensembl transtripts involved in fusion geneENST idsENST00000392592, ENST00000472748, 
ENST00000422440, 
ENST00000264106, 
ENST00000264107, ENST00000343713, 
ENST00000375221, ENST00000409080, 
ENST00000409532, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 10 X 6=6603 X 3 X 2=18
# samples 123
** MAII scorelog2(12/660*10)=-2.4594316186373
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: SLC25A12 [Title/Abstract] AND ITGA6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SLC25A12 [Title/Abstract] AND ITGA6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SLC25A12(172749714)-ITGA6(173333852), # samples:1
Anticipated loss of major functional domain due to fusion event.SLC25A12-ITGA6 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.
SLC25A12-ITGA6 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.
SLC25A12-ITGA6 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.
SLC25A12-ITGA6 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
HgeneSLC25A12

GO:0015810

aspartate transmembrane transport

11566871

HgeneSLC25A12

GO:0015813

L-glutamate transmembrane transport

11566871

HgeneSLC25A12

GO:0043490

malate-aspartate shuttle

11566871

HgeneSLC25A12

GO:0051592

response to calcium ion

11566871



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/chr2:172749714/chr2:173333852)
- 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 SLC25A12 (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 ITGA6 (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)
ENST00000422440SLC25A12chr2172749714-ENST00000409532ITGA6chr2173333852+3390104382923961
ENST00000422440SLC25A12chr2172749714-ENST00000264107ITGA6chr2173333852+5101104382938966
ENST00000422440SLC25A12chr2172749714-ENST00000343713ITGA6chr2173333852+5309104382923961
ENST00000422440SLC25A12chr2172749714-ENST00000264106ITGA6chr2173333852+53111043831091023
ENST00000422440SLC25A12chr2172749714-ENST00000375221ITGA6chr2173333852+54411043830551005
ENST00000422440SLC25A12chr2172749714-ENST00000409080ITGA6chr2173333852+5015104382992984

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
ENST00000422440ENST00000409532SLC25A12chr2172749714-ITGA6chr2173333852+8.55E-050.9999144
ENST00000422440ENST00000264107SLC25A12chr2172749714-ITGA6chr2173333852+5.95E-050.9999405
ENST00000422440ENST00000343713SLC25A12chr2172749714-ITGA6chr2173333852+3.52E-050.9999647
ENST00000422440ENST00000264106SLC25A12chr2172749714-ITGA6chr2173333852+0.0001124920.99988747
ENST00000422440ENST00000375221SLC25A12chr2172749714-ITGA6chr2173333852+3.67E-050.9999633
ENST00000422440ENST00000409080SLC25A12chr2172749714-ITGA6chr2173333852+5.97E-050.9999403

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 SLC25A12-ITGA6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SLC25A12chr2172749714ITGA6chr217333385210418QTTKRGDPHELRNIFLQTCAHRYEKR

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Potential FusionNeoAntigen Information of SLC25A12-ITGA6 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.
SLC25A12-ITGA6_172749714_173333852.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)
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B39:13HELRNIFL0.9760.8808816
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:01DPHELRNIF0.98370.7927615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:08DPHELRNIF0.96130.7137615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:03DPHELRNIF0.89210.8244615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:05DPHELRNIF0.86780.545615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:04DPHELRNIF0.5890.8384615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:02DPHELRNIF0.5890.8384615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B73:01LRNIFLQTC0.97990.92621019
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B42:02DPHELRNIF0.85050.5151615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:12DPHELRNIF0.5890.8384615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B39:10DPHELRNIF0.1530.826615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B07:12GDPHELRNIF0.77320.5621515
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B07:12RGDPHELRNIF0.97660.5514415
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B42:02RGDPHELRNIF0.96330.6667415
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B42:01RGDPHELRNIF0.93450.6594415
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B40:04HELRNIFL0.99950.5198816
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B41:03HELRNIFL0.98890.5398816
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:77DPHELRNIF0.98370.7927615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:23DPHELRNIF0.98040.7683615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:24DPHELRNIF0.97580.7829615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:17DPHELRNIF0.880.7138615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:30DPHELRNIF0.880.7138615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:11DPHELRNIF0.79980.7508615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B18:04DPHELRNIF0.71990.8814615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:09DPHELRNIF0.5890.8384615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B18:07DPHELRNIF0.55560.7858615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B18:03DPHELRNIF0.44850.8449615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B08:12DPHELRNIF0.38160.6321615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B67:01DPHELRNIF0.21020.7336615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B35:43DPHELRNIF0.05930.6876615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B15:08DPHELRNIF0.05780.6851615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B15:11DPHELRNIF0.05140.6859615
SLC25A12-ITGA6chr2172749714chr2173333852104HLA-B55:04RGDPHELRNIF0.96450.6024415

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Potential FusionNeoAntigen Information of SLC25A12-ITGA6 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 SLC25A12-ITGA6

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
1307DPHELRNIFLQTCASLC25A12ITGA6chr2172749714chr2173333852104

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SLC25A12-ITGA6

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-B14:023BVN1307DPHELRNIFLQTCA-7.15543-7.26883
HLA-B14:023BVN1307DPHELRNIFLQTCA-4.77435-5.80965
HLA-B52:013W391307DPHELRNIFLQTCA-6.80875-6.92215
HLA-B52:013W391307DPHELRNIFLQTCA-4.20386-5.23916
HLA-A11:014UQ21307DPHELRNIFLQTCA-7.5194-8.5547
HLA-A11:014UQ21307DPHELRNIFLQTCA-6.9601-7.0735
HLA-A24:025HGA1307DPHELRNIFLQTCA-7.52403-7.63743
HLA-A24:025HGA1307DPHELRNIFLQTCA-5.82433-6.85963
HLA-B27:056PYJ1307DPHELRNIFLQTCA-3.28285-4.31815
HLA-B44:053DX81307DPHELRNIFLQTCA-5.91172-6.94702
HLA-B44:053DX81307DPHELRNIFLQTCA-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of SLC25A12-ITGA6

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
SLC25A12-ITGA6chr2172749714chr21733338521019LRNIFLQTCTTTCTACAGACATGTGCTCACCGATAT
SLC25A12-ITGA6chr2172749714chr2173333852415RGDPHELRNIFCATGAGTTAAGAAACATATTTCTACAGACATGT
SLC25A12-ITGA6chr2172749714chr2173333852515GDPHELRNIFGAGTTAAGAAACATATTTCTACAGACATGT
SLC25A12-ITGA6chr2172749714chr2173333852615DPHELRNIFTTAAGAAACATATTTCTACAGACATGT
SLC25A12-ITGA6chr2172749714chr2173333852816HELRNIFLAACATATTTCTACAGACATGTGCT

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 SLC25A12-ITGA6

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
Non-CancerSLC25A12-ITGA6chr2172749714ENST00000422440chr2173333852ENST00000264106271N

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Potential target of CAR-T therapy development for SLC25A12-ITGA6

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
TgeneITGA6chr2:172749714chr2:173333852ENST000002641062261051_107601131.0TransmembraneHelical
TgeneITGA6chr2:172749714chr2:173333852ENST000002641072261051_107601648.6666666666667TransmembraneHelical
TgeneITGA6chr2:172749714chr2:173333852ENST000003437132261051_107601728.3333333333333TransmembraneHelical
TgeneITGA6chr2:172749714chr2:173333852ENST000003752212271051_107601772.3333333333333TransmembraneHelical
TgeneITGA6chr2:172749714chr2:173333852ENST000004090802251051_107601092.0TransmembraneHelical
TgeneITGA6chr2:172749714chr2:173333852ENST000004095322261051_107601085.3333333333333TransmembraneHelical

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 SLC25A12-ITGA6

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 SLC25A12-ITGA6

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