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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:FANCA-GRWD1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FANCA-GRWD1
FusionPDB ID: 29307
FusionGDB2.0 ID: 29307
HgeneTgene
Gene symbol

FANCA

GRWD1

Gene ID

2175

83743

Gene nameFA complementation group Aglutamate rich WD repeat containing 1
SynonymsFA|FA-H|FA1|FAA|FACA|FAH|FANCHCDW4|GRWD|RRB1|WDR28
Cytomap

16q24.3

19q13.33

Type of geneprotein-codingprotein-coding
DescriptionFanconi anemia group A proteinFanconi anemia complementation group AFanconi anemia, complementation group HFanconi anemia, type 1glutamate-rich WD repeat-containing protein 1CUL4- and DDB1-associated WDR protein 4WD repeat domain 28glutamate rich WD repeat protein GRWDregulator of ribosome biogenesis 1 homolog
Modification date2020031320200329
UniProtAcc

O15360

Main function of 5'-partner protein: FUNCTION: DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be involved in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability.

Q9BQ67

Main function of 5'-partner protein: FUNCTION: Histone binding-protein that regulates chromatin dynamics and minichromosome maintenance (MCM) loading at replication origins, possibly by promoting chromatin openness (PubMed:25990725). {ECO:0000269|PubMed:25990725}.
Ensembl transtripts involved in fusion geneENST idsENST00000389301, ENST00000389302, 
ENST00000534992, ENST00000563673, 
ENST00000568369, ENST00000543736, 
ENST00000567284, 
ENST00000253237, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 12 X 5=7804 X 5 X 3=60
# samples 134
** MAII scorelog2(13/780*10)=-2.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/60*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: FANCA [Title/Abstract] AND GRWD1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FANCA [Title/Abstract] AND GRWD1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FANCA(89877114)-GRWD1(48953569), # samples:1
Anticipated loss of major functional domain due to fusion event.FANCA-GRWD1 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.
FANCA-GRWD1 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.
FANCA-GRWD1 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.
FANCA-GRWD1 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
TgeneGRWD1

GO:0006334

nucleosome assembly

25990725



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/chr16:89877114/chr19:48953569)
- 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 FANCA (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 GRWD1 (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)
ENST00000389301FANCAchr1689877114-ENST00000253237GRWD1chr1948953569+5423553311425464
ENST00000568369FANCAchr1689877114-ENST00000253237GRWD1chr1948953569+5423553311425464
ENST00000389302FANCAchr1689877114-ENST00000253237GRWD1chr1948953569+5434564421436464
ENST00000563673FANCAchr1689877114-ENST00000253237GRWD1chr1948953569+5412542201414464
ENST00000534992FANCAchr1689877114-ENST00000253237GRWD1chr1948953569+5432562401434464

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
ENST00000389301ENST00000253237FANCAchr1689877114-GRWD1chr1948953569+0.029463370.9705366
ENST00000568369ENST00000253237FANCAchr1689877114-GRWD1chr1948953569+0.029463370.9705366
ENST00000389302ENST00000253237FANCAchr1689877114-GRWD1chr1948953569+0.0296871120.9703129
ENST00000563673ENST00000253237FANCAchr1689877114-GRWD1chr1948953569+0.0299573860.9700426
ENST00000534992ENST00000253237FANCAchr1689877114-GRWD1chr1948953569+0.0296759740.970324

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 FANCA-GRWD1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FANCAchr1689877114GRWD1chr1948953569542173FSRLSFCQELWKIQVSWLGEEPVAGV
FANCAchr1689877114GRWD1chr1948953569553173FSRLSFCQELWKIQVSWLGEEPVAGV
FANCAchr1689877114GRWD1chr1948953569562173FSRLSFCQELWKIQVSWLGEEPVAGV
FANCAchr1689877114GRWD1chr1948953569564173FSRLSFCQELWKIQVSWLGEEPVAGV

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Potential FusionNeoAntigen Information of FANCA-GRWD1 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.
FANCA-GRWD1_89877114_48953569.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)
FANCA-GRWD1chr1689877114chr1948953569553HLA-B45:01QELWKIQVS0.99330.913716
FANCA-GRWD1chr1689877114chr1948953569553HLA-B50:02QELWKIQVS0.98020.7466716
FANCA-GRWD1chr1689877114chr1948953569553HLA-B57:01ELWKIQVSW0.96420.9874817
FANCA-GRWD1chr1689877114chr1948953569553HLA-A31:08ELWKIQVSW0.91710.5888817
FANCA-GRWD1chr1689877114chr1948953569553HLA-A32:13ELWKIQVSW0.89840.9915817
FANCA-GRWD1chr1689877114chr1948953569553HLA-B58:02ELWKIQVSW0.88310.9609817
FANCA-GRWD1chr1689877114chr1948953569553HLA-B58:01ELWKIQVSW0.85490.9679817
FANCA-GRWD1chr1689877114chr1948953569553HLA-B53:01ELWKIQVSW0.76240.5563817
FANCA-GRWD1chr1689877114chr1948953569553HLA-B50:01QELWKIQVS0.25140.7215716
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:03QELWKIQVSW0.99930.9671717
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:02QELWKIQVSW0.9990.7691717
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:05QELWKIQVSW0.99710.8176717
FANCA-GRWD1chr1689877114chr1948953569553HLA-A32:13QELWKIQVSW0.86150.9669717
FANCA-GRWD1chr1689877114chr1948953569553HLA-B40:06QELWKIQV0.99990.8347715
FANCA-GRWD1chr1689877114chr1948953569553HLA-B40:06QELWKIQVS0.99170.7528716
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:08ELWKIQVSW0.41560.7219817
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:04QELWKIQVSW0.99860.6015717
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:09QELWKIQVSW0.99780.805717
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:08QELWKIQVSW0.99760.7861717
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:10QELWKIQVSW0.87640.9666717
FANCA-GRWD1chr1689877114chr1948953569553HLA-B57:10ELWKIQVSW0.96420.9874817
FANCA-GRWD1chr1689877114chr1948953569553HLA-A32:01ELWKIQVSW0.8640.9762817
FANCA-GRWD1chr1689877114chr1948953569553HLA-A25:01ELWKIQVSW0.85370.9115817
FANCA-GRWD1chr1689877114chr1948953569553HLA-B15:13ELWKIQVSW0.82470.8318817
FANCA-GRWD1chr1689877114chr1948953569553HLA-B15:24ELWKIQVSW0.67960.9514817
FANCA-GRWD1chr1689877114chr1948953569553HLA-B53:02ELWKIQVSW0.59260.5717817
FANCA-GRWD1chr1689877114chr1948953569553HLA-B50:04QELWKIQVS0.25140.7215716
FANCA-GRWD1chr1689877114chr1948953569553HLA-B50:05QELWKIQVS0.25140.7215716
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:26QELWKIQVSW0.99930.9671717
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:13QELWKIQVSW0.99930.9671717
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:07QELWKIQVSW0.99930.9671717
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:22QELWKIQVSW0.9990.7691717
FANCA-GRWD1chr1689877114chr1948953569553HLA-B44:21QELWKIQVSW0.99410.6307717
FANCA-GRWD1chr1689877114chr1948953569553HLA-A32:01QELWKIQVSW0.89850.9551717

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Potential FusionNeoAntigen Information of FANCA-GRWD1 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.
FANCA-GRWD1_89877114_48953569.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)
FANCA-GRWD1chr1689877114chr1948953569553DRB1-1503KIQVSWLGEEPVAGV1126
FANCA-GRWD1chr1689877114chr1948953569553DRB1-1523KIQVSWLGEEPVAGV1126
FANCA-GRWD1chr1689877114chr1948953569553DRB1-1523WKIQVSWLGEEPVAG1025

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Fusion breakpoint peptide structures of FANCA-GRWD1

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
907CQELWKIQVSWLGEFANCAGRWD1chr1689877114chr1948953569553

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FANCA-GRWD1

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-B14:023BVN907CQELWKIQVSWLGE-6.21704-6.40714
HLA-B14:023BVN907CQELWKIQVSWLGE-6.10956-6.87556
HLA-B52:013W39907CQELWKIQVSWLGE-6.22589-6.41599
HLA-B52:013W39907CQELWKIQVSWLGE-3.60797-4.37397
HLA-A11:014UQ2907CQELWKIQVSWLGE-8.83727-9.60327
HLA-A24:025HGA907CQELWKIQVSWLGE-8.49982-8.68992
HLA-A24:025HGA907CQELWKIQVSWLGE-5.16998-5.93598
HLA-B44:053DX8907CQELWKIQVSWLGE-5.64434-5.83444
HLA-B44:053DX8907CQELWKIQVSWLGE-5.27233-6.03833
HLA-A02:016TDR907CQELWKIQVSWLGE-7.61076-7.80086

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Vaccine Design for the FusionNeoAntigens of FANCA-GRWD1

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
FANCA-GRWD1chr1689877114chr1948953569715QELWKIQVGAATTATGGAAAATACAGGTGTCA
FANCA-GRWD1chr1689877114chr1948953569716QELWKIQVSGAATTATGGAAAATACAGGTGTCATGG
FANCA-GRWD1chr1689877114chr1948953569717QELWKIQVSWGAATTATGGAAAATACAGGTGTCATGGCTG
FANCA-GRWD1chr1689877114chr1948953569817ELWKIQVSWTTATGGAAAATACAGGTGTCATGGCTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
FANCA-GRWD1chr1689877114chr19489535691025WKIQVSWLGEEPVAGAAAATACAGGTGTCATGGCTGGGTGAAGAGCCTGTGGCTGGGGTG
FANCA-GRWD1chr1689877114chr19489535691126KIQVSWLGEEPVAGVATACAGGTGTCATGGCTGGGTGAAGAGCCTGTGGCTGGGGTGTGG

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Information of the samples that have these potential fusion neoantigens of FANCA-GRWD1

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
STADFANCA-GRWD1chr1689877114ENST00000389301chr1948953569ENST00000253237TCGA-BR-A4J9

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Potential target of CAR-T therapy development for FANCA-GRWD1

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 FANCA-GRWD1

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 FANCA-GRWD1

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