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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:FARP1-NME1-NME2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FARP1-NME1-NME2
FusionPDB ID: 29379
FusionGDB2.0 ID: 29379
HgeneTgene
Gene symbol

FARP1

NME1-NME2

Gene ID

10160

654364

Gene nameFERM, ARH/RhoGEF and pleckstrin domain protein 1NME1-NME2 readthrough
SynonymsCDEP|FARP1-IT1|PLEKHC2|PPP1R75NM23-LV|NMELV
Cytomap

13q32.2

17q21.33

Type of geneprotein-codingprotein-coding
DescriptionFERM, ARHGEF and pleckstrin domain-containing protein 1FERM, RhoGEF (ARHGEF) and pleckstrin domain protein 1 (chondrocyte-derived)FERM, RhoGEF and pleckstrin domain-containing protein 1PH domain-containing family C member 2chondrocyte-derived ezrin-liNME1-NME2 proteinNME1-NME2 readthrough transcript
Modification date2020031320200313
UniProtAcc

Q9Y4F1

Main function of 5'-partner protein: FUNCTION: Functions as guanine nucleotide exchange factor for RAC1. May play a role in semaphorin signaling. Plays a role in the assembly and disassembly of dendritic filopodia, the formation of dendritic spines, regulation of dendrite length and ultimately the formation of synapses (By similarity). {ECO:0000250}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000319562, ENST00000376581, 
ENST00000376586, ENST00000595437, 
ENST00000593990, 
ENST00000393183, 
ENST00000393185, ENST00000393190, 
ENST00000503064, ENST00000512737, 
ENST00000513177, ENST00000514264, 
ENST00000393198, ENST00000608447, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score19 X 13 X 10=24706 X 7 X 3=126
# samples 227
** MAII scorelog2(22/2470*10)=-3.48893561294738
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/126*10)=-0.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: FARP1 [Title/Abstract] AND NME1-NME2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FARP1 [Title/Abstract] AND NME1-NME2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FARP1(98865667)-NME1-NME2(49237341), # samples:1
Anticipated loss of major functional domain due to fusion event.FARP1-NME1-NME2 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.
FARP1-NME1-NME2 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
HgeneFARP1

GO:0010923

negative regulation of phosphatase activity

19389623



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/chr13:98865667/chr17:49237341)
- 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 FARP1 (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 NME1-NME2 (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)
ENST00000595437FARP1chr1398865667-ENST00000393198NME1-NME2chr1749237341+12274102391087282
ENST00000595437FARP1chr1398865667-ENST00000608447NME1-NME2chr1749237341+12264102391087282
ENST00000376586FARP1chr1398865667-ENST00000393198NME1-NME2chr1749237341+13245073361184282
ENST00000376586FARP1chr1398865667-ENST00000608447NME1-NME2chr1749237341+13235073361184282
ENST00000319562FARP1chr1398865667-ENST00000393198NME1-NME2chr1749237341+12534362651113282
ENST00000319562FARP1chr1398865667-ENST00000608447NME1-NME2chr1749237341+12524362651113282
ENST00000376581FARP1chr1398865667-ENST00000393198NME1-NME2chr1749237341+102420736884282
ENST00000376581FARP1chr1398865667-ENST00000608447NME1-NME2chr1749237341+102320736884282

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
ENST00000595437ENST00000393198FARP1chr1398865667-NME1-NME2chr1749237341+0.0024866830.9975133
ENST00000595437ENST00000608447FARP1chr1398865667-NME1-NME2chr1749237341+0.0025401110.99745995
ENST00000376586ENST00000393198FARP1chr1398865667-NME1-NME2chr1749237341+0.0019188310.9980812
ENST00000376586ENST00000608447FARP1chr1398865667-NME1-NME2chr1749237341+0.0019446880.99805534
ENST00000319562ENST00000393198FARP1chr1398865667-NME1-NME2chr1749237341+0.0020964220.9979036
ENST00000319562ENST00000608447FARP1chr1398865667-NME1-NME2chr1749237341+0.0021253240.99787474
ENST00000376581ENST00000393198FARP1chr1398865667-NME1-NME2chr1749237341+0.0012570870.998743
ENST00000376581ENST00000608447FARP1chr1398865667-NME1-NME2chr1749237341+0.0012713840.9987286

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 FARP1-NME1-NME2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FARP1chr1398865667NME1chr1749237341207128PGTIRGDFCIQVGRTMANLERTFIAI
FARP1chr1398865667NME1chr174923734120757QMLDDTQEAFEVPASEDLLKEHYVDL
FARP1chr1398865667NME1chr1749237341410128PGTIRGDFCIQVGRTMANLERTFIAI
FARP1chr1398865667NME1chr174923734141057QMLDDTQEAFEVPASEDLLKEHYVDL
FARP1chr1398865667NME1chr1749237341436128PGTIRGDFCIQVGRTMANLERTFIAI
FARP1chr1398865667NME1chr174923734143657QMLDDTQEAFEVPASEDLLKEHYVDL
FARP1chr1398865667NME1chr1749237341507128PGTIRGDFCIQVGRTMANLERTFIAI
FARP1chr1398865667NME1chr174923734150757QMLDDTQEAFEVPASEDLLKEHYVDL

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Potential FusionNeoAntigen Information of FARP1-NME1-NME2 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.
FARP1-NME1-NME2_98865667_49237341.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)
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-B27:04GRTMANLERTF10.53841223
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C03:19FCIQVGRTM0.98920.9725716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C03:07FCIQVGRTM0.98710.9275716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C03:08FCIQVGRTM0.97920.7292716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C12:12FCIQVGRTM0.75440.8302716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C03:14FCIQVGRTM0.73380.9473716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C12:04FCIQVGRTM0.56920.9909716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C03:04FCIQVGRTM0.99490.9699716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C03:03FCIQVGRTM0.99490.9699716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C03:05FCIQVGRTM0.99280.7816716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C03:02FCIQVGRTM0.99240.9137716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C03:67FCIQVGRTM0.99140.9361716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C03:17FCIQVGRTM0.98950.9047716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C12:02FCIQVGRTM0.90220.9561716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C16:04FCIQVGRTM0.88860.971716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C16:01FCIQVGRTM0.7560.9553716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C12:03FCIQVGRTM0.72350.9652716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C03:06FCIQVGRTM0.69240.9744716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C02:10FCIQVGRTM0.50580.9639716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-C02:02FCIQVGRTM0.50580.9639716
FARP1-NME1-NME2chr1398865667chr1749237341436HLA-B27:06GRTMANLERTF0.99990.5631223

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Potential FusionNeoAntigen Information of FARP1-NME1-NME2 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 FARP1-NME1-NME2

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FARP1-NME1-NME2

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

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Vaccine Design for the FusionNeoAntigens of FARP1-NME1-NME2

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

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 FARP1-NME1-NME2

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
LGGFARP1-NME1-NME2chr1398865667ENST00000319562chr1749237341ENST00000393198TCGA-DB-5275-01A

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Potential target of CAR-T therapy development for FARP1-NME1-NME2

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 FARP1-NME1-NME2

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 FARP1-NME1-NME2

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