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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:FAM65C-ZNF335

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FAM65C-ZNF335
FusionPDB ID: 29157
FusionGDB2.0 ID: 29157
HgeneTgene
Gene symbol

FAM65C

ZNF335

Gene ID

140876

63925

Gene nameRIPOR family member 3zinc finger protein 335
SynonymsC20orf175|C20orf176|FAM65CMCPH10|NIF-1|NIF1|NIF2
Cytomap

20q13.13

20q13.12

Type of geneprotein-codingprotein-coding
DescriptionRIPOR family member 3family with sequence similarity 65 member Cprotein FAM65Czinc finger protein 335NRC-interacting factor 1zinc-finger/leucine-zipper co-transducer NIF1
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000045083, ENST00000327979, 
ENST00000535356, ENST00000462842, 
ENST00000494955, ENST00000322927, 
ENST00000426788, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 4=1442 X 2 X 2=8
# samples 62
** MAII scorelog2(6/144*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: FAM65C [Title/Abstract] AND ZNF335 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FAM65C [Title/Abstract] AND ZNF335 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FAM65C(49221182)-ZNF335(44579234), # samples:2
Anticipated loss of major functional domain due to fusion event.FAM65C-ZNF335 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.
FAM65C-ZNF335 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.
FAM65C-ZNF335 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.
FAM65C-ZNF335 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.
FAM65C-ZNF335 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
FAM65C-ZNF335 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
FAM65C-ZNF335 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted 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


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/chr20:49221182/chr20:44579234)
- 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 FAM65C (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 ZNF335 (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)
ENST00000535356FAM65Cchr2049221182-ENST00000322927ZNF335chr2044579234-24771337982176692
ENST00000535356FAM65Cchr2049221182-ENST00000426788ZNF335chr2044579234-24761337982176692
ENST00000045083FAM65Cchr2049221182-ENST00000322927ZNF335chr2044579234-253213922882231647
ENST00000045083FAM65Cchr2049221182-ENST00000426788ZNF335chr2044579234-253113922882231647

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
ENST00000535356ENST00000322927FAM65Cchr2049221182-ZNF335chr2044579234-0.0304325190.96956754
ENST00000535356ENST00000426788FAM65Cchr2049221182-ZNF335chr2044579234-0.0306568430.9693431
ENST00000045083ENST00000322927FAM65Cchr2049221182-ZNF335chr2044579234-0.0157298370.98427016
ENST00000045083ENST00000426788FAM65Cchr2049221182-ZNF335chr2044579234-0.0159264820.9840735

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 FAM65C-ZNF335

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FAM65Cchr2049221182ZNF335chr20445792341337413PPSTPSFRERYYLAHMAQHSSLRPHQ
FAM65Cchr2049221182ZNF335chr20445792341392368PPSTPSFRERYYLAHMAQHSSLRPHQ

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Potential FusionNeoAntigen Information of FAM65C-ZNF335 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.
FAM65C-ZNF335_49221182_44579234.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)
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B39:06ERYYLAHMA0.98760.6917817
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B39:24LAHMAQHSSL0.96820.63761222
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B15:10LAHMAQHSSL0.96040.52771222
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B15:37LAHMAQHSSL0.94860.53791222
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B39:01LAHMAQHSSL0.85020.94621222
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B50:01RERYYLAHMA0.23420.7006717
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B07:10YLAHMAQHSSL0.98750.56021122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B39:24YLAHMAQHSSL0.96740.731122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B15:10YLAHMAQHSSL0.81790.5321122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B39:01YLAHMAQHSSL0.80260.97521122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B38:01YLAHMAQHSSL0.67830.98781122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B38:02YLAHMAQHSSL0.67320.98981122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B15:37YLAHMAQHSSL0.66190.50161122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B27:14ERYYLAHMA0.99770.6813817
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B73:01ERYYLAHMA0.99360.5551817
FAM65C-ZNF335chr2049221182chr20445792341392HLA-C07:67YYLAHMAQH0.17280.98951019
FAM65C-ZNF335chr2049221182chr20445792341392HLA-C07:80YYLAHMAQH0.17280.98951019
FAM65C-ZNF335chr2049221182chr20445792341392HLA-C07:46YYLAHMAQH0.16060.97911019
FAM65C-ZNF335chr2049221182chr20445792341392HLA-C07:10YYLAHMAQH0.10840.98981019
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B40:06RERYYLAHMA0.96610.632717
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B73:01RERYYLAHMA0.85850.5394717
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B27:14RERYYLAHMA0.84960.7566717
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B39:05LAHMAQHSSL0.56820.93891222
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B39:09YLAHMAQHSSL0.83660.89481122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B39:12YLAHMAQHSSL0.83540.97641122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B39:05YLAHMAQHSSL0.65740.96861122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B15:53RERYYLAHM0.46620.8239716
FAM65C-ZNF335chr2049221182chr20445792341392HLA-C07:02YYLAHMAQH0.17280.98951019
FAM65C-ZNF335chr2049221182chr20445792341392HLA-C07:17YYLAHMAQH0.08750.99131019
FAM65C-ZNF335chr2049221182chr20445792341392HLA-C14:02YYLAHMAQH0.00140.98731019
FAM65C-ZNF335chr2049221182chr20445792341392HLA-C14:03YYLAHMAQH0.00140.98731019
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B15:09LAHMAQHSSL0.72630.74871222
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B50:05RERYYLAHMA0.23420.7006717
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B50:04RERYYLAHMA0.23420.7006717
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B39:31YLAHMAQHSSL0.82980.97531122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B39:11YLAHMAQHSSL0.81720.94381122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B15:09YLAHMAQHSSL0.69930.74031122
FAM65C-ZNF335chr2049221182chr20445792341392HLA-B38:05YLAHMAQHSSL0.67830.98781122

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Potential FusionNeoAntigen Information of FAM65C-ZNF335 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.
FAM65C-ZNF335_49221182_44579234.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)
FAM65C-ZNF335chr2049221182chr20445792341392DRB1-0103ERYYLAHMAQHSSLR823
FAM65C-ZNF335chr2049221182chr20445792341392DRB1-0103RERYYLAHMAQHSSL722
FAM65C-ZNF335chr2049221182chr20445792341392DRB1-0103FRERYYLAHMAQHSS621
FAM65C-ZNF335chr2049221182chr20445792341392DRB1-0902FRERYYLAHMAQHSS621
FAM65C-ZNF335chr2049221182chr20445792341392DRB1-1367ERYYLAHMAQHSSLR823
FAM65C-ZNF335chr2049221182chr20445792341392DRB1-1367RERYYLAHMAQHSSL722

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Fusion breakpoint peptide structures of FAM65C-ZNF335

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
2542FRERYYLAHMAQHSFAM65CZNF335chr2049221182chr20445792341392

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FAM65C-ZNF335

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-B14:023BVN2542FRERYYLAHMAQHS-7.15543-7.26883
HLA-B14:023BVN2542FRERYYLAHMAQHS-4.77435-5.80965
HLA-B52:013W392542FRERYYLAHMAQHS-6.80875-6.92215
HLA-B52:013W392542FRERYYLAHMAQHS-4.20386-5.23916
HLA-A11:014UQ22542FRERYYLAHMAQHS-7.5194-8.5547
HLA-A11:014UQ22542FRERYYLAHMAQHS-6.9601-7.0735
HLA-A24:025HGA2542FRERYYLAHMAQHS-7.52403-7.63743
HLA-A24:025HGA2542FRERYYLAHMAQHS-5.82433-6.85963
HLA-B27:056PYJ2542FRERYYLAHMAQHS-3.28285-4.31815
HLA-B44:053DX82542FRERYYLAHMAQHS-5.91172-6.94702
HLA-B44:053DX82542FRERYYLAHMAQHS-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of FAM65C-ZNF335

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
FAM65C-ZNF335chr2049221182chr20445792341019YYLAHMAQHTACTACCTGGCGCACATGGCACAGCAC
FAM65C-ZNF335chr2049221182chr20445792341122YLAHMAQHSSLTACCTGGCGCACATGGCACAGCACTCAAGCCTA
FAM65C-ZNF335chr2049221182chr20445792341222LAHMAQHSSLCTGGCGCACATGGCACAGCACTCAAGCCTA
FAM65C-ZNF335chr2049221182chr2044579234716RERYYLAHMCGGGAGAGATACTACCTGGCGCACATG
FAM65C-ZNF335chr2049221182chr2044579234717RERYYLAHMACGGGAGAGATACTACCTGGCGCACATGGCA
FAM65C-ZNF335chr2049221182chr2044579234817ERYYLAHMAGAGAGATACTACCTGGCGCACATGGCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
FAM65C-ZNF335chr2049221182chr2044579234621FRERYYLAHMAQHSSTTCCGGGAGAGATACTACCTGGCGCACATGGCACAGCACTCAAGC
FAM65C-ZNF335chr2049221182chr2044579234722RERYYLAHMAQHSSLCGGGAGAGATACTACCTGGCGCACATGGCACAGCACTCAAGCCTA
FAM65C-ZNF335chr2049221182chr2044579234823ERYYLAHMAQHSSLRGAGAGATACTACCTGGCGCACATGGCACAGCACTCAAGCCTACGG

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Information of the samples that have these potential fusion neoantigens of FAM65C-ZNF335

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
BRCAFAM65C-ZNF335chr2049221182ENST00000045083chr2044579234ENST00000322927TCGA-E2-A105-01A

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Potential target of CAR-T therapy development for FAM65C-ZNF335

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 FAM65C-ZNF335

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 FAM65C-ZNF335

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