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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:FKTN-ULK4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FKTN-ULK4
FusionPDB ID: 30551
FusionGDB2.0 ID: 30551
HgeneTgene
Gene symbol

FKTN

ULK4

Gene ID

2218

54986

Gene namefukutinunc-51 like kinase 4
SynonymsCMD1X|FCMD|LGMD2M|LGMDR13|MDDGA4|MDDGB4|MDDGC4FAM7C1|REC01035
Cytomap

9q31.2

3p22.1

Type of geneprotein-codingprotein-coding
DescriptionfukutinFukuyama type congenital muscular dystrophy proteinpatient fukutinribitol-5-phosphate transferaseserine/threonine-protein kinase ULK4
Modification date2020032820200313
UniProtAcc

O75072

Main function of 5'-partner protein: FUNCTION: Catalyzes the transfer of CDP-ribitol to the distal N-acetylgalactosamine of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1) (PubMed:17034757, PubMed:25279699, PubMed:26923585, PubMed:29477842). This constitutes the first step in the formation of the ribitol 5-phosphate tandem repeat which links the phosphorylated O-mannosyl trisaccharide to the ligand binding moiety composed of repeats of 3-xylosyl-alpha-1,3-glucuronic acid-beta-1 (PubMed:17034757, PubMed:25279699, PubMed:26923585, PubMed:29477842). Required for normal location of POMGNT1 in Golgi membranes, and for normal POMGNT1 activity (PubMed:17034757). May interact with and reinforce a large complex encompassing the outside and inside of muscle membranes (PubMed:25279699). Could be involved in brain development (Probable). {ECO:0000269|PubMed:17034757, ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:26923585, ECO:0000269|PubMed:29477842, ECO:0000305|PubMed:11115853}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000490134, ENST00000223528, 
ENST00000357998, ENST00000448551, 
ENST00000540160, ENST00000602661, 
ENST00000301831, ENST00000414606, 
ENST00000420927, ENST00000489118, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 3=2714 X 21 X 5=1470
# samples 318
** MAII scorelog2(3/27*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(18/1470*10)=-3.02974734339405
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: FKTN [Title/Abstract] AND ULK4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FKTN [Title/Abstract] AND ULK4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FKTN(108358938)-ULK4(41795980), # samples:1
Anticipated loss of major functional domain due to fusion event.FKTN-ULK4 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.
FKTN-ULK4 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.
FKTN-ULK4 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.
FKTN-ULK4 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


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/chr9:108358938/chr3:41795980)
- 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 FKTN (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 ULK4 (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)
ENST00000602661FKTNchr9108358938-ENST00000301831ULK4chr341795980-23383812162015599
ENST00000223528FKTNchr9108358938-ENST00000301831ULK4chr341795980-22462891241923599
ENST00000540160FKTNchr9108358938-ENST00000301831ULK4chr341795980-22442871221921599
ENST00000448551FKTNchr9108358938-ENST00000301831ULK4chr341795980-23363792142013599
ENST00000357998FKTNchr9108358938-ENST00000301831ULK4chr341795980-22382811161915599

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
ENST00000602661ENST00000301831FKTNchr9108358938-ULK4chr341795980-0.0039058120.99609417
ENST00000223528ENST00000301831FKTNchr9108358938-ULK4chr341795980-0.0050594420.99494064
ENST00000540160ENST00000301831FKTNchr9108358938-ULK4chr341795980-0.0051960780.99480385
ENST00000448551ENST00000301831FKTNchr9108358938-ULK4chr341795980-0.0040169150.9959831
ENST00000357998ENST00000301831FKTNchr9108358938-ULK4chr341795980-0.0042237970.99577624

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 FKTN-ULK4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FKTNchr9108358938ULK4chr34179598028155SKGSRIGFDSTQWGFVSTIIRLLDSP
FKTNchr9108358938ULK4chr34179598028755SKGSRIGFDSTQWGFVSTIIRLLDSP
FKTNchr9108358938ULK4chr34179598028955SKGSRIGFDSTQWGFVSTIIRLLDSP
FKTNchr9108358938ULK4chr34179598037955SKGSRIGFDSTQWGFVSTIIRLLDSP
FKTNchr9108358938ULK4chr34179598038155SKGSRIGFDSTQWGFVSTIIRLLDSP

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Potential FusionNeoAntigen Information of FKTN-ULK4 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.
FKTN-ULK4_108358938_41795980.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)
FKTN-ULK4chr9108358938chr341795980289HLA-B48:01TQWGFVSTI0.98970.81881019
FKTN-ULK4chr9108358938chr341795980289HLA-B39:06TQWGFVSTI0.98740.80951019
FKTN-ULK4chr9108358938chr341795980289HLA-B39:24TQWGFVSTI0.98160.57011019
FKTN-ULK4chr9108358938chr341795980289HLA-A24:23GFDSTQWGF0.96940.5573615
FKTN-ULK4chr9108358938chr341795980289HLA-A24:15GFDSTQWGF0.96070.6534615
FKTN-ULK4chr9108358938chr341795980289HLA-A02:21TQWGFVSTI0.95820.6611019
FKTN-ULK4chr9108358938chr341795980289HLA-A24:31GFDSTQWGF0.94680.6371615
FKTN-ULK4chr9108358938chr341795980289HLA-A02:11TQWGFVSTI0.94440.56211019
FKTN-ULK4chr9108358938chr341795980289HLA-A02:30TQWGFVSTI0.94120.5281019
FKTN-ULK4chr9108358938chr341795980289HLA-A02:67TQWGFVSTI0.94120.5281019
FKTN-ULK4chr9108358938chr341795980289HLA-A02:24TQWGFVSTI0.94120.5281019
FKTN-ULK4chr9108358938chr341795980289HLA-B13:02TQWGFVSTI0.94010.88451019
FKTN-ULK4chr9108358938chr341795980289HLA-A02:04TQWGFVSTI0.93840.66661019
FKTN-ULK4chr9108358938chr341795980289HLA-A02:17TQWGFVSTI0.93340.50021019
FKTN-ULK4chr9108358938chr341795980289HLA-A24:10GFDSTQWGF0.91760.565615
FKTN-ULK4chr9108358938chr341795980289HLA-A24:17GFDSTQWGF0.90670.6111615
FKTN-ULK4chr9108358938chr341795980289HLA-B39:01TQWGFVSTI0.88710.92191019
FKTN-ULK4chr9108358938chr341795980289HLA-A31:08GFDSTQWGF0.84260.5168615
FKTN-ULK4chr9108358938chr341795980289HLA-A02:29TQWGFVSTI0.84170.53961019
FKTN-ULK4chr9108358938chr341795980289HLA-B39:13TQWGFVSTI0.82970.96321019
FKTN-ULK4chr9108358938chr341795980289HLA-B13:01TQWGFVSTI0.82030.99121019
FKTN-ULK4chr9108358938chr341795980289HLA-A32:13TQWGFVSTI0.81280.94491019
FKTN-ULK4chr9108358938chr341795980289HLA-A02:35TQWGFVSTI0.81270.56571019
FKTN-ULK4chr9108358938chr341795980289HLA-A02:20TQWGFVSTI0.80370.53321019
FKTN-ULK4chr9108358938chr341795980289HLA-B38:01TQWGFVSTI0.76440.97481019
FKTN-ULK4chr9108358938chr341795980289HLA-A24:14GFDSTQWGF0.650.6703615
FKTN-ULK4chr9108358938chr341795980289HLA-B52:01TQWGFVSTI0.47960.99041019
FKTN-ULK4chr9108358938chr341795980289HLA-B13:02TQWGFVSTII0.75660.84761020
FKTN-ULK4chr9108358938chr341795980289HLA-B13:02STQWGFVSTI0.60580.8255919
FKTN-ULK4chr9108358938chr341795980289HLA-B15:04TQWGFVSTI0.96050.97221019
FKTN-ULK4chr9108358938chr341795980289HLA-C04:10GFDSTQWGF0.95440.8777615
FKTN-ULK4chr9108358938chr341795980289HLA-C04:07GFDSTQWGF0.95010.8762615
FKTN-ULK4chr9108358938chr341795980289HLA-A02:01TQWGFVSTI0.94120.5281019
FKTN-ULK4chr9108358938chr341795980289HLA-B39:09TQWGFVSTI0.89310.68721019
FKTN-ULK4chr9108358938chr341795980289HLA-B48:03TQWGFVSTI0.84380.63811019
FKTN-ULK4chr9108358938chr341795980289HLA-C02:06TQWGFVSTI0.62470.97371019
FKTN-ULK4chr9108358938chr341795980289HLA-B51:07TQWGFVSTI0.33730.98651019
FKTN-ULK4chr9108358938chr341795980289HLA-C04:14GFDSTQWGF0.32820.8628615
FKTN-ULK4chr9108358938chr341795980289HLA-C04:07IGFDSTQWGF0.99950.8734515
FKTN-ULK4chr9108358938chr341795980289HLA-C04:10IGFDSTQWGF0.99950.8882515
FKTN-ULK4chr9108358938chr341795980289HLA-B15:73TQWGFVSTI0.97510.93941019
FKTN-ULK4chr9108358938chr341795980289HLA-A24:03GFDSTQWGF0.96940.5573615
FKTN-ULK4chr9108358938chr341795980289HLA-A32:01TQWGFVSTI0.96730.9621019
FKTN-ULK4chr9108358938chr341795980289HLA-C18:01GFDSTQWGF0.96210.8861615
FKTN-ULK4chr9108358938chr341795980289HLA-A02:14TQWGFVSTI0.96030.53331019
FKTN-ULK4chr9108358938chr341795980289HLA-A02:06TQWGFVSTI0.95820.6611019
FKTN-ULK4chr9108358938chr341795980289HLA-B15:30TQWGFVSTI0.9550.891019
FKTN-ULK4chr9108358938chr341795980289HLA-C04:01GFDSTQWGF0.95010.8762615
FKTN-ULK4chr9108358938chr341795980289HLA-B39:02TQWGFVSTI0.93330.95881019
FKTN-ULK4chr9108358938chr341795980289HLA-B40:12TQWGFVSTI0.84380.63811019
FKTN-ULK4chr9108358938chr341795980289HLA-B40:49TQWGFVSTI0.78480.60351019
FKTN-ULK4chr9108358938chr341795980289HLA-B38:05TQWGFVSTI0.76440.97481019
FKTN-ULK4chr9108358938chr341795980289HLA-B40:21TQWGFVSTI0.75350.671019
FKTN-ULK4chr9108358938chr341795980289HLA-C06:08TQWGFVSTI0.73710.98951019
FKTN-ULK4chr9108358938chr341795980289HLA-C04:04GFDSTQWGF0.19680.8707615
FKTN-ULK4chr9108358938chr341795980289HLA-C04:01IGFDSTQWGF0.99950.8734515

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Potential FusionNeoAntigen Information of FKTN-ULK4 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.
FKTN-ULK4_108358938_41795980.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)
FKTN-ULK4chr9108358938chr341795980289DRB1-0422GSRIGFDSTQWGFVS217

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Fusion breakpoint peptide structures of FKTN-ULK4

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
2769GFDSTQWGFVSTIIFKTNULK4chr9108358938chr341795980289

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FKTN-ULK4

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-B14:023BVN2769GFDSTQWGFVSTII-7.9962-8.1096
HLA-B14:023BVN2769GFDSTQWGFVSTII-5.70842-6.74372
HLA-B52:013W392769GFDSTQWGFVSTII-6.83737-6.95077
HLA-B52:013W392769GFDSTQWGFVSTII-4.4836-5.5189
HLA-A11:014UQ22769GFDSTQWGFVSTII-10.0067-10.1201
HLA-A11:014UQ22769GFDSTQWGFVSTII-9.03915-10.0745
HLA-A24:025HGA2769GFDSTQWGFVSTII-6.56204-6.67544
HLA-A24:025HGA2769GFDSTQWGFVSTII-5.42271-6.45801
HLA-B44:053DX82769GFDSTQWGFVSTII-7.85648-8.89178
HLA-B44:053DX82769GFDSTQWGFVSTII-5.3978-5.5112
HLA-A02:016TDR2769GFDSTQWGFVSTII-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of FKTN-ULK4

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
FKTN-ULK4chr9108358938chr3417959801019TQWGFVSTIACACAGTGGGGTTTTGTCTCCACAATT
FKTN-ULK4chr9108358938chr3417959801020TQWGFVSTIIACACAGTGGGGTTTTGTCTCCACAATTATC
FKTN-ULK4chr9108358938chr341795980515IGFDSTQWGFATTGGATTTGATAGCACACAGTGGGGTTTT
FKTN-ULK4chr9108358938chr341795980615GFDSTQWGFGGATTTGATAGCACACAGTGGGGTTTT
FKTN-ULK4chr9108358938chr341795980919STQWGFVSTIAGCACACAGTGGGGTTTTGTCTCCACAATT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
FKTN-ULK4chr9108358938chr341795980217GSRIGFDSTQWGFVSGGAAGCCGAATTGGATTTGATAGCACACAGTGGGGTTTTGTCTCC

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Information of the samples that have these potential fusion neoantigens of FKTN-ULK4

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
STADFKTN-ULK4chr9108358938ENST00000223528chr341795980ENST00000301831TCGA-FP-A8CX-01A

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Potential target of CAR-T therapy development for FKTN-ULK4

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
HgeneFKTNchr9:108358938chr3:41795980ENST00000223528-3108_2855462.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneFKTNchr9:108358938chr3:41795980ENST00000357998-2108_2855431.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneFKTNchr9:108358938chr3:41795980ENST00000448551-4128_2855431.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneFKTNchr9:108358938chr3:41795980ENST00000602661-4118_2855462.0TransmembraneHelical%3B Signal-anchor for type II membrane protein

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 FKTN-ULK4

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 FKTN-ULK4

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