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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:CARKD-ABCC4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CARKD-ABCC4
FusionPDB ID: 13048
FusionGDB2.0 ID: 13048
HgeneTgene
Gene symbol

CARKD

ABCC4

Gene ID

55739

10257

Gene nameNAD(P)HX dehydrataseATP binding cassette subfamily C member 4
SynonymsCARKD|LP3298|PEBEL2MOAT-B|MOATB|MRP4
Cytomap

13q34

13q32.1

Type of geneprotein-codingprotein-coding
DescriptionATP-dependent (S)-NAD(P)H-hydrate dehydrataseATP-dependent NAD(P)H-hydrate dehydrataseATP-dependent NAD(P)HX dehydratasecarbohydrate kinase domain containingcarbohydrate kinase domain-containing proteinmultidrug resistance-associated protein 4MRP/cMOAT-related ABC transporterbA464I2.1 (ATP-binding cassette, sub-family C (CFTR/MRP), member 4)canalicular multispecific organic anion transporter (ABC superfamily)multi-specific organic anion transporter
Modification date2020031320200313
UniProtAcc.

O15439

Main function of 5'-partner protein: FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12883481, PubMed:12523936, PubMed:12835412, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12883481, PubMed:12523936, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:18300232, PubMed:17344354). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685). {ECO:0000269|PubMed:11106685, ECO:0000269|PubMed:11856762, ECO:0000269|PubMed:12105214, ECO:0000269|PubMed:12523936, ECO:0000269|PubMed:12835412, ECO:0000269|PubMed:12883481, ECO:0000269|PubMed:15364914, ECO:0000269|PubMed:15454390, ECO:0000269|PubMed:16282361, ECO:0000269|PubMed:17344354, ECO:0000269|PubMed:17959747, ECO:0000269|PubMed:18300232, ECO:0000269|PubMed:26721430}.
Ensembl transtripts involved in fusion geneENST idsENST00000470164, ENST00000397191, 
ENST00000424185, ENST00000458711, 
ENST00000309957, 
ENST00000376887, 
ENST00000412704, ENST00000431522, 
ENST00000536256, ENST00000474158, 
ENST00000538287, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 1 X 2=820 X 18 X 5=1800
# samples 421
** MAII scorelog2(4/8*10)=2.32192809488736log2(21/1800*10)=-3.09953567355091
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CARKD [Title/Abstract] AND ABCC4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CARKD [Title/Abstract] AND ABCC4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CARKD(111267994)-ABCC4(95768255), # samples:1
Anticipated loss of major functional domain due to fusion event.CARKD-ABCC4 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.
CARKD-ABCC4 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.
CARKD-ABCC4 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.
CARKD-ABCC4 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.
CARKD-ABCC4 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
TgeneABCC4

GO:0032310

prostaglandin secretion

25173977



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/chr13:111267994/chr13:95768255)
- 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 CARKD (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 ABCC4 (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)
ENST00000397191CARKDchr13111267994+ENST00000412704ABCC4chr1395768255-333364181586522
ENST00000397191CARKDchr13111267994+ENST00000376887ABCC4chr1395768255-333164181586522
ENST00000397191CARKDchr13111267994+ENST00000536256ABCC4chr1395768255-5556414634967
ENST00000397191CARKDchr13111267994+ENST00000431522ABCC4chr1395768255-5536414634967

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
ENST00000397191ENST00000412704CARKDchr13111267994+ABCC4chr1395768255-0.0002710910.99972886
ENST00000397191ENST00000376887CARKDchr13111267994+ABCC4chr1395768255-0.0002669680.99973303
ENST00000397191ENST00000536256CARKDchr13111267994+ABCC4chr1395768255-0.616327640.38367236
ENST00000397191ENST00000431522CARKDchr13111267994+ABCC4chr1395768255-0.63400310.36599684

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 CARKD-ABCC4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CARKDchr13111267994ABCC4chr13957682556415LGPRCGAIRACRRGRILNRFSKDIGH

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Potential FusionNeoAntigen Information of CARKD-ABCC4 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.
CARKD-ABCC4_111267994_95768255.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)
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:02RRGRILNRF0.99970.60881120
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:04RRGRILNRF0.99970.75661120
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:05RRGRILNRF0.99970.87041120
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:05RGRILNRFSK0.99310.9041222
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:05RRGRILNRFSK0.99960.90371122
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:14RRGRILNRF0.99960.81171120
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:03RRGRILNRF0.98890.88641120
CARKD-ABCC4chr13111267994chr139576825564HLA-C07:95RRGRILNRF0.98530.52811120
CARKD-ABCC4chr13111267994chr139576825564HLA-C07:05RRGRILNRF0.9680.80621120
CARKD-ABCC4chr13111267994chr139576825564HLA-C07:27RRGRILNRF0.9550.78821120
CARKD-ABCC4chr13111267994chr139576825564HLA-C07:46RRGRILNRF0.80870.6081120
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:14RGRILNRFSK0.98230.78891222
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:03RGRILNRFSK0.77860.91651222
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:14RRGRILNRFSK0.99940.78581122
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:03RRGRILNRFSK0.98210.91641122
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:08RRGRILNRF0.99970.7971120
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:10RRGRILNRF0.99960.87911120
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:06RRGRILNRF0.99910.6571120
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:09RRGRILNRF0.99550.81691120
CARKD-ABCC4chr13111267994chr139576825564HLA-C07:01RRGRILNRF0.99160.50351120
CARKD-ABCC4chr13111267994chr139576825564HLA-C07:22RRGRILNRF0.7320.65271120
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:10RGRILNRFSK0.98060.84881222
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:10RRGRILNRFSK0.99940.85781122
CARKD-ABCC4chr13111267994chr139576825564HLA-B27:10RACRRGRILNR0.96860.8292819

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Potential FusionNeoAntigen Information of CARKD-ABCC4 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 CARKD-ABCC4

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
290AIRACRRGRILNRFCARKDABCC4chr13111267994chr139576825564

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CARKD-ABCC4

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-B14:023BVN290AIRACRRGRILNRF-7.9962-8.1096
HLA-B14:023BVN290AIRACRRGRILNRF-5.70842-6.74372
HLA-B52:013W39290AIRACRRGRILNRF-6.83737-6.95077
HLA-B52:013W39290AIRACRRGRILNRF-4.4836-5.5189
HLA-A11:014UQ2290AIRACRRGRILNRF-10.0067-10.1201
HLA-A11:014UQ2290AIRACRRGRILNRF-9.03915-10.0745
HLA-A24:025HGA290AIRACRRGRILNRF-6.56204-6.67544
HLA-A24:025HGA290AIRACRRGRILNRF-5.42271-6.45801
HLA-B44:053DX8290AIRACRRGRILNRF-7.85648-8.89178
HLA-B44:053DX8290AIRACRRGRILNRF-5.3978-5.5112
HLA-A02:016TDR290AIRACRRGRILNRF-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of CARKD-ABCC4

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
CARKD-ABCC4chr13111267994chr13957682551120RRGRILNRFGACGAGGAAGAATTTTAAATCGTTTCT
CARKD-ABCC4chr13111267994chr13957682551122RRGRILNRFSKGACGAGGAAGAATTTTAAATCGTTTCTCCAAAG
CARKD-ABCC4chr13111267994chr13957682551222RGRILNRFSKGAGGAAGAATTTTAAATCGTTTCTCCAAAG
CARKD-ABCC4chr13111267994chr1395768255819RACRRGRILNRGGGCTTGCAGACGAGGAAGAATTTTAAATCGTT

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 CARKD-ABCC4

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
STADCARKD-ABCC4chr13111267994ENST00000397191chr1395768255ENST00000376887TCGA-CD-8525-01A

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Potential target of CAR-T therapy development for CARKD-ABCC4

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
TgeneABCC4chr13:111267994chr13:95768255ENST0000037688718311038_105801326.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000003768871831836_85601326.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000003768871831858_87801326.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000003768871831954_97401326.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000003768871831977_99701326.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST0000041270417301038_105801279.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000004127041730771_79101279.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000004127041730836_85601279.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000004127041730858_87801279.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000004127041730954_97401279.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000004127041730977_99701279.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST0000043152218211038_10580860.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000004315221821836_8560860.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000004315221821858_8780860.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000004315221821954_9740860.0TransmembraneHelical
TgeneABCC4chr13:111267994chr13:95768255ENST000004315221821977_9970860.0TransmembraneHelical

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 CARKD-ABCC4

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 CARKD-ABCC4

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