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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:CD63-CAPN2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CD63-CAPN2
FusionPDB ID: 14581
FusionGDB2.0 ID: 14581
HgeneTgene
Gene symbol

CD63

CAPN2

Gene ID

967

824

Gene nameCD63 moleculecalpain 2
SynonymsLAMP-3|ME491|MLA1|OMA81H|TSPAN30CANP2|CANPL2|CANPml|mCANP
Cytomap

12q13.2

1q41

Type of geneprotein-codingprotein-coding
DescriptionCD63 antigenCD63 antigen (melanoma 1 antigen)granulophysinlysosomal-associated membrane protein 3lysosome-associated membrane glycoprotein 3melanoma-associated antigen ME491melanoma-associated antigen MLA1ocular melanoma-associated antigentetraspacalpain-2 catalytic subunitCANP 2M-calpaincalcium-activated neutral proteinase 2calpain 2, (m/II) large subunitcalpain 2, large [catalytic] subunitcalpain 2, large subunitcalpain M-typecalpain, large polypeptide L2millimolar-calpain
Modification date2020032720200313
UniProtAcc

P08962

Main function of 5'-partner protein: FUNCTION: Functions as cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activation of AKT, FAK/PTK2 and MAP kinases. Promotes cell survival, reorganization of the actin cytoskeleton, cell adhesion, spreading and migration, via its role in the activation of AKT and FAK/PTK2. Plays a role in VEGFA signaling via its role in regulating the internalization of KDR/VEGFR2. Plays a role in intracellular vesicular transport processes, and is required for normal trafficking of the PMEL luminal domain that is essential for the development and maturation of melanocytes. Plays a role in the adhesion of leukocytes onto endothelial cells via its role in the regulation of SELP trafficking. May play a role in mast cell degranulation in response to Ms4a2/FceRI stimulation, but not in mast cell degranulation in response to other stimuli. {ECO:0000269|PubMed:16917503, ECO:0000269|PubMed:21803846, ECO:0000269|PubMed:21962903, ECO:0000269|PubMed:23632027, ECO:0000269|PubMed:24635319}.

P17655

Main function of 5'-partner protein: FUNCTION: Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves MYOC at 'Arg-226' (PubMed:17650508). Proteolytically cleaves CPEB3 following neuronal stimulation which abolishes CPEB3 translational repressor activity, leading to translation of CPEB3 target mRNAs (By similarity). {ECO:0000250|UniProtKB:O08529, ECO:0000269|PubMed:17650508}.
Ensembl transtripts involved in fusion geneENST idsENST00000257857, ENST00000420846, 
ENST00000546939, ENST00000548160, 
ENST00000548898, ENST00000549117, 
ENST00000550776, ENST00000552067, 
ENST00000552692, ENST00000552754, 
ENST00000474026, ENST00000295006, 
ENST00000433674, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 19 X 9=393311 X 7 X 7=539
# samples 2311
** MAII scorelog2(23/3933*10)=-4.09592441999854
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/539*10)=-2.29278174922785
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CD63 [Title/Abstract] AND CAPN2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CD63 [Title/Abstract] AND CAPN2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CD63(56120484)-CAPN2(223946972), # samples:1
Anticipated loss of major functional domain due to fusion event.CD63-CAPN2 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.
CD63-CAPN2 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.
CD63-CAPN2 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.
CD63-CAPN2 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.
CD63-CAPN2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
CD63-CAPN2 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
HgeneCD63

GO:0034613

cellular protein localization

15647390

HgeneCD63

GO:1901379

regulation of potassium ion transmembrane transport

15647390

TgeneCAPN2

GO:0051603

proteolysis involved in cellular protein catabolic process

12150984



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/chr12:56120484/chr1:223946972)
- 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 CD63 (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 CAPN2 (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)
ENST00000548898CD63chr1256120484-ENST00000433674CAPN2chr1223946972+214319839983314
ENST00000548898CD63chr1256120484-ENST00000295006CAPN2chr1223946972+214519839983314
ENST00000420846CD63chr1256120484-ENST00000433674CAPN2chr1223946972+25566111611396411
ENST00000420846CD63chr1256120484-ENST00000295006CAPN2chr1223946972+25586111611396411
ENST00000548160CD63chr1256120484-ENST00000433674CAPN2chr1223946972+2211266831051322
ENST00000548160CD63chr1256120484-ENST00000295006CAPN2chr1223946972+2213266831051322
ENST00000552692CD63chr1256120484-ENST00000433674CAPN2chr1223946972+25125671411352403
ENST00000552692CD63chr1256120484-ENST00000295006CAPN2chr1223946972+25145671411352403
ENST00000257857CD63chr1256120484-ENST00000433674CAPN2chr1223946972+26507052551490411
ENST00000257857CD63chr1256120484-ENST00000295006CAPN2chr1223946972+26527052551490411
ENST00000552754CD63chr1256120484-ENST00000433674CAPN2chr1223946972+231036581150380
ENST00000552754CD63chr1256120484-ENST00000295006CAPN2chr1223946972+231236581150380

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
ENST00000548898ENST00000433674CD63chr1256120484-CAPN2chr1223946972+0.0006785060.99932146
ENST00000548898ENST00000295006CD63chr1256120484-CAPN2chr1223946972+0.0006812240.99931884
ENST00000420846ENST00000433674CD63chr1256120484-CAPN2chr1223946972+0.0004463590.9995536
ENST00000420846ENST00000295006CD63chr1256120484-CAPN2chr1223946972+0.0004471580.9995528
ENST00000548160ENST00000433674CD63chr1256120484-CAPN2chr1223946972+0.0006014210.9993986
ENST00000548160ENST00000295006CD63chr1256120484-CAPN2chr1223946972+0.0006046310.9993954
ENST00000552692ENST00000433674CD63chr1256120484-CAPN2chr1223946972+0.0003939240.9996061
ENST00000552692ENST00000295006CD63chr1256120484-CAPN2chr1223946972+0.0003939410.9996061
ENST00000257857ENST00000433674CD63chr1256120484-CAPN2chr1223946972+0.0004356970.99956435
ENST00000257857ENST00000295006CD63chr1256120484-CAPN2chr1223946972+0.0004361080.9995639
ENST00000552754ENST00000433674CD63chr1256120484-CAPN2chr1223946972+0.0002789730.999721
ENST00000552754ENST00000295006CD63chr1256120484-CAPN2chr1223946972+0.0002814920.9997185

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 CD63-CAPN2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CD63chr1256120484CAPN2chr122394697219853NHTASILDRMQADLSGQTNIHLSKNF
CD63chr1256120484CAPN2chr122394697226661NHTASILDRMQADLSGQTNIHLSKNF
CD63chr1256120484CAPN2chr1223946972365119NHTASILDRMQADLSGQTNIHLSKNF
CD63chr1256120484CAPN2chr1223946972567142NHTASILDRMQADLSGQTNIHLSKNF
CD63chr1256120484CAPN2chr1223946972611150NHTASILDRMQADLSGQTNIHLSKNF
CD63chr1256120484CAPN2chr1223946972705150NHTASILDRMQADLSGQTNIHLSKNF

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Potential FusionNeoAntigen Information of CD63-CAPN2 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.
CD63-CAPN2_56120484_223946972.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)
CD63-CAPN2chr1256120484chr1223946972705HLA-B13:02MQADLSGQTNI0.97820.6963920
CD63-CAPN2chr1256120484chr1223946972705HLA-C04:10ILDRMQADL0.99970.8951514
CD63-CAPN2chr1256120484chr1223946972705HLA-C05:09ILDRMQADL0.99970.9793514
CD63-CAPN2chr1256120484chr1223946972705HLA-C08:15ILDRMQADL0.99950.9881514
CD63-CAPN2chr1256120484chr1223946972705HLA-A02:07ILDRMQADL0.90640.6555514
CD63-CAPN2chr1256120484chr1223946972705HLA-C04:03ILDRMQADL0.99970.9327514
CD63-CAPN2chr1256120484chr1223946972705HLA-C05:01ILDRMQADL0.99970.9793514
CD63-CAPN2chr1256120484chr1223946972705HLA-C08:02ILDRMQADL0.99950.9881514

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Potential FusionNeoAntigen Information of CD63-CAPN2 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.
CD63-CAPN2_56120484_223946972.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)
CD63-CAPN2chr1256120484chr1223946972705DRB4-0101ASILDRMQADLSGQT318
CD63-CAPN2chr1256120484chr1223946972705DRB4-0101TASILDRMQADLSGQ217
CD63-CAPN2chr1256120484chr1223946972705DRB4-0103ASILDRMQADLSGQT318
CD63-CAPN2chr1256120484chr1223946972705DRB4-0103TASILDRMQADLSGQ217
CD63-CAPN2chr1256120484chr1223946972705DRB4-0104ASILDRMQADLSGQT318
CD63-CAPN2chr1256120484chr1223946972705DRB4-0104TASILDRMQADLSGQ217
CD63-CAPN2chr1256120484chr1223946972705DRB4-0106ASILDRMQADLSGQT318
CD63-CAPN2chr1256120484chr1223946972705DRB4-0106TASILDRMQADLSGQ217
CD63-CAPN2chr1256120484chr1223946972705DRB4-0107ASILDRMQADLSGQT318
CD63-CAPN2chr1256120484chr1223946972705DRB4-0107TASILDRMQADLSGQ217
CD63-CAPN2chr1256120484chr1223946972705DRB4-0108ASILDRMQADLSGQT318
CD63-CAPN2chr1256120484chr1223946972705DRB4-0108TASILDRMQADLSGQ217

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Fusion breakpoint peptide structures of CD63-CAPN2

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
4865LDRMQADLSGQTNICD63CAPN2chr1256120484chr1223946972705

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CD63-CAPN2

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-B14:023BVN4865LDRMQADLSGQTNI-7.9962-8.1096
HLA-B14:023BVN4865LDRMQADLSGQTNI-5.70842-6.74372
HLA-B52:013W394865LDRMQADLSGQTNI-6.83737-6.95077
HLA-B52:013W394865LDRMQADLSGQTNI-4.4836-5.5189
HLA-A11:014UQ24865LDRMQADLSGQTNI-10.0067-10.1201
HLA-A11:014UQ24865LDRMQADLSGQTNI-9.03915-10.0745
HLA-A24:025HGA4865LDRMQADLSGQTNI-6.56204-6.67544
HLA-A24:025HGA4865LDRMQADLSGQTNI-5.42271-6.45801
HLA-B44:053DX84865LDRMQADLSGQTNI-7.85648-8.89178
HLA-B44:053DX84865LDRMQADLSGQTNI-5.3978-5.5112
HLA-A02:016TDR4865LDRMQADLSGQTNI-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of CD63-CAPN2

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
CD63-CAPN2chr1256120484chr1223946972514ILDRMQADLATCCTGGACAGGATGCAGGCAGATTTA
CD63-CAPN2chr1256120484chr1223946972920MQADLSGQTNIATGCAGGCAGATTTAAGTGGGCAGACCAACATC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CD63-CAPN2chr1256120484chr1223946972217TASILDRMQADLSGQACTGCTTCGATCCTGGACAGGATGCAGGCAGATTTAAGTGGGCAG
CD63-CAPN2chr1256120484chr1223946972318ASILDRMQADLSGQTGCTTCGATCCTGGACAGGATGCAGGCAGATTTAAGTGGGCAGACC

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Information of the samples that have these potential fusion neoantigens of CD63-CAPN2

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
STADCD63-CAPN2chr1256120484ENST00000257857chr1223946972ENST00000295006TCGA-BR-8059-01A

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Potential target of CAR-T therapy development for CD63-CAPN2

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
HgeneCD63chr12:56120484chr1:223946972ENST00000257857-5812_32142239.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000257857-5852_72142239.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000257857-5882_102142239.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000546939-4712_3260157.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000549117-5812_32142239.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000549117-5852_72142239.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000549117-5882_102142239.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000550776-4712_3260157.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000552692-4712_32142239.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000552692-4752_72142239.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000552692-4782_102142239.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000552754-4712_32119216.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000552754-4752_72119216.0TransmembraneHelical
HgeneCD63chr12:56120484chr1:223946972ENST00000552754-4782_102119216.0TransmembraneHelical

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 CD63-CAPN2

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 CD63-CAPN2

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