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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:IL12RB2-PDE4B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: IL12RB2-PDE4B
FusionPDB ID: 39430
FusionGDB2.0 ID: 39430
HgeneTgene
Gene symbol

IL12RB2

PDE4B

Gene ID

3595

5142

Gene nameinterleukin 12 receptor subunit beta 2phosphodiesterase 4B
Synonyms-DPDE4|PDEIVB
Cytomap

1p31.3

1p31.3

Type of geneprotein-codingprotein-coding
Descriptioninterleukin-12 receptor subunit beta-2IL-12 receptor subunit beta-2IL-12R subunit beta-2interleukin 12 receptor, beta 2interleukin-12 receptor beta-2 chaincAMP-specific 3',5'-cyclic phosphodiesterase 4Bdunce-like phosphodiesterase E4phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)
Modification date2020031520200313
UniProtAcc

Q99665

Main function of 5'-partner protein: FUNCTION: Receptor for interleukin-12. This subunit is the signaling component coupling to the JAK2/STAT4 pathway. Promotes the proliferation of T-cells as well as NK cells. Induces the promotion of T-cells towards the Th1 phenotype by strongly enhancing IFN-gamma production.
.
Ensembl transtripts involved in fusion geneENST idsENST00000262345, ENST00000371000, 
ENST00000541374, ENST00000544434, 
ENST00000465396, 
ENST00000371045, 
ENST00000371048, ENST00000480109, 
ENST00000329654, ENST00000371049, 
ENST00000423207, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 5 X 3=6011 X 9 X 5=495
# samples 412
** MAII scorelog2(4/60*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/495*10)=-2.04439411935845
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: IL12RB2 [Title/Abstract] AND PDE4B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: IL12RB2 [Title/Abstract] AND PDE4B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)IL12RB2(67796493)-PDE4B(66837996), # samples:3
Anticipated loss of major functional domain due to fusion event.IL12RB2-PDE4B 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.
IL12RB2-PDE4B 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.
IL12RB2-PDE4B 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.
IL12RB2-PDE4B 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.
IL12RB2-PDE4B seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
IL12RB2-PDE4B seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
IL12RB2-PDE4B 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
HgeneIL12RB2

GO:0032729

positive regulation of interferon-gamma production

11114383



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/chr1:67796493/chr1:66837996)
- 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 IL12RB2 (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 PDE4B (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)
ENST00000371000IL12RB2chr167796493+ENST00000423207PDE4Bchr166837996+385915986341662342
ENST00000262345IL12RB2chr167796493+ENST00000423207PDE4Bchr166837996+385915986341662342
ENST00000541374IL12RB2chr167796493+ENST00000423207PDE4Bchr166837996+343811772131241342
ENST00000544434IL12RB2chr167796493+ENST00000423207PDE4Bchr166837996+32691008441072342

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
ENST00000371000ENST00000423207IL12RB2chr167796493+PDE4Bchr166837996+0.0013347430.9986652
ENST00000262345ENST00000423207IL12RB2chr167796493+PDE4Bchr166837996+0.0013347430.9986652
ENST00000541374ENST00000423207IL12RB2chr167796493+PDE4Bchr166837996+0.0007104820.9992895
ENST00000544434ENST00000423207IL12RB2chr167796493+PDE4Bchr166837996+0.0007157510.9992843

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 IL12RB2-PDE4B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
IL12RB2chr167796493PDE4Bchr1668379961008321DWSESLRAQTPEEGWFHRLHCPSIVG
IL12RB2chr167796493PDE4Bchr1668379961177321DWSESLRAQTPEEGWFHRLHCPSIVG
IL12RB2chr167796493PDE4Bchr1668379961598321DWSESLRAQTPEEGWFHRLHCPSIVG

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Potential FusionNeoAntigen Information of IL12RB2-PDE4B 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.
IL12RB2-PDE4B_67796493_66837996.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)
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B18:01EEGWFHRL0.99580.93011119
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B57:01RAQTPEEGW0.99670.9936615
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B58:02RAQTPEEGW0.99310.9878615
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B58:01RAQTPEEGW0.99210.9893615
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B15:17RAQTPEEGW0.97380.9789615
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B15:16RAQTPEEGW0.94620.9664615
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B18:01EEGWFHRLH0.89630.92521120
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B57:03RAQTPEEGW0.88690.9961615
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-A32:13RAQTPEEGW0.43980.9698615
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B27:02LRAQTPEEGW0.99880.5981515
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-A68:03QTPEEGWFHR0.9810.5036818
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-A68:05QTPEEGWFHR0.96560.5153818
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B58:01LRAQTPEEGW0.93960.9934515
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-A68:08QTPEEGWFHR0.93350.6434818
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B35:03TPEEGWFHRL0.91150.9687919
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B35:04TPEEGWFHRL0.72030.9907919
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B35:02TPEEGWFHRL0.72030.9907919
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B07:12TPEEGWFHRL0.94650.7321919
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B56:04TPEEGWFHRL0.84260.6288919
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B35:12TPEEGWFHRL0.72030.9907919
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B39:10TPEEGWFHRL0.68250.9859919
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B18:05EEGWFHRL0.99580.93011119
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B18:03EEGWFHRL0.99370.92591119
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B57:10RAQTPEEGW0.99670.9936615
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B58:06RAQTPEEGW0.98660.9852615
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B57:04RAQTPEEGW0.98450.8345615
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B18:05EEGWFHRLH0.89630.92521120
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B18:06EEGWFHRLH0.8910.93471120
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B18:03EEGWFHRLH0.78360.92391120
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B57:02RAQTPEEGW0.66650.9798615
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B18:11EEGWFHRLH0.50090.91091120
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B56:02TPEEGWFHRL0.84260.6288919
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B35:22TPEEGWFHRL0.79740.7463919
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B35:09TPEEGWFHRL0.72030.9907919
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B67:01TPEEGWFHRL0.68810.9684919
IL12RB2-PDE4Bchr167796493chr1668379961598HLA-B51:05TPEEGWFHRL0.68290.5152919

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Potential FusionNeoAntigen Information of IL12RB2-PDE4B 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.
IL12RB2-PDE4B_67796493_66837996.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)
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0101SESLRAQTPEEGWFH217
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0101WSESLRAQTPEEGWF116
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0101DWSESLRAQTPEEGW015
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0103SESLRAQTPEEGWFH217
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0103WSESLRAQTPEEGWF116
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0103DWSESLRAQTPEEGW015
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0104SESLRAQTPEEGWFH217
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0104WSESLRAQTPEEGWF116
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0106SESLRAQTPEEGWFH217
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0106WSESLRAQTPEEGWF116
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0106DWSESLRAQTPEEGW015
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0107SESLRAQTPEEGWFH217
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0107WSESLRAQTPEEGWF116
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0107DWSESLRAQTPEEGW015
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0108SESLRAQTPEEGWFH217
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0108WSESLRAQTPEEGWF116
IL12RB2-PDE4Bchr167796493chr1668379961598DRB4-0108DWSESLRAQTPEEGW015

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Fusion breakpoint peptide structures of IL12RB2-PDE4B

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
7704RAQTPEEGWFHRLHIL12RB2PDE4Bchr167796493chr1668379961598

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of IL12RB2-PDE4B

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-B14:023BVN7704RAQTPEEGWFHRLH-6.77616-6.88956
HLA-B14:023BVN7704RAQTPEEGWFHRLH-3.78478-4.82008
HLA-B52:013W397704RAQTPEEGWFHRLH-6.1015-6.2149
HLA-B52:013W397704RAQTPEEGWFHRLH-3.96189-4.99719
HLA-A11:014UQ27704RAQTPEEGWFHRLH-10.999-11.1124
HLA-A11:014UQ27704RAQTPEEGWFHRLH-2.42708-3.46238
HLA-A24:025HGA7704RAQTPEEGWFHRLH-6.05112-6.16452
HLA-A24:025HGA7704RAQTPEEGWFHRLH-5.05906-6.09436
HLA-B44:053DX87704RAQTPEEGWFHRLH-4.22612-4.33952
HLA-B44:053DX87704RAQTPEEGWFHRLH-3.0405-4.0758

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Vaccine Design for the FusionNeoAntigens of IL12RB2-PDE4B

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
IL12RB2-PDE4Bchr167796493chr1668379961119EEGWFHRLAAGAAGGTTGGTTTCATCGACTAC
IL12RB2-PDE4Bchr167796493chr1668379961120EEGWFHRLHAAGAAGGTTGGTTTCATCGACTACATT
IL12RB2-PDE4Bchr167796493chr166837996515LRAQTPEEGWTGAGAGCACAAACACCAGAAGAAGGTTGGT
IL12RB2-PDE4Bchr167796493chr166837996615RAQTPEEGWGAGCACAAACACCAGAAGAAGGTTGGT
IL12RB2-PDE4Bchr167796493chr166837996818QTPEEGWFHRAAACACCAGAAGAAGGTTGGTTTCATCGAC
IL12RB2-PDE4Bchr167796493chr166837996919TPEEGWFHRLCACCAGAAGAAGGTTGGTTTCATCGACTAC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
IL12RB2-PDE4Bchr167796493chr166837996015DWSESLRAQTPEEGWATTGGAGTGAATCATTGAGAGCACAAACACCAGAAGAAGGTTGGT
IL12RB2-PDE4Bchr167796493chr166837996116WSESLRAQTPEEGWFGGAGTGAATCATTGAGAGCACAAACACCAGAAGAAGGTTGGTTTC
IL12RB2-PDE4Bchr167796493chr166837996217SESLRAQTPEEGWFHGTGAATCATTGAGAGCACAAACACCAGAAGAAGGTTGGTTTCATC

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Information of the samples that have these potential fusion neoantigens of IL12RB2-PDE4B

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
BRCAIL12RB2-PDE4Bchr167796493ENST00000262345chr166837996ENST00000423207TCGA-AN-A0FJ-01A

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Potential target of CAR-T therapy development for IL12RB2-PDE4B

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 IL12RB2-PDE4B

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 IL12RB2-PDE4B

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