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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:PPP1R12B-LGR6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PPP1R12B-LGR6
FusionPDB ID: 67767
FusionGDB2.0 ID: 67767
HgeneTgene
Gene symbol

PPP1R12B

LGR6

Gene ID

4660

59352

Gene nameprotein phosphatase 1 regulatory subunit 12Bleucine rich repeat containing G protein-coupled receptor 6
SynonymsMYPT2|PP1bp55GPCR|VTS20631
Cytomap

1q32.1

1q32.1

Type of geneprotein-codingprotein-coding
Descriptionprotein phosphatase 1 regulatory subunit 12Bmyosin phosphatase target subunit 2myosin phosphatase-targeting subunit 2protein phosphatase 1, regulatory (inhibitor) subunit 12Bleucine-rich repeat-containing G-protein coupled receptor 6gonadotropin receptor
Modification date2020031320200313
UniProtAcc.

Q9HBX8

Main function of 5'-partner protein: FUNCTION: Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a marker of multipotent stem cells in the epidermis. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. May act as a tumor suppressor. {ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:22615920}.
Ensembl transtripts involved in fusion geneENST idsENST00000336894, ENST00000356764, 
ENST00000480184, ENST00000608999, 
ENST00000290419, ENST00000367270, 
ENST00000391959, 
ENST00000308543, 
ENST00000439764, ENST00000255432, 
ENST00000367278, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 9 X 4=4322 X 2 X 2=8
# samples 122
** MAII scorelog2(12/432*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: PPP1R12B [Title/Abstract] AND LGR6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PPP1R12B [Title/Abstract] AND LGR6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PPP1R12B(202386045)-LGR6(202245434), # samples:1
Anticipated loss of major functional domain due to fusion event.PPP1R12B-LGR6 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.
PPP1R12B-LGR6 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.
PPP1R12B-LGR6 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.
PPP1R12B-LGR6 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
TgeneLGR6

GO:0030177

positive regulation of Wnt signaling pathway

22615920

TgeneLGR6

GO:0030335

positive regulation of cell migration

22615920



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/chr1:202386045/chr1:202245434)
- 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 PPP1R12B (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 LGR6 (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)
ENST00000608999PPP1R12Bchr1202386045-ENST00000367278LGR6chr1202245434+3625575603050996
ENST00000608999PPP1R12Bchr1202386045-ENST00000255432LGR6chr1202245434+3625575603050996
ENST00000336894PPP1R12Bchr1202386045-ENST00000367278LGR6chr1202245434+3622572573047996
ENST00000336894PPP1R12Bchr1202386045-ENST00000255432LGR6chr1202245434+3622572573047996
ENST00000480184PPP1R12Bchr1202386045-ENST00000367278LGR6chr1202245434+3604554393029996
ENST00000480184PPP1R12Bchr1202386045-ENST00000255432LGR6chr1202245434+3604554393029996
ENST00000356764PPP1R12Bchr1202386045-ENST00000367278LGR6chr1202245434+3596546313021996
ENST00000356764PPP1R12Bchr1202386045-ENST00000255432LGR6chr1202245434+3596546313021996

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
ENST00000608999ENST00000367278PPP1R12Bchr1202386045-LGR6chr1202245434+0.0022230360.9977769
ENST00000608999ENST00000255432PPP1R12Bchr1202386045-LGR6chr1202245434+0.0022230360.9977769
ENST00000336894ENST00000367278PPP1R12Bchr1202386045-LGR6chr1202245434+0.0022911530.9977088
ENST00000336894ENST00000255432PPP1R12Bchr1202386045-LGR6chr1202245434+0.0022911530.9977088
ENST00000480184ENST00000367278PPP1R12Bchr1202386045-LGR6chr1202245434+0.0023701030.9976299
ENST00000480184ENST00000255432PPP1R12Bchr1202386045-LGR6chr1202245434+0.0023701030.9976299
ENST00000356764ENST00000367278PPP1R12Bchr1202386045-LGR6chr1202245434+0.0023330770.99766695
ENST00000356764ENST00000255432PPP1R12Bchr1202386045-LGR6chr1202245434+0.0023330770.99766695

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 PPP1R12B-LGR6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PPP1R12Bchr1202386045LGR6chr1202245434546172HAAASCGYLNIAERLDANLISLVPER
PPP1R12Bchr1202386045LGR6chr1202245434554172HAAASCGYLNIAERLDANLISLVPER
PPP1R12Bchr1202386045LGR6chr1202245434572172HAAASCGYLNIAERLDANLISLVPER
PPP1R12Bchr1202386045LGR6chr1202245434575172HAAASCGYLNIAERLDANLISLVPER

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Potential FusionNeoAntigen Information of PPP1R12B-LGR6 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.
PPP1R12B-LGR6_202386045_202245434.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)
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B45:01AERLDANLI0.94840.84621120
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B50:02AERLDANLI0.9270.52441120
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B41:01AERLDANLI0.2590.8371120
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B50:01AERLDANLI0.03590.71961120
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B27:04ERLDANLISL0.99990.51951222
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B39:01ERLDANLISL0.99920.73081222
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B39:06ERLDANLISL0.99880.6091222
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B38:02ERLDANLISL0.99870.83331222
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B38:01ERLDANLISL0.99860.79381222
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-C08:15IAERLDANL0.99970.97391019
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B40:06AERLDANLI0.9980.82821120
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B39:12ERLDANLISL0.9990.741222
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B39:05ERLDANLISL0.99860.69321222
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B14:03ERLDANLISL0.96660.69721222
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B39:08AERLDANLISL0.99630.78091122
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-C08:02IAERLDANL0.99970.97391019
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B40:04AERLDANLI0.99310.71281120
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B41:03AERLDANLI0.31970.62721120
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B50:05AERLDANLI0.03590.71961120
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B50:04AERLDANLI0.03590.71961120
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B27:09ERLDANLISL0.99980.57491222
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B39:31ERLDANLISL0.99920.72691222
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B38:05ERLDANLISL0.99860.79381222
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B39:11ERLDANLISL0.99050.59611222
PPP1R12B-LGR6chr1202386045chr1202245434572HLA-B40:04AERLDANLISL0.99990.61641122

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Potential FusionNeoAntigen Information of PPP1R12B-LGR6 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.
PPP1R12B-LGR6_202386045_202245434.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)
PPP1R12B-LGR6chr1202386045chr1202245434572DRB3-0301AERLDANLISLVPER1126

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Fusion breakpoint peptide structures of PPP1R12B-LGR6

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
3254GYLNIAERLDANLIPPP1R12BLGR6chr1202386045chr1202245434572

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PPP1R12B-LGR6

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-B14:023BVN3254GYLNIAERLDANLI-7.24289-7.35629
HLA-B14:023BVN3254GYLNIAERLDANLI-6.44411-7.47941
HLA-B52:013W393254GYLNIAERLDANLI-6.85231-6.96571
HLA-B52:013W393254GYLNIAERLDANLI-5.09533-6.13063
HLA-A11:014UQ23254GYLNIAERLDANLI-8.61576-8.72916
HLA-A24:025HGA3254GYLNIAERLDANLI-6.80714-7.84244
HLA-A24:025HGA3254GYLNIAERLDANLI-6.33574-6.44914
HLA-B44:053DX83254GYLNIAERLDANLI-7.01739-7.13079
HLA-B44:053DX83254GYLNIAERLDANLI-3.37818-4.41348

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Vaccine Design for the FusionNeoAntigens of PPP1R12B-LGR6

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
PPP1R12B-LGR6chr1202386045chr12022454341019IAERLDANLCATAGCAGAGCGCCTAGATGCCAACCT
PPP1R12B-LGR6chr1202386045chr12022454341120AERLDANLIAGCAGAGCGCCTAGATGCCAACCTCAT
PPP1R12B-LGR6chr1202386045chr12022454341122AERLDANLISLAGCAGAGCGCCTAGATGCCAACCTCATCTCCCT
PPP1R12B-LGR6chr1202386045chr12022454341222ERLDANLISLAGAGCGCCTAGATGCCAACCTCATCTCCCT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PPP1R12B-LGR6chr1202386045chr12022454341126AERLDANLISLVPERAGCAGAGCGCCTAGATGCCAACCTCATCTCCCTGGTCCCGGAGAG

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Information of the samples that have these potential fusion neoantigens of PPP1R12B-LGR6

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
LUSCPPP1R12B-LGR6chr1202386045ENST00000336894chr1202245434ENST00000255432TCGA-37-4130-01A

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Potential target of CAR-T therapy development for PPP1R12B-LGR6

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
TgeneLGR6chr1:202386045chr1:202245434ENST00000255432318568_5880916.0TransmembraneHelical%3B Name%3D1
TgeneLGR6chr1:202386045chr1:202245434ENST00000255432318599_6190916.0TransmembraneHelical%3B Name%3D2
TgeneLGR6chr1:202386045chr1:202245434ENST00000255432318645_6650916.0TransmembraneHelical%3B Name%3D3
TgeneLGR6chr1:202386045chr1:202245434ENST00000255432318688_7080916.0TransmembraneHelical%3B Name%3D4
TgeneLGR6chr1:202386045chr1:202245434ENST00000255432318728_7480916.0TransmembraneHelical%3B Name%3D5
TgeneLGR6chr1:202386045chr1:202245434ENST00000255432318775_7950916.0TransmembraneHelical%3B Name%3D6
TgeneLGR6chr1:202386045chr1:202245434ENST00000255432318810_8300916.0TransmembraneHelical%3B Name%3D7
TgeneLGR6chr1:202386045chr1:202245434ENST00000367278318568_5880968.0TransmembraneHelical%3B Name%3D1
TgeneLGR6chr1:202386045chr1:202245434ENST00000367278318599_6190968.0TransmembraneHelical%3B Name%3D2
TgeneLGR6chr1:202386045chr1:202245434ENST00000367278318645_6650968.0TransmembraneHelical%3B Name%3D3
TgeneLGR6chr1:202386045chr1:202245434ENST00000367278318688_7080968.0TransmembraneHelical%3B Name%3D4
TgeneLGR6chr1:202386045chr1:202245434ENST00000367278318728_7480968.0TransmembraneHelical%3B Name%3D5
TgeneLGR6chr1:202386045chr1:202245434ENST00000367278318775_7950968.0TransmembraneHelical%3B Name%3D6
TgeneLGR6chr1:202386045chr1:202245434ENST00000367278318810_8300968.0TransmembraneHelical%3B Name%3D7
TgeneLGR6chr1:202386045chr1:202245434ENST00000439764016568_5880829.0TransmembraneHelical%3B Name%3D1
TgeneLGR6chr1:202386045chr1:202245434ENST00000439764016599_6190829.0TransmembraneHelical%3B Name%3D2
TgeneLGR6chr1:202386045chr1:202245434ENST00000439764016645_6650829.0TransmembraneHelical%3B Name%3D3
TgeneLGR6chr1:202386045chr1:202245434ENST00000439764016688_7080829.0TransmembraneHelical%3B Name%3D4
TgeneLGR6chr1:202386045chr1:202245434ENST00000439764016728_7480829.0TransmembraneHelical%3B Name%3D5
TgeneLGR6chr1:202386045chr1:202245434ENST00000439764016775_7950829.0TransmembraneHelical%3B Name%3D6
TgeneLGR6chr1:202386045chr1:202245434ENST00000439764016810_8300829.0TransmembraneHelical%3B Name%3D7

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 PPP1R12B-LGR6

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 PPP1R12B-LGR6

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