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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:DOCK5-DLC1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DOCK5-DLC1
FusionPDB ID: 23807
FusionGDB2.0 ID: 23807
HgeneTgene
Gene symbol

DOCK5

DLC1

Gene ID

80005

10395

Gene namededicator of cytokinesis 5DLC1 Rho GTPase activating protein
Synonyms-ARHGAP7|HP|STARD12|p122-RhoGAP
Cytomap

8p21.2

8p22

Type of geneprotein-codingprotein-coding
Descriptiondedicator of cytokinesis protein 5rho GTPase-activating protein 7Rho-GTPase-activating protein 7START domain-containing protein 12StAR-related lipid transfer (START) domain containing 12deleted in liver cancer 1 proteindeleted in liver cancer 1 variant 2deleted in liver cancer varia
Modification date2020031320200313
UniProtAcc

Q9H7D0

Main function of 5'-partner protein: FUNCTION: Guanine nucleotide exchange factor (GEF) for Rho and Rac. GEF proteins activate small GTPases by exchanging bound GDP for free GTP (By similarity). Along with DOCK1, mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen (PubMed:19004829). {ECO:0000250|UniProtKB:B2RY04, ECO:0000269|PubMed:19004829}.

Q96QB1

Main function of 5'-partner protein: FUNCTION: Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. Also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality. {ECO:0000269|PubMed:18786931, ECO:0000269|PubMed:19170769, ECO:0000269|PubMed:19710422}.
Ensembl transtripts involved in fusion geneENST idsENST00000276440, ENST00000410074, 
ENST00000481100, 
ENST00000520226, 
ENST00000316609, ENST00000510318, 
ENST00000511869, ENST00000276297, 
ENST00000358919, ENST00000512044, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 4=12017 X 14 X 5=1190
# samples 719
** MAII scorelog2(7/120*10)=-0.777607578663552
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(19/1190*10)=-2.64689024986436
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DOCK5 [Title/Abstract] AND DLC1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DOCK5 [Title/Abstract] AND DLC1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DOCK5(25042466)-DLC1(12973166), # samples:1
Anticipated loss of major functional domain due to fusion event.DOCK5-DLC1 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.
DOCK5-DLC1 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.
DOCK5-DLC1 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.
DOCK5-DLC1 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
TgeneDLC1

GO:0006915

apoptotic process

17292327

TgeneDLC1

GO:0006919

activation of cysteine-type endopeptidase activity involved in apoptotic process

17888903

TgeneDLC1

GO:0008285

negative regulation of cell proliferation

12545165|17932950

TgeneDLC1

GO:0030336

negative regulation of cell migration

17932950|19158340

TgeneDLC1

GO:0035307

positive regulation of protein dephosphorylation

17292327

TgeneDLC1

GO:0051497

negative regulation of stress fiber assembly

17932950

TgeneDLC1

GO:0051895

negative regulation of focal adhesion assembly

19158340

TgeneDLC1

GO:1900119

positive regulation of execution phase of apoptosis

17888903



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/chr8:25042466/chr8:12973166)
- 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 DOCK5 (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 DLC1 (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)
ENST00000276440DOCK5chr825042466+ENST00000276297DLC1chr812973166-5776874433251093
ENST00000276440DOCK5chr825042466+ENST00000358919DLC1chr812973166-3948874433251093
ENST00000276440DOCK5chr825042466+ENST00000512044DLC1chr812973166-3560874433251093
ENST00000410074DOCK5chr825042466+ENST00000276297DLC1chr812973166-591822918634671093
ENST00000410074DOCK5chr825042466+ENST00000358919DLC1chr812973166-409022918634671093
ENST00000410074DOCK5chr825042466+ENST00000512044DLC1chr812973166-370222918634671093
ENST00000481100DOCK5chr825042466+ENST00000276297DLC1chr812973166-586918013734181093
ENST00000481100DOCK5chr825042466+ENST00000358919DLC1chr812973166-404118013734181093
ENST00000481100DOCK5chr825042466+ENST00000512044DLC1chr812973166-365318013734181093

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
ENST00000276440ENST00000276297DOCK5chr825042466+DLC1chr812973166-0.0002855820.99971443
ENST00000276440ENST00000358919DOCK5chr825042466+DLC1chr812973166-0.0011233080.99887663
ENST00000276440ENST00000512044DOCK5chr825042466+DLC1chr812973166-0.0019436570.9980564
ENST00000410074ENST00000276297DOCK5chr825042466+DLC1chr812973166-0.0003560320.9996439
ENST00000410074ENST00000358919DOCK5chr825042466+DLC1chr812973166-0.0014045860.9985954
ENST00000410074ENST00000512044DOCK5chr825042466+DLC1chr812973166-0.0023415630.9976584
ENST00000481100ENST00000276297DOCK5chr825042466+DLC1chr812973166-0.0003365350.9996635
ENST00000481100ENST00000358919DOCK5chr825042466+DLC1chr812973166-0.0013343040.9986657
ENST00000481100ENST00000512044DOCK5chr825042466+DLC1chr812973166-0.0022643410.9977356

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 DOCK5-DLC1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DOCK5chr825042466DLC1chr81297316618014ARWIPTKRQKYGVEIEAKEACDWLRA
DOCK5chr825042466DLC1chr81297316622914ARWIPTKRQKYGVEIEAKEACDWLRA
DOCK5chr825042466DLC1chr8129731668714ARWIPTKRQKYGVEIEAKEACDWLRA

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Potential FusionNeoAntigen Information of DOCK5-DLC1 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.
DOCK5-DLC1_25042466_12973166.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)
DOCK5-DLC1chr825042466chr81297316687HLA-B50:02VEIEAKEA0.99970.54551220
DOCK5-DLC1chr825042466chr81297316687HLA-B45:01VEIEAKEA0.9990.8441220
DOCK5-DLC1chr825042466chr81297316687HLA-B50:01VEIEAKEA0.99430.72571220
DOCK5-DLC1chr825042466chr81297316687HLA-B41:01VEIEAKEA0.99060.90771220
DOCK5-DLC1chr825042466chr81297316687HLA-B13:02RQKYGVEI0.98230.5638715
DOCK5-DLC1chr825042466chr81297316687HLA-B52:01RQKYGVEI0.60340.8446715
DOCK5-DLC1chr825042466chr81297316687HLA-B27:05KRQKYGVEI0.99960.6738615
DOCK5-DLC1chr825042466chr81297316687HLA-B27:04KRQKYGVEI0.99950.588615
DOCK5-DLC1chr825042466chr81297316687HLA-B39:06QKYGVEIEA0.99560.8876817
DOCK5-DLC1chr825042466chr81297316687HLA-B45:01VEIEAKEAC0.93020.70461221
DOCK5-DLC1chr825042466chr81297316687HLA-B50:02VEIEAKEAC0.8730.52241221
DOCK5-DLC1chr825042466chr81297316687HLA-B41:01VEIEAKEAC0.38030.89421221
DOCK5-DLC1chr825042466chr81297316687HLA-B50:01VEIEAKEAC0.18350.72791221
DOCK5-DLC1chr825042466chr81297316687HLA-B44:03VEIEAKEACDW0.99940.92151223
DOCK5-DLC1chr825042466chr81297316687HLA-B40:06VEIEAKEA0.99990.64821220
DOCK5-DLC1chr825042466chr81297316687HLA-B27:14KRQKYGVEI0.99960.5766615
DOCK5-DLC1chr825042466chr81297316687HLA-B40:06VEIEAKEAC0.98670.56981221
DOCK5-DLC1chr825042466chr81297316687HLA-C07:05KRQKYGVEI0.9860.8788615
DOCK5-DLC1chr825042466chr81297316687HLA-C07:27KRQKYGVEI0.9850.8647615
DOCK5-DLC1chr825042466chr81297316687HLA-B27:03KRQKYGVEI0.97530.6886615
DOCK5-DLC1chr825042466chr81297316687HLA-B73:01QKYGVEIEA0.88870.6654817
DOCK5-DLC1chr825042466chr81297316687HLA-B15:04RQKYGVEIEA0.9620.7974717
DOCK5-DLC1chr825042466chr81297316687HLA-B27:14KRQKYGVEIEA0.99990.5369617
DOCK5-DLC1chr825042466chr81297316687HLA-B50:04VEIEAKEA0.99430.72571220
DOCK5-DLC1chr825042466chr81297316687HLA-B50:05VEIEAKEA0.99430.72571220
DOCK5-DLC1chr825042466chr81297316687HLA-B27:08KRQKYGVEI0.99960.556615
DOCK5-DLC1chr825042466chr81297316687HLA-B27:06KRQKYGVEI0.99950.5987615
DOCK5-DLC1chr825042466chr81297316687HLA-B27:10KRQKYGVEI0.99950.6898615
DOCK5-DLC1chr825042466chr81297316687HLA-B27:09KRQKYGVEI0.99910.6714615
DOCK5-DLC1chr825042466chr81297316687HLA-C06:08KRQKYGVEI0.97320.9782615
DOCK5-DLC1chr825042466chr81297316687HLA-C07:04KRQKYGVEI0.69380.8618615
DOCK5-DLC1chr825042466chr81297316687HLA-C06:06KRQKYGVEI0.34150.9632615
DOCK5-DLC1chr825042466chr81297316687HLA-C06:17KRQKYGVEI0.1850.9802615
DOCK5-DLC1chr825042466chr81297316687HLA-C06:02KRQKYGVEI0.1850.9802615
DOCK5-DLC1chr825042466chr81297316687HLA-B50:04VEIEAKEAC0.18350.72791221
DOCK5-DLC1chr825042466chr81297316687HLA-B50:05VEIEAKEAC0.18350.72791221
DOCK5-DLC1chr825042466chr81297316687HLA-B44:26VEIEAKEACDW0.99940.92151223
DOCK5-DLC1chr825042466chr81297316687HLA-B44:13VEIEAKEACDW0.99940.92151223
DOCK5-DLC1chr825042466chr81297316687HLA-B44:07VEIEAKEACDW0.99940.92151223

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Potential FusionNeoAntigen Information of DOCK5-DLC1 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.
DOCK5-DLC1_25042466_12973166.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)
DOCK5-DLC1chr825042466chr81297316687DRB1-1114ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1120ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1168ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1186ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1302ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1316ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1323ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1329ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1331ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1334ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1336ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1339ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1341ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1373ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1374ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1396ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1397ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1399ARWIPTKRQKYGVEI015
DOCK5-DLC1chr825042466chr81297316687DRB1-1442ARWIPTKRQKYGVEI015

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Fusion breakpoint peptide structures of DOCK5-DLC1

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
4574KRQKYGVEIEAKEADOCK5DLC1chr825042466chr81297316687

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DOCK5-DLC1

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-B14:023BVN4574KRQKYGVEIEAKEA-7.15543-7.26883
HLA-B14:023BVN4574KRQKYGVEIEAKEA-4.77435-5.80965
HLA-B52:013W394574KRQKYGVEIEAKEA-6.80875-6.92215
HLA-B52:013W394574KRQKYGVEIEAKEA-4.20386-5.23916
HLA-A11:014UQ24574KRQKYGVEIEAKEA-7.5194-8.5547
HLA-A11:014UQ24574KRQKYGVEIEAKEA-6.9601-7.0735
HLA-A24:025HGA4574KRQKYGVEIEAKEA-7.52403-7.63743
HLA-A24:025HGA4574KRQKYGVEIEAKEA-5.82433-6.85963
HLA-B27:056PYJ4574KRQKYGVEIEAKEA-3.28285-4.31815
HLA-B44:053DX84574KRQKYGVEIEAKEA-5.91172-6.94702
HLA-B44:053DX84574KRQKYGVEIEAKEA-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of DOCK5-DLC1

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
DOCK5-DLC1chr825042466chr8129731661220VEIEAKEATTGAAATTGAAGCCAAGGAAGCTT
DOCK5-DLC1chr825042466chr8129731661221VEIEAKEACTTGAAATTGAAGCCAAGGAAGCTTGTG
DOCK5-DLC1chr825042466chr8129731661223VEIEAKEACDWTTGAAATTGAAGCCAAGGAAGCTTGTGATTGGC
DOCK5-DLC1chr825042466chr812973166615KRQKYGVEIAGAGGCAGAAGTACGGGGTTGAAATTG
DOCK5-DLC1chr825042466chr812973166617KRQKYGVEIEAAGAGGCAGAAGTACGGGGTTGAAATTGAAGCCA
DOCK5-DLC1chr825042466chr812973166715RQKYGVEIGGCAGAAGTACGGGGTTGAAATTG
DOCK5-DLC1chr825042466chr812973166717RQKYGVEIEAGGCAGAAGTACGGGGTTGAAATTGAAGCCA
DOCK5-DLC1chr825042466chr812973166817QKYGVEIEAAGAAGTACGGGGTTGAAATTGAAGCCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
DOCK5-DLC1chr825042466chr812973166015ARWIPTKRQKYGVEICCCGCTGGATCCCGACCAAGAGGCAGAAGTACGGGGTTGAAATTG

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Information of the samples that have these potential fusion neoantigens of DOCK5-DLC1

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
STADDOCK5-DLC1chr825042466ENST00000276440chr812973166ENST00000276297TCGA-VQ-A91N

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Potential target of CAR-T therapy development for DOCK5-DLC1

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 DOCK5-DLC1

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 DOCK5-DLC1

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