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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:LAMTOR1-UVRAG

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LAMTOR1-UVRAG
FusionPDB ID: 44006
FusionGDB2.0 ID: 44006
HgeneTgene
Gene symbol

LAMTOR1

UVRAG

Gene ID

55004

7405

Gene namelate endosomal/lysosomal adaptor, MAPK and MTOR activator 1UV radiation resistance associated
SynonymsC11orf59|PDRO|Ragulator1|p18|p27RF-RhoDHTX|VPS38|p63
Cytomap

11q13.4

11q13.5

Type of geneprotein-codingprotein-coding
Descriptionragulator complex protein LAMTOR1RhoA activator C11orf59late endosomal/lysosomal adaptor and MAPK and MTOR activator 1lipid raft adaptor protein p18p27Kip1-releasing factor from RhoAp27kip1 releasing factor from RhoAprotein associated with DRMs and UV radiation resistance-associated gene proteinbeclin 1 binding proteindisrupted in heterotaxy
Modification date2020032720200313
UniProtAcc

Q6IAA8

Main function of 5'-partner protein: FUNCTION: As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. LAMTOR1 is directly responsible for anchoring the Ragulator complex to membranes. Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes. May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes. May also play a role in RHOA activation. {ECO:0000269|PubMed:19654316, ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:20544018, ECO:0000269|PubMed:22980980}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000278671, ENST00000545249, 
ENST00000539797, ENST00000535107, 
ENST00000538404, 
ENST00000528420, 
ENST00000525872, ENST00000531818, 
ENST00000532130, ENST00000533454, 
ENST00000538870, ENST00000539288, 
ENST00000356136, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 4=6428 X 21 X 11=6468
# samples 436
** MAII scorelog2(4/64*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(36/6468*10)=-4.16725086714399
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LAMTOR1 [Title/Abstract] AND UVRAG [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LAMTOR1 [Title/Abstract] AND UVRAG [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LAMTOR1(71809335)-UVRAG(75562928), # samples:1
Anticipated loss of major functional domain due to fusion event.LAMTOR1-UVRAG 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.
LAMTOR1-UVRAG 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.
LAMTOR1-UVRAG 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.
LAMTOR1-UVRAG 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
TgeneUVRAG

GO:0071900

regulation of protein serine/threonine kinase activity

22542840

TgeneUVRAG

GO:0097352

autophagosome maturation

28306502

TgeneUVRAG

GO:0097680

double-strand break repair via classical nonhomologous end joining

22542840



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/chr11:71809335/chr11:75562928)
- 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 LAMTOR1 (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 UVRAG (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)
ENST00000545249LAMTOR1chr1171809335-ENST00000356136UVRAGchr1175562928+4180415222397791
ENST00000278671LAMTOR1chr1171809335-ENST00000356136UVRAGchr1175562928+43215561632538791

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
ENST00000545249ENST00000356136LAMTOR1chr1171809335-UVRAGchr1175562928+0.0022807870.9977192
ENST00000278671ENST00000356136LAMTOR1chr1171809335-UVRAGchr1175562928+0.0023108540.9976891

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 LAMTOR1-UVRAG

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LAMTOR1chr1171809335UVRAGchr1175562928415130VLASEPIPFSDLQQRRLRHLRNIAAR
LAMTOR1chr1171809335UVRAGchr1175562928556130VLASEPIPFSDLQQRRLRHLRNIAAR

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Potential FusionNeoAntigen Information of LAMTOR1-UVRAG 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.
LAMTOR1-UVRAG_71809335_75562928.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)
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-B35:03IPFSDLQQRRL0.99320.885617
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-B35:04IPFSDLQQRRL0.96660.8758617
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-B35:02IPFSDLQQRRL0.96660.8758617
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C04:10FSDLQQRRL10.7269817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C05:09FSDLQQRRL10.8613817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C08:15FSDLQQRRL0.99990.9579817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C04:07FSDLQQRRL0.99990.752817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C01:17FSDLQQRRL0.99980.9134817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C03:07FSDLQQRRL0.99930.8846817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C03:19FSDLQQRRL0.99870.9721817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C03:08FSDLQQRRL0.99840.865817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C15:06FSDLQQRRL0.99790.78817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C15:04FSDLQQRRL0.99710.7384817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C04:06FSDLQQRRL0.99590.8017817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C01:30FSDLQQRRL0.99370.9461817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C08:13FSDLQQRRL0.98180.8715817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C08:04FSDLQQRRL0.98180.8715817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C03:14FSDLQQRRL0.96780.919817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C08:03FSDLQQRRL0.89920.9635817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C07:13FSDLQQRRL0.89460.8842817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C07:29FSDLQQRRL0.86650.9099817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C04:14FSDLQQRRL0.85820.7637817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C06:03FSDLQQRRL0.77410.9811817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C12:04FSDLQQRRL0.77360.9854817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C12:12FSDLQQRRL0.59630.8537817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C02:06FSDLQQRRL0.50220.8594817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-B35:12IPFSDLQQRRL0.96660.8758617
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-B39:10IPFSDLQQRRL0.8520.8791617
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C05:01FSDLQQRRL10.8613817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C04:03FSDLQQRRL10.7565817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C04:01FSDLQQRRL0.99990.752817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C18:01FSDLQQRRL0.99990.7349817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C08:02FSDLQQRRL0.99990.9579817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C01:03FSDLQQRRL0.99990.8461817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C01:02FSDLQQRRL0.99980.9123817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C03:04FSDLQQRRL0.99920.981817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C03:03FSDLQQRRL0.99920.981817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C06:06FSDLQQRRL0.99890.9852817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C03:05FSDLQQRRL0.99780.9002817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C15:05FSDLQQRRL0.99770.7753817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C03:17FSDLQQRRL0.99740.9425817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C15:09FSDLQQRRL0.99710.7384817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C03:02FSDLQQRRL0.99660.9579817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C03:67FSDLQQRRL0.99610.9688817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C15:02FSDLQQRRL0.99540.7394817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C04:04FSDLQQRRL0.99240.7994817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C03:06FSDLQQRRL0.97020.9758817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C16:02FSDLQQRRL0.92770.9889817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C08:01FSDLQQRRL0.89920.9635817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C07:04FSDLQQRRL0.88110.9238817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C16:01FSDLQQRRL0.87010.9687817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C16:04FSDLQQRRL0.82590.9555817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C12:03FSDLQQRRL0.66170.9532817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C17:01FSDLQQRRL0.64250.6375817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C12:02FSDLQQRRL0.56530.9459817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C02:02FSDLQQRRL0.42360.9158817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-C02:10FSDLQQRRL0.42360.9158817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-B07:13FSDLQQRRL0.02410.6427817
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-B35:13IPFSDLQQRRL0.99230.888617
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-B35:09IPFSDLQQRRL0.96660.8758617
LAMTOR1-UVRAGchr1171809335chr1175562928556HLA-B67:01IPFSDLQQRRL0.85870.819617

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Potential FusionNeoAntigen Information of LAMTOR1-UVRAG 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.
LAMTOR1-UVRAG_71809335_75562928.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)
LAMTOR1-UVRAGchr1171809335chr1175562928556DRB1-0415LQQRRLRHLRNIAAR1126
LAMTOR1-UVRAGchr1171809335chr1175562928556DRB1-0436LQQRRLRHLRNIAAR1126
LAMTOR1-UVRAGchr1171809335chr1175562928556DRB1-0453LQQRRLRHLRNIAAR1126
LAMTOR1-UVRAGchr1171809335chr1175562928556DRB1-1216EPIPFSDLQQRRLRH419
LAMTOR1-UVRAGchr1171809335chr1175562928556DRB1-1216PIPFSDLQQRRLRHL520
LAMTOR1-UVRAGchr1171809335chr1175562928556DRB1-1615LQQRRLRHLRNIAAR1126

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Fusion breakpoint peptide structures of LAMTOR1-UVRAG

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
3881IPFSDLQQRRLRHLLAMTOR1UVRAGchr1171809335chr1175562928556

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LAMTOR1-UVRAG

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-B14:023BVN3881IPFSDLQQRRLRHL-7.9962-8.1096
HLA-B14:023BVN3881IPFSDLQQRRLRHL-5.70842-6.74372
HLA-B52:013W393881IPFSDLQQRRLRHL-6.83737-6.95077
HLA-B52:013W393881IPFSDLQQRRLRHL-4.4836-5.5189
HLA-A11:014UQ23881IPFSDLQQRRLRHL-10.0067-10.1201
HLA-A11:014UQ23881IPFSDLQQRRLRHL-9.03915-10.0745
HLA-A24:025HGA3881IPFSDLQQRRLRHL-6.56204-6.67544
HLA-A24:025HGA3881IPFSDLQQRRLRHL-5.42271-6.45801
HLA-B44:053DX83881IPFSDLQQRRLRHL-7.85648-8.89178
HLA-B44:053DX83881IPFSDLQQRRLRHL-5.3978-5.5112
HLA-A02:016TDR3881IPFSDLQQRRLRHL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of LAMTOR1-UVRAG

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
LAMTOR1-UVRAGchr1171809335chr1175562928617IPFSDLQQRRLCCGTTCTCTGATTTGCAGCAGCGGCGTCTTCGA
LAMTOR1-UVRAGchr1171809335chr1175562928817FSDLQQRRLTCTGATTTGCAGCAGCGGCGTCTTCGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
LAMTOR1-UVRAGchr1171809335chr11755629281126LQQRRLRHLRNIAARCAGCAGCGGCGTCTTCGACATCTTCGGAACATTGCTGCCCGGAAC
LAMTOR1-UVRAGchr1171809335chr1175562928419EPIPFSDLQQRRLRHCCCATCCCGTTCTCTGATTTGCAGCAGCGGCGTCTTCGACATCTT
LAMTOR1-UVRAGchr1171809335chr1175562928520PIPFSDLQQRRLRHLATCCCGTTCTCTGATTTGCAGCAGCGGCGTCTTCGACATCTTCGG

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Information of the samples that have these potential fusion neoantigens of LAMTOR1-UVRAG

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
HNSCLAMTOR1-UVRAGchr1171809335ENST00000278671chr1175562928ENST00000356136TCGA-UF-A7JV-01A

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Potential target of CAR-T therapy development for LAMTOR1-UVRAG

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 LAMTOR1-UVRAG

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 LAMTOR1-UVRAG

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