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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:MICU2-ATP8A2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MICU2-ATP8A2
FusionPDB ID: 53580
FusionGDB2.0 ID: 53580
HgeneTgene
Gene symbol

MICU2

ATP8A2

Gene ID

221154

51761

Gene namemitochondrial calcium uptake 2ATPase phospholipid transporting 8A2
Synonyms1110008L20Rik|EFHA1ATP|ATPIB|CAMRQ4|IB|ML-1
Cytomap

13q12.11

13q12.13

Type of geneprotein-codingprotein-coding
Descriptioncalcium uptake protein 2, mitochondrialEF hand domain family A1EF hand domain family, member A1EF-hand domain-containing family member A1Smhs2 homologphospholipid-transporting ATPase IBATPase, aminophospholipid transporter, class I, type 8A, member 2ATPase, aminophospholipid transporter-like, class I, type 8A, member 2P4-ATPase flippase complex alpha subunit ATP8A2probable phospholipid-transporting
Modification date2020031520200329
UniProtAcc

Q8IYU8

Main function of 5'-partner protein: FUNCTION: Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:24503055, PubMed:24560927, PubMed:26903221). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulate and inhibit MCU activity, depending on the concentration of calcium (PubMed:24560927). MICU2 acts as a gatekeeper of MCU that senses calcium level via its EF-hand domains: prevents channel opening at resting calcium, avoiding energy dissipation and cell-death triggering (PubMed:24560927). {ECO:0000269|PubMed:24503055, ECO:0000269|PubMed:24560927, ECO:0000269|PubMed:26387864, ECO:0000269|PubMed:26903221}.

Q9NTI2

Main function of 5'-partner protein: FUNCTION: Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. Reconstituted to liposomes, the ATP8A2:TMEM30A flippase complex predominantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). Phospholipid translocation is not associated with a countertransport of an inorganic ion or other charged substrate from the cytoplasmic side toward the exoplasm in connection with the phosphorylation from ATP. ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth. Proposed to function in the generation and maintenance of phospholipid asymmetry in photoreceptor disk membranes and neuronal axon membranes. May be involved in vesicle trafficking in neuronal cells. Required for normal visual and auditory function; involved in photoreceptor and inner ear spiral ganglion cell survival. {ECO:0000250|UniProtKB:C7EXK4}.
Ensembl transtripts involved in fusion geneENST idsENST00000382374, ENST00000479790, 
ENST00000491840, ENST00000255283, 
ENST00000381655, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 3 X 3=4513 X 13 X 7=1183
# samples 515
** MAII scorelog2(5/45*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(15/1183*10)=-2.97941566784391
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MICU2 [Title/Abstract] AND ATP8A2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MICU2 [Title/Abstract] AND ATP8A2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MICU2(22178078)-ATP8A2(26402256), # samples:2
Anticipated loss of major functional domain due to fusion event.MICU2-ATP8A2 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.
MICU2-ATP8A2 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.
MICU2-ATP8A2 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.
MICU2-ATP8A2 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
HgeneMICU2

GO:0006851

mitochondrial calcium ion transmembrane transport

24560927

HgeneMICU2

GO:0051562

negative regulation of mitochondrial calcium ion concentration

24560927



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/chr13:22178078/chr13:26402256)
- 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 MICU2 (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 ATP8A2 (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)
ENST00000382374MICU2chr1322178078-ENST00000381655ATP8A2chr1326402256+7030276661163365

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
ENST00000382374ENST00000381655MICU2chr1322178078-ATP8A2chr1326402256+0.0143144620.9856856

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 MICU2-ATP8A2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MICU2chr1322178078ATP8A2chr132640225627669SVAARDGSFTVSAQLWFAFVNGFSGQ

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Potential FusionNeoAntigen Information of MICU2-ATP8A2 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.
MICU2-ATP8A2_22178078_26402256.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)
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:01FTVSAQLW0.99810.9913816
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B58:01FTVSAQLW0.99650.9866816
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B15:17FTVSAQLW0.99610.9842816
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B58:02FTVSAQLW0.99570.9883816
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:03FTVSAQLW0.99020.9954816
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:01VSAQLWFAF0.9960.97331019
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B15:17VSAQLWFAF0.99540.96031019
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B15:16VSAQLWFAF0.99350.9311019
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B58:01VSAQLWFAF0.9930.95341019
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B58:02VSAQLWFAF0.9930.93841019
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A24:23SFTVSAQLW0.99090.714716
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:03VSAQLWFAF0.98910.98961019
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A24:20SFTVSAQLW0.98910.7452716
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A24:15SFTVSAQLW0.98850.7692716
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A24:25SFTVSAQLW0.98840.7481716
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A24:31SFTVSAQLW0.98560.7571716
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B15:17FTVSAQLWF0.97950.965817
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A24:10SFTVSAQLW0.97670.7011716
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B15:16FTVSAQLWF0.97550.9481817
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A24:17SFTVSAQLW0.97550.6886716
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B58:01FTVSAQLWF0.97470.9669817
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B15:16GSFTVSAQL0.97410.8247615
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B15:17GSFTVSAQL0.97390.8897615
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A31:08SFTVSAQLW0.96130.758716
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A32:13VSAQLWFAF0.89160.89971019
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:03FTVSAQLWF0.86470.9895817
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A24:14SFTVSAQLW0.62020.6638716
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:01GSFTVSAQLW0.99990.9916616
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B58:02GSFTVSAQLW0.99910.9844616
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B58:01GSFTVSAQLW0.99870.9876616
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:03GSFTVSAQLW0.99740.9971616
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B15:17GSFTVSAQLW0.9960.9791616
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B15:16GSFTVSAQLW0.98860.9791616
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C15:06GSFTVSAQL0.99860.869615
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C03:08GSFTVSAQL0.99820.9057615
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A24:02SFTVSAQLW0.98910.7452716
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C15:04FTVSAQLWF0.87640.8752817
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C02:06GSFTVSAQL0.62130.9465615
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C03:14FTVSAQLWF0.55460.9621817
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:04FTVSAQLW0.99830.832816
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:10FTVSAQLW0.99810.9913816
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B58:06FTVSAQLW0.99630.9913816
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:02FTVSAQLW0.99520.961816
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C14:03SFTVSAQL0.85680.9505715
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C14:02SFTVSAQL0.85680.9505715
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C15:02GSFTVSAQL0.99840.7918615
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C15:05GSFTVSAQL0.99820.8574615
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:04VSAQLWFAF0.99650.68051019
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:10VSAQLWFAF0.9960.97331019
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A24:03SFTVSAQLW0.99090.714716
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:02VSAQLWFAF0.98690.95321019
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:02FTVSAQLWF0.97360.9362817
MICU2-ATP8A2chr1322178078chr1326402256276HLA-A32:01VSAQLWFAF0.9570.90971019
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C03:02FTVSAQLWF0.94950.9798817
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C15:09FTVSAQLWF0.87640.8752817
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C17:01GSFTVSAQL0.54250.9666615
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B15:13SFTVSAQLW0.53770.9474716
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C02:10FTVSAQLWF0.12310.9804817
MICU2-ATP8A2chr1322178078chr1326402256276HLA-C02:02FTVSAQLWF0.12310.9804817
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:10GSFTVSAQLW0.99990.9916616
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:04GSFTVSAQLW0.99960.8305616
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B58:06GSFTVSAQLW0.99810.9828616
MICU2-ATP8A2chr1322178078chr1326402256276HLA-B57:02GSFTVSAQLW0.99590.9823616

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Potential FusionNeoAntigen Information of MICU2-ATP8A2 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.

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)

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Fusion breakpoint peptide structures of MICU2-ATP8A2

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
3118GSFTVSAQLWFAFVMICU2ATP8A2chr1322178078chr1326402256276

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MICU2-ATP8A2

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-B14:023BVN3118GSFTVSAQLWFAFV-7.54146-7.65486
HLA-B14:023BVN3118GSFTVSAQLWFAFV-5.05101-6.08631
HLA-B52:013W393118GSFTVSAQLWFAFV-7.48565-7.59905
HLA-B52:013W393118GSFTVSAQLWFAFV-5.61839-6.65369
HLA-A11:014UQ23118GSFTVSAQLWFAFV-5.36758-5.48098
HLA-A11:014UQ23118GSFTVSAQLWFAFV-2.41377-3.44907
HLA-A24:025HGA3118GSFTVSAQLWFAFV-8.3266-8.44
HLA-A24:025HGA3118GSFTVSAQLWFAFV-5.24481-6.28011
HLA-B44:053DX83118GSFTVSAQLWFAFV-4.07996-5.11526
HLA-B44:053DX83118GSFTVSAQLWFAFV-3.86967-3.98307

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Vaccine Design for the FusionNeoAntigens of MICU2-ATP8A2

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
MICU2-ATP8A2chr1322178078chr13264022561019VSAQLWFAFTCCGCACAGCTTTGGTTCGCCTTTGTT
MICU2-ATP8A2chr1322178078chr1326402256615GSFTVSAQLAGTTTTACAGTCTCCGCACAGCTTTGG
MICU2-ATP8A2chr1322178078chr1326402256616GSFTVSAQLWAGTTTTACAGTCTCCGCACAGCTTTGGTTC
MICU2-ATP8A2chr1322178078chr1326402256715SFTVSAQLTTTACAGTCTCCGCACAGCTTTGG
MICU2-ATP8A2chr1322178078chr1326402256716SFTVSAQLWTTTACAGTCTCCGCACAGCTTTGGTTC
MICU2-ATP8A2chr1322178078chr1326402256816FTVSAQLWACAGTCTCCGCACAGCTTTGGTTC
MICU2-ATP8A2chr1322178078chr1326402256817FTVSAQLWFACAGTCTCCGCACAGCTTTGGTTCGCC

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

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Information of the samples that have these potential fusion neoantigens of MICU2-ATP8A2

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
BRCAMICU2-ATP8A2chr1322178078ENST00000382374chr1326402256ENST00000381655TCGA-E9-A22D-01A

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Potential target of CAR-T therapy development for MICU2-ATP8A2

check button Predicted 3D structure. We used RoseTTAFold.
281_MICU2-ATP8A2_33c2a_pred.pdb


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
TgeneATP8A2chr13:22178078chr13:26402256ENST0000038165526371029_104901189.0TransmembraneHelical
TgeneATP8A2chr13:22178078chr13:26402256ENST0000038165526371064_108401189.0TransmembraneHelical
TgeneATP8A2chr13:22178078chr13:26402256ENST000003816552637911_93101189.0TransmembraneHelical
TgeneATP8A2chr13:22178078chr13:26402256ENST000003816552637960_98001189.0TransmembraneHelical
TgeneATP8A2chr13:22178078chr13:26402256ENST000003816552637998_101801189.0TransmembraneHelical

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
MICU2chr1322178078ENST00000382374ATP8A2chr1326402256ENST00000381655

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Related Drugs to MICU2-ATP8A2

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 MICU2-ATP8A2

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