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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:NLRC5-ILF2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NLRC5-ILF2
FusionPDB ID: 59373
FusionGDB2.0 ID: 59373
HgeneTgene
Gene symbol

NLRC5

ILF2

Gene ID

84166

3608

Gene nameNLR family CARD domain containing 5interleukin enhancer binding factor 2
SynonymsCLR16.1|NOD27|NOD4NF45|PRO3063
Cytomap

16q13

1q21.3

Type of geneprotein-codingprotein-coding
Descriptionprotein NLRC5NOD-like receptor C5caterpiller protein 16.1nucleotide-binding oligomerization domain protein 4nucleotide-binding oligomerization domain, leucine rich repeat and CARD domain containing 5nucleotide-binding oligomerization domains 27interleukin enhancer-binding factor 2interleukin enhancer binding factor 2, 45kDinterleukin enhancer binding factor 2, 45kDanuclear factor of activated T-cells, 45-kDa
Modification date2020031320200313
UniProtAcc

Q86WI3

Main function of 5'-partner protein: FUNCTION: Probable regulator of the NF-kappa-B and type I interferon signaling pathways. May also regulate the type II interferon signaling pathway. Plays a role in homeostatic control of innate immunity and in antiviral defense mechanisms. {ECO:0000269|PubMed:20061403, ECO:0000269|PubMed:20434986}.

Q12905

Main function of 5'-partner protein: FUNCTION: Appears to function predominantly as a heterodimeric complex with ILF3. This complex may regulate transcription of the IL2 gene during T-cell activation. It can also promote the formation of stable DNA-dependent protein kinase holoenzyme complexes on DNA. Essential for the efficient reshuttling of ILF3 (isoform 1 and isoform 2) into the nucleus. {ECO:0000269|PubMed:10574923, ECO:0000269|PubMed:11739746, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:9442054}.
Ensembl transtripts involved in fusion geneENST idsENST00000262510, ENST00000308149, 
ENST00000436936, ENST00000539144, 
ENST00000543141, 
ENST00000368681, 
ENST00000480213, ENST00000361891, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 10 X 6=4808 X 8 X 3=192
# samples 108
** MAII scorelog2(10/480*10)=-2.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/192*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NLRC5 [Title/Abstract] AND ILF2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NLRC5 [Title/Abstract] AND ILF2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NLRC5(57054919)-ILF2(153636950), # samples:1
Anticipated loss of major functional domain due to fusion event.NLRC5-ILF2 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.
NLRC5-ILF2 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.
NLRC5-ILF2 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.
NLRC5-ILF2 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.
NLRC5-ILF2 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
NLRC5-ILF2 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneNLRC5

GO:0032088

negative regulation of NF-kappaB transcription factor activity

20434986

HgeneNLRC5

GO:0043549

regulation of kinase activity

20434986

HgeneNLRC5

GO:0045345

positive regulation of MHC class I biosynthetic process

20639463

HgeneNLRC5

GO:0045944

positive regulation of transcription by RNA polymerase II

20639463

HgeneNLRC5

GO:0060335

positive regulation of interferon-gamma-mediated signaling pathway

20061403

HgeneNLRC5

GO:0060339

negative regulation of type I interferon-mediated signaling pathway

20434986

HgeneNLRC5

GO:0060340

positive regulation of type I interferon-mediated signaling pathway

20061403

TgeneILF2

GO:0006351

transcription, DNA-templated

11739746

TgeneILF2

GO:0045893

positive regulation of transcription, DNA-templated

11739746



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/chr16:57054919/chr1:153636950)
- 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 NLRC5 (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 ILF2 (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)
ENST00000262510NLRC5chr1657054919+ENST00000361891ILF2chr1153636950-14765202251115296
ENST00000436936NLRC5chr1657054919+ENST00000361891ILF2chr1153636950-14765202251115296
ENST00000308149NLRC5chr1657054919+ENST00000361891ILF2chr1153636950-14765202251115296
ENST00000539144NLRC5chr1657054919+ENST00000361891ILF2chr1153636950-12512950890296

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
ENST00000262510ENST00000361891NLRC5chr1657054919+ILF2chr1153636950-0.0056857730.99431425
ENST00000436936ENST00000361891NLRC5chr1657054919+ILF2chr1153636950-0.0056857730.99431425
ENST00000308149ENST00000361891NLRC5chr1657054919+ILF2chr1153636950-0.0056857730.99431425
ENST00000539144ENST00000361891NLRC5chr1657054919+ILF2chr1153636950-0.0038243570.99617565

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 NLRC5-ILF2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NLRC5chr1657054919ILF2chr115363695029598LEVLLLSTFGYDDVDIKVLQSALAAI
NLRC5chr1657054919ILF2chr115363695052098LEVLLLSTFGYDDVDIKVLQSALAAI

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Potential FusionNeoAntigen Information of NLRC5-ILF2 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.
NLRC5-ILF2_57054919_153636950.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)
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:10GYDDVDIKV0.98190.6619918
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:07GYDDVDIKV0.97820.6418918
NLRC5-ILF2chr1657054919chr1153636950520HLA-B39:08YDDVDIKVL0.73140.52881019
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:14GYDDVDIKV0.44280.6814918
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:10GYDDVDIKVL0.99960.6538919
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:07GYDDVDIKVL0.99950.6516919
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:10FGYDDVDIKV0.99650.7019818
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:07FGYDDVDIKV0.99610.6822818
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:14GYDDVDIKVL0.97530.6541919
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:14FGYDDVDIKV0.94950.6889818
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:10TFGYDDVDIKV0.99910.7165718
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:07TFGYDDVDIKV0.9990.7046718
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:03GYDDVDIKV0.98870.6728918
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:01GYDDVDIKV0.97820.6418918
NLRC5-ILF2chr1657054919chr1153636950520HLA-C18:01GYDDVDIKV0.97210.6723918
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:04GYDDVDIKV0.45630.7093918
NLRC5-ILF2chr1657054919chr1153636950520HLA-C07:04GYDDVDIKV0.05280.8224918
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:01GYDDVDIKVL0.99950.6516919
NLRC5-ILF2chr1657054919chr1153636950520HLA-C18:01GYDDVDIKVL0.99940.6648919
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:01FGYDDVDIKV0.99610.6822818
NLRC5-ILF2chr1657054919chr1153636950520HLA-C18:01FGYDDVDIKV0.99030.7084818
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:04FGYDDVDIKV0.97360.7402818
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:04GYDDVDIKVL0.9680.6824919
NLRC5-ILF2chr1657054919chr1153636950520HLA-C04:01TFGYDDVDIKV0.9990.7046718

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Potential FusionNeoAntigen Information of NLRC5-ILF2 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.
NLRC5-ILF2_57054919_153636950.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)
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0102YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0102DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0111DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0123YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0123DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0129DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0415YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0415DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0436YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0436DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0440DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0440YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0442DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0442YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0444DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0444YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0453DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0453YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0455DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0455YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0456DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0456YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0458DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0458YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0468DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0468YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0470DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0470YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0478YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0478DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0479DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0479YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-0488DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-1002YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-1002DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-1204DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-1209DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-1521DDVDIKVLQSALAAI1126
NLRC5-ILF2chr1657054919chr1153636950520DRB1-1615YDDVDIKVLQSALAA1025
NLRC5-ILF2chr1657054919chr1153636950520DRB1-1615DDVDIKVLQSALAAI1126

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Fusion breakpoint peptide structures of NLRC5-ILF2

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
9102STFGYDDVDIKVLQNLRC5ILF2chr1657054919chr1153636950520

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NLRC5-ILF2

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-B14:023BVN9102STFGYDDVDIKVLQ-5.42908-5.54248
HLA-B14:023BVN9102STFGYDDVDIKVLQ-5.06008-6.09538
HLA-B52:013W399102STFGYDDVDIKVLQ-9.1987-9.3121
HLA-B52:013W399102STFGYDDVDIKVLQ-7.53083-8.56613
HLA-A11:014UQ29102STFGYDDVDIKVLQ-8.87547-8.98887
HLA-A24:025HGA9102STFGYDDVDIKVLQ-7.78065-7.89405
HLA-A24:025HGA9102STFGYDDVDIKVLQ-7.11918-8.15448
HLA-B27:056PYJ9102STFGYDDVDIKVLQ-7.64943-7.76283
HLA-B27:056PYJ9102STFGYDDVDIKVLQ-6.50173-7.53703
HLA-B44:053DX89102STFGYDDVDIKVLQ-7.26947-7.38287
HLA-B44:053DX89102STFGYDDVDIKVLQ-6.09544-7.13074

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Vaccine Design for the FusionNeoAntigens of NLRC5-ILF2

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
NLRC5-ILF2chr1657054919chr11536369501019YDDVDIKVLATGATGATGTGGATATCAAAGTATTGC
NLRC5-ILF2chr1657054919chr1153636950718TFGYDDVDIKVCTTTTGGCTATGATGATGTGGATATCAAAGTAT
NLRC5-ILF2chr1657054919chr1153636950818FGYDDVDIKVTTGGCTATGATGATGTGGATATCAAAGTAT
NLRC5-ILF2chr1657054919chr1153636950918GYDDVDIKVGCTATGATGATGTGGATATCAAAGTAT
NLRC5-ILF2chr1657054919chr1153636950919GYDDVDIKVLGCTATGATGATGTGGATATCAAAGTATTGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
NLRC5-ILF2chr1657054919chr11536369501025YDDVDIKVLQSALAAATGATGATGTGGATATCAAAGTATTGCAGAGTGCCTTAGCAGCCA
NLRC5-ILF2chr1657054919chr11536369501126DDVDIKVLQSALAAIATGATGTGGATATCAAAGTATTGCAGAGTGCCTTAGCAGCCATCC

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Information of the samples that have these potential fusion neoantigens of NLRC5-ILF2

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
UCECNLRC5-ILF2chr1657054919ENST00000262510chr1153636950ENST00000361891TCGA-D1-A2G7

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Potential target of CAR-T therapy development for NLRC5-ILF2

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 NLRC5-ILF2

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 NLRC5-ILF2

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