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Fusion Protein:NPEPPS-CREB3L1 |
Fusion Protein Summary |
Fusion gene summary |
Fusion partner gene information | Fusion gene name: NPEPPS-CREB3L1 | FusionPDB ID: 59877 | FusionGDB2.0 ID: 59877 | Hgene | Tgene | Gene symbol | NPEPPS | CREB3L1 | Gene ID | 9520 | 90993 |
Gene name | aminopeptidase puromycin sensitive | cAMP responsive element binding protein 3 like 1 | |
Synonyms | AAP-S|MP100|PSA | OASIS|OI16 | |
Cytomap | 17q21.32 | 11p11.2 | |
Type of gene | protein-coding | protein-coding | |
Description | puromycin-sensitive aminopeptidasecytosol alanyl aminopeptidasemetalloproteinase MP100 | cyclic AMP-responsive element-binding protein 3-like protein 1BBF-2 homologcAMP-responsive element-binding protein 3-like protein 1old astrocyte specifically-induced substance | |
Modification date | 20200313 | 20200327 | |
UniProtAcc | P55786 | Q96BA8 | |
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000525037, ENST00000322157, ENST00000530173, ENST00000544660, | ENST00000288400, ENST00000529193, ENST00000534616, |
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 18 X 9 X 9=1458 | 10 X 10 X 4=400 |
# samples | 19 | 8 | |
** MAII score | log2(19/1458*10)=-2.93991939599599 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(8/400*10)=-2.32192809488736 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
Context (manual curation of fusion genes in FusionPDB) | PubMed: NPEPPS [Title/Abstract] AND CREB3L1 [Title/Abstract] AND fusion [Title/Abstract] | ||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | NPEPPS(45623359)-CREB3L1(46341815), # samples:2 | ||
Anticipated loss of major functional domain due to fusion event. | NPEPPS-CREB3L1 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. NPEPPS-CREB3L1 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. NPEPPS-CREB3L1 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. NPEPPS-CREB3L1 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) |
Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
Partner | Gene | GO ID | GO term | PubMed ID |
Hgene | NPEPPS | GO:0071456 | cellular response to hypoxia | 21056661 |
Tgene | CREB3L1 | GO:0010629 | negative regulation of gene expression | 27121396 |
Tgene | CREB3L1 | GO:0032967 | positive regulation of collagen biosynthetic process | 25310401 |
Tgene | CREB3L1 | GO:0040037 | negative regulation of fibroblast growth factor receptor signaling pathway | 27121396 |
Tgene | CREB3L1 | GO:0045892 | negative regulation of transcription, DNA-templated | 27121396 |
Fusion gene breakpoints across NPEPPS (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
Fusion gene breakpoints across CREB3L1 (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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Fusion Gene Sample Information |
Fusion gene information from FusionGDB2.0. |
Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0) * All genome coordinats were lifted-over on hg19. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
Source | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
ChimerDB4 | UCS | TCGA-NA-A5I1-01A | NPEPPS | chr17 | 45623359 | + | CREB3L1 | chr11 | 46341815 | + |
ChimerDB4 | UCS | TCGA-NA-A5I1 | NPEPPS | chr17 | 45623359 | + | CREB3L1 | chr11 | 46341815 | + |
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Fusion ORF Analysis |
Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB. |
Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
ENST00000530173 | NPEPPS | chr17 | 45623359 | + | ENST00000529193 | CREB3L1 | chr11 | 46341815 | + | 1336 | 358 | 30 | 659 | 209 |
ENST00000530173 | NPEPPS | chr17 | 45623359 | + | ENST00000288400 | CREB3L1 | chr11 | 46341815 | + | 1334 | 358 | 30 | 659 | 209 |
ENST00000322157 | NPEPPS | chr17 | 45623359 | + | ENST00000529193 | CREB3L1 | chr11 | 46341815 | + | 1555 | 577 | 66 | 878 | 270 |
ENST00000322157 | NPEPPS | chr17 | 45623359 | + | ENST00000288400 | CREB3L1 | chr11 | 46341815 | + | 1553 | 577 | 66 | 878 | 270 |
ENST00000544660 | NPEPPS | chr17 | 45623359 | + | ENST00000529193 | CREB3L1 | chr11 | 46341815 | + | 1292 | 314 | 13 | 615 | 200 |
ENST00000544660 | NPEPPS | chr17 | 45623359 | + | ENST00000288400 | CREB3L1 | chr11 | 46341815 | + | 1290 | 314 | 13 | 615 | 200 |
DeepORF 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. |
Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
ENST00000530173 | ENST00000529193 | NPEPPS | chr17 | 45623359 | + | CREB3L1 | chr11 | 46341815 | + | 0.025895497 | 0.97410446 |
ENST00000530173 | ENST00000288400 | NPEPPS | chr17 | 45623359 | + | CREB3L1 | chr11 | 46341815 | + | 0.026064781 | 0.9739352 |
ENST00000322157 | ENST00000529193 | NPEPPS | chr17 | 45623359 | + | CREB3L1 | chr11 | 46341815 | + | 0.044976186 | 0.95502377 |
ENST00000322157 | ENST00000288400 | NPEPPS | chr17 | 45623359 | + | CREB3L1 | chr11 | 46341815 | + | 0.046533797 | 0.9534662 |
ENST00000544660 | ENST00000529193 | NPEPPS | chr17 | 45623359 | + | CREB3L1 | chr11 | 46341815 | + | 0.009365995 | 0.9906341 |
ENST00000544660 | ENST00000288400 | NPEPPS | chr17 | 45623359 | + | CREB3L1 | chr11 | 46341815 | + | 0.009596954 | 0.99040306 |
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Fusion Amino Acid Sequences |
For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >59877_59877_1_NPEPPS-CREB3L1_NPEPPS_chr17_45623359_ENST00000322157_CREB3L1_chr11_46341815_ENST00000288400_length(amino acids)=270AA_BP=170 MRALLPFPPLRPLPRRQPARQSARTASFPAPSAPAGSLPRPPGSPGRSPPAVARARWMWLAAAAPSLARRLLFLGPPPPPLLLLVFSRSS RRRLHSLGLAAMPEKRPFERLPADVSPINYSLCLKPDLLDFTFEGKLEAAAQVRQATNQIVMNCADIDIITASYAPEGDEVPSRSLLFYD DGAGLWEDGRSTLLPMEPPDGWEINPGGPAEQRPRDHLQHDHLDSTHETTKYLSEAWPKDGGNGTSPDFSHSKEWFHDRDLGPNTTIKLS -------------------------------------------------------------- >59877_59877_2_NPEPPS-CREB3L1_NPEPPS_chr17_45623359_ENST00000322157_CREB3L1_chr11_46341815_ENST00000529193_length(amino acids)=270AA_BP=170 MRALLPFPPLRPLPRRQPARQSARTASFPAPSAPAGSLPRPPGSPGRSPPAVARARWMWLAAAAPSLARRLLFLGPPPPPLLLLVFSRSS RRRLHSLGLAAMPEKRPFERLPADVSPINYSLCLKPDLLDFTFEGKLEAAAQVRQATNQIVMNCADIDIITASYAPEGDEVPSRSLLFYD DGAGLWEDGRSTLLPMEPPDGWEINPGGPAEQRPRDHLQHDHLDSTHETTKYLSEAWPKDGGNGTSPDFSHSKEWFHDRDLGPNTTIKLS -------------------------------------------------------------- >59877_59877_3_NPEPPS-CREB3L1_NPEPPS_chr17_45623359_ENST00000530173_CREB3L1_chr11_46341815_ENST00000288400_length(amino acids)=209AA_BP=109 MASFSMDCSPSFCVPGLWNPFIIFRSRSSRRRLHSLGLAAMPEKRPFERLPADVSPINYSLCLKPDLLDFTFEGKLEAAAQVRQATNQIV MNCADIDIITASYAPEGDEVPSRSLLFYDDGAGLWEDGRSTLLPMEPPDGWEINPGGPAEQRPRDHLQHDHLDSTHETTKYLSEAWPKDG -------------------------------------------------------------- >59877_59877_4_NPEPPS-CREB3L1_NPEPPS_chr17_45623359_ENST00000530173_CREB3L1_chr11_46341815_ENST00000529193_length(amino acids)=209AA_BP=109 MASFSMDCSPSFCVPGLWNPFIIFRSRSSRRRLHSLGLAAMPEKRPFERLPADVSPINYSLCLKPDLLDFTFEGKLEAAAQVRQATNQIV MNCADIDIITASYAPEGDEVPSRSLLFYDDGAGLWEDGRSTLLPMEPPDGWEINPGGPAEQRPRDHLQHDHLDSTHETTKYLSEAWPKDG -------------------------------------------------------------- >59877_59877_5_NPEPPS-CREB3L1_NPEPPS_chr17_45623359_ENST00000544660_CREB3L1_chr11_46341815_ENST00000288400_length(amino acids)=200AA_BP=100 MLFLGPPPPPLLLLVFSRSSRRRLHSLGLAAMPEKRPFERLPADVSPINYSLCLKPDLLDFTFEGKLEAAAQVRQATNQIVMNCADIDII TASYAPEGDEVPSRSLLFYDDGAGLWEDGRSTLLPMEPPDGWEINPGGPAEQRPRDHLQHDHLDSTHETTKYLSEAWPKDGGNGTSPDFS -------------------------------------------------------------- >59877_59877_6_NPEPPS-CREB3L1_NPEPPS_chr17_45623359_ENST00000544660_CREB3L1_chr11_46341815_ENST00000529193_length(amino acids)=200AA_BP=100 MLFLGPPPPPLLLLVFSRSSRRRLHSLGLAAMPEKRPFERLPADVSPINYSLCLKPDLLDFTFEGKLEAAAQVRQATNQIVMNCADIDII TASYAPEGDEVPSRSLLFYDDGAGLWEDGRSTLLPMEPPDGWEINPGGPAEQRPRDHLQHDHLDSTHETTKYLSEAWPKDGGNGTSPDFS -------------------------------------------------------------- |
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Fusion Protein Functional Features |
Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr17:45623359/chr11:46341815) - 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. |
Main function of each fusion partner protein. (from UniProt) |
Hgene | Tgene |
NPEPPS | CREB3L1 |
FUNCTION: Aminopeptidase with broad substrate specificity for several peptides. Involved in proteolytic events essential for cell growth and viability. May act as regulator of neuropeptide activity. Plays a role in the antigen-processing pathway for MHC class I molecules. Involved in the N-terminal trimming of cytotoxic T-cell epitope precursors. Digests the poly-Q peptides found in many cellular proteins. Digests tau from normal brain more efficiently than tau from Alzheimer disease brain. {ECO:0000269|PubMed:10978616, ECO:0000269|PubMed:11062501, ECO:0000269|PubMed:17154549, ECO:0000269|PubMed:17318184, ECO:0000269|PubMed:19917696}. | FUNCTION: Transcription factor involved in unfolded protein response (UPR). Binds the DNA consensus sequence 5'-GTGXGCXGC-3' (PubMed:21767813). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in bone formation through the transcription of COL1A1, and possibly COL1A2, and the secretion of bone matrix proteins. Directly binds to the UPR element (UPRE)-like sequence in an osteoblast-specific COL1A1 promoter region and induces its transcription. Does not regulate COL1A1 in other tissues, such as skin (By similarity). Required to protect astrocytes from ER stress-induced cell death. In astrocytes, binds to the cAMP response element (CRE) of the BiP/HSPA5 promoter and participate in its transcriptional activation (By similarity). Required for TGFB1 to activate genes involved in the assembly of collagen extracellular matrix (PubMed:25310401). {ECO:0000250|UniProtKB:Q9Z125, ECO:0000269|PubMed:12054625, ECO:0000269|PubMed:21767813, ECO:0000269|PubMed:25310401}.; FUNCTION: (Microbial infection) May play a role in limiting virus spread by inhibiting proliferation of virus-infected cells. Upon infection with diverse DNA and RNA viruses, inhibits cell-cycle progression by binding to promoters and activating transcription of genes encoding cell-cycle inhibitors, such as p21/CDKN1A (PubMed:21767813). {ECO:0000269|PubMed:21767813}. |
Retention 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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
- Retained protein feature among the 13 regional features. |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000288400 | 9 | 12 | 423_426 | 419.3333333333333 | 520.0 | Motif | S1P recognition | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000529193 | 9 | 12 | 423_426 | 419.3333333333333 | 520.0 | Motif | S1P recognition |
- Not-retained protein feature among the 13 regional features. |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
Hgene | NPEPPS | chr17:45623359 | chr11:46341815 | ENST00000322157 | + | 2 | 23 | 726_730 | 113.33333333333333 | 920.0 | Motif | Nuclear localization signal |
Hgene | NPEPPS | chr17:45623359 | chr11:46341815 | ENST00000322157 | + | 2 | 23 | 316_320 | 113.33333333333333 | 920.0 | Region | Substrate binding |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000288400 | 9 | 12 | 146_154 | 419.3333333333333 | 520.0 | Compositional bias | Note=Poly-Ala | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000529193 | 9 | 12 | 146_154 | 419.3333333333333 | 520.0 | Compositional bias | Note=Poly-Ala | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000288400 | 9 | 12 | 290_353 | 419.3333333333333 | 520.0 | Domain | bZIP | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000529193 | 9 | 12 | 290_353 | 419.3333333333333 | 520.0 | Domain | bZIP | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000288400 | 9 | 12 | 392_395 | 419.3333333333333 | 520.0 | Motif | S2P recognition | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000529193 | 9 | 12 | 392_395 | 419.3333333333333 | 520.0 | Motif | S2P recognition | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000288400 | 9 | 12 | 1_60 | 419.3333333333333 | 520.0 | Region | Note=Required for transcriptional activation | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000288400 | 9 | 12 | 292_321 | 419.3333333333333 | 520.0 | Region | Basic motif | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000288400 | 9 | 12 | 332_353 | 419.3333333333333 | 520.0 | Region | Leucine-zipper | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000529193 | 9 | 12 | 1_60 | 419.3333333333333 | 520.0 | Region | Note=Required for transcriptional activation | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000529193 | 9 | 12 | 292_321 | 419.3333333333333 | 520.0 | Region | Basic motif | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000529193 | 9 | 12 | 332_353 | 419.3333333333333 | 520.0 | Region | Leucine-zipper | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000288400 | 9 | 12 | 1_374 | 419.3333333333333 | 520.0 | Topological domain | Cytoplasmic | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000288400 | 9 | 12 | 396_519 | 419.3333333333333 | 520.0 | Topological domain | Lumenal | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000529193 | 9 | 12 | 1_374 | 419.3333333333333 | 520.0 | Topological domain | Cytoplasmic | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000529193 | 9 | 12 | 396_519 | 419.3333333333333 | 520.0 | Topological domain | Lumenal | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000288400 | 9 | 12 | 375_395 | 419.3333333333333 | 520.0 | Transmembrane | Helical%3B Signal-anchor for type II membrane protein | |
Tgene | CREB3L1 | chr17:45623359 | chr11:46341815 | ENST00000529193 | 9 | 12 | 375_395 | 419.3333333333333 | 520.0 | Transmembrane | Helical%3B Signal-anchor for type II membrane protein |
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Fusion Protein Structures |
PDB and CIF files of the predicted fusion proteins * Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
Fusion protein PDB link (fusion AA seq ID in FusionPDB) | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | AA seq | Len(AA seq) |
PDB file >>>460_NPEPPS_45623359_CREB3L1_46341815_ranked_0.pdb | NPEPPS | 45623359 | 45623359 | ENST00000288400 | CREB3L1 | chr11 | 46341815 | + | MRALLPFPPLRPLPRRQPARQSARTASFPAPSAPAGSLPRPPGSPGRSPPAVARARWMWLAAAAPSLARRLLFLGPPPPPLLLLVFSRSS RRRLHSLGLAAMPEKRPFERLPADVSPINYSLCLKPDLLDFTFEGKLEAAAQVRQATNQIVMNCADIDIITASYAPEGDEVPSRSLLFYD DGAGLWEDGRSTLLPMEPPDGWEINPGGPAEQRPRDHLQHDHLDSTHETTKYLSEAWPKDGGNGTSPDFSHSKEWFHDRDLGPNTTIKLS | 270 |
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pLDDT score distribution |
pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
NPEPPS_pLDDT.png |
CREB3L1_pLDDT.png |
pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
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Ramachandran Plot of Fusion Protein Structure |
Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide. |
Fusion AA seq ID in FusionPDB and their Ramachandran plots |
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Fusion Protein-Protein Interaction |
Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160) |
Gene | PPI interactors |
Protein-protein interactors based on sequence similarity (STRING) |
Gene | STRING network |
NPEPPS | |
CREB3L1 |
- Retained interactions in fusion protein (protein functional feature from UniProt). |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
- Lost interactions due to fusion (protein functional feature from UniProt). |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Related Drugs to NPEPPS-CREB3L1 |
Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to NPEPPS-CREB3L1 |
Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Disease | Source | PMID |
Diseases associated with fusion partners. (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |