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Center for Computational Systems Medicine level1
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:NEDD4L-MBD2

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NEDD4L-MBD2
FusionPDB ID: 58422
FusionGDB2.0 ID: 58422
HgeneTgene
Gene symbol

NEDD4L

MBD2

Gene ID

23327

64174

Gene nameNEDD4 like E3 ubiquitin protein ligasedipeptidase 2
SynonymsNEDD4-2|NEDD4.2|PVNH7|RSP5|hNEDD4-2MBD2
Cytomap

18q21.31

16q22.1

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase NEDD4-likeHECT-type E3 ubiquitin transferase NED4Lneural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligaseubiquitin-protein ligase Rsp5dipeptidase 2
Modification date2020032920200313
UniProtAcc

Q96PU5

Q9UBB5

Ensembl transtripts involved in fusion geneENST idsENST00000256830, ENST00000356462, 
ENST00000382850, ENST00000400345, 
ENST00000589054, ENST00000256832, 
ENST00000357895, ENST00000431212, 
ENST00000435432, ENST00000456173, 
ENST00000456986, ENST00000586263, 
ENST00000588516, 
ENST00000398398, 
ENST00000579025, ENST00000583046, 
ENST00000256429, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score28 X 18 X 11=554413 X 7 X 7=637
# samples 3515
** MAII scorelog2(35/5544*10)=-3.98550043030488
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/637*10)=-2.08633087176042
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: NEDD4L [Title/Abstract] AND MBD2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NEDD4L(55711940)-MBD2(51715381), # samples:1
Anticipated loss of major functional domain due to fusion event.NEDD4L-MBD2 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.
NEDD4L-MBD2 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.
NEDD4L-MBD2 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.
NEDD4L-MBD2 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
HgeneNEDD4L

GO:0003254

regulation of membrane depolarization

15217910

HgeneNEDD4L

GO:0006511

ubiquitin-dependent protein catabolic process

21463633

HgeneNEDD4L

GO:0010038

response to metal ion

11244092

HgeneNEDD4L

GO:0016567

protein ubiquitination

15217910|25631046

HgeneNEDD4L

GO:0034765

regulation of ion transmembrane transport

17289006

HgeneNEDD4L

GO:0042391

regulation of membrane potential

17289006

HgeneNEDD4L

GO:0043161

proteasome-mediated ubiquitin-dependent protein catabolic process

21463633

HgeneNEDD4L

GO:0060306

regulation of membrane repolarization

21463633

HgeneNEDD4L

GO:0070936

protein K48-linked ubiquitination

21463633

HgeneNEDD4L

GO:1901016

regulation of potassium ion transmembrane transporter activity

17289006

HgeneNEDD4L

GO:1901017

negative regulation of potassium ion transmembrane transporter activity

21463633

HgeneNEDD4L

GO:1901380

negative regulation of potassium ion transmembrane transport

21463633

HgeneNEDD4L

GO:1902306

negative regulation of sodium ion transmembrane transport

15217910

HgeneNEDD4L

GO:1903861

positive regulation of dendrite extension

23999003

HgeneNEDD4L

GO:2000009

negative regulation of protein localization to cell surface

21463633

HgeneNEDD4L

GO:2000650

negative regulation of sodium ion transmembrane transporter activity

15217910


check buttonFusion gene breakpoints across NEDD4L (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 MBD2 (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 Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4THCATCGA-ET-A40PNEDD4Lchr18

55711940

+MBD2chr18

51715381

-


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Fusion ORF Analysis


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)
ENST00000356462NEDD4Lchr1855711940+ENST00000256429MBD2chr1851715381-3491342210875221
ENST00000400345NEDD4Lchr1855711940+ENST00000256429MBD2chr1851715381-3480331199864221
ENST00000589054NEDD4Lchr1855711940+ENST00000256429MBD2chr1851715381-3474325193858221
ENST00000382850NEDD4Lchr1855711940+ENST00000256429MBD2chr1851715381-331016129694221
ENST00000256830NEDD4Lchr1855711940+ENST00000256429MBD2chr1851715381-3197480581193

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
ENST00000356462ENST00000256429NEDD4Lchr1855711940+MBD2chr1851715381-0.0012736540.9987263
ENST00000400345ENST00000256429NEDD4Lchr1855711940+MBD2chr1851715381-0.0012762490.9987237
ENST00000589054ENST00000256429NEDD4Lchr1855711940+MBD2chr1851715381-0.0012553780.9987446
ENST00000382850ENST00000256429NEDD4Lchr1855711940+MBD2chr1851715381-0.0011161080.9988839
ENST00000256830ENST00000256429NEDD4Lchr1855711940+MBD2chr1851715381-0.0010120640.998988

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Fusion Amino Acid Sequences


check button 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

>58422_58422_1_NEDD4L-MBD2_NEDD4L_chr18_55711940_ENST00000256830_MBD2_chr18_51715381_ENST00000256429_length(amino acids)=193AA_BP=16
MATGLGEPVYGLSEDEGKPDLNTTLPIRQTASIFKQPVTKVTNHPSNKVKSDPQRMNEQPRQLFWEKRLQGLSASDVTEQIIKTMELPKG
LQGVGPGSNDETLLSAVASALHTSSAPITGQVSAAVEKNPAVWLNTSQPLCKAFIVTDEDIRKQEERVQQVRKKLEEALMADILSRAADT

--------------------------------------------------------------

>58422_58422_2_NEDD4L-MBD2_NEDD4L_chr18_55711940_ENST00000356462_MBD2_chr18_51715381_ENST00000256429_length(amino acids)=221AA_BP=44
MEAEGRTGRPRRSTAAGSASDPARGAGSMATGLGEPVYGLSEDEGKPDLNTTLPIRQTASIFKQPVTKVTNHPSNKVKSDPQRMNEQPRQ
LFWEKRLQGLSASDVTEQIIKTMELPKGLQGVGPGSNDETLLSAVASALHTSSAPITGQVSAAVEKNPAVWLNTSQPLCKAFIVTDEDIR

--------------------------------------------------------------

>58422_58422_3_NEDD4L-MBD2_NEDD4L_chr18_55711940_ENST00000382850_MBD2_chr18_51715381_ENST00000256429_length(amino acids)=221AA_BP=44
MEAEGRTGRPRRSTAAGSASDPARGAGSMATGLGEPVYGLSEDEGKPDLNTTLPIRQTASIFKQPVTKVTNHPSNKVKSDPQRMNEQPRQ
LFWEKRLQGLSASDVTEQIIKTMELPKGLQGVGPGSNDETLLSAVASALHTSSAPITGQVSAAVEKNPAVWLNTSQPLCKAFIVTDEDIR

--------------------------------------------------------------

>58422_58422_4_NEDD4L-MBD2_NEDD4L_chr18_55711940_ENST00000400345_MBD2_chr18_51715381_ENST00000256429_length(amino acids)=221AA_BP=44
MEAEGRTGRPRRSTAAGSASDPARGAGSMATGLGEPVYGLSEDEGKPDLNTTLPIRQTASIFKQPVTKVTNHPSNKVKSDPQRMNEQPRQ
LFWEKRLQGLSASDVTEQIIKTMELPKGLQGVGPGSNDETLLSAVASALHTSSAPITGQVSAAVEKNPAVWLNTSQPLCKAFIVTDEDIR

--------------------------------------------------------------

>58422_58422_5_NEDD4L-MBD2_NEDD4L_chr18_55711940_ENST00000589054_MBD2_chr18_51715381_ENST00000256429_length(amino acids)=221AA_BP=44
MEAEGRTGRPRRSTAAGSASDPARGAGSMATGLGEPVYGLSEDEGKPDLNTTLPIRQTASIFKQPVTKVTNHPSNKVKSDPQRMNEQPRQ
LFWEKRLQGLSASDVTEQIIKTMELPKGLQGVGPGSNDETLLSAVASALHTSSAPITGQVSAAVEKNPAVWLNTSQPLCKAFIVTDEDIR

--------------------------------------------------------------

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Fusion Protein Functional Features


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/chr18:55711940/chr18:51715381)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
NEDD4L

Q96PU5

MBD2

Q9UBB5

FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5 (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338). {ECO:0000250|UniProtKB:Q8CFI0, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15489223, ECO:0000269|PubMed:15496141, ECO:0000269|PubMed:15576372, ECO:0000269|PubMed:19144635, ECO:0000269|PubMed:23999003, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:26363003, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27694961}.FUNCTION: Binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binds hemimethylated DNA as well. Recruits histone deacetylases and DNA methyltransferases. Acts as transcriptional repressor and plays a role in gene silencing. Functions as a scaffold protein, targeting GATAD2A and GATAD2B to chromatin to promote repression. May enhance the activation of some unmethylated cAMP-responsive promoters. {ECO:0000269|PubMed:10471499, ECO:0000269|PubMed:10947852, ECO:0000269|PubMed:12665568, ECO:0000269|PubMed:16415179, ECO:0000269|PubMed:24307175, ECO:0000269|PubMed:9774669}.

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, 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

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
TgeneMBD2chr18:55711940chr18:51715381ENST000005830460350_960303.0Compositional biasNote=Arg-rich
TgeneMBD2chr18:55711940chr18:51715381ENST00000583046036_1400303.0Compositional biasNote=Gly-rich
TgeneMBD2chr18:55711940chr18:51715381ENST0000058304603145_2130303.0DomainMBD

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000256830+128193_22616.0872.0DomainWW 1
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000256830+128385_41816.0872.0DomainWW 2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000256830+128497_53016.0872.0DomainWW 3
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000256830+1284_12616.0872.0DomainC2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000256830+128548_58116.0872.0DomainWW 4
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000256830+128640_97416.0872.0DomainHECT
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000356462+129193_22616.0912.0DomainWW 1
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000356462+129385_41816.0912.0DomainWW 2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000356462+129497_53016.0912.0DomainWW 3
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000356462+1294_12616.0912.0DomainC2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000356462+129548_58116.0912.0DomainWW 4
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000356462+129640_97416.0912.0DomainHECT
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000357895+131193_2260968.0DomainWW 1
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000357895+131385_4180968.0DomainWW 2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000357895+131497_5300968.0DomainWW 3
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000357895+1314_1260968.0DomainC2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000357895+131548_5810968.0DomainWW 4
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000357895+131640_9740968.0DomainHECT
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000382850+130193_22616.0956.0DomainWW 1
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000382850+130385_41816.0956.0DomainWW 2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000382850+130497_53016.0956.0DomainWW 3
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000382850+1304_12616.0956.0DomainC2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000382850+130548_58116.0956.0DomainWW 4
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000382850+130640_97416.0956.0DomainHECT
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000400345+131193_22616.0976.0DomainWW 1
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000400345+131385_41816.0976.0DomainWW 2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000400345+131497_53016.0976.0DomainWW 3
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000400345+1314_12616.0976.0DomainC2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000400345+131548_58116.0976.0DomainWW 4
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000400345+131640_97416.0976.0DomainHECT
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000431212+130193_2260855.0DomainWW 1
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000431212+130385_4180855.0DomainWW 2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000431212+130497_5300855.0DomainWW 3
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000431212+1304_1260855.0DomainC2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000431212+130548_5810855.0DomainWW 4
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000431212+130640_9740855.0DomainHECT
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000435432+131193_2260835.0DomainWW 1
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000435432+131385_4180835.0DomainWW 2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000435432+131497_5300835.0DomainWW 3
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000435432+1314_1260835.0DomainC2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000435432+131548_5810835.0DomainWW 4
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000435432+131640_9740835.0DomainHECT
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000456173+129193_2260835.0DomainWW 1
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000456173+129385_4180835.0DomainWW 2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000456173+129497_5300835.0DomainWW 3
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000456173+1294_1260835.0DomainC2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000456173+129548_5810835.0DomainWW 4
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000456173+129640_9740835.0DomainHECT
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000456986+131193_2260855.0DomainWW 1
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000456986+131385_4180855.0DomainWW 2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000456986+131497_5300855.0DomainWW 3
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000456986+1314_1260855.0DomainC2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000456986+131548_5810855.0DomainWW 4
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000456986+131640_9740855.0DomainHECT
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000586263+130193_2260948.0DomainWW 1
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000586263+130385_4180948.0DomainWW 2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000586263+130497_5300948.0DomainWW 3
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000586263+1304_1260948.0DomainC2
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000586263+130548_5810948.0DomainWW 4
HgeneNEDD4Lchr18:55711940chr18:51715381ENST00000586263+130640_9740948.0DomainHECT
TgeneMBD2chr18:55711940chr18:51715381ENST000002564291750_96234.01015.6666666666666Compositional biasNote=Arg-rich
TgeneMBD2chr18:55711940chr18:51715381ENST00000256429176_140234.01015.6666666666666Compositional biasNote=Gly-rich
TgeneMBD2chr18:55711940chr18:51715381ENST0000025642917145_213234.01015.6666666666666DomainMBD


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Fusion Protein-Protein Interaction


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)
GenePPI interactors


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
NEDD4L
MBD2


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to NEDD4L-MBD2


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 NEDD4L-MBD2


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