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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:LETM2-ERCC2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LETM2-ERCC2
FusionPDB ID: 44492
FusionGDB2.0 ID: 44492
HgeneTgene
Gene symbol

LETM2

ERCC2

Gene ID

137994

2068

Gene nameleucine zipper and EF-hand containing transmembrane protein 2ERCC excision repair 2, TFIIH core complex helicase subunit
SynonymsSLC55A2COFS2|EM9|TFIIH|TTD|TTD1|XPD
Cytomap

8p11.23

19q13.32

Type of geneprotein-codingprotein-coding
DescriptionLETM1 domain-containing protein LETM2, mitochondrialLETM1 and EF-hand domain-containing protein 2leucine zipper-EF-hand containing transmembrane protein 1-like proteinleucine zipper-EF-hand containing transmembrane protein 2general transcription and DNA repair factor IIH helicase subunit XPDBTF2 p80CXPDDNA excision repair protein ERCC-2DNA repair protein complementing XP-D cellsTFIIH 80 kDa subunitTFIIH basal transcription factor complex 80 kDa subunitTFIIH basal tran
Modification date2020031320200315
UniProtAcc

Q2VYF4

Main function of 5'-partner protein:

P18074

Main function of 5'-partner protein: FUNCTION: ATP-dependent 5'-3' DNA helicase, component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. The ATP-dependent helicase activity of XPD/ERCC2 is required for DNA opening. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. XPD/ERCC2 acts by forming a bridge between CAK and the core-TFIIH complex. Involved in the regulation of vitamin-D receptor activity. As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation. Might have a role in aging process and could play a causative role in the generation of skin cancers. {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:15494306, ECO:0000269|PubMed:20797633, ECO:0000269|PubMed:8413672}.
Ensembl transtripts involved in fusion geneENST idsENST00000528827, ENST00000297720, 
ENST00000379957, ENST00000523983, 
ENST00000524874, ENST00000527710, 
ENST00000519476, 
ENST00000221481, 
ENST00000391940, ENST00000391944, 
ENST00000391945, ENST00000485403, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score1 X 1 X 1=13 X 4 X 3=36
# samples 13
** MAII scorelog2(1/1*10)=3.32192809488736log2(3/36*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LETM2 [Title/Abstract] AND ERCC2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LETM2 [Title/Abstract] AND ERCC2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LETM2(38262024)-ERCC2(45872405), # samples:2
Anticipated loss of major functional domain due to fusion event.LETM2-ERCC2 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.
LETM2-ERCC2 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.
LETM2-ERCC2 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.
LETM2-ERCC2 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
TgeneERCC2

GO:0006283

transcription-coupled nucleotide-excision repair

8663148

TgeneERCC2

GO:0006366

transcription by RNA polymerase II

9852112

TgeneERCC2

GO:0045893

positive regulation of transcription, DNA-templated

8692842

TgeneERCC2

GO:0045944

positive regulation of transcription by RNA polymerase II

8692841



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/chr8:38262024/chr19:45872405)
- 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 LETM2 (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 ERCC2 (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)
ENST00000297720LETM2chr838262024+ENST00000391945ERCC2chr1945872405-5135116519633421048
ENST00000297720LETM2chr838262024+ENST00000391944ERCC2chr1945872405-313511651963108970
ENST00000297720LETM2chr838262024+ENST00000485403ERCC2chr1945872405-245111651962349717
ENST00000297720LETM2chr838262024+ENST00000391940ERCC2chr1945872405-235011651962349718
ENST00000297720LETM2chr838262024+ENST00000221481ERCC2chr1945872405-178811651961443415
ENST00000524874LETM2chr838262024+ENST00000391945ERCC2chr1945872405-5171120112733781083
ENST00000524874LETM2chr838262024+ENST00000391944ERCC2chr1945872405-3171120112731441005
ENST00000524874LETM2chr838262024+ENST00000485403ERCC2chr1945872405-248712011272385752
ENST00000524874LETM2chr838262024+ENST00000391940ERCC2chr1945872405-238612011272385753
ENST00000524874LETM2chr838262024+ENST00000221481ERCC2chr1945872405-182412011271479450
ENST00000379957LETM2chr838262024+ENST00000391945ERCC2chr1945872405-5315134512735221131
ENST00000379957LETM2chr838262024+ENST00000391944ERCC2chr1945872405-3315134512732881053
ENST00000379957LETM2chr838262024+ENST00000485403ERCC2chr1945872405-263113451272529800
ENST00000379957LETM2chr838262024+ENST00000391940ERCC2chr1945872405-253013451272529801
ENST00000379957LETM2chr838262024+ENST00000221481ERCC2chr1945872405-196813451271623498
ENST00000523983LETM2chr838262024+ENST00000391945ERCC2chr1945872405-5219124913634261096
ENST00000523983LETM2chr838262024+ENST00000391944ERCC2chr1945872405-3219124913631921018
ENST00000523983LETM2chr838262024+ENST00000485403ERCC2chr1945872405-253512491362433765
ENST00000523983LETM2chr838262024+ENST00000391940ERCC2chr1945872405-243412491362433766
ENST00000523983LETM2chr838262024+ENST00000221481ERCC2chr1945872405-187212491361527463
ENST00000527710LETM2chr838262024+ENST00000391945ERCC2chr1945872405-47037331572910917
ENST00000527710LETM2chr838262024+ENST00000391944ERCC2chr1945872405-27037331572676839
ENST00000527710LETM2chr838262024+ENST00000485403ERCC2chr1945872405-20197331571917586
ENST00000527710LETM2chr838262024+ENST00000391940ERCC2chr1945872405-19187331571917587
ENST00000527710LETM2chr838262024+ENST00000221481ERCC2chr1945872405-13567331571011284

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
ENST00000297720ENST00000391945LETM2chr838262024+ERCC2chr1945872405-0.0025119130.997488
ENST00000297720ENST00000391944LETM2chr838262024+ERCC2chr1945872405-0.0051057230.99489427
ENST00000297720ENST00000485403LETM2chr838262024+ERCC2chr1945872405-0.0137276380.98627234
ENST00000297720ENST00000391940LETM2chr838262024+ERCC2chr1945872405-0.0147546960.9852453
ENST00000297720ENST00000221481LETM2chr838262024+ERCC2chr1945872405-0.0071438340.99285614
ENST00000524874ENST00000391945LETM2chr838262024+ERCC2chr1945872405-0.0022299770.9977701
ENST00000524874ENST00000391944LETM2chr838262024+ERCC2chr1945872405-0.0043748530.9956252
ENST00000524874ENST00000485403LETM2chr838262024+ERCC2chr1945872405-0.016646280.98335373
ENST00000524874ENST00000391940LETM2chr838262024+ERCC2chr1945872405-0.0175173260.9824827
ENST00000524874ENST00000221481LETM2chr838262024+ERCC2chr1945872405-0.0167010630.98329896
ENST00000379957ENST00000391945LETM2chr838262024+ERCC2chr1945872405-0.0023999930.9976
ENST00000379957ENST00000391944LETM2chr838262024+ERCC2chr1945872405-0.0041258020.9958742
ENST00000379957ENST00000485403LETM2chr838262024+ERCC2chr1945872405-0.0120496180.98795044
ENST00000379957ENST00000391940LETM2chr838262024+ERCC2chr1945872405-0.0129832430.98701674
ENST00000379957ENST00000221481LETM2chr838262024+ERCC2chr1945872405-0.0150649130.98493505
ENST00000523983ENST00000391945LETM2chr838262024+ERCC2chr1945872405-0.0025638310.9974362
ENST00000523983ENST00000391944LETM2chr838262024+ERCC2chr1945872405-0.0045738810.9954261
ENST00000523983ENST00000485403LETM2chr838262024+ERCC2chr1945872405-0.0120653910.9879346
ENST00000523983ENST00000391940LETM2chr838262024+ERCC2chr1945872405-0.0135049510.986495
ENST00000523983ENST00000221481LETM2chr838262024+ERCC2chr1945872405-0.0089796310.9910204
ENST00000527710ENST00000391945LETM2chr838262024+ERCC2chr1945872405-0.0026170210.99738294
ENST00000527710ENST00000391944LETM2chr838262024+ERCC2chr1945872405-0.0106554470.98934454
ENST00000527710ENST00000485403LETM2chr838262024+ERCC2chr1945872405-0.0135248310.98647517
ENST00000527710ENST00000391940LETM2chr838262024+ERCC2chr1945872405-0.0147649720.985235
ENST00000527710ENST00000221481LETM2chr838262024+ERCC2chr1945872405-0.0065480310.99345195

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 LETM2-ERCC2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LETM2chr838262024ERCC2chr19458724051165323VKPKPIEIPLSGEGHGVLEMPSGTGK
LETM2chr838262024ERCC2chr19458724051201358VKPKPIEIPLSGEGHGVLEMPSGTGK
LETM2chr838262024ERCC2chr19458724051249371VKPKPIEIPLSGEGHGVLEMPSGTGK
LETM2chr838262024ERCC2chr19458724051345406VKPKPIEIPLSGEGHGVLEMPSGTGK
LETM2chr838262024ERCC2chr1945872405733192VKPKPIEIPLSGEGHGVLEMPSGTGK

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Potential FusionNeoAntigen Information of LETM2-ERCC2 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.
LETM2-ERCC2_38262024_45872405.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)
LETM2-ERCC2chr838262024chr19458724051165HLA-B40:01GEGHGVLEM0.99720.71711120
LETM2-ERCC2chr838262024chr19458724051165HLA-B44:03GEGHGVLEM0.9910.98991120
LETM2-ERCC2chr838262024chr19458724051165HLA-B47:01GEGHGVLEM0.90910.71741120
LETM2-ERCC2chr838262024chr19458724051165HLA-B39:13GEGHGVLEM0.33090.9881120
LETM2-ERCC2chr838262024chr19458724051165HLA-B41:02GEGHGVLEM0.21240.52931120
LETM2-ERCC2chr838262024chr19458724051165HLA-B48:03GEGHGVLEM0.9950.74371120
LETM2-ERCC2chr838262024chr19458724051165HLA-B44:09GEGHGVLEM0.99340.53991120
LETM2-ERCC2chr838262024chr19458724051165HLA-C03:08LSGEGHGVL0.99320.9697918
LETM2-ERCC2chr838262024chr19458724051165HLA-B44:10GEGHGVLEM0.98680.86981120
LETM2-ERCC2chr838262024chr19458724051165HLA-B40:03GEGHGVLEM0.97430.65641120
LETM2-ERCC2chr838262024chr19458724051165HLA-B39:08GEGHGVLEM0.43910.96861120
LETM2-ERCC2chr838262024chr19458724051165HLA-B42:01IPLSGEGHGVL0.99020.8304718
LETM2-ERCC2chr838262024chr19458724051165HLA-B39:10IPLSGEGHGVL0.96640.9309718
LETM2-ERCC2chr838262024chr19458724051165HLA-B40:04GEGHGVLEM0.99820.87291120
LETM2-ERCC2chr838262024chr19458724051165HLA-B40:36GEGHGVLEM0.99740.71761120
LETM2-ERCC2chr838262024chr19458724051165HLA-B40:49GEGHGVLEM0.99710.72631120
LETM2-ERCC2chr838262024chr19458724051165HLA-C03:03LSGEGHGVL0.99580.9961918
LETM2-ERCC2chr838262024chr19458724051165HLA-C03:04LSGEGHGVL0.99580.9961918
LETM2-ERCC2chr838262024chr19458724051165HLA-B40:12GEGHGVLEM0.9950.74371120
LETM2-ERCC2chr838262024chr19458724051165HLA-B44:07GEGHGVLEM0.9910.98991120
LETM2-ERCC2chr838262024chr19458724051165HLA-B44:13GEGHGVLEM0.9910.98991120
LETM2-ERCC2chr838262024chr19458724051165HLA-B44:26GEGHGVLEM0.9910.98991120
LETM2-ERCC2chr838262024chr19458724051165HLA-C03:06LSGEGHGVL0.85780.9962918
LETM2-ERCC2chr838262024chr19458724051165HLA-B41:03GEGHGVLEM0.370.92091120
LETM2-ERCC2chr838262024chr19458724051165HLA-B15:53GEGHGVLEM0.06520.92211120
LETM2-ERCC2chr838262024chr19458724051165HLA-B55:04IPLSGEGHGVL0.99540.5949718
LETM2-ERCC2chr838262024chr19458724051165HLA-B67:01IPLSGEGHGVL0.95460.7754718

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Potential FusionNeoAntigen Information of LETM2-ERCC2 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 LETM2-ERCC2

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
1801EIPLSGEGHGVLEMLETM2ERCC2chr838262024chr19458724051165

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LETM2-ERCC2

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-B14:023BVN1801EIPLSGEGHGVLEM-7.9962-8.1096
HLA-B14:023BVN1801EIPLSGEGHGVLEM-5.70842-6.74372
HLA-B52:013W391801EIPLSGEGHGVLEM-6.83737-6.95077
HLA-B52:013W391801EIPLSGEGHGVLEM-4.4836-5.5189
HLA-A11:014UQ21801EIPLSGEGHGVLEM-10.0067-10.1201
HLA-A11:014UQ21801EIPLSGEGHGVLEM-9.03915-10.0745
HLA-A24:025HGA1801EIPLSGEGHGVLEM-6.56204-6.67544
HLA-A24:025HGA1801EIPLSGEGHGVLEM-5.42271-6.45801
HLA-B44:053DX81801EIPLSGEGHGVLEM-7.85648-8.89178
HLA-B44:053DX81801EIPLSGEGHGVLEM-5.3978-5.5112
HLA-A02:016TDR1801EIPLSGEGHGVLEM-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of LETM2-ERCC2

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
LETM2-ERCC2chr838262024chr19458724051120GEGHGVLEMGGGGAGGGTCATGGAGTCCTGGAGATG
LETM2-ERCC2chr838262024chr1945872405718IPLSGEGHGVLATACCACTCAGTGGGGAGGGTCATGGAGTCCTG
LETM2-ERCC2chr838262024chr1945872405918LSGEGHGVLCTCAGTGGGGAGGGTCATGGAGTCCTG

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 LETM2-ERCC2

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
LUSCLETM2-ERCC2chr838262024ENST00000297720chr1945872405ENST00000221481TCGA-85-A53L-01A

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Potential target of CAR-T therapy development for LETM2-ERCC2

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
HgeneLETM2chr8:38262024chr19:45872405ENST00000297720+710178_198311397.0TransmembraneHelical
HgeneLETM2chr8:38262024chr19:45872405ENST00000379957+811178_198406492.0TransmembraneHelical
HgeneLETM2chr8:38262024chr19:45872405ENST00000523983+811178_198359445.0TransmembraneHelical

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

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Related Drugs to LETM2-ERCC2

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 LETM2-ERCC2

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