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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:ADCY3-HADHA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ADCY3-HADHA
FusionPDB ID: 2228
FusionGDB2.0 ID: 2228
HgeneTgene
Gene symbol

ADCY3

HADHA

Gene ID

114

3030

Gene nameadenylate cyclase 8hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha
SynonymsAC8|ADCY3|HBAC1ECHA|GBP|HADH|LCEH|LCHAD|MTPA|TP-ALPHA
Cytomap

8q24.22

2p23.3

Type of geneprotein-codingprotein-coding
Descriptionadenylate cyclase type 8ATP pyrophosphate-lyase 8HEL-S-172mPadenylate cyclase 8 (brain)adenylate cyclase type VIIIadenylyl cyclase 8adenylyl cyclase-8, brainca(2+)/calmodulin-activated adenylyl cyclaseepididymis secretory sperm binding protein Li trifunctional enzyme subunit alpha, mitochondrial3-ketoacyl-Coenzyme A (CoA) thiolase, alpha subunit3-oxoacyl-CoA thiolase78 kDa gastrin-binding proteingastrin-binding proteinhydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (
Modification date2020031320200313
UniProtAcc

O60266

Main function of 5'-partner protein: FUNCTION: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis. Required for the perception of odorants. Required for normal sperm motility and normal male fertility. Plays a role in regulating insulin levels and body fat accumulation in response to a high fat diet. {ECO:0000250|UniProtKB:Q8VHH7}.

P40939

Main function of 5'-partner protein: FUNCTION: Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway (PubMed:8135828, PubMed:1550553, PubMed:29915090, PubMed:30850536). The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA (PubMed:29915090). Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids (PubMed:30850536). Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA described here carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the trifunctional enzyme subunit beta/HADHB bears the 3-ketoacyl-CoA thiolase activity (PubMed:8135828, PubMed:29915090, PubMed:30850536). Independently of the subunit beta, the trifunctional enzyme subunit alpha/HADHA also has a monolysocardiolipin acyltransferase activity (PubMed:23152787). It acylates monolysocardiolipin into cardiolipin, a major mitochondrial membrane phospholipid which plays a key role in apoptosis and supports mitochondrial respiratory chain complexes in the generation of ATP (PubMed:23152787). Allows the acylation of monolysocardiolipin with different acyl-CoA substrates including oleoyl-CoA for which it displays the highest activity (PubMed:23152787). {ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:23152787, ECO:0000269|PubMed:29915090, ECO:0000269|PubMed:30850536, ECO:0000269|PubMed:8135828, ECO:0000303|PubMed:29915090, ECO:0000303|PubMed:30850536}.
Ensembl transtripts involved in fusion geneENST idsENST00000260600, ENST00000405392, 
ENST00000450524, 
ENST00000457468, 
ENST00000461025, ENST00000380649, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 6 X 5=2107 X 6 X 7=294
# samples 79
** MAII scorelog2(7/210*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/294*10)=-1.70781924850669
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ADCY3 [Title/Abstract] AND HADHA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ADCY3 [Title/Abstract] AND HADHA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADCY3(25141182)-HADHA(26417507), # samples:1
Anticipated loss of major functional domain due to fusion event.
* 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
TgeneHADHA

GO:0035965

cardiolipin acyl-chain remodeling

23152787



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/chr2:25141182/chr2:26417507)
- 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 ADCY3 (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 HADHA (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)
ENST00000260600ADCY3chr225141182-ENST00000380649HADHAchr226417507-281415278522198448

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
ENST00000260600ENST00000380649ADCY3chr225141182-HADHAchr226417507-0.0021410160.99785894

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 ADCY3-HADHA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ADCY3chr225141182HADHAchr2264175071527225QQEELKGMQLLREDGPGFYTTRCLAP

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Potential FusionNeoAntigen Information of ADCY3-HADHA 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.
ADCY3-HADHA_25141182_26417507.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)
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:01LLREDGPGF0.99560.9363918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:25LLREDGPGF0.93710.9707918
ADCY3-HADHAchr225141182chr2264175071527HLA-B50:02REDGPGFYT0.93460.62351120
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:02LLREDGPGF0.91060.9739918
ADCY3-HADHAchr225141182chr2264175071527HLA-B45:01REDGPGFYT0.86950.93551120
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:03LLREDGPGF0.55560.8458918
ADCY3-HADHAchr225141182chr2264175071527HLA-B41:01REDGPGFYT0.30590.95551120
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:18LREDGPGFY0.09740.90811019
ADCY3-HADHAchr225141182chr2264175071527HLA-B50:01REDGPGFYT0.00410.83621120
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:01LLREDGPGFY0.99990.9579919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:25LLREDGPGFY0.99480.9751919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:02LLREDGPGFY0.99050.9759919
ADCY3-HADHAchr225141182chr2264175071527HLA-B45:01REDGPGFYTT0.95010.92951121
ADCY3-HADHAchr225141182chr2264175071527HLA-B41:01REDGPGFYTT0.62230.9691121
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:01MQLLREDGPGF0.99720.8279718
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:07LLREDGPGF0.99420.6746918
ADCY3-HADHAchr225141182chr2264175071527HLA-B40:06REDGPGFYT0.99130.88051120
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:04LLREDGPGF0.91530.9291918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:21LLREDGPGF0.90990.9624918
ADCY3-HADHAchr225141182chr2264175071527HLA-C07:95LREDGPGFY0.8620.66481019
ADCY3-HADHAchr225141182chr2264175071527HLA-C07:27LREDGPGFY0.77080.96151019
ADCY3-HADHAchr225141182chr2264175071527HLA-C07:19LREDGPGFY0.71440.74461019
ADCY3-HADHAchr225141182chr2264175071527HLA-C07:80LREDGPGFY0.61140.93521019
ADCY3-HADHAchr225141182chr2264175071527HLA-C07:67LREDGPGFY0.61140.93521019
ADCY3-HADHAchr225141182chr2264175071527HLA-C07:46LREDGPGFY0.59470.83671019
ADCY3-HADHAchr225141182chr2264175071527HLA-C07:10LREDGPGFY0.58270.9721019
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:31LLREDGPGF0.37520.9416918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:05LLREDGPGF0.31630.9347918
ADCY3-HADHAchr225141182chr2264175071527HLA-C12:16LREDGPGFY0.01280.96961019
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:07LLREDGPGFY0.99960.6979919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:04LLREDGPGFY0.99230.9641919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:05MQLLREDGPGF0.83180.797718
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:27LLREDGPGF0.9960.948918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:34LLREDGPGF0.99560.9363918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:33LLREDGPGF0.99560.9363918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:125LLREDGPGF0.99560.9363918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:135LLREDGPGF0.99560.9471918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:35LLREDGPGF0.99480.832918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:50LLREDGPGF0.99340.923918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:24LLREDGPGF0.99030.9417918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:12LLREDGPGF0.9750.9206918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:39LLREDGPGF0.9350.9321918
ADCY3-HADHAchr225141182chr2264175071527HLA-C07:01LREDGPGFY0.86570.68441019
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:13LLREDGPGF0.76420.9157918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:73LLREDGPGF0.69730.8159918
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:30LLREDGPGF0.61490.8443918
ADCY3-HADHAchr225141182chr2264175071527HLA-C07:02LREDGPGFY0.61140.93521019
ADCY3-HADHAchr225141182chr2264175071527HLA-C07:17LREDGPGFY0.60140.95861019
ADCY3-HADHAchr225141182chr2264175071527HLA-C07:22LREDGPGFY0.60020.69461019
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:20LLREDGPGF0.30430.9586918
ADCY3-HADHAchr225141182chr2264175071527HLA-B50:04REDGPGFYT0.00410.83621120
ADCY3-HADHAchr225141182chr2264175071527HLA-B50:05REDGPGFYT0.00410.83621120
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:34LLREDGPGFY0.99990.9579919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:125LLREDGPGFY0.99990.9579919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:27LLREDGPGFY0.99990.9687919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:33LLREDGPGFY0.99990.9579919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:135LLREDGPGFY0.99980.9629919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:50LLREDGPGFY0.99980.9372919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:35LLREDGPGFY0.99950.8283919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:12LLREDGPGFY0.99910.9416919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:39LLREDGPGFY0.99440.9449919
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:33MQLLREDGPGF0.99720.8279718
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:34MQLLREDGPGF0.99720.8279718
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:125MQLLREDGPGF0.99720.8279718
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:24MQLLREDGPGF0.9970.8854718
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:135MQLLREDGPGF0.99640.8473718
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:53MQLLREDGPGF0.99640.7912718
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:12MQLLREDGPGF0.98560.8027718
ADCY3-HADHAchr225141182chr2264175071527HLA-B15:20MQLLREDGPGF0.83410.9056718
ADCY3-HADHAchr225141182chr2264175071527HLA-B35:28MQLLREDGPGF0.82580.9126718

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Potential FusionNeoAntigen Information of ADCY3-HADHA 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 ADCY3-HADHA

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
2981GMQLLREDGPGFYTADCY3HADHAchr225141182chr2264175071527

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ADCY3-HADHA

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-B14:023BVN2981GMQLLREDGPGFYT-7.15543-7.26883
HLA-B14:023BVN2981GMQLLREDGPGFYT-4.77435-5.80965
HLA-B52:013W392981GMQLLREDGPGFYT-6.80875-6.92215
HLA-B52:013W392981GMQLLREDGPGFYT-4.20386-5.23916
HLA-A11:014UQ22981GMQLLREDGPGFYT-7.5194-8.5547
HLA-A11:014UQ22981GMQLLREDGPGFYT-6.9601-7.0735
HLA-A24:025HGA2981GMQLLREDGPGFYT-7.52403-7.63743
HLA-A24:025HGA2981GMQLLREDGPGFYT-5.82433-6.85963
HLA-B27:056PYJ2981GMQLLREDGPGFYT-3.28285-4.31815
HLA-B44:053DX82981GMQLLREDGPGFYT-5.91172-6.94702
HLA-B44:053DX82981GMQLLREDGPGFYT-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ADCY3-HADHA

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
ADCY3-HADHAchr225141182chr2264175071019LREDGPGFYCTGCGGGAGGATGGACCTGGCTTCTAT
ADCY3-HADHAchr225141182chr2264175071120REDGPGFYTCGGGAGGATGGACCTGGCTTCTATACT
ADCY3-HADHAchr225141182chr2264175071121REDGPGFYTTCGGGAGGATGGACCTGGCTTCTATACTACC
ADCY3-HADHAchr225141182chr226417507718MQLLREDGPGFATGCAGCTGCTGCGGGAGGATGGACCTGGCTTC
ADCY3-HADHAchr225141182chr226417507918LLREDGPGFCTGCTGCGGGAGGATGGACCTGGCTTC
ADCY3-HADHAchr225141182chr226417507919LLREDGPGFYCTGCTGCGGGAGGATGGACCTGGCTTCTAT

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 ADCY3-HADHA

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
LUSCADCY3-HADHAchr225141182ENST00000260600chr226417507ENST00000380649TCGA-43-3394-01A

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Potential target of CAR-T therapy development for ADCY3-HADHA

check button Predicted 3D structure. We used RoseTTAFold.
15_ADCY3-HADHA_9502a_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
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121105_1252251145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121139_1592251145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-121173_1932251145.0TransmembraneHelical
HgeneADCY3chr2:25141182chr2:26417507ENST00000260600-12180_1002251145.0TransmembraneHelical

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
ADCY3chr225141182ENST00000260600HADHAchr226417507ENST00000380649

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Related Drugs to ADCY3-HADHA

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 ADCY3-HADHA

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