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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:SMYD3-ZMYM4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SMYD3-ZMYM4
FusionPDB ID: 84388
FusionGDB2.0 ID: 84388
HgeneTgene
Gene symbol

SMYD3

ZMYM4

Gene ID

64754

9202

Gene nameSET and MYND domain containing 3zinc finger MYM-type containing 4
SynonymsKMT3E|ZMYND1|ZNFN3A1|bA74P14.1CDIR|MYM|ZNF198L3|ZNF262
Cytomap

1q44

1p34.3

Type of geneprotein-codingprotein-coding
Descriptionhistone-lysine N-methyltransferase SMYD3SET and MYND domain-containing protein 3bA74P14.1 (novel protein)zinc finger MYND domain-containing protein 1zinc finger protein, subfamily 3A (MYND domain containing), 1zinc finger, MYND domain containing 1zinc finger MYM-type protein 4cell death inhibiting RNAzinc finger protein 262zinc finger, MYM-type 4
Modification date2020032020200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000388985, ENST00000403792, 
ENST00000490107, ENST00000541742, 
ENST00000366517, 
ENST00000482131, 
ENST00000314607, ENST00000373297, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score22 X 13 X 10=286013 X 13 X 7=1183
# samples 2414
** MAII scorelog2(24/2860*10)=-3.57490883605723
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(14/1183*10)=-3.07895134139482
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SMYD3 [Title/Abstract] AND ZMYM4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SMYD3 [Title/Abstract] AND ZMYM4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZMYM4(35827390)-SMYD3(246093239), # samples:3
SMYD3(246490503)-ZMYM4(35835630), # samples:3
Anticipated loss of major functional domain due to fusion event.SMYD3-ZMYM4 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.
SMYD3-ZMYM4 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.
SMYD3-ZMYM4 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.
SMYD3-ZMYM4 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.
ZMYM4-SMYD3 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.
ZMYM4-SMYD3 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.
SMYD3-ZMYM4 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
SMYD3-ZMYM4 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
SMYD3-ZMYM4 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


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/chr1:35827390/chr1:246093239)
- 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 SMYD3 (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 ZMYM4 (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)
ENST00000490107SMYD3chr1246490503-ENST00000373297ZMYM4chr135835630+63775711641101364
ENST00000490107SMYD3chr1246490503-ENST00000314607ZMYM4chr135835630+66455711643771453
ENST00000388985SMYD3chr1246490503-ENST00000373297ZMYM4chr135835630+6337531040701356
ENST00000388985SMYD3chr1246490503-ENST00000314607ZMYM4chr135835630+6605531043371445
ENST00000403792SMYD3chr1246490503-ENST00000373297ZMYM4chr135835630+64326265041651371
ENST00000403792SMYD3chr1246490503-ENST00000314607ZMYM4chr135835630+67006265044321460

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
ENST00000490107ENST00000373297SMYD3chr1246490503-ZMYM4chr135835630+8.21E-050.99991786
ENST00000490107ENST00000314607SMYD3chr1246490503-ZMYM4chr135835630+6.26E-050.9999373
ENST00000388985ENST00000373297SMYD3chr1246490503-ZMYM4chr135835630+7.77E-050.9999223
ENST00000388985ENST00000314607SMYD3chr1246490503-ZMYM4chr135835630+5.95E-050.9999405
ENST00000403792ENST00000373297SMYD3chr1246490503-ZMYM4chr135835630+8.77E-050.99991226
ENST00000403792ENST00000314607SMYD3chr1246490503-ZMYM4chr135835630+6.67E-050.99993324

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 SMYD3-ZMYM4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SMYD3chr1246490503ZMYM4chr135835630531176QLPPAFDLFEAFAKEYSHGQQQKTQE
SMYD3chr1246490503ZMYM4chr135835630571184QLPPAFDLFEAFAKEYSHGQQQKTQE
SMYD3chr1246490503ZMYM4chr135835630626191QLPPAFDLFEAFAKEYSHGQQQKTQE

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Potential FusionNeoAntigen Information of SMYD3-ZMYM4 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.
SMYD3-ZMYM4_246490503_35835630.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)
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B18:01FEAFAKEY0.99920.967816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B44:03FEAFAKEY0.99760.9779816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B15:02DLFEAFAKEY0.9880.8953616
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B15:21LFEAFAKEY0.94780.9283716
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B15:21DLFEAFAKEY0.98850.8681616
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B15:31DLFEAFAKEY0.9790.8616
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B18:07FEAFAKEY0.99940.9437816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B18:08FEAFAKEY0.99930.9331816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B18:04FEAFAKEY0.99920.9724816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B18:05FEAFAKEY0.99920.967816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B18:06FEAFAKEY0.99910.9737816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B18:03FEAFAKEY0.99880.964816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B18:11FEAFAKEY0.99790.9309816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B44:07FEAFAKEY0.99760.9779816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B44:13FEAFAKEY0.99760.9779816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B44:26FEAFAKEY0.99760.9779816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B35:20FEAFAKEY0.99090.9591816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B15:53FEAFAKEY0.98960.9185816
SMYD3-ZMYM4chr1246490503chr135835630531HLA-C14:03LFEAFAKEY0.36380.9684716
SMYD3-ZMYM4chr1246490503chr135835630531HLA-C14:02LFEAFAKEY0.36380.9684716
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B18:07EAFAKEYSH0.16770.8603918
SMYD3-ZMYM4chr1246490503chr135835630531HLA-A25:01DLFEAFAKEY0.99550.8064616
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B35:20DLFEAFAKEY0.98180.8836616
SMYD3-ZMYM4chr1246490503chr135835630531HLA-B18:04DLFEAFAKEY0.90390.9118616

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Potential FusionNeoAntigen Information of SMYD3-ZMYM4 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.
SMYD3-ZMYM4_246490503_35835630.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)
SMYD3-ZMYM4chr1246490503chr135835630531DRB1-1105FDLFEAFAKEYSHGQ520
SMYD3-ZMYM4chr1246490503chr135835630531DRB1-1119FDLFEAFAKEYSHGQ520
SMYD3-ZMYM4chr1246490503chr135835630531DRB1-1131FDLFEAFAKEYSHGQ520
SMYD3-ZMYM4chr1246490503chr135835630531DRB1-1132FDLFEAFAKEYSHGQ520
SMYD3-ZMYM4chr1246490503chr135835630531DRB1-1145FDLFEAFAKEYSHGQ520
SMYD3-ZMYM4chr1246490503chr135835630531DRB1-1169FDLFEAFAKEYSHGQ520
SMYD3-ZMYM4chr1246490503chr135835630531DRB1-1169AFDLFEAFAKEYSHG419
SMYD3-ZMYM4chr1246490503chr135835630531DRB1-1182FDLFEAFAKEYSHGQ520
SMYD3-ZMYM4chr1246490503chr135835630531DRB1-1182AFDLFEAFAKEYSHG419
SMYD3-ZMYM4chr1246490503chr135835630531DRB1-1382FDLFEAFAKEYSHGQ520
SMYD3-ZMYM4chr1246490503chr135835630531DRB1-1424FDLFEAFAKEYSHGQ520
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0101PPAFDLFEAFAKEYS217
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0101LPPAFDLFEAFAKEY116
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0102PPAFDLFEAFAKEYS217
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0102LPPAFDLFEAFAKEY116
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0102QLPPAFDLFEAFAKE015
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0103PPAFDLFEAFAKEYS217
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0103LPPAFDLFEAFAKEY116
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0103QLPPAFDLFEAFAKE015
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0103PAFDLFEAFAKEYSH318
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0104PPAFDLFEAFAKEYS217
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0104LPPAFDLFEAFAKEY116
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0104QLPPAFDLFEAFAKE015
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0105PPAFDLFEAFAKEYS217
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0105LPPAFDLFEAFAKEY116
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0108NPPAFDLFEAFAKEYS217
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0108NLPPAFDLFEAFAKEY116
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0108NQLPPAFDLFEAFAKE015
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0111PPAFDLFEAFAKEYS217
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0111LPPAFDLFEAFAKEY116
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0111QLPPAFDLFEAFAKE015
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0113PPAFDLFEAFAKEYS217
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0113LPPAFDLFEAFAKEY116
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0114PPAFDLFEAFAKEYS217
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0114LPPAFDLFEAFAKEY116
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0203PPAFDLFEAFAKEYS217
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0203LPPAFDLFEAFAKEY116
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0203QLPPAFDLFEAFAKE015
SMYD3-ZMYM4chr1246490503chr135835630531DRB5-0203PAFDLFEAFAKEYSH318

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Fusion breakpoint peptide structures of SMYD3-ZMYM4

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
1207DLFEAFAKEYSHGQSMYD3ZMYM4chr1246490503chr135835630531

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SMYD3-ZMYM4

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-B14:023BVN1207DLFEAFAKEYSHGQ-7.15543-7.26883
HLA-B14:023BVN1207DLFEAFAKEYSHGQ-4.77435-5.80965
HLA-B52:013W391207DLFEAFAKEYSHGQ-6.80875-6.92215
HLA-B52:013W391207DLFEAFAKEYSHGQ-4.20386-5.23916
HLA-A11:014UQ21207DLFEAFAKEYSHGQ-7.5194-8.5547
HLA-A11:014UQ21207DLFEAFAKEYSHGQ-6.9601-7.0735
HLA-A24:025HGA1207DLFEAFAKEYSHGQ-7.52403-7.63743
HLA-A24:025HGA1207DLFEAFAKEYSHGQ-5.82433-6.85963
HLA-B27:056PYJ1207DLFEAFAKEYSHGQ-3.28285-4.31815
HLA-B44:053DX81207DLFEAFAKEYSHGQ-5.91172-6.94702
HLA-B44:053DX81207DLFEAFAKEYSHGQ-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of SMYD3-ZMYM4

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
SMYD3-ZMYM4chr1246490503chr135835630616DLFEAFAKEYCTTTTTGAAGCCTTTGCAAAAGAGTATAGT
SMYD3-ZMYM4chr1246490503chr135835630716LFEAFAKEYTTTGAAGCCTTTGCAAAAGAGTATAGT
SMYD3-ZMYM4chr1246490503chr135835630816FEAFAKEYGAAGCCTTTGCAAAAGAGTATAGT
SMYD3-ZMYM4chr1246490503chr135835630918EAFAKEYSHGCCTTTGCAAAAGAGTATAGTCATGGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SMYD3-ZMYM4chr1246490503chr135835630015QLPPAFDLFEAFAKECTGCCACCTGCCTTTGACCTTTTTGAAGCCTTTGCAAAAGAGTAT
SMYD3-ZMYM4chr1246490503chr135835630116LPPAFDLFEAFAKEYCCACCTGCCTTTGACCTTTTTGAAGCCTTTGCAAAAGAGTATAGT
SMYD3-ZMYM4chr1246490503chr135835630217PPAFDLFEAFAKEYSCCTGCCTTTGACCTTTTTGAAGCCTTTGCAAAAGAGTATAGTCAT
SMYD3-ZMYM4chr1246490503chr135835630318PAFDLFEAFAKEYSHGCCTTTGACCTTTTTGAAGCCTTTGCAAAAGAGTATAGTCATGGC
SMYD3-ZMYM4chr1246490503chr135835630419AFDLFEAFAKEYSHGTTTGACCTTTTTGAAGCCTTTGCAAAAGAGTATAGTCATGGCCAA
SMYD3-ZMYM4chr1246490503chr135835630520FDLFEAFAKEYSHGQGACCTTTTTGAAGCCTTTGCAAAAGAGTATAGTCATGGCCAACAG

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Information of the samples that have these potential fusion neoantigens of SMYD3-ZMYM4

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
SKCMSMYD3-ZMYM4chr1246490503ENST00000388985chr135835630ENST00000314607TCGA-DA-A1I7-06A

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Potential target of CAR-T therapy development for SMYD3-ZMYM4

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 SMYD3-ZMYM4

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 SMYD3-ZMYM4

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