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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:HAND2-SLC30A9

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HAND2-SLC30A9
FusionPDB ID: 35596
FusionGDB2.0 ID: 35596
HgeneTgene
Gene symbol

HAND2

SLC30A9

Gene ID

9464

10463

Gene nameheart and neural crest derivatives expressed 2solute carrier family 30 member 9
SynonymsDHAND2|Hed|Thing2|bHLHa26|dHandBILAPES|C4orf1|GAC63|HUEL|ZNT9
Cytomap

4q34.1

4p13

Type of geneprotein-codingprotein-coding
Descriptionheart- and neural crest derivatives-expressed protein 2basic helix-loop-helix transcription factor HAND2class A basic helix-loop-helix protein 26deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2zinc transporter 9GRIP1-dependent nuclear receptor coactivatorexpressed in human embryonic lunghuman embryonic lung proteinsolute carrier family 30 (zinc transporter), member 9znT-9
Modification date2020031320200313
UniProtAcc

P61296

Main function of 5'-partner protein: FUNCTION: Essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries. Required for vascular development and regulation of angiogenesis, possibly through a VEGF signaling pathway. Plays also an important role in limb development, particularly in the establishment of anterior-posterior polarization, acting as an upstream regulator of sonic hedgehog (SHH) induction in the limb bud. Is involved in the development of branchial arches, which give rise to unique structures in the head and neck. Binds DNA on E-box consensus sequence 5'-CANNTG-3' (By similarity). {ECO:0000250}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000359562, ENST00000505300, 
ENST00000264451, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 3 X 1=65 X 10 X 3=150
# samples 38
** MAII scorelog2(3/6*10)=2.32192809488736log2(8/150*10)=-0.906890595608519
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: HAND2 [Title/Abstract] AND SLC30A9 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: HAND2 [Title/Abstract] AND SLC30A9 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HAND2(174449886)-SLC30A9(42041003), # samples:3
Anticipated loss of major functional domain due to fusion event.HAND2-SLC30A9 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.
HAND2-SLC30A9 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
HgeneHAND2

GO:0010613

positive regulation of cardiac muscle hypertrophy

24161931

HgeneHAND2

GO:0034103

regulation of tissue remodeling

24161931

HgeneHAND2

GO:0045944

positive regulation of transcription by RNA polymerase II

15486975|16280598|24161931

HgeneHAND2

GO:2000679

positive regulation of transcription regulatory region DNA binding

16280598



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/chr4:174449886/chr4:42041003)
- 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 HAND2 (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 SLC30A9 (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)
ENST00000359562HAND2chr4174449886-ENST00000264451SLC30A9chr442041003+686414958292532567
ENST00000359562HAND2chr4174449885-ENST00000264451SLC30A9chr442041002+686414958292532567

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
ENST00000359562ENST00000264451HAND2chr4174449886-SLC30A9chr442041003+0.0003387610.9996612
ENST00000359562ENST00000264451HAND2chr4174449885-SLC30A9chr442041002+0.0003387610.9996612

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 HAND2-SLC30A9

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
HAND2chr4174449885SLC30A9chr4420410021495222KTDVKEEKRKKELPRSRTASVFFKGP
HAND2chr4174449886SLC30A9chr4420410031495222KTDVKEEKRKKELPRSRTASVFFKGP

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Potential FusionNeoAntigen Information of HAND2-SLC30A9 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.
HAND2-SLC30A9_174449885_42041002.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)
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B08:09ELPRSRTA0.99790.79211119
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B08:09LPRSRTASV0.99610.51151221
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B45:01KELPRSRTA0.99560.96841019
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B14:01LPRSRTASV0.99440.72071221
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B14:02LPRSRTASV0.99440.72071221
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B50:02KELPRSRTA0.99430.75571019
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B41:01KELPRSRTA0.66590.95551019
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B50:01KELPRSRTA0.25560.80021019
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B08:09ELPRSRTASV0.99410.74691121
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B35:01LPRSRTASVF0.93410.76941222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B35:08LPRSRTASVF0.93220.75561222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B35:05LPRSRTASVF0.90950.52751222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B41:01KKELPRSRTA0.63230.9699919
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B50:01KKELPRSRTA0.57720.8188919
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B50:02KKELPRSRTA0.42250.7858919
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B50:01RKKELPRSRTA0.69760.932819
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B40:06KELPRSRTA0.99830.73631019
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B40:03KELPRSRTA0.89610.52121019
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B14:03LPRSRTASV0.83290.74281221
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B39:10LPRSRTASV0.28910.78031221
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B07:12LPRSRTASVF0.98970.57021222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B40:06KKELPRSRTA0.64630.9003919
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B07:12LPRSRTASVFF0.99540.58691223
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B42:01LPRSRTASVFF0.99310.50261223
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B42:02LPRSRTASVFF0.99290.50371223
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B42:01KELPRSRTASV0.98960.72371021
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B40:06RKKELPRSRTA0.82380.9341819
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B41:03KELPRSRTA0.69010.78691019
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B67:01LPRSRTASV0.42060.65711221
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B50:04KELPRSRTA0.25560.80021019
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B50:05KELPRSRTA0.25560.80021019
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B27:10KRKKELPRSR0.99640.8966717
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B35:77LPRSRTASVF0.93410.76941222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B35:23LPRSRTASVF0.93390.76541222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B35:43LPRSRTASVF0.91730.7021222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B15:08LPRSRTASVF0.91380.69741222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B15:11LPRSRTASVF0.91310.69571222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B35:17LPRSRTASVF0.90590.671222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B35:30LPRSRTASVF0.90590.671222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B35:24LPRSRTASVF0.88810.76951222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B35:11LPRSRTASVF0.83830.77441222
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B50:05KKELPRSRTA0.57720.8188919
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B50:04KKELPRSRTA0.57720.8188919
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B50:04RKKELPRSRTA0.69760.932819
HAND2-SLC30A9chr4174449885chr4420410021495HLA-B50:05RKKELPRSRTA0.69760.932819

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Potential FusionNeoAntigen Information of HAND2-SLC30A9 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.
HAND2-SLC30A9_174449885_42041002.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)
HAND2-SLC30A9chr4174449885chr4420410021495DRB1-1332KTDVKEEKRKKELPR015
HAND2-SLC30A9chr4174449885chr4420410021495DRB1-1348KTDVKEEKRKKELPR015
HAND2-SLC30A9chr4174449885chr4420410021495DRB1-1375KTDVKEEKRKKELPR015
HAND2-SLC30A9chr4174449885chr4420410021495DRB1-1381KTDVKEEKRKKELPR015
HAND2-SLC30A9chr4174449885chr4420410021495DRB1-1389KTDVKEEKRKKELPR015
HAND2-SLC30A9chr4174449885chr4420410021495DRB1-1394KTDVKEEKRKKELPR015

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Fusion breakpoint peptide structures of HAND2-SLC30A9

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
1863EKRKKELPRSRTASHAND2SLC30A9chr4174449885chr4420410021495

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HAND2-SLC30A9

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-B14:023BVN1863EKRKKELPRSRTAS-7.9962-8.1096
HLA-B14:023BVN1863EKRKKELPRSRTAS-5.70842-6.74372
HLA-B52:013W391863EKRKKELPRSRTAS-6.83737-6.95077
HLA-B52:013W391863EKRKKELPRSRTAS-4.4836-5.5189
HLA-A11:014UQ21863EKRKKELPRSRTAS-10.0067-10.1201
HLA-A11:014UQ21863EKRKKELPRSRTAS-9.03915-10.0745
HLA-A24:025HGA1863EKRKKELPRSRTAS-6.56204-6.67544
HLA-A24:025HGA1863EKRKKELPRSRTAS-5.42271-6.45801
HLA-B44:053DX81863EKRKKELPRSRTAS-7.85648-8.89178
HLA-B44:053DX81863EKRKKELPRSRTAS-5.3978-5.5112
HLA-A02:016TDR1863EKRKKELPRSRTAS-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of HAND2-SLC30A9

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
HAND2-SLC30A9chr4174449885chr4420410021019KELPRSRTAAAGGAGCTGCCACGCTCCAGAACAGCA
HAND2-SLC30A9chr4174449885chr4420410021021KELPRSRTASVAAGGAGCTGCCACGCTCCAGAACAGCATCAGTG
HAND2-SLC30A9chr4174449885chr4420410021119ELPRSRTAGAGCTGCCACGCTCCAGAACAGCA
HAND2-SLC30A9chr4174449885chr4420410021121ELPRSRTASVGAGCTGCCACGCTCCAGAACAGCATCAGTG
HAND2-SLC30A9chr4174449885chr4420410021221LPRSRTASVCTGCCACGCTCCAGAACAGCATCAGTG
HAND2-SLC30A9chr4174449885chr4420410021222LPRSRTASVFCTGCCACGCTCCAGAACAGCATCAGTGTTT
HAND2-SLC30A9chr4174449885chr4420410021223LPRSRTASVFFCTGCCACGCTCCAGAACAGCATCAGTGTTTTTT
HAND2-SLC30A9chr4174449885chr442041002717KRKKELPRSRAAGAGGAAGAAGGAGCTGCCACGCTCCAGA
HAND2-SLC30A9chr4174449885chr442041002819RKKELPRSRTAAGGAAGAAGGAGCTGCCACGCTCCAGAACAGCA
HAND2-SLC30A9chr4174449885chr442041002919KKELPRSRTAAAGAAGGAGCTGCCACGCTCCAGAACAGCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
HAND2-SLC30A9chr4174449885chr442041002015KTDVKEEKRKKELPRAAGACCGACGTGAAAGAGGAGAAGAGGAAGAAGGAGCTGCCACGC

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Information of the samples that have these potential fusion neoantigens of HAND2-SLC30A9

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
PCPGHAND2-SLC30A9chr4174449885ENST00000359562chr442041002ENST00000264451TCGA-SP-A6QI

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Potential target of CAR-T therapy development for HAND2-SLC30A9

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
TgeneSLC30A9chr4:174449885chr4:42041002ENST00000264451618239_2590569.0TransmembraneHelical
TgeneSLC30A9chr4:174449885chr4:42041002ENST00000264451618314_3340569.0TransmembraneHelical
TgeneSLC30A9chr4:174449885chr4:42041002ENST00000264451618342_3620569.0TransmembraneHelical
TgeneSLC30A9chr4:174449885chr4:42041002ENST00000264451618392_4120569.0TransmembraneHelical
TgeneSLC30A9chr4:174449885chr4:42041002ENST00000264451618424_4440569.0TransmembraneHelical
TgeneSLC30A9chr4:174449886chr4:42041003ENST00000264451618239_2590569.0TransmembraneHelical
TgeneSLC30A9chr4:174449886chr4:42041003ENST00000264451618314_3340569.0TransmembraneHelical
TgeneSLC30A9chr4:174449886chr4:42041003ENST00000264451618342_3620569.0TransmembraneHelical
TgeneSLC30A9chr4:174449886chr4:42041003ENST00000264451618392_4120569.0TransmembraneHelical
TgeneSLC30A9chr4:174449886chr4:42041003ENST00000264451618424_4440569.0TransmembraneHelical

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 HAND2-SLC30A9

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 HAND2-SLC30A9

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