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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:LOH12CR1-HDAC7

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LOH12CR1-HDAC7
FusionPDB ID: 49406
FusionGDB2.0 ID: 49406
HgeneTgene
Gene symbol

LOH12CR1

HDAC7

Gene ID

118426

51564

Gene nameBLOC-1 related complex subunit 5histone deacetylase 7
SynonymsLOH12CR1|LOH1CR12HD7|HD7A|HDAC7A
Cytomap

12p13.2

12q13.11

Type of geneprotein-codingprotein-coding
DescriptionBLOC-1-related complex subunit 5loss of heterozygosity 12 chromosomal region 1 proteinloss of heterozygosity, 12, chromosomal region 1myristoylated lysosomal proteinmyrlysinhistone deacetylase 7histone deacetylase 7A
Modification date2020031320200327
UniProtAcc.

Q8WUI4

Main function of 5'-partner protein: FUNCTION: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation by repressing transcription of myocyte enhancer factors such as MEF2A, MEF2B and MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors (By similarity). May be involved in Epstein-Barr virus (EBV) latency, possibly by repressing the viral BZLF1 gene. Positively regulates the transcriptional repressor activity of FOXP3 (PubMed:17360565). Serves as a corepressor of RARA, causing its deacetylation and inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). {ECO:0000250|UniProtKB:Q8C2B3, ECO:0000269|PubMed:12239305, ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:28167758}.
Ensembl transtripts involved in fusion geneENST idsENST00000298571, ENST00000314565, 
ENST00000542728, 
ENST00000488927, 
ENST00000080059, ENST00000354334, 
ENST00000380610, ENST00000427332, 
ENST00000552960, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 3 X 6=10810 X 9 X 5=450
# samples 610
** MAII scorelog2(6/108*10)=-0.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/450*10)=-2.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LOH12CR1 [Title/Abstract] AND HDAC7 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LOH12CR1 [Title/Abstract] AND HDAC7 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LOH12CR1(12510443)-HDAC7(48185787), # samples:1
Anticipated loss of major functional domain due to fusion event.LOH12CR1-HDAC7 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.
LOH12CR1-HDAC7 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.
LOH12CR1-HDAC7 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.
LOH12CR1-HDAC7 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.
LOH12CR1-HDAC7 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
LOH12CR1-HDAC7 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
LOH12CR1-HDAC7 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
TgeneHDAC7

GO:0032703

negative regulation of interleukin-2 production

17360565



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/chr12:12510443/chr12:48185787)
- 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 LOH12CR1 (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 HDAC7 (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)
ENST00000314565LOH12CR1chr1212510443-ENST00000080059HDAC7chr1248185787-28063892261686486
ENST00000314565LOH12CR1chr1212510443-ENST00000354334HDAC7chr1248185787-28063892261686486
ENST00000314565LOH12CR1chr1212510443-ENST00000552960HDAC7chr1248185787-18773892261686486
ENST00000314565LOH12CR1chr1212510443-ENST00000380610HDAC7chr1248185787-19143892261704492
ENST00000314565LOH12CR1chr1212510443-ENST00000427332HDAC7chr1248185787-16873892261686487
ENST00000298571LOH12CR1chr1212510443-ENST00000080059HDAC7chr1248185787-250992341389451
ENST00000298571LOH12CR1chr1212510443-ENST00000354334HDAC7chr1248185787-250992341389451
ENST00000298571LOH12CR1chr1212510443-ENST00000552960HDAC7chr1248185787-158092341389451
ENST00000298571LOH12CR1chr1212510443-ENST00000380610HDAC7chr1248185787-161792341407457
ENST00000298571LOH12CR1chr1212510443-ENST00000427332HDAC7chr1248185787-139092341389452

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
ENST00000314565ENST00000080059LOH12CR1chr1212510443-HDAC7chr1248185787-0.016168410.98383164
ENST00000314565ENST00000354334LOH12CR1chr1212510443-HDAC7chr1248185787-0.016168410.98383164
ENST00000314565ENST00000552960LOH12CR1chr1212510443-HDAC7chr1248185787-0.0251605850.9748394
ENST00000314565ENST00000380610LOH12CR1chr1212510443-HDAC7chr1248185787-0.083842810.9161572
ENST00000314565ENST00000427332LOH12CR1chr1212510443-HDAC7chr1248185787-0.0259929820.974007
ENST00000298571ENST00000080059LOH12CR1chr1212510443-HDAC7chr1248185787-0.0168584550.98314154
ENST00000298571ENST00000354334LOH12CR1chr1212510443-HDAC7chr1248185787-0.0168584550.98314154
ENST00000298571ENST00000552960LOH12CR1chr1212510443-HDAC7chr1248185787-0.027211370.9727886
ENST00000298571ENST00000380610LOH12CR1chr1212510443-HDAC7chr1248185787-0.0719019850.92809796
ENST00000298571ENST00000427332LOH12CR1chr1212510443-HDAC7chr1248185787-0.0259595480.97404045

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 LOH12CR1-HDAC7

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LOH12CR1chr1212510443HDAC7chr124818578738954SEAESRPNDLNSSGLIYDSVMLKHQC
LOH12CR1chr1212510443HDAC7chr12481857879219SEAESRPNDLNSSGLIYDSVMLKHQC

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Potential FusionNeoAntigen Information of LOH12CR1-HDAC7 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.
LOH12CR1-HDAC7_12510443_48185787.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)
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B15:02DLNSSGLIY0.72790.5557817
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B15:02NDLNSSGLIY0.82260.6977717
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B35:03RPNDLNSSGL0.75770.7349515
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B35:02RPNDLNSSGL0.52270.7342515
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B35:04RPNDLNSSGL0.52270.7342515
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-A30:08SGLIYDSVMLK0.97350.72551223
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-A74:03SGLIYDSVMLK0.88460.51161223
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-A74:09SGLIYDSVMLK0.88460.51161223
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-A74:11SGLIYDSVMLK0.88460.51161223
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B15:21DLNSSGLIY0.76490.5358817
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B39:10RPNDLNSSGL0.7170.6596515
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B35:12RPNDLNSSGL0.52270.7342515
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B35:24DLNSSGLIY0.86310.5055817
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B35:11DLNSSGLIY0.71910.5118817
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B15:12DLNSSGLIY0.68480.5051817
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B35:20DLNSSGLIY0.61060.5086817
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B18:04DLNSSGLIY0.42450.5331817
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B35:13RPNDLNSSGL0.71940.745515
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B67:01RPNDLNSSGL0.70340.5821515
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-B35:09RPNDLNSSGL0.52270.7342515
LOH12CR1-HDAC7chr1212510443chr124818578792HLA-A74:01SGLIYDSVMLK0.88460.51161223

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Potential FusionNeoAntigen Information of LOH12CR1-HDAC7 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.
LOH12CR1-HDAC7_12510443_48185787.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)
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0301NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0313NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0318NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0320NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0322NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0326NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0328NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0330NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0332NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0334NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0336NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0342NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0344NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0346NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0348NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0350NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0352NSSGLIYDSVMLKHQ1025
LOH12CR1-HDAC7chr1212510443chr124818578792DRB1-0354NSSGLIYDSVMLKHQ1025

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Fusion breakpoint peptide structures of LOH12CR1-HDAC7

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
6818PNDLNSSGLIYDSVLOH12CR1HDAC7chr1212510443chr124818578792

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LOH12CR1-HDAC7

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-B14:023BVN6818PNDLNSSGLIYDSV-7.9962-8.1096
HLA-B14:023BVN6818PNDLNSSGLIYDSV-5.70842-6.74372
HLA-B52:013W396818PNDLNSSGLIYDSV-6.83737-6.95077
HLA-B52:013W396818PNDLNSSGLIYDSV-4.4836-5.5189
HLA-A11:014UQ26818PNDLNSSGLIYDSV-10.0067-10.1201
HLA-A11:014UQ26818PNDLNSSGLIYDSV-9.03915-10.0745
HLA-A24:025HGA6818PNDLNSSGLIYDSV-6.56204-6.67544
HLA-A24:025HGA6818PNDLNSSGLIYDSV-5.42271-6.45801
HLA-B44:053DX86818PNDLNSSGLIYDSV-7.85648-8.89178
HLA-B44:053DX86818PNDLNSSGLIYDSV-5.3978-5.5112
HLA-A02:016TDR6818PNDLNSSGLIYDSV-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of LOH12CR1-HDAC7

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
LOH12CR1-HDAC7chr1212510443chr12481857871223SGLIYDSVMLKCAGGGCTGATCTATGACTCGGTCATGCTGAAGC
LOH12CR1-HDAC7chr1212510443chr1248185787515RPNDLNSSGLGACCCAACGATCTGAACTCCTCAGGGCTGA
LOH12CR1-HDAC7chr1212510443chr1248185787717NDLNSSGLIYACGATCTGAACTCCTCAGGGCTGATCTATG
LOH12CR1-HDAC7chr1212510443chr1248185787817DLNSSGLIYATCTGAACTCCTCAGGGCTGATCTATG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
LOH12CR1-HDAC7chr1212510443chr12481857871025NSSGLIYDSVMLKHQACTCCTCAGGGCTGATCTATGACTCGGTCATGCTGAAGCACCAGT

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Information of the samples that have these potential fusion neoantigens of LOH12CR1-HDAC7

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
PRADLOH12CR1-HDAC7chr1212510443ENST00000298571chr1248185787ENST00000080059TCGA-V1-A8WS-01A

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Potential target of CAR-T therapy development for LOH12CR1-HDAC7

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 LOH12CR1-HDAC7

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 LOH12CR1-HDAC7

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