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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:CLU-MYH9

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CLU-MYH9
FusionPDB ID: 17454
FusionGDB2.0 ID: 17454
HgeneTgene
Gene symbol

CLU

MYH9

Gene ID

1191

4627

Gene nameclusterinmyosin heavy chain 9
SynonymsAAG4|APO-J|APOJ|CLI|CLU1|CLU2|KUB1|NA1/NA2|SGP-2|SGP2|SP-40|TRPM-2|TRPM2BDPLT6|DFNA17|EPSTS|FTNS|MATINS|MHA|NMHC-II-A|NMMHC-IIA|NMMHCA
Cytomap

8p21.1

22q12.3

Type of geneprotein-codingprotein-coding
Descriptionclusterinaging-associated protein 4apolipoprotein Jcomplement cytolysis inhibitorcomplement lysis inhibitorcomplement-associated protein SP-40,40epididymis secretory sperm binding proteinku70-binding protein 1sulfated glycoprotein 2testosterone-rmyosin-9cellular myosin heavy chain, type Amyosin, heavy chain 9, non-musclenon-muscle myosin heavy chain 9non-muscle myosin heavy chain Anon-muscle myosin heavy chain IIanon-muscle myosin heavy polypeptide 9nonmuscle myosin heavy chain II-A
Modification date2020032720200315
UniProtAcc

Q15846

Main function of 5'-partner protein:

P35579

Main function of 5'-partner protein: FUNCTION: Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Promotes also cell motility together with S100A4 (PubMed:16707441). During cell spreading, plays an important role in cytoskeleton reorganization, focal contacts formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10 (PubMed:20052411). {ECO:0000250|UniProtKB:Q8VDD5, ECO:0000269|PubMed:16707441, ECO:0000269|PubMed:20052411}.
Ensembl transtripts involved in fusion geneENST idsENST00000316403, ENST00000405140, 
ENST00000523500, ENST00000546343, 
ENST00000560366, 
ENST00000401701, 
ENST00000475726, ENST00000216181, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score38 X 38 X 12=1732844 X 46 X 15=30360
# samples 4956
** MAII scorelog2(49/17328*10)=-5.14417958860576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(56/30360*10)=-5.76060115335786
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CLU [Title/Abstract] AND MYH9 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CLU [Title/Abstract] AND MYH9 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CLU(27463871)-MYH9(36723533), # samples:1
Anticipated loss of major functional domain due to fusion event.CLU-MYH9 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.
CLU-MYH9 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.
CLU-MYH9 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.
CLU-MYH9 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.
CLU-MYH9 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
CLU-MYH9 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
CLU-MYH9 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
HgeneCLU

GO:0000902

cell morphogenesis

15857407

HgeneCLU

GO:0001774

microglial cell activation

15857407

HgeneCLU

GO:0017038

protein import

24446231

HgeneCLU

GO:0031333

negative regulation of protein complex assembly

22179788|23106396

HgeneCLU

GO:0031334

positive regulation of protein complex assembly

22179788

HgeneCLU

GO:0032760

positive regulation of tumor necrosis factor production

15857407

HgeneCLU

GO:0045429

positive regulation of nitric oxide biosynthetic process

15857407

HgeneCLU

GO:0050821

protein stabilization

11123922|12176985

HgeneCLU

GO:0051131

chaperone-mediated protein complex assembly

17412999

HgeneCLU

GO:0051788

response to misfolded protein

19996109

HgeneCLU

GO:0061077

chaperone-mediated protein folding

11123922

HgeneCLU

GO:0061518

microglial cell proliferation

15857407

HgeneCLU

GO:1900221

regulation of amyloid-beta clearance

24446231

HgeneCLU

GO:1901214

regulation of neuron death

17412999

HgeneCLU

GO:1901216

positive regulation of neuron death

15857407

HgeneCLU

GO:1902430

negative regulation of amyloid-beta formation

12047389|17412999

HgeneCLU

GO:1905907

negative regulation of amyloid fibril formation

22179788

TgeneMYH9

GO:0001525

angiogenesis

16403913

TgeneMYH9

GO:0001778

plasma membrane repair

27325790

TgeneMYH9

GO:0006509

membrane protein ectodomain proteolysis

16186248

TgeneMYH9

GO:0030048

actin filament-based movement

12237319|15845534

TgeneMYH9

GO:0031032

actomyosin structure organization

24072716



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/chr8:27463871/chr22:36723533)
- 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 CLU (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 MYH9 (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)
ENST00000405140CLUchr827463871-ENST00000216181MYH9chr2236723533-751273265961241821

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
ENST00000405140ENST00000216181CLUchr827463871-MYH9chr2236723533-0.0211014240.9788986

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 CLU-MYH9

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CLUchr827463871MYH9chr223672353373224TRLQKWLRPGWPPDREDQSILCTGES

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Potential FusionNeoAntigen Information of CLU-MYH9 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.
CLU-MYH9_27463871_36723533.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)
CLU-MYH9chr827463871chr2236723533732HLA-B07:12WPPDREDQSIL0.99790.58581021

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Potential FusionNeoAntigen Information of CLU-MYH9 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 CLU-MYH9

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
5546LRPGWPPDREDQSICLUMYH9chr827463871chr2236723533732

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CLU-MYH9

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-B14:023BVN5546LRPGWPPDREDQSI-7.15543-7.26883
HLA-B14:023BVN5546LRPGWPPDREDQSI-4.77435-5.80965
HLA-B52:013W395546LRPGWPPDREDQSI-6.80875-6.92215
HLA-B52:013W395546LRPGWPPDREDQSI-4.20386-5.23916
HLA-A11:014UQ25546LRPGWPPDREDQSI-7.5194-8.5547
HLA-A11:014UQ25546LRPGWPPDREDQSI-6.9601-7.0735
HLA-A24:025HGA5546LRPGWPPDREDQSI-7.52403-7.63743
HLA-A24:025HGA5546LRPGWPPDREDQSI-5.82433-6.85963
HLA-B27:056PYJ5546LRPGWPPDREDQSI-3.28285-4.31815
HLA-B44:053DX85546LRPGWPPDREDQSI-5.91172-6.94702
HLA-B44:053DX85546LRPGWPPDREDQSI-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CLU-MYH9

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
CLU-MYH9chr827463871chr22367235331021WPPDREDQSILGGCCGCCAGACCGAGAAGATCAATCCATCTTGT

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 CLU-MYH9

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
BLCACLU-MYH9chr827463871ENST00000405140chr2236723533ENST00000216181TCGA-UY-A9PE-01A

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Potential target of CAR-T therapy development for CLU-MYH9

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 CLU-MYH9

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 CLU-MYH9

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
HgeneCLUC0022660Kidney Failure, Acute6CTD_human
HgeneCLUC1565662Acute Kidney Insufficiency6CTD_human
HgeneCLUC2609414Acute kidney injury6CTD_human
HgeneCLUC0002395Alzheimer's Disease3CTD_human
HgeneCLUC0011265Presenile dementia3CTD_human
HgeneCLUC0022658Kidney Diseases3CTD_human
HgeneCLUC0276496Familial Alzheimer Disease (FAD)3CTD_human
HgeneCLUC0494463Alzheimer Disease, Late Onset3CTD_human
HgeneCLUC0546126Acute Confusional Senile Dementia3CTD_human
HgeneCLUC0750900Alzheimer's Disease, Focal Onset3CTD_human
HgeneCLUC0750901Alzheimer Disease, Early Onset3CTD_human
HgeneCLUC0013221Drug toxicity2CTD_human
HgeneCLUC0029408Degenerative polyarthritis2CTD_human
HgeneCLUC0041755Adverse reaction to drug2CTD_human
HgeneCLUC0086743Osteoarthrosis Deformans2CTD_human
HgeneCLUC0019193Hepatitis, Toxic1CTD_human
HgeneCLUC0022333Jacksonian Seizure1CTD_human
HgeneCLUC0024141Lupus Erythematosus, Systemic1CTD_human
HgeneCLUC0025202melanoma1CTD_human
HgeneCLUC0027686Pathologic Neovascularization1CTD_human
HgeneCLUC0033578Prostatic Neoplasms1CTD_human
HgeneCLUC0036341Schizophrenia1PSYGENET
HgeneCLUC0036572Seizures1CTD_human
HgeneCLUC0087031Juvenile-Onset Still Disease1CTD_human
HgeneCLUC0149958Complex partial seizures1CTD_human
HgeneCLUC0234533Generalized seizures1CTD_human
HgeneCLUC0234535Clonic Seizures1CTD_human
HgeneCLUC0234985Mental deterioration1CTD_human
HgeneCLUC0242380Libman-Sacks Disease1CTD_human
HgeneCLUC0270824Visual seizure1CTD_human
HgeneCLUC0270844Tonic Seizures1CTD_human
HgeneCLUC0270846Epileptic drop attack1CTD_human
HgeneCLUC0333641Atrophic1CTD_human
HgeneCLUC0338656Impaired cognition1CTD_human
HgeneCLUC0376358Malignant neoplasm of prostate1CTD_human
HgeneCLUC0422850Seizures, Somatosensory1CTD_human
HgeneCLUC0422852Seizures, Auditory1CTD_human
HgeneCLUC0422853Olfactory seizure1CTD_human
HgeneCLUC0422854Gustatory seizure1CTD_human
HgeneCLUC0422855Vertiginous seizure1CTD_human
HgeneCLUC0494475Tonic - clonic seizures1CTD_human
HgeneCLUC0751056Non-epileptic convulsion1CTD_human
HgeneCLUC0751110Single Seizure1CTD_human
HgeneCLUC0751123Atonic Absence Seizures1CTD_human
HgeneCLUC0751494Convulsive Seizures1CTD_human
HgeneCLUC0751495Seizures, Focal1CTD_human
HgeneCLUC0751496Seizures, Sensory1CTD_human
HgeneCLUC0860207Drug-Induced Liver Disease1CTD_human
HgeneCLUC1262760Hepatitis, Drug-Induced1CTD_human
HgeneCLUC1270972Mild cognitive disorder1CTD_human
HgeneCLUC1862939AMYOTROPHIC LATERAL SCLEROSIS 11CTD_human
HgeneCLUC1862941Amyotrophic Lateral Sclerosis, Sporadic1CTD_human
HgeneCLUC3495559Juvenile arthritis1CTD_human
HgeneCLUC3495874Nonepileptic Seizures1CTD_human
HgeneCLUC3658290Drug-Induced Acute Liver Injury1CTD_human
HgeneCLUC3714758Juvenile psoriatic arthritis1CTD_human
HgeneCLUC4048158Convulsions1CTD_human
HgeneCLUC4277682Chemical and Drug Induced Liver Injury1CTD_human
HgeneCLUC4279912Chemically-Induced Liver Toxicity1CTD_human
HgeneCLUC4316903Absence Seizures1CTD_human
HgeneCLUC4317109Epileptic Seizures1CTD_human
HgeneCLUC4317123Myoclonic Seizures1CTD_human
HgeneCLUC4505436Generalized Absence Seizures1CTD_human
HgeneCLUC4551993Amyotrophic Lateral Sclerosis, Familial1CTD_human
HgeneCLUC4552091Polyarthritis, Juvenile, Rheumatoid Factor Negative1CTD_human
HgeneCLUC4704862Polyarthritis, Juvenile, Rheumatoid Factor Positive1CTD_human