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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:THRB-LMCD1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: THRB-LMCD1
FusionPDB ID: 90743
FusionGDB2.0 ID: 90743
HgeneTgene
Gene symbol

THRB

LMCD1

Gene ID

7068

29995

Gene namethyroid hormone receptor betaLIM and cysteine rich domains 1
SynonymsC-ERBA-2|C-ERBA-BETA|ERBA2|GRTH|NR1A2|PRTH|THR1|THRB1|THRB2-
Cytomap

3p24.2

3p25.3

Type of geneprotein-codingprotein-coding
Descriptionthyroid hormone receptor betanuclear receptor subfamily 1 group A member 2oncogene ERBA2thyroid hormone nuclear receptor beta variant 1thyroid hormone receptor, beta (erythroblastic leukemia viral (v-erb-a) oncogene homolog 2, avian)LIM and cysteine-rich domains protein 1dyxin
Modification date2020031320200313
UniProtAcc.

Q9NZU5

Main function of 5'-partner protein: FUNCTION: Transcriptional cofactor that restricts GATA6 function by inhibiting DNA-binding, resulting in repression of GATA6 transcriptional activation of downstream target genes. Represses GATA6-mediated trans activation of lung- and cardiac tissue-specific promoters. Inhibits DNA-binding by GATA4 and GATA1 to the cTNC promoter (By similarity). Plays a critical role in the development of cardiac hypertrophy via activation of calcineurin/nuclear factor of activated T-cells signaling pathway. {ECO:0000250, ECO:0000269|PubMed:20026769}.
Ensembl transtripts involved in fusion geneENST idsENST00000280696, ENST00000356447, 
ENST00000396671, ENST00000416420, 
ENST00000397386, ENST00000454244, 
ENST00000157600, ENST00000535732, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 9 X 5=4504 X 2 X 3=24
# samples 104
** MAII scorelog2(10/450*10)=-2.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/24*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: THRB [Title/Abstract] AND LMCD1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: THRB [Title/Abstract] AND LMCD1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)THRB(24184992)-LMCD1(8574423), # samples:3
Anticipated loss of major functional domain due to fusion event.THRB-LMCD1 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.
THRB-LMCD1 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.
THRB-LMCD1 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.
THRB-LMCD1 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.
THRB-LMCD1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
THRB-LMCD1 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
THRB-LMCD1 seems lost the major protein functional domain in Hgene 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


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/chr3:24184992/chr3:8574423)
- 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 THRB (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 LMCD1 (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)
ENST00000396671THRBchr324184992-ENST00000157600LMCD1chr38574423+266410873492142597
ENST00000396671THRBchr324184992-ENST00000535732LMCD1chr38574423+178910873491788480
ENST00000356447THRBchr324184992-ENST00000157600LMCD1chr38574423+260010232852078597
ENST00000356447THRBchr324184992-ENST00000535732LMCD1chr38574423+172510232851724479
ENST00000280696THRBchr324184992-ENST00000157600LMCD1chr38574423+260110242232079618
ENST00000280696THRBchr324184992-ENST00000535732LMCD1chr38574423+172610242231725501

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
ENST00000396671ENST00000157600THRBchr324184992-LMCD1chr38574423+0.0056582660.99434173
ENST00000396671ENST00000535732THRBchr324184992-LMCD1chr38574423+0.0101427930.9898572
ENST00000356447ENST00000157600THRBchr324184992-LMCD1chr38574423+0.00472790.9952721
ENST00000356447ENST00000535732THRBchr324184992-LMCD1chr38574423+0.0081094830.99189055
ENST00000280696ENST00000157600THRBchr324184992-LMCD1chr38574423+0.0023448540.99765515
ENST00000280696ENST00000535732THRBchr324184992-LMCD1chr38574423+0.0025804170.9974196

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 THRB-LMCD1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
THRBchr324184992LMCD1chr385744231023244TNAQGSHWKQKRKFLMSLGQLQSARG
THRBchr324184992LMCD1chr385744231024265TNAQGSHWKQKRKFLMSLGQLQSARG
THRBchr324184992LMCD1chr385744231087244TNAQGSHWKQKRKFLMSLGQLQSARG

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Potential FusionNeoAntigen Information of THRB-LMCD1 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.
THRB-LMCD1_24184992_8574423.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)
THRB-LMCD1chr324184992chr385744231024HLA-B27:04KRKFLMSL0.99990.78411018
THRB-LMCD1chr324184992chr385744231024HLA-B14:01QKRKFLMSL0.98690.6942918
THRB-LMCD1chr324184992chr385744231024HLA-B14:02QKRKFLMSL0.98690.6942918
THRB-LMCD1chr324184992chr385744231024HLA-B14:01SHWKQKRKF0.73750.626514
THRB-LMCD1chr324184992chr385744231024HLA-B14:02SHWKQKRKF0.73750.626514
THRB-LMCD1chr324184992chr385744231024HLA-B38:01SHWKQKRKF0.49140.8689514
THRB-LMCD1chr324184992chr385744231024HLA-B15:10SHWKQKRKF0.45570.5766514
THRB-LMCD1chr324184992chr385744231024HLA-B15:18SHWKQKRKF0.45050.6963514
THRB-LMCD1chr324184992chr385744231024HLA-B38:02SHWKQKRKF0.43960.8769514
THRB-LMCD1chr324184992chr385744231024HLA-B15:03SHWKQKRKF0.33820.7255514
THRB-LMCD1chr324184992chr385744231024HLA-B15:37SHWKQKRKF0.10810.6246514
THRB-LMCD1chr324184992chr385744231024HLA-C07:05KRKFLMSL0.99920.97351018
THRB-LMCD1chr324184992chr385744231024HLA-C07:95SHWKQKRKF0.74970.6496514
THRB-LMCD1chr324184992chr385744231024HLA-B39:12SHWKQKRKF0.73080.7102514
THRB-LMCD1chr324184992chr385744231024HLA-C07:05SHWKQKRKF0.71320.9271514
THRB-LMCD1chr324184992chr385744231024HLA-C07:27SHWKQKRKF0.64450.9325514
THRB-LMCD1chr324184992chr385744231024HLA-C07:46SHWKQKRKF0.60520.8432514
THRB-LMCD1chr324184992chr385744231024HLA-C07:19SHWKQKRKF0.60440.6402514
THRB-LMCD1chr324184992chr385744231024HLA-B14:03QKRKFLMSL0.57830.7723918
THRB-LMCD1chr324184992chr385744231024HLA-C07:67SHWKQKRKF0.56380.9181514
THRB-LMCD1chr324184992chr385744231024HLA-C07:80SHWKQKRKF0.56380.9181514
THRB-LMCD1chr324184992chr385744231024HLA-C07:10SHWKQKRKF0.5040.9283514
THRB-LMCD1chr324184992chr385744231024HLA-B14:03SHWKQKRKF0.08670.7166514
THRB-LMCD1chr324184992chr385744231024HLA-C12:16SHWKQKRKF0.01380.9434514
THRB-LMCD1chr324184992chr385744231024HLA-B15:04KQKRKFLMSL0.97940.7669818
THRB-LMCD1chr324184992chr385744231024HLA-B27:06KRKFLMSL0.99990.77961018
THRB-LMCD1chr324184992chr385744231024HLA-B27:10KRKFLMSL0.99980.9091018
THRB-LMCD1chr324184992chr385744231024HLA-C07:01SHWKQKRKF0.73720.6397514
THRB-LMCD1chr324184992chr385744231024HLA-C07:17SHWKQKRKF0.71460.9451514
THRB-LMCD1chr324184992chr385744231024HLA-B39:31SHWKQKRKF0.64190.7035514
THRB-LMCD1chr324184992chr385744231024HLA-C07:02SHWKQKRKF0.56380.9181514
THRB-LMCD1chr324184992chr385744231024HLA-B38:05SHWKQKRKF0.49140.8689514
THRB-LMCD1chr324184992chr385744231024HLA-B15:68QKRKFLMSL0.41910.5187918
THRB-LMCD1chr324184992chr385744231024HLA-B48:02SHWKQKRKF0.38010.8957514
THRB-LMCD1chr324184992chr385744231024HLA-B15:09SHWKQKRKF0.22950.5905514
THRB-LMCD1chr324184992chr385744231024HLA-C06:06SHWKQKRKF0.07610.9876514
THRB-LMCD1chr324184992chr385744231024HLA-B15:68SHWKQKRKF0.01310.5999514
THRB-LMCD1chr324184992chr385744231024HLA-C06:17SHWKQKRKF0.00430.989514
THRB-LMCD1chr324184992chr385744231024HLA-C06:02SHWKQKRKF0.00430.989514

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Potential FusionNeoAntigen Information of THRB-LMCD1 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.
THRB-LMCD1_24184992_8574423.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)
THRB-LMCD1chr324184992chr385744231024DRB1-0902KRKFLMSLGQLQSAR1025
THRB-LMCD1chr324184992chr385744231024DRB5-0112KRKFLMSLGQLQSAR1025

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Fusion breakpoint peptide structures of THRB-LMCD1

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
3548HWKQKRKFLMSLGQTHRBLMCD1chr324184992chr385744231024

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of THRB-LMCD1

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-B14:023BVN3548HWKQKRKFLMSLGQ-7.15543-7.26883
HLA-B14:023BVN3548HWKQKRKFLMSLGQ-4.77435-5.80965
HLA-B52:013W393548HWKQKRKFLMSLGQ-6.80875-6.92215
HLA-B52:013W393548HWKQKRKFLMSLGQ-4.20386-5.23916
HLA-A11:014UQ23548HWKQKRKFLMSLGQ-7.5194-8.5547
HLA-A11:014UQ23548HWKQKRKFLMSLGQ-6.9601-7.0735
HLA-A24:025HGA3548HWKQKRKFLMSLGQ-7.52403-7.63743
HLA-A24:025HGA3548HWKQKRKFLMSLGQ-5.82433-6.85963
HLA-B27:056PYJ3548HWKQKRKFLMSLGQ-3.28285-4.31815
HLA-B44:053DX83548HWKQKRKFLMSLGQ-5.91172-6.94702
HLA-B44:053DX83548HWKQKRKFLMSLGQ-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of THRB-LMCD1

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
THRB-LMCD1chr324184992chr385744231018KRKFLMSLAAATTCCTGATGTCCCTGGGCCAG
THRB-LMCD1chr324184992chr38574423514SHWKQKRKFTGGAAGCAAAAACGGAAATTCCTGATG
THRB-LMCD1chr324184992chr38574423818KQKRKFLMSLAAACGGAAATTCCTGATGTCCCTGGGCCAG
THRB-LMCD1chr324184992chr38574423918QKRKFLMSLCGGAAATTCCTGATGTCCCTGGGCCAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
THRB-LMCD1chr324184992chr385744231025KRKFLMSLGQLQSARAAATTCCTGATGTCCCTGGGCCAGCTGCAGTCAGCAAGAGGTGTG

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Information of the samples that have these potential fusion neoantigens of THRB-LMCD1

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
BRCATHRB-LMCD1chr324184992ENST00000280696chr38574423ENST00000157600TCGA-A2-A0CW-01A

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Potential target of CAR-T therapy development for THRB-LMCD1

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 THRB-LMCD1

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 THRB-LMCD1

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