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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:SETD5-LMCD1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SETD5-LMCD1
FusionPDB ID: 80910
FusionGDB2.0 ID: 80910
HgeneTgene
Gene symbol

SETD5

LMCD1

Gene ID

55209

29995

Gene nameSET domain containing 5LIM and cysteine rich domains 1
Synonyms--
Cytomap

3p25.3

3p25.3

Type of geneprotein-codingprotein-coding
Descriptionhistone-lysine N-methyltransferase SETD5SET domain-containing protein 5LIM 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 idsENST00000302463, ENST00000402198, 
ENST00000402466, ENST00000406341, 
ENST00000407969, ENST00000488236, 
ENST00000397386, ENST00000454244, 
ENST00000157600, ENST00000535732, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score19 X 16 X 7=21284 X 2 X 3=24
# samples 234
** MAII scorelog2(23/2128*10)=-3.20979238455681
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: SETD5 [Title/Abstract] AND LMCD1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SETD5 [Title/Abstract] AND LMCD1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SETD5(9483929)-LMCD1(8574423), # samples:3
Anticipated loss of major functional domain due to fusion event.SETD5-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.
SETD5-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.
SETD5-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.
SETD5-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.
* 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/chr3:9483929/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 SETD5 (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)
ENST00000402198SETD5chr39483929+ENST00000157600LMCD1chr38574423+308915124262567713
ENST00000402198SETD5chr39483929+ENST00000535732LMCD1chr38574423+221415124262213595
ENST00000402466SETD5chr39483929+ENST00000157600LMCD1chr38574423+312815514262606726
ENST00000402466SETD5chr39483929+ENST00000535732LMCD1chr38574423+225315514262252608
ENST00000406341SETD5chr39483929+ENST00000157600LMCD1chr38574423+284412671812322713
ENST00000406341SETD5chr39483929+ENST00000535732LMCD1chr38574423+196912671811968596
ENST00000407969SETD5chr39483929+ENST00000157600LMCD1chr38574423+2725114852203732
ENST00000407969SETD5chr39483929+ENST00000535732LMCD1chr38574423+1850114851849615
ENST00000302463SETD5chr39483929+ENST00000157600LMCD1chr38574423+272411471962202668
ENST00000302463SETD5chr39483929+ENST00000535732LMCD1chr38574423+184911471961848551

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
ENST00000402198ENST00000157600SETD5chr39483929+LMCD1chr38574423+0.0022627260.9977373
ENST00000402198ENST00000535732SETD5chr39483929+LMCD1chr38574423+0.0042561950.9957438
ENST00000402466ENST00000157600SETD5chr39483929+LMCD1chr38574423+0.0031319920.99686795
ENST00000402466ENST00000535732SETD5chr39483929+LMCD1chr38574423+0.0052100030.99478996
ENST00000406341ENST00000157600SETD5chr39483929+LMCD1chr38574423+0.0019949710.9980051
ENST00000406341ENST00000535732SETD5chr39483929+LMCD1chr38574423+0.0036843260.99631566
ENST00000407969ENST00000157600SETD5chr39483929+LMCD1chr38574423+0.0028496670.99715036
ENST00000407969ENST00000535732SETD5chr39483929+LMCD1chr38574423+0.0037891760.9962108
ENST00000302463ENST00000157600SETD5chr39483929+LMCD1chr38574423+0.0050269990.99497294
ENST00000302463ENST00000535732SETD5chr39483929+LMCD1chr38574423+0.0039011180.9960989

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 SETD5-LMCD1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SETD5chr39483929LMCD1chr385744231147317ARFIRRSCTPNAEMSLGQLQSARGVA
SETD5chr39483929LMCD1chr385744231148381ARFIRRSCTPNAEMSLGQLQSARGVA
SETD5chr39483929LMCD1chr385744231267362ARFIRRSCTPNAEMSLGQLQSARGVA
SETD5chr39483929LMCD1chr385744231512362ARFIRRSCTPNAEMSLGQLQSARGVA
SETD5chr39483929LMCD1chr385744231551375ARFIRRSCTPNAEMSLGQLQSARGVA

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Potential FusionNeoAntigen Information of SETD5-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.
SETD5-LMCD1_9483929_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)
SETD5-LMCD1chr39483929chr385744231147HLA-B44:03AEMSLGQL0.99740.96571119
SETD5-LMCD1chr39483929chr385744231147HLA-B47:01AEMSLGQL0.97290.50571119
SETD5-LMCD1chr39483929chr385744231147HLA-B39:13AEMSLGQL0.89120.89331119
SETD5-LMCD1chr39483929chr385744231147HLA-B35:03TPNAEMSL0.82890.7464816
SETD5-LMCD1chr39483929chr385744231147HLA-B35:04TPNAEMSL0.65360.882816
SETD5-LMCD1chr39483929chr385744231147HLA-B35:02TPNAEMSL0.65360.882816
SETD5-LMCD1chr39483929chr385744231147HLA-B15:16RSCTPNAEM0.98640.7606514
SETD5-LMCD1chr39483929chr385744231147HLA-B44:03AEMSLGQLQ0.84010.95841120
SETD5-LMCD1chr39483929chr385744231147HLA-B44:02AEMSLGQLQ0.79620.61081120
SETD5-LMCD1chr39483929chr385744231147HLA-B27:07RRSCTPNAEM0.99740.5167414
SETD5-LMCD1chr39483929chr385744231147HLA-B45:01AEMSLGQLQS0.96030.97691121
SETD5-LMCD1chr39483929chr385744231147HLA-B50:02AEMSLGQLQS0.95040.81831121
SETD5-LMCD1chr39483929chr385744231147HLA-B45:01AEMSLGQLQSA0.99970.98781122
SETD5-LMCD1chr39483929chr385744231147HLA-B50:02AEMSLGQLQSA0.99960.87181122
SETD5-LMCD1chr39483929chr385744231147HLA-B41:01AEMSLGQLQSA0.98930.96911122
SETD5-LMCD1chr39483929chr385744231147HLA-B50:01AEMSLGQLQSA0.96660.96221122
SETD5-LMCD1chr39483929chr385744231147HLA-B44:10AEMSLGQL0.99970.54271119
SETD5-LMCD1chr39483929chr385744231147HLA-B39:08AEMSLGQL0.96230.9051119
SETD5-LMCD1chr39483929chr385744231147HLA-B42:02TPNAEMSL0.83910.5476816
SETD5-LMCD1chr39483929chr385744231147HLA-B42:01TPNAEMSL0.8180.5397816
SETD5-LMCD1chr39483929chr385744231147HLA-B35:12TPNAEMSL0.65360.882816
SETD5-LMCD1chr39483929chr385744231147HLA-B39:10TPNAEMSL0.53020.8142816
SETD5-LMCD1chr39483929chr385744231147HLA-C08:15NAEMSLGQL0.99980.97181019
SETD5-LMCD1chr39483929chr385744231147HLA-B44:09AEMSLGQLQ0.90460.77421120
SETD5-LMCD1chr39483929chr385744231147HLA-C01:17CTPNAEMSL0.80030.9296716
SETD5-LMCD1chr39483929chr385744231147HLA-C01:30CTPNAEMSL0.680.9392716
SETD5-LMCD1chr39483929chr385744231147HLA-C01:17SCTPNAEMSL0.9910.9458616
SETD5-LMCD1chr39483929chr385744231147HLA-B40:06AEMSLGQLQSA0.99980.95311122
SETD5-LMCD1chr39483929chr385744231147HLA-B40:04AEMSLGQL0.99970.721119
SETD5-LMCD1chr39483929chr385744231147HLA-B44:07AEMSLGQL0.99740.96571119
SETD5-LMCD1chr39483929chr385744231147HLA-B44:13AEMSLGQL0.99740.96571119
SETD5-LMCD1chr39483929chr385744231147HLA-B44:26AEMSLGQL0.99740.96571119
SETD5-LMCD1chr39483929chr385744231147HLA-B39:02AEMSLGQL0.90310.89671119
SETD5-LMCD1chr39483929chr385744231147HLA-B41:03AEMSLGQL0.87770.74821119
SETD5-LMCD1chr39483929chr385744231147HLA-B35:09TPNAEMSL0.65360.882816
SETD5-LMCD1chr39483929chr385744231147HLA-B67:01TPNAEMSL0.53240.6574816
SETD5-LMCD1chr39483929chr385744231147HLA-C08:02NAEMSLGQL0.99980.97181019
SETD5-LMCD1chr39483929chr385744231147HLA-B44:07AEMSLGQLQ0.84010.95841120
SETD5-LMCD1chr39483929chr385744231147HLA-B44:13AEMSLGQLQ0.84010.95841120
SETD5-LMCD1chr39483929chr385744231147HLA-B44:26AEMSLGQLQ0.84010.95841120
SETD5-LMCD1chr39483929chr385744231147HLA-B44:22AEMSLGQLQ0.79620.61081120
SETD5-LMCD1chr39483929chr385744231147HLA-C01:02CTPNAEMSL0.78770.9271716
SETD5-LMCD1chr39483929chr385744231147HLA-C01:03CTPNAEMSL0.74950.9024716
SETD5-LMCD1chr39483929chr385744231147HLA-B27:08RRSCTPNAEM0.99950.6513414
SETD5-LMCD1chr39483929chr385744231147HLA-B27:06RRSCTPNAEM0.99890.7384414
SETD5-LMCD1chr39483929chr385744231147HLA-B27:09RRSCTPNAEM0.99720.7006414
SETD5-LMCD1chr39483929chr385744231147HLA-C01:03SCTPNAEMSL0.99440.9053616
SETD5-LMCD1chr39483929chr385744231147HLA-C01:02SCTPNAEMSL0.99120.943616
SETD5-LMCD1chr39483929chr385744231147HLA-B50:05AEMSLGQLQSA0.96660.96221122
SETD5-LMCD1chr39483929chr385744231147HLA-B50:04AEMSLGQLQSA0.96660.96221122

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Potential FusionNeoAntigen Information of SETD5-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.

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 SETD5-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
8452SCTPNAEMSLGQLQSETD5LMCD1chr39483929chr385744231147

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SETD5-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-B14:023BVN8452SCTPNAEMSLGQLQ-7.15543-7.26883
HLA-B14:023BVN8452SCTPNAEMSLGQLQ-4.77435-5.80965
HLA-B52:013W398452SCTPNAEMSLGQLQ-6.80875-6.92215
HLA-B52:013W398452SCTPNAEMSLGQLQ-4.20386-5.23916
HLA-A11:014UQ28452SCTPNAEMSLGQLQ-7.5194-8.5547
HLA-A11:014UQ28452SCTPNAEMSLGQLQ-6.9601-7.0735
HLA-A24:025HGA8452SCTPNAEMSLGQLQ-7.52403-7.63743
HLA-A24:025HGA8452SCTPNAEMSLGQLQ-5.82433-6.85963
HLA-B27:056PYJ8452SCTPNAEMSLGQLQ-3.28285-4.31815
HLA-B44:053DX88452SCTPNAEMSLGQLQ-5.91172-6.94702
HLA-B44:053DX88452SCTPNAEMSLGQLQ-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of SETD5-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
SETD5-LMCD1chr39483929chr385744231019NAEMSLGQLAATGCAGAGATGTCCCTGGGCCAGCTG
SETD5-LMCD1chr39483929chr385744231119AEMSLGQLGCAGAGATGTCCCTGGGCCAGCTG
SETD5-LMCD1chr39483929chr385744231120AEMSLGQLQGCAGAGATGTCCCTGGGCCAGCTGCAG
SETD5-LMCD1chr39483929chr385744231121AEMSLGQLQSGCAGAGATGTCCCTGGGCCAGCTGCAGTCA
SETD5-LMCD1chr39483929chr385744231122AEMSLGQLQSAGCAGAGATGTCCCTGGGCCAGCTGCAGTCAGCA
SETD5-LMCD1chr39483929chr38574423414RRSCTPNAEMAGAAGATCATGTACACCAAATGCAGAGATG
SETD5-LMCD1chr39483929chr38574423514RSCTPNAEMAGATCATGTACACCAAATGCAGAGATG
SETD5-LMCD1chr39483929chr38574423616SCTPNAEMSLTCATGTACACCAAATGCAGAGATGTCCCTG
SETD5-LMCD1chr39483929chr38574423716CTPNAEMSLTGTACACCAAATGCAGAGATGTCCCTG
SETD5-LMCD1chr39483929chr38574423816TPNAEMSLACACCAAATGCAGAGATGTCCCTG

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 SETD5-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
BRCASETD5-LMCD1chr39483929ENST00000302463chr38574423ENST00000157600TCGA-LL-A8F5-01A

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Potential target of CAR-T therapy development for SETD5-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 SETD5-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 SETD5-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