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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:RUNX1-YTHDF2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RUNX1-YTHDF2
FusionPDB ID: 78699
FusionGDB2.0 ID: 78699
HgeneTgene
Gene symbol

RUNX1

YTHDF2

Gene ID

861

51441

Gene nameRUNX family transcription factor 1YTH N6-methyladenosine RNA binding protein 2
SynonymsAML1|AML1-EVI-1|AMLCR1|CBF2alpha|CBFA2|EVI-1|PEBP2aB|PEBP2alphaCAHL|HGRG8|NY-REN-2
Cytomap

21q22.12

1p35.3

Type of geneprotein-codingprotein-coding
Descriptionrunt-related transcription factor 1AML1-EVI-1 fusion proteinPEA2-alpha BPEBP2-alpha BSL3-3 enhancer factor 1 alpha B subunitSL3/AKV core-binding factor alpha B subunitacute myeloid leukemia 1 proteincore-binding factor, runt domain, alpha subunit 2YTH domain-containing family protein 29430020E02RikCLL-associated antigen KW-14YTH N(6)-methyladenosine RNA binding protein 2YTH domain family, member 2high-glucose-regulated protein 8renal carcinoma antigen NY-REN-2
Modification date2020032220200313
UniProtAcc

Q06455

Main function of 5'-partner protein: FUNCTION: Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes (PubMed:12559562, PubMed:15203199, PubMed:10688654). Can repress the expression of MMP7 in a ZBTB33-dependent manner (PubMed:23251453). Can repress transactivation mediated by TCF12 (PubMed:16803958). Acts as a negative regulator of adipogenesis (By similarity). The AML1-MTG8/ETO fusion protein frequently found in leukemic cells is involved in leukemogenesis and contributes to hematopoietic stem/progenitor cell self-renewal (PubMed:23812588). {ECO:0000250|UniProtKB:Q61909, ECO:0000269|PubMed:10688654, ECO:0000269|PubMed:10973986, ECO:0000269|PubMed:16803958, ECO:0000269|PubMed:23251453, ECO:0000269|PubMed:23812588, ECO:0000303|PubMed:12559562, ECO:0000303|PubMed:15203199}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000300305, ENST00000325074, 
ENST00000344691, ENST00000358356, 
ENST00000399240, ENST00000437180, 
ENST00000486278, ENST00000494829, 
ENST00000478283, ENST00000373812, 
ENST00000541996, ENST00000542507, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score46 X 68 X 13=4066410 X 8 X 8=640
# samples 8914
** MAII scorelog2(89/40664*10)=-5.51380298959468
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(14/640*10)=-2.1926450779424
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RUNX1 [Title/Abstract] AND YTHDF2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RUNX1 [Title/Abstract] AND YTHDF2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RUNX1(36231803)-YTHDF2(29095441), # samples:1
RUNX1(36231770)-YTHDF2(29095441), # samples:1
Anticipated loss of major functional domain due to fusion event.RUNX1-YTHDF2 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.
RUNX1-YTHDF2 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.
RUNX1-YTHDF2 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.
RUNX1-YTHDF2 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.
RUNX1-YTHDF2 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
RUNX1-YTHDF2 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
RUNX1-YTHDF2 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
RUNX1-YTHDF2 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneRUNX1

GO:0030097

hemopoiesis

21873977

HgeneRUNX1

GO:0045893

positive regulation of transcription, DNA-templated

10207087|14970218

HgeneRUNX1

GO:0045944

positive regulation of transcription by RNA polymerase II

9199349|10207087|14970218|21873977

TgeneYTHDF2

GO:0006402

mRNA catabolic process

27558897|30559377|30930054

TgeneYTHDF2

GO:0061157

mRNA destabilization

27558897|30559377|30930054

TgeneYTHDF2

GO:1903679

positive regulation of cap-independent translational initiation

26458103



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/chr21:36231803/chr1:29095441)
- 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 RUNX1 (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 YTHDF2 (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)
ENST00000437180RUNX1chr2136231770-ENST00000373812YTHDF2chr129095441+1650803190888232

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
ENST00000437180ENST00000373812RUNX1chr2136231770-YTHDF2chr129095441+0.0140379380.9859621

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 RUNX1-YTHDF2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RUNX1chr2136231770YTHDF2chr129095441803200TYHRAIKITVDGPREPRRTSRSWEIK

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Potential FusionNeoAntigen Information of RUNX1-YTHDF2 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.
RUNX1-YTHDF2_36231770_29095441.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)
RUNX1-YTHDF2chr2136231770chr129095441803HLA-B07:05GPREPRRTS0.99140.55711120
RUNX1-YTHDF2chr2136231770chr129095441803HLA-B07:02GPREPRRTS0.99080.75491120
RUNX1-YTHDF2chr2136231770chr129095441803HLA-A68:08ITVDGPREPR0.95990.5048717
RUNX1-YTHDF2chr2136231770chr129095441803HLA-A68:06ITVDGPREPR0.9560.5056717
RUNX1-YTHDF2chr2136231770chr129095441803HLA-A11:10TVDGPREPRR0.94850.5135818
RUNX1-YTHDF2chr2136231770chr129095441803HLA-A31:06ITVDGPREPR0.90830.5662717
RUNX1-YTHDF2chr2136231770chr129095441803HLA-A68:08TVDGPREPRR0.90410.7457818
RUNX1-YTHDF2chr2136231770chr129095441803HLA-A66:03ITVDGPREPR0.86690.5787717
RUNX1-YTHDF2chr2136231770chr129095441803HLA-A34:02TVDGPREPRR0.51230.6237818
RUNX1-YTHDF2chr2136231770chr129095441803HLA-B07:04GPREPRRTS0.63930.65021120
RUNX1-YTHDF2chr2136231770chr129095441803HLA-B07:22GPREPRRTS0.99080.75491120
RUNX1-YTHDF2chr2136231770chr129095441803HLA-B07:09GPREPRRTS0.98510.74761120
RUNX1-YTHDF2chr2136231770chr129095441803HLA-B07:26GPREPRRTS0.11780.59671120
RUNX1-YTHDF2chr2136231770chr129095441803HLA-A66:02ITVDGPREPR0.93250.5454717

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Potential FusionNeoAntigen Information of RUNX1-YTHDF2 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.
RUNX1-YTHDF2_36231770_29095441.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)
RUNX1-YTHDF2chr2136231770chr129095441803DRB1-1452HRAIKITVDGPREPR217
RUNX1-YTHDF2chr2136231770chr129095441803DRB5-0106HRAIKITVDGPREPR217
RUNX1-YTHDF2chr2136231770chr129095441803DRB5-0106YHRAIKITVDGPREP116
RUNX1-YTHDF2chr2136231770chr129095441803DRB5-0111HRAIKITVDGPREPR217
RUNX1-YTHDF2chr2136231770chr129095441803DRB5-0205HRAIKITVDGPREPR217
RUNX1-YTHDF2chr2136231770chr129095441803DRB5-0205YHRAIKITVDGPREP116

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Fusion breakpoint peptide structures of RUNX1-YTHDF2

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
4318KITVDGPREPRRTSRUNX1YTHDF2chr2136231770chr129095441803

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RUNX1-YTHDF2

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-B14:023BVN4318KITVDGPREPRRTS-6.77781-6.89121
HLA-B14:023BVN4318KITVDGPREPRRTS-3.08719-4.12249
HLA-B52:013W394318KITVDGPREPRRTS-6.66315-6.77655
HLA-B52:013W394318KITVDGPREPRRTS-2.65785-3.69315
HLA-A24:025HGA4318KITVDGPREPRRTS-7.20627-7.31967
HLA-A24:025HGA4318KITVDGPREPRRTS-6.50211-7.53741
HLA-B44:053DX84318KITVDGPREPRRTS-7.75024-7.86364
HLA-B44:053DX84318KITVDGPREPRRTS-6.53073-7.56603
HLA-A02:016TDR4318KITVDGPREPRRTS-4.4528-5.4881

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Vaccine Design for the FusionNeoAntigens of RUNX1-YTHDF2

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
RUNX1-YTHDF2chr2136231770chr1290954411120GPREPRRTSCTCGAAGAACGTCAAGGTCGTGGGAAA
RUNX1-YTHDF2chr2136231770chr129095441717ITVDGPREPRGGCCCCGAGAACCTCGAAGAACGTCAAGGT
RUNX1-YTHDF2chr2136231770chr129095441818TVDGPREPRRCCCGAGAACCTCGAAGAACGTCAAGGTCGT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
RUNX1-YTHDF2chr2136231770chr129095441116YHRAIKITVDGPREPTCAAAATCACAGTGGATGGGCCCCGAGAACCTCGAAGAACGTCAA
RUNX1-YTHDF2chr2136231770chr129095441217HRAIKITVDGPREPRAAATCACAGTGGATGGGCCCCGAGAACCTCGAAGAACGTCAAGGT

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Information of the samples that have these potential fusion neoantigens of RUNX1-YTHDF2

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
N/ARUNX1-YTHDF2chr2136231770ENST00000437180chr129095441ENST00000373812EU093085

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Potential target of CAR-T therapy development for RUNX1-YTHDF2

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 RUNX1-YTHDF2

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 RUNX1-YTHDF2

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
HgeneRUNX1C1832388Platelet Disorder, Familial, with Associated Myeloid Malignancy11CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
HgeneRUNX1C0023467Leukemia, Myelocytic, Acute4CGI;CTD_human;GENOMICS_ENGLAND
HgeneRUNX1C0026998Acute Myeloid Leukemia, M13CTD_human
HgeneRUNX1C1879321Acute Myeloid Leukemia (AML-M2)3CTD_human
HgeneRUNX1C0023485Precursor B-Cell Lymphoblastic Leukemia-Lymphoma2CTD_human
HgeneRUNX1C0003873Rheumatoid Arthritis1CTD_human
HgeneRUNX1C0006413Burkitt Lymphoma1ORPHANET
HgeneRUNX1C0017636Glioblastoma1CTD_human
HgeneRUNX1C0023452Childhood Acute Lymphoblastic Leukemia1CTD_human
HgeneRUNX1C0023453L2 Acute Lymphoblastic Leukemia1CTD_human
HgeneRUNX1C0023473Myeloid Leukemia, Chronic1ORPHANET
HgeneRUNX1C0033578Prostatic Neoplasms1CTD_human
HgeneRUNX1C0040034Thrombocytopenia1GENOMICS_ENGLAND
HgeneRUNX1C0334588Giant Cell Glioblastoma1CTD_human
HgeneRUNX1C0349639Juvenile Myelomonocytic Leukemia1CTD_human
HgeneRUNX1C0376358Malignant neoplasm of prostate1CTD_human
HgeneRUNX1C1292769Precursor B-cell lymphoblastic leukemia1ORPHANET
HgeneRUNX1C1621958Glioblastoma Multiforme1CTD_human
HgeneRUNX1C1961102Precursor Cell Lymphoblastic Leukemia Lymphoma1CTD_human
HgeneRUNX1C2713368Hematopoetic Myelodysplasia1CTD_human
HgeneRUNX1C3463824MYELODYSPLASTIC SYNDROME1CTD_human