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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:KIF11-HIF1AN

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KIF11-HIF1AN
FusionPDB ID: 42521
FusionGDB2.0 ID: 42521
HgeneTgene
Gene symbol

KIF11

HIF1AN

Gene ID

3832

55662

Gene namekinesin family member 11hypoxia inducible factor 1 subunit alpha inhibitor
SynonymsEG5|HKSP|KNSL1|MCLMR|TRIP5FIH1
Cytomap

10q23.33

10q24.31

Type of geneprotein-codingprotein-coding
Descriptionkinesin-like protein KIF11TR-interacting protein 5TRIP-5kinesin-like protein 1kinesin-like spindle protein HKSPkinesin-related motor protein Eg5thyroid receptor-interacting protein 5hypoxia-inducible factor 1-alpha inhibitorFIH-1factor inhibiting HIF-1factor inhibiting HIF1hypoxia inducible factor 1 alpha subunit inhibitorhypoxia-inducible factor asparagine hydroxylasepeptide-aspartate beta-dioxygenase
Modification date2020032920200313
UniProtAcc

P52732

Main function of 5'-partner protein: FUNCTION: Motor protein required for establishing a bipolar spindle during mitosis (PubMed:19001501). Required in non-mitotic cells for transport of secretory proteins from the Golgi complex to the cell surface (PubMed:23857769). {ECO:0000269|PubMed:19001501, ECO:0000269|PubMed:23857769}.

Q9NWT6

Main function of 5'-partner protein: FUNCTION: Hydroxylates HIF-1 alpha at 'Asn-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation. {ECO:0000269|PubMed:12042299, ECO:0000269|PubMed:12080085, ECO:0000269|PubMed:17003112, ECO:0000269|PubMed:17573339, ECO:0000269|PubMed:18299578, ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:21177872, ECO:0000269|PubMed:21251231}.
Ensembl transtripts involved in fusion geneENST idsENST00000260731, ENST00000528044, 
ENST00000299163, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 9 X 5=4504 X 3 X 3=36
# samples 104
** MAII scorelog2(10/450*10)=-2.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: KIF11 [Title/Abstract] AND HIF1AN [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KIF11 [Title/Abstract] AND HIF1AN [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KIF11(94376589)-HIF1AN(102296168), # samples:1
Anticipated loss of major functional domain due to fusion event.KIF11-HIF1AN 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.
KIF11-HIF1AN 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.
KIF11-HIF1AN 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.
KIF11-HIF1AN 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
HgeneKIF11

GO:0090307

mitotic spindle assembly

19001501

TgeneHIF1AN

GO:0036138

peptidyl-histidine hydroxylation

21251231

TgeneHIF1AN

GO:0042264

peptidyl-aspartic acid hydroxylation

21177872

TgeneHIF1AN

GO:0042265

peptidyl-asparagine hydroxylation

12080085|12215170|14734545|21177872

TgeneHIF1AN

GO:0045663

positive regulation of myoblast differentiation

18299578

TgeneHIF1AN

GO:0045746

negative regulation of Notch signaling pathway

18299578

TgeneHIF1AN

GO:0055114

oxidation-reduction process

12080085|12215170

TgeneHIF1AN

GO:0061428

negative regulation of transcription from RNA polymerase II promoter in response to hypoxia

11641274



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/chr10:94376589/chr10:102296168)
- 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 KIF11 (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 HIF1AN (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)
ENST00000260731KIF11chr1094376589-ENST00000299163HIF1ANchr10102296168+139521218122090692

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
ENST00000260731ENST00000299163KIF11chr1094376589-HIF1ANchr10102296168+0.0005696760.99943024

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 KIF11-HIF1AN

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KIF11chr1094376589HIF1ANchr101022961681218400KPEVNQKLTKKALIKEPVVLTDTNLV

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Potential FusionNeoAntigen Information of KIF11-HIF1AN 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.
KIF11-HIF1AN_94376589_102296168.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)
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B08:01LIKEPVVL0.99850.7621220
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:22ALIKEPVVL0.99360.85411120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:24ALIKEPVVL0.98990.83351120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:67ALIKEPVVL0.98990.83351120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:30ALIKEPVVL0.98990.83351120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:11ALIKEPVVL0.98960.84391120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:60ALIKEPVVL0.98960.82811120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:27ALIKEPVVL0.98950.83031120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:13ALIKEPVVL0.98810.85971120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:04ALIKEPVVL0.98570.82521120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:21ALIKEPVVL0.98490.89211120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:17ALIKEPVVL0.98230.62511120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:16ALIKEPVVL0.98170.79141120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:38ALIKEPVVL0.97790.8031120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:35ALIKEPVVL0.91330.8511120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:19ALIKEPVVL0.9130.71971120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:29ALIKEPVVL0.83960.83421120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:20ALIKEPVVL0.82540.83871120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B48:01ALIKEPVVL0.40550.59731120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B13:02ALIKEPVVL0.15670.65341120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B39:13ALIKEPVVL0.11670.98561120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B13:01ALIKEPVVL0.10960.98921120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:02ALIKEPVVL0.9940.65521120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:05ALIKEPVVL0.99070.77451120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:07ALIKEPVVL0.990.85681120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:01ALIKEPVVL0.98990.83351120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B15:04ALIKEPVVL0.96910.97711120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B39:08ALIKEPVVL0.56420.96811120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B15:05ALIKEPVVL0.10670.96251120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B08:18LIKEPVVL0.99850.7621220
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B08:12LIKEPVVL0.98250.91021220
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:03ALIKEPVVL0.99350.86881120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:14ALIKEPVVL0.98490.85571120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A02:06ALIKEPVVL0.98490.89211120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-A30:01KLTKKALIK0.98470.8615
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B15:50ALIKEPVVL0.97750.98181120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B15:73ALIKEPVVL0.96020.97981120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B15:30ALIKEPVVL0.90360.95881120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-C01:03ALIKEPVVL0.81030.98151120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-C17:01ALIKEPVVL0.63050.9781120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B35:13ALIKEPVVL0.24060.96211120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B39:02ALIKEPVVL0.23230.98541120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B15:20ALIKEPVVL0.10430.96951120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B40:21ALIKEPVVL0.05640.50231120
KIF11-HIF1ANchr1094376589chr101022961681218HLA-B40:21KALIKEPVVL0.47330.52521020

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Potential FusionNeoAntigen Information of KIF11-HIF1AN 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 KIF11-HIF1AN

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
4411KLTKKALIKEPVVLKIF11HIF1ANchr1094376589chr101022961681218

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KIF11-HIF1AN

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-B14:023BVN4411KLTKKALIKEPVVL-7.9962-8.1096
HLA-B14:023BVN4411KLTKKALIKEPVVL-5.70842-6.74372
HLA-B52:013W394411KLTKKALIKEPVVL-6.83737-6.95077
HLA-B52:013W394411KLTKKALIKEPVVL-4.4836-5.5189
HLA-A11:014UQ24411KLTKKALIKEPVVL-10.0067-10.1201
HLA-A11:014UQ24411KLTKKALIKEPVVL-9.03915-10.0745
HLA-A24:025HGA4411KLTKKALIKEPVVL-6.56204-6.67544
HLA-A24:025HGA4411KLTKKALIKEPVVL-5.42271-6.45801
HLA-B44:053DX84411KLTKKALIKEPVVL-7.85648-8.89178
HLA-B44:053DX84411KLTKKALIKEPVVL-5.3978-5.5112
HLA-A02:016TDR4411KLTKKALIKEPVVL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of KIF11-HIF1AN

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
KIF11-HIF1ANchr1094376589chr101022961681020KALIKEPVVLCTTATTAAGGAGCCTGTGGTGCTGACCGAC
KIF11-HIF1ANchr1094376589chr101022961681120ALIKEPVVLATTAAGGAGCCTGTGGTGCTGACCGAC
KIF11-HIF1ANchr1094376589chr101022961681220LIKEPVVLAAGGAGCCTGTGGTGCTGACCGAC
KIF11-HIF1ANchr1094376589chr10102296168615KLTKKALIKACCAAAAAAGCTCTTATTAAGGAGCCT

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 KIF11-HIF1AN

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
SARCKIF11-HIF1ANchr1094376589ENST00000260731chr10102296168ENST00000299163TCGA-JV-A75J-01A

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Potential target of CAR-T therapy development for KIF11-HIF1AN

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 KIF11-HIF1AN

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 KIF11-HIF1AN

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