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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:FANCI-ABHD2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FANCI-ABHD2
FusionPDB ID: 29335
FusionGDB2.0 ID: 29335
HgeneTgene
Gene symbol

FANCI

ABHD2

Gene ID

55215

11057

Gene nameFA complementation group Iabhydrolase domain containing 2, acylglycerol lipase
SynonymsKIAA1794HS1-2|LABH2|PHPS1-2
Cytomap

15q26.1

15q26.1

Type of geneprotein-codingprotein-coding
DescriptionFanconi anemia group I proteinFanconi anemia complementation group Imonoacylglycerol lipase ABHD22-arachidonoylglycerol hydrolaseabhydrolase domain containing 2abhydrolase domain-containing protein 2acetylesterasealpha/beta hydrolase domain containing protein 2lung alpha/beta hydrolase 2progesterone-sensitive lipas
Modification date2020031320200313
UniProtAcc

Q9NVI1

Main function of 5'-partner protein: FUNCTION: Plays an essential role in the repair of DNA double-strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA repair sites. Required for maintenance of chromosomal stability. Specifically binds branched DNA: binds both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Participates in S phase and G2 phase checkpoint activation upon DNA damage. {ECO:0000269|PubMed:17412408, ECO:0000269|PubMed:17452773, ECO:0000269|PubMed:17460694, ECO:0000269|PubMed:19111657}.

P08910

Main function of 5'-partner protein: FUNCTION: Progesterone-dependent acylglycerol lipase that catalyzes hydrolysis of endocannabinoid arachidonoylglycerol (AG) from cell membrane (PubMed:26989199). Acts as a progesterone receptor: progesterone-binding activates the acylglycerol lipase activity, mediating degradation of 1-arachidonoylglycerol (1AG) and 2-arachidonoylglycerol (2AG) to glycerol and arachidonic acid (AA) (PubMed:26989199). Also displays an ester hydrolase activity against acetyl ester, butanoate ester and hexadecanoate ester (PubMed:27247428). Plays a key role in sperm capacitation in response to progesterone by mediating degradation of 2AG, an inhibitor of the sperm calcium channel CatSper, leading to calcium influx via CatSper and sperm activation (PubMed:26989199). May also play a role in smooth muscle cells migration (By similarity). {ECO:0000250|UniProtKB:Q9QXM0, ECO:0000269|PubMed:26989199, ECO:0000269|PubMed:27247428}.
Ensembl transtripts involved in fusion geneENST idsENST00000300027, ENST00000310775, 
ENST00000451393, ENST00000566615, 
ENST00000567996, 
ENST00000562254, 
ENST00000352732, ENST00000355100, 
ENST00000565973, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 5 X 4=10011 X 11 X 4=484
# samples 613
** MAII scorelog2(6/100*10)=-0.736965594166206
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/484*10)=-1.89649542424614
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: FANCI [Title/Abstract] AND ABHD2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FANCI [Title/Abstract] AND ABHD2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FANCI(89822005)-ABHD2(89719043), # samples:2
ABHD2(89736550)-FANCI(89790859), # samples:1
Anticipated loss of major functional domain due to fusion event.FANCI-ABHD2 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.
FANCI-ABHD2 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
HgeneFANCI

GO:0031398

positive regulation of protein ubiquitination

18029348

TgeneABHD2

GO:0032570

response to progesterone

26989199

TgeneABHD2

GO:0043401

steroid hormone mediated signaling pathway

26989199

TgeneABHD2

GO:0046464

acylglycerol catabolic process

26989199

TgeneABHD2

GO:0048240

sperm capacitation

26989199



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/chr15:89822005/chr15:89719043)
- 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 FANCI (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 ABHD2 (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)
ENST00000300027FANCIchr1589822005+ENST00000352732ABHD2chr1589719043+916214851042224706
ENST00000300027FANCIchr1589822005+ENST00000565973ABHD2chr1589719043+255314851042224706
ENST00000300027FANCIchr1589822005+ENST00000355100ABHD2chr1589719043+916214851042224706
ENST00000310775FANCIchr1589822005+ENST00000352732ABHD2chr1589719043+91441467862206706
ENST00000310775FANCIchr1589822005+ENST00000565973ABHD2chr1589719043+25351467862206706
ENST00000310775FANCIchr1589822005+ENST00000355100ABHD2chr1589719043+91441467862206706

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
ENST00000300027ENST00000352732FANCIchr1589822005+ABHD2chr1589719043+0.0011648860.99883515
ENST00000300027ENST00000565973FANCIchr1589822005+ABHD2chr1589719043+0.0036460770.996354
ENST00000300027ENST00000355100FANCIchr1589822005+ABHD2chr1589719043+0.0011648860.99883515
ENST00000310775ENST00000352732FANCIchr1589822005+ABHD2chr1589719043+0.0011598150.99884015
ENST00000310775ENST00000565973FANCIchr1589822005+ABHD2chr1589719043+0.0037107450.99628925
ENST00000310775ENST00000355100FANCIchr1589822005+ABHD2chr1589719043+0.0011598150.99884015

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 FANCI-ABHD2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FANCIchr1589822005ABHD2chr15897190431467460VVTRASSPISHFLGCTWEFGAMVNYI
FANCIchr1589822005ABHD2chr15897190431485460VVTRASSPISHFLGCTWEFGAMVNYI

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Potential FusionNeoAntigen Information of FANCI-ABHD2 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.
FANCI-ABHD2_89822005_89719043.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)
FANCI-ABHD2chr1589822005chr15897190431485HLA-B38:01SHFLGCTW0.78470.9985917
FANCI-ABHD2chr1589822005chr15897190431485HLA-B57:01ISHFLGCTW0.99930.9945817
FANCI-ABHD2chr1589822005chr15897190431485HLA-B58:01ISHFLGCTW0.99910.9928817
FANCI-ABHD2chr1589822005chr15897190431485HLA-B58:02ISHFLGCTW0.99860.9936817
FANCI-ABHD2chr1589822005chr15897190431485HLA-B57:03ISHFLGCTW0.99630.9977817
FANCI-ABHD2chr1589822005chr15897190431485HLA-A24:23HFLGCTWEF0.99590.53141019
FANCI-ABHD2chr1589822005chr15897190431485HLA-B15:16ISHFLGCTW0.99580.943817
FANCI-ABHD2chr1589822005chr15897190431485HLA-B15:17ISHFLGCTW0.99560.9845817
FANCI-ABHD2chr1589822005chr15897190431485HLA-A24:25HFLGCTWEF0.99340.60541019
FANCI-ABHD2chr1589822005chr15897190431485HLA-A24:20HFLGCTWEF0.99180.60211019
FANCI-ABHD2chr1589822005chr15897190431485HLA-A24:15HFLGCTWEF0.99140.62061019
FANCI-ABHD2chr1589822005chr15897190431485HLA-A24:31HFLGCTWEF0.98880.61941019
FANCI-ABHD2chr1589822005chr15897190431485HLA-A29:10HFLGCTWEF0.98460.52291019
FANCI-ABHD2chr1589822005chr15897190431485HLA-A24:17HFLGCTWEF0.97370.58281019
FANCI-ABHD2chr1589822005chr15897190431485HLA-A31:08HFLGCTWEF0.95920.66731019
FANCI-ABHD2chr1589822005chr15897190431485HLA-A32:13ISHFLGCTW0.81250.9946817
FANCI-ABHD2chr1589822005chr15897190431485HLA-A24:14HFLGCTWEF0.7870.65241019
FANCI-ABHD2chr1589822005chr15897190431485HLA-B08:09SPISHFLGC0.39150.6358615
FANCI-ABHD2chr1589822005chr15897190431485HLA-B15:10SHFLGCTWEF0.99030.8833919
FANCI-ABHD2chr1589822005chr15897190431485HLA-B15:18SHFLGCTWEF0.99010.9241919
FANCI-ABHD2chr1589822005chr15897190431485HLA-B39:01SHFLGCTWEF0.990.9925919
FANCI-ABHD2chr1589822005chr15897190431485HLA-B38:01SHFLGCTWEF0.98550.9978919
FANCI-ABHD2chr1589822005chr15897190431485HLA-B38:02SHFLGCTWEF0.98540.9978919
FANCI-ABHD2chr1589822005chr15897190431485HLA-B15:37SHFLGCTWEF0.95240.8958919
FANCI-ABHD2chr1589822005chr15897190431485HLA-A24:02HFLGCTWEF0.99180.60211019
FANCI-ABHD2chr1589822005chr15897190431485HLA-A29:01HFLGCTWEF0.98460.52291019
FANCI-ABHD2chr1589822005chr15897190431485HLA-A29:02HFLGCTWEF0.98460.52291019
FANCI-ABHD2chr1589822005chr15897190431485HLA-B39:05SHFLGCTWEF0.97990.9906919
FANCI-ABHD2chr1589822005chr15897190431485HLA-B38:05SHFLGCTW0.78470.9985917
FANCI-ABHD2chr1589822005chr15897190431485HLA-B57:10ISHFLGCTW0.99930.9945817
FANCI-ABHD2chr1589822005chr15897190431485HLA-B57:04ISHFLGCTW0.99910.8815817
FANCI-ABHD2chr1589822005chr15897190431485HLA-B58:06ISHFLGCTW0.99760.9891817
FANCI-ABHD2chr1589822005chr15897190431485HLA-A24:03HFLGCTWEF0.99590.53141019
FANCI-ABHD2chr1589822005chr15897190431485HLA-B57:02ISHFLGCTW0.99540.9902817
FANCI-ABHD2chr1589822005chr15897190431485HLA-A32:01ISHFLGCTW0.92470.9954817
FANCI-ABHD2chr1589822005chr15897190431485HLA-B15:24ISHFLGCTW0.84840.9903817
FANCI-ABHD2chr1589822005chr15897190431485HLA-C14:03HFLGCTWEF0.19140.99041019
FANCI-ABHD2chr1589822005chr15897190431485HLA-C14:02HFLGCTWEF0.19140.99041019
FANCI-ABHD2chr1589822005chr15897190431485HLA-B39:31SHFLGCTWEF0.99010.9927919
FANCI-ABHD2chr1589822005chr15897190431485HLA-B38:05SHFLGCTWEF0.98550.9978919
FANCI-ABHD2chr1589822005chr15897190431485HLA-B15:09SHFLGCTWEF0.95450.9839919
FANCI-ABHD2chr1589822005chr15897190431485HLA-B15:13SPISHFLGCTW0.98820.7749617

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Potential FusionNeoAntigen Information of FANCI-ABHD2 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 FANCI-ABHD2

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
8883SPISHFLGCTWEFGFANCIABHD2chr1589822005chr15897190431485

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FANCI-ABHD2

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-B14:023BVN8883SPISHFLGCTWEFG-7.9962-8.1096
HLA-B14:023BVN8883SPISHFLGCTWEFG-5.70842-6.74372
HLA-B52:013W398883SPISHFLGCTWEFG-6.83737-6.95077
HLA-B52:013W398883SPISHFLGCTWEFG-4.4836-5.5189
HLA-A11:014UQ28883SPISHFLGCTWEFG-10.0067-10.1201
HLA-A11:014UQ28883SPISHFLGCTWEFG-9.03915-10.0745
HLA-A24:025HGA8883SPISHFLGCTWEFG-6.56204-6.67544
HLA-A24:025HGA8883SPISHFLGCTWEFG-5.42271-6.45801
HLA-B44:053DX88883SPISHFLGCTWEFG-7.85648-8.89178
HLA-B44:053DX88883SPISHFLGCTWEFG-5.3978-5.5112
HLA-A02:016TDR8883SPISHFLGCTWEFG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of FANCI-ABHD2

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
FANCI-ABHD2chr1589822005chr15897190431019HFLGCTWEFATTTCTTAGGCTGCACGTGGGAATTTG
FANCI-ABHD2chr1589822005chr1589719043615SPISHFLGCCTCCCATCAGTCATTTCTTAGGCTGCA
FANCI-ABHD2chr1589822005chr1589719043617SPISHFLGCTWCTCCCATCAGTCATTTCTTAGGCTGCACGTGGG
FANCI-ABHD2chr1589822005chr1589719043817ISHFLGCTWTCAGTCATTTCTTAGGCTGCACGTGGG
FANCI-ABHD2chr1589822005chr1589719043917SHFLGCTWGTCATTTCTTAGGCTGCACGTGGG
FANCI-ABHD2chr1589822005chr1589719043919SHFLGCTWEFGTCATTTCTTAGGCTGCACGTGGGAATTTG

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 FANCI-ABHD2

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
BLCAFANCI-ABHD2chr1589822005ENST00000300027chr1589719043ENST00000352732TCGA-DK-AA6S-01A

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Potential target of CAR-T therapy development for FANCI-ABHD2

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 FANCI-ABHD2

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 FANCI-ABHD2

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