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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:AHCYL1-ZFYVE9

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: AHCYL1-ZFYVE9
FusionPDB ID: 3058
FusionGDB2.0 ID: 3058
HgeneTgene
Gene symbol

AHCYL1

ZFYVE9

Gene ID

10768

9372

Gene nameadenosylhomocysteinase like 1zinc finger FYVE-type containing 9
SynonymsDCAL|IRBIT|PPP1R78|PRO0233|XPVKONAMADHIP|NSP|PPP1R173|SARA|SMADIP
Cytomap

1p13.3

1p32.3

Type of geneprotein-codingprotein-coding
DescriptionS-adenosylhomocysteine hydrolase-like protein 1DC-expressed AHCY-like moleculeIP(3)Rs binding protein released with IP(3)S-adenosyl homocysteine hydrolase homologS-adenosyl-L-homocysteine hydrolase 2adenosylhomocysteinase 2adoHcyase 2dendritic cellzinc finger FYVE domain-containing protein 9MAD, mothers against decapentaplegic homolog interacting protein, receptor activation anchorMADH-interacting proteinnovel serine proteaseprotein phosphatase 1, regulatory subunit 173smad anchor for receptor
Modification date2020031320200313
UniProtAcc

O43865

Main function of 5'-partner protein: FUNCTION: Multifaceted cellular regulator which coordinates several essential cellular functions including regulation of epithelial HCO3(-) and fluid secretion, mRNA processing and DNA replication. Regulates ITPR1 sensitivity to inositol 1,4,5-trisphosphate, competing for the common binding site and acting as endogenous 'pseudoligand' whose inhibitory activity can be modulated by its phosphorylation status. Promotes the formation of contact points between the endoplasmic reticulum (ER) and mitochondria, facilitating transfer of Ca(2+) from the ER to mitochondria (PubMed:27995898). Under normal cellular conditions, functions cooperatively with BCL2L10 to limit ITPR1-mediated Ca(2+) release but, under apoptotic stress conditions, dephosphorylated which promotes dissociation of both AHCYL1 and BCL2L10 from mitochondria-associated endoplasmic reticulum membranes, inhibits BCL2L10 interaction with ITPR1 and leads to increased Ca(2+) transfer to mitochondria which promotes apoptosis (PubMed:27995898). In the pancreatic and salivary ducts, at resting state, attenuates inositol 1,4,5-trisphosphate-induced calcium release by interacting with ITPR1 (PubMed:16793548). When extracellular stimuli induce ITPR1 phosphorylation or inositol 1,4,5-trisphosphate production, dissociates from ITPR1 to interact with CFTR and SLC26A6, mediating their synergistic activation by calcium and cAMP that stimulates the epithelial secretion of electrolytes and fluid (By similarity). Also activates basolateral SLC4A4 isoform 1 to coordinate fluid and HCO3(-) secretion (PubMed:16769890). Inhibits the effect of STK39 on SLC4A4 and CFTR by recruiting PP1 phosphatase which activates SLC4A4, SLC26A6 and CFTR through dephosphorylation (By similarity). Mediates the induction of SLC9A3 surface expression produced by Angiotensin-2 (PubMed:20584908). Depending on the cell type, activates SLC9A3 in response to calcium or reverses SLC9A3R2-dependent calcium inhibition (PubMed:18829453). May modulate the polyadenylation state of specific mRNAs, both by controlling the subcellular location of FIP1L1 and by inhibiting PAPOLA activity, in response to a stimulus that alters its phosphorylation state (PubMed:19224921). Acts as a (dATP)-dependent inhibitor of ribonucleotide reductase large subunit RRM1, controlling the endogenous dNTP pool and ensuring normal cell cycle progression (PubMed:25237103). In vitro does not exhibit any S-adenosyl-L-homocysteine hydrolase activity (By similarity). {ECO:0000250|UniProtKB:B5DFN2, ECO:0000250|UniProtKB:Q80SW1, ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:18829453, ECO:0000269|PubMed:19224921, ECO:0000269|PubMed:20584908, ECO:0000269|PubMed:25237103, ECO:0000269|PubMed:27995898}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000475081, ENST00000369799, 
ENST00000359172, ENST00000393614, 
ENST00000287727, ENST00000357206, 
ENST00000371591, ENST00000469134, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 9 X 4=4327 X 6 X 4=168
# samples 147
** MAII scorelog2(14/432*10)=-1.6256044852185
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/168*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: AHCYL1 [Title/Abstract] AND ZFYVE9 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: AHCYL1 [Title/Abstract] AND ZFYVE9 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)AHCYL1(110527794)-ZFYVE9(52798440), # samples:1
Anticipated loss of major functional domain due to fusion event.AHCYL1-ZFYVE9 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.
AHCYL1-ZFYVE9 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
HgeneAHCYL1

GO:0006378

mRNA polyadenylation

19224921

HgeneAHCYL1

GO:0031440

regulation of mRNA 3'-end processing

19224921

HgeneAHCYL1

GO:0038166

angiotensin-activated signaling pathway

20584908

HgeneAHCYL1

GO:0051592

response to calcium ion

18829453



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/chr1:110527794/chr1:52798440)
- 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 AHCYL1 (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 ZFYVE9 (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)
ENST00000369799AHCYL1chr1110527794+ENST00000357206ZFYVE9chr152798440+1621487401326428
ENST00000369799AHCYL1chr1110527794+ENST00000287727ZFYVE9chr152798440+1791487401326428
ENST00000369799AHCYL1chr1110527794+ENST00000371591ZFYVE9chr152798440+1792487401326428

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
ENST00000369799ENST00000357206AHCYL1chr1110527794+ZFYVE9chr152798440+0.0014194440.9985806
ENST00000369799ENST00000287727AHCYL1chr1110527794+ZFYVE9chr152798440+0.0016904970.9983095
ENST00000369799ENST00000371591AHCYL1chr1110527794+ZFYVE9chr152798440+0.001675190.9983248

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 AHCYL1-ZFYVE9

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
AHCYL1chr1110527794ZFYVE9chr152798440487149YSFMATVTKAPKKMMKAMNKSNEHVL

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Potential FusionNeoAntigen Information of AHCYL1-ZFYVE9 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.
AHCYL1-ZFYVE9_110527794_52798440.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)
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-B08:09APKKMMKA0.9890.6224917
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-B08:09APKKMMKAM0.90960.5626918
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-A30:08VTKAPKKMMK0.99350.5701616
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-B39:10APKKMMKAM0.09080.8375918
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-A30:01KKMMKAMNK0.80460.85441120
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-B08:12APKKMMKAM0.58760.6308918
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-B35:11APKKMMKAM0.35790.8756918
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-B35:30APKKMMKAM0.31260.5564918
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-B35:17APKKMMKAM0.31260.5564918
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-B67:01APKKMMKAM0.15560.7323918
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-B35:43APKKMMKAM0.01260.7251918
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-B15:08APKKMMKAM0.01120.7276918
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-B15:11APKKMMKAM0.01080.7206918
AHCYL1-ZFYVE9chr1110527794chr152798440487HLA-A30:01VTKAPKKMMK0.99290.7249616

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Potential FusionNeoAntigen Information of AHCYL1-ZFYVE9 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.
AHCYL1-ZFYVE9_110527794_52798440.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)
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-0801PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-0805PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-0805KKMMKAMNKSNEHVL1126
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-0806PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-0806KKMMKAMNKSNEHVL1126
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-0816PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-0822PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-0822KKMMKAMNKSNEHVL1126
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-0822APKKMMKAMNKSNEH924
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-0826PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-0839PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-0840PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1303PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1312PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1321PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1349PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1355PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1358PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1358KKMMKAMNKSNEHVL1126
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1358APKKMMKAMNKSNEH924
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1381PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1381KKMMKAMNKSNEHVL1126
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1381APKKMMKAMNKSNEH924
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1388PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1389PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1389KKMMKAMNKSNEHVL1126
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1389APKKMMKAMNKSNEH924
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1390PKKMMKAMNKSNEHV1025
AHCYL1-ZFYVE9chr1110527794chr152798440487DRB1-1395PKKMMKAMNKSNEHV1025

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Fusion breakpoint peptide structures of AHCYL1-ZFYVE9

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
10309VTKAPKKMMKAMNKAHCYL1ZFYVE9chr1110527794chr152798440487

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of AHCYL1-ZFYVE9

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-B14:023BVN10309VTKAPKKMMKAMNK-8.55667-8.74867
HLA-B14:023BVN10309VTKAPKKMMKAMNK-3.49457-4.25557
HLA-B52:013W3910309VTKAPKKMMKAMNK-7.26725-7.45925
HLA-B52:013W3910309VTKAPKKMMKAMNK-4.01461-4.77561
HLA-A24:025HGA10309VTKAPKKMMKAMNK-7.65911-8.42011
HLA-A24:025HGA10309VTKAPKKMMKAMNK-7.10204-7.29404
HLA-B44:053DX810309VTKAPKKMMKAMNK-7.5556-8.3166
HLA-B44:053DX810309VTKAPKKMMKAMNK-2.76159-2.95359
HLA-B35:011A1N10309VTKAPKKMMKAMNK-5.4014-6.1624
HLA-B35:011A1N10309VTKAPKKMMKAMNK-4.87859-5.07059

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Vaccine Design for the FusionNeoAntigens of AHCYL1-ZFYVE9

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
AHCYL1-ZFYVE9chr1110527794chr1527984401120KKMMKAMNKAAGAAGATGATGAAAGCCATGAACAAG
AHCYL1-ZFYVE9chr1110527794chr152798440616VTKAPKKMMKGTCACCAAGGCGCCCAAGAAGATGATGAAA
AHCYL1-ZFYVE9chr1110527794chr152798440917APKKMMKAGCGCCCAAGAAGATGATGAAAGCC
AHCYL1-ZFYVE9chr1110527794chr152798440918APKKMMKAMGCGCCCAAGAAGATGATGAAAGCCATG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
AHCYL1-ZFYVE9chr1110527794chr1527984401025PKKMMKAMNKSNEHVCCCAAGAAGATGATGAAAGCCATGAACAAGTCCAATGAGCATGTC
AHCYL1-ZFYVE9chr1110527794chr1527984401126KKMMKAMNKSNEHVLAAGAAGATGATGAAAGCCATGAACAAGTCCAATGAGCATGTCCTG
AHCYL1-ZFYVE9chr1110527794chr152798440924APKKMMKAMNKSNEHGCGCCCAAGAAGATGATGAAAGCCATGAACAAGTCCAATGAGCAT

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Information of the samples that have these potential fusion neoantigens of AHCYL1-ZFYVE9

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
STADAHCYL1-ZFYVE9chr1110527794ENST00000369799chr152798440ENST00000287727TCGA-HU-A4GH-01A

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Potential target of CAR-T therapy development for AHCYL1-ZFYVE9

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 AHCYL1-ZFYVE9

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 AHCYL1-ZFYVE9

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