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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:ADH1B-ALB

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ADH1B-ALB
FusionPDB ID: 2410
FusionGDB2.0 ID: 2410
HgeneTgene
Gene symbol

ADH1B

ALB

Gene ID

125

213

Gene namealcohol dehydrogenase 1B (class I), beta polypeptidealbumin
SynonymsADH2|HEL-S-117HSA|PRO0883|PRO0903|PRO1341
Cytomap

4q23

4q13.3

Type of geneprotein-codingprotein-coding
Descriptionall-trans-retinol dehydrogenase [NAD(+)] ADH1BADH, beta subunitalcohol dehydrogenase 2 (class I), beta polypeptidealcohol dehydrogenase subunit betaaldehyde reductaseepididymis secretory protein Li 117serum albumin
Modification date2020031320200329
UniProtAcc

P00325

Main function of 5'-partner protein: FUNCTION: Catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives such as all-trans-4-hydroxyretinol and may participate in retinoid metabolism (PubMed:15369820, PubMed:16787387). In vitro can also catalyzes the NADH-dependent reduction of all-trans-retinal and its derivatives such as all-trans-4-oxoretinal (PubMed:15369820, PubMed:16787387). Catalyzes in the oxidative direction with higher efficiency (PubMed:16787387). Has the same affinity for all-trans-4-hydroxyretinol and all-trans-4-oxoretinal (PubMed:15369820). {ECO:0000269|PubMed:15369820, ECO:0000269|PubMed:16787387}.

P02768

Main function of 5'-partner protein: FUNCTION: Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017). {ECO:0000250|UniProtKB:P02769, ECO:0000269|PubMed:19021548, ECO:0000269|PubMed:6234017, ECO:0000305|PubMed:1630489}.
Ensembl transtripts involved in fusion geneENST idsENST00000305046, ENST00000394887, 
ENST00000504498, 
ENST00000505649, 
ENST00000295897, ENST00000401494, 
ENST00000415165, ENST00000503124, 
ENST00000509063, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 2=1849 X 62 X 5=15190
# samples 364
** MAII scorelog2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(64/15190*10)=-4.56890615450208
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ADH1B [Title/Abstract] AND ALB [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ADH1B [Title/Abstract] AND ALB [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADH1B(100242471)-ALB(74279137), # samples:1
Anticipated loss of major functional domain due to fusion event.ADH1B-ALB 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.
ADH1B-ALB 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.
ADH1B-ALB 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.
ADH1B-ALB 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
HgeneADH1B

GO:0001523

retinoid metabolic process

15369820|16787387

HgeneADH1B

GO:0006069

ethanol oxidation

2398055

TgeneALB

GO:0009267

cellular response to starvation

16245148

TgeneALB

GO:0043066

negative regulation of apoptotic process

16153637

TgeneALB

GO:0051659

maintenance of mitochondrion location

16153637



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/chr4:100242471/chr4:74279137)
- 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 ADH1B (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 ALB (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)
ENST00000305046ADH1Bchr4100242471-ENST00000295897ALBchr474279137+141786381072344
ENST00000305046ADH1Bchr4100242471-ENST00000415165ALBchr474279137+126186381072344
ENST00000305046ADH1Bchr4100242471-ENST00000503124ALBchr474279137+122786381072344
ENST00000305046ADH1Bchr4100242471-ENST00000509063ALBchr474279137+113086381057339
ENST00000305046ADH1Bchr4100242471-ENST00000401494ALBchr474279137+122786381072344

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
ENST00000305046ENST00000295897ADH1Bchr4100242471-ALBchr474279137+0.0014359510.99856406
ENST00000305046ENST00000415165ADH1Bchr4100242471-ALBchr474279137+0.0015067650.9984932
ENST00000305046ENST00000503124ADH1Bchr4100242471-ALBchr474279137+0.0012161410.9987839
ENST00000305046ENST00000509063ADH1Bchr4100242471-ALBchr474279137+0.0020620790.99793786
ENST00000305046ENST00000401494ADH1Bchr4100242471-ALBchr474279137+0.0012161410.9987839

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 ADH1B-ALB

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ADH1Bchr4100242471ALBchr4742791378616GREDRNDMSTAGKADLAKYICENQDS

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Potential FusionNeoAntigen Information of ADH1B-ALB 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.
ADH1B-ALB_100242471_74279137.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)
ADH1B-ALBchr4100242471chr47427913786HLA-C05:09KADLAKYI10.84641220
ADH1B-ALBchr4100242471chr47427913786HLA-C08:15KADLAKYI0.99990.93411220
ADH1B-ALBchr4100242471chr47427913786HLA-B73:01DRNDMSTAGKA0.99720.9043314
ADH1B-ALBchr4100242471chr47427913786HLA-C04:03KADLAKYI10.66471220
ADH1B-ALBchr4100242471chr47427913786HLA-C05:01KADLAKYI10.84641220
ADH1B-ALBchr4100242471chr47427913786HLA-C08:02KADLAKYI0.99990.93411220

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Potential FusionNeoAntigen Information of ADH1B-ALB 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 ADH1B-ALB

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
1265DMSTAGKADLAKYIADH1BALBchr4100242471chr47427913786

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ADH1B-ALB

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-B14:023BVN1265DMSTAGKADLAKYI-6.49513-7.53823
HLA-B14:023BVN1265DMSTAGKADLAKYI-5.42079-5.53259
HLA-B52:013W391265DMSTAGKADLAKYI-5.86639-6.90949
HLA-B52:013W391265DMSTAGKADLAKYI-5.61291-5.72471
HLA-A11:014UQ21265DMSTAGKADLAKYI-3.46825-4.51135
HLA-A24:025HGA1265DMSTAGKADLAKYI-6.23799-6.34979
HLA-A24:025HGA1265DMSTAGKADLAKYI-3.82387-4.86697
HLA-B27:056PYJ1265DMSTAGKADLAKYI-5.76358-6.80668
HLA-B44:053DX81265DMSTAGKADLAKYI-4.7768-4.8886
HLA-B44:053DX81265DMSTAGKADLAKYI-3.57735-4.62045
HLA-A02:016TDR1265DMSTAGKADLAKYI-3.77444-3.88624

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Vaccine Design for the FusionNeoAntigens of ADH1B-ALB

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
ADH1B-ALBchr4100242471chr4742791371220KADLAKYIAAAGCGGACCTTGCCAAGTATATC
ADH1B-ALBchr4100242471chr474279137314DRNDMSTAGKAGACAGAAACGACATGAGCACAGCAGGAAAAGCG

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 ADH1B-ALB

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
Non-CancerADH1B-ALBchr4100242471ENST00000305046chr474279137ENST00000295897TCGA-DD-A11C-11A

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Potential target of CAR-T therapy development for ADH1B-ALB

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 ADH1B-ALB

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 ADH1B-ALB

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