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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:NDRG1-SNTB1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NDRG1-SNTB1
FusionPDB ID: 57977
FusionGDB2.0 ID: 57977
HgeneTgene
Gene symbol

NDRG1

SNTB1

Gene ID

10397

6641

Gene nameN-myc downstream regulated 1syntrophin beta 1
SynonymsCAP43|CMT4D|DRG-1|DRG1|GC4|HMSNL|NDR1|NMSL|PROXY1|RIT42|RTP|TARG1|TDD559-DAP|A1B|BSYN2|DAPA1B|SNT2|SNT2B1|TIP-43
Cytomap

8q24.22

8q24.12

Type of geneprotein-codingprotein-coding
Descriptionprotein NDRG1N-myc downstream-regulated gene 1 proteindifferentiation-related gene 1 proteinnickel-specific induction protein Cap43protein regulated by oxygen-1reducing agents and tunicamycin-responsive proteinbeta-1-syntrophin59 kDa dystrophin-associated protein A1 basic component 1dystrophin-associated protein A1, 59kD, basic component 1syntrophin, beta 1 (dystrophin-associated protein A1, 59kDa, basic component 1)syntrophin-2tax interaction protein 43
Modification date2020032820200313
UniProtAcc

Q92597

Main function of 5'-partner protein: FUNCTION: Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53-mediated caspase activation and apoptosis. Has a role in cell trafficking, notably of the Schwann cell, and is necessary for the maintenance and development of the peripheral nerve myelin sheath. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy. {ECO:0000269|PubMed:15247272, ECO:0000269|PubMed:15377670, ECO:0000269|PubMed:17786215, ECO:0000269|PubMed:9766676}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000323851, ENST00000354944, 
ENST00000414097, ENST00000537882, 
ENST00000518066, ENST00000518176, 
ENST00000521414, ENST00000522476, 
ENST00000519177, ENST00000395601, 
ENST00000517992, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score27 X 21 X 12=68046 X 6 X 6=216
# samples 408
** MAII scorelog2(40/6804*10)=-4.08831123588866
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/216*10)=-1.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NDRG1 [Title/Abstract] AND SNTB1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NDRG1 [Title/Abstract] AND SNTB1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NDRG1(134292475)-SNTB1(121706148), # samples:2
Anticipated loss of major functional domain due to fusion event.NDRG1-SNTB1 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.
NDRG1-SNTB1 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.
NDRG1-SNTB1 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.
NDRG1-SNTB1 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.
NDRG1-SNTB1 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
NDRG1-SNTB1 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor 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


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/chr8:134292475/chr8:121706148)
- 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 NDRG1 (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 SNTB1 (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)
ENST00000414097NDRG1chr8134292475-ENST00000395601SNTB1chr8121706148-51459679752012345
ENST00000414097NDRG1chr8134292475-ENST00000517992SNTB1chr8121706148-23699679752012345
ENST00000414097NDRG1chr8134292474-ENST00000395601SNTB1chr8121706148-51459679752012345
ENST00000414097NDRG1chr8134292474-ENST00000517992SNTB1chr8121706148-23699679752012345
ENST00000414097NDRG1chr8134292478-ENST00000395601SNTB1chr8121706151-51459679752012345
ENST00000414097NDRG1chr8134292478-ENST00000517992SNTB1chr8121706151-23699679752012345

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
ENST00000414097ENST00000395601NDRG1chr8134292475-SNTB1chr8121706148-0.0037838740.9962161
ENST00000414097ENST00000517992NDRG1chr8134292475-SNTB1chr8121706148-0.04692930.9530707
ENST00000414097ENST00000395601NDRG1chr8134292474-SNTB1chr8121706148-0.0037838740.9962161
ENST00000414097ENST00000517992NDRG1chr8134292474-SNTB1chr8121706148-0.04692930.9530707
ENST00000414097ENST00000395601NDRG1chr8134292478-SNTB1chr8121706151-0.0037838740.9962161
ENST00000414097ENST00000517992NDRG1chr8134292478-SNTB1chr8121706151-0.04692930.9530707

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 NDRG1-SNTB1

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

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Potential FusionNeoAntigen Information of NDRG1-SNTB1 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.

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)

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Potential FusionNeoAntigen Information of NDRG1-SNTB1 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 NDRG1-SNTB1

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NDRG1-SNTB1

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

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Vaccine Design for the FusionNeoAntigens of NDRG1-SNTB1

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

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 NDRG1-SNTB1

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

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Potential target of CAR-T therapy development for NDRG1-SNTB1

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 NDRG1-SNTB1

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 NDRG1-SNTB1

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
HgeneNDRG1C0027627Neoplasm Metastasis2CTD_human
HgeneNDRG1C1832334CHARCOT-MARIE-TOOTH DISEASE, TYPE 4D2CTD_human;GENOMICS_ENGLAND;ORPHANET
HgeneNDRG1C0004114Astrocytoma1CTD_human
HgeneNDRG1C0006142Malignant neoplasm of breast1CTD_human
HgeneNDRG1C0007131Non-Small Cell Lung Carcinoma1CTD_human
HgeneNDRG1C0007134Renal Cell Carcinoma1CTD_human
HgeneNDRG1C0017636Glioblastoma1CTD_human
HgeneNDRG1C0022665Kidney Neoplasm1CTD_human
HgeneNDRG1C0023893Liver Cirrhosis, Experimental1CTD_human
HgeneNDRG1C0023903Liver neoplasms1CTD_human
HgeneNDRG1C0025202melanoma1CTD_human
HgeneNDRG1C0026640Mouth Neoplasms1CTD_human
HgeneNDRG1C0029295Oropharyngeal Neoplasms1CTD_human
HgeneNDRG1C0033578Prostatic Neoplasms1CTD_human
HgeneNDRG1C0149925Small cell carcinoma of lung1CTD_human
HgeneNDRG1C0153381Malignant neoplasm of mouth1CTD_human
HgeneNDRG1C0205768Subependymal Giant Cell Astrocytoma1CTD_human
HgeneNDRG1C0206658Smooth Muscle Tumor1CTD_human
HgeneNDRG1C0206734Hemangioblastoma1CTD_human
HgeneNDRG1C0279702Conventional (Clear Cell) Renal Cell Carcinoma1CTD_human
HgeneNDRG1C0280783Juvenile Pilocytic Astrocytoma1CTD_human
HgeneNDRG1C0280785Diffuse Astrocytoma1CTD_human
HgeneNDRG1C0334579Anaplastic astrocytoma1CTD_human
HgeneNDRG1C0334580Protoplasmic astrocytoma1CTD_human
HgeneNDRG1C0334581Gemistocytic astrocytoma1CTD_human
HgeneNDRG1C0334582Fibrillary Astrocytoma1CTD_human
HgeneNDRG1C0334583Pilocytic Astrocytoma1CTD_human
HgeneNDRG1C0334588Giant Cell Glioblastoma1CTD_human
HgeneNDRG1C0338070Childhood Cerebral Astrocytoma1CTD_human
HgeneNDRG1C0345904Malignant neoplasm of liver1CTD_human
HgeneNDRG1C0376358Malignant neoplasm of prostate1CTD_human
HgeneNDRG1C0547065Mixed oligoastrocytoma1CTD_human
HgeneNDRG1C0678222Breast Carcinoma1CTD_human
HgeneNDRG1C0740457Malignant neoplasm of kidney1CTD_human
HgeneNDRG1C0750935Cerebral Astrocytoma1CTD_human
HgeneNDRG1C0750936Intracranial Astrocytoma1CTD_human
HgeneNDRG1C0751692Multiple Hemangioblastomas1CTD_human
HgeneNDRG1C0887833Carcinoma, Pancreatic Ductal1CTD_human
HgeneNDRG1C1168401Squamous cell carcinoma of the head and neck1CTD_human
HgeneNDRG1C1257931Mammary Neoplasms, Human1CTD_human
HgeneNDRG1C1266042Chromophobe Renal Cell Carcinoma1CTD_human
HgeneNDRG1C1266043Sarcomatoid Renal Cell Carcinoma1CTD_human
HgeneNDRG1C1266044Collecting Duct Carcinoma of the Kidney1CTD_human
HgeneNDRG1C1306837Papillary Renal Cell Carcinoma1CTD_human
HgeneNDRG1C1458155Mammary Neoplasms1CTD_human
HgeneNDRG1C1621958Glioblastoma Multiforme1CTD_human
HgeneNDRG1C1704230Grade I Astrocytoma1CTD_human
HgeneNDRG1C2349952Oropharyngeal Carcinoma1CTD_human
HgeneNDRG1C4704874Mammary Carcinoma, Human1CTD_human