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Center for Computational Systems Medicine level1
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:FZD6-LAPTM4B

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FZD6-LAPTM4B
FusionPDB ID: 31964
FusionGDB2.0 ID: 31964
HgeneTgene
Gene symbol

FZD6

LAPTM4B

Gene ID

8323

55353

Gene namefrizzled class receptor 6lysosomal protein transmembrane 4 beta
SynonymsFZ-6|FZ6|HFZ6|NDNC1|NDNC10LAPTM4beta|LC27
Cytomap

8q22.3

8q22.1

Type of geneprotein-codingprotein-coding
Descriptionfrizzled-6frizzled 6, seven transmembrane spanning receptorfrizzled family receptor 6frizzled homolog 6seven transmembrane helix receptorlysosomal-associated transmembrane protein 4Blysosomal associated protein transmembrane 4 betalysosome-associated transmembrane protein 4-beta
Modification date2020032720200313
UniProtAcc

O60353

Q86VI4

Ensembl transtripts involved in fusion geneENST idsENST00000540287, ENST00000358755, 
ENST00000522566, ENST00000523739, 
ENST00000445593, ENST00000521545, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 4 X 6=19214 X 8 X 8=896
# samples 816
** MAII scorelog2(8/192*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/896*10)=-2.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: FZD6 [Title/Abstract] AND LAPTM4B [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FZD6(104312512)-LAPTM4B(98863625), # samples:1
Anticipated loss of major functional domain due to fusion event.FZD6-LAPTM4B 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.
FZD6-LAPTM4B 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.
FZD6-LAPTM4B 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.
FZD6-LAPTM4B 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.
FZD6-LAPTM4B seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target 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
HgeneFZD6

GO:0035567

non-canonical Wnt signaling pathway

14747478

HgeneFZD6

GO:0043433

negative regulation of DNA-binding transcription factor activity

14747478

TgeneLAPTM4B

GO:0032509

endosome transport via multivesicular body sorting pathway

25588945

TgeneLAPTM4B

GO:0032911

negative regulation of transforming growth factor beta1 production

26126825


check buttonFusion gene breakpoints across FZD6 (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 LAPTM4B (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 Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4Non-CancerTCGA-HU-A4GC-11AFZD6chr8

104312512

+LAPTM4Bchr8

98863625

+


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Fusion ORF Analysis


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)
ENST00000522566FZD6chr8104312512+ENST00000445593LAPTM4Bchr898863625+20844671255154295
ENST00000522566FZD6chr8104312512+ENST00000521545LAPTM4Bchr898863625+54546728154488
ENST00000358755FZD6chr8104312512+ENST00000445593LAPTM4Bchr898863625+211149440894104
ENST00000358755FZD6chr8104312512+ENST00000521545LAPTM4Bchr898863625+57249440894104
ENST00000523739FZD6chr8104312512+ENST00000445593LAPTM4Bchr898863625+19623451133142095
ENST00000523739FZD6chr8104312512+ENST00000521545LAPTM4Bchr898863625+4233453206086

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
ENST00000522566ENST00000445593FZD6chr8104312512+LAPTM4Bchr898863625+0.75932390.24067608
ENST00000522566ENST00000521545FZD6chr8104312512+LAPTM4Bchr898863625+0.121714060.8782859
ENST00000358755ENST00000445593FZD6chr8104312512+LAPTM4Bchr898863625+0.73837550.26162452
ENST00000358755ENST00000521545FZD6chr8104312512+LAPTM4Bchr898863625+0.137193050.862807
ENST00000523739ENST00000445593FZD6chr8104312512+LAPTM4Bchr898863625+0.76721980.23278022
ENST00000523739ENST00000521545FZD6chr8104312512+LAPTM4Bchr898863625+0.190516780.8094832

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Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>31964_31964_1_FZD6-LAPTM4B_FZD6_chr8_104312512_ENST00000358755_LAPTM4B_chr8_98863625_ENST00000445593_length(amino acids)=104AA_BP=
MGTVIGSQVKRLCPLRRGRKIHVNKNVNISIFFKFLILPHGLDESLFASSEDPHPKIKCSNSSFHYFTHFQAFLKMSPGSITRGAVEGRC

--------------------------------------------------------------

>31964_31964_2_FZD6-LAPTM4B_FZD6_chr8_104312512_ENST00000358755_LAPTM4B_chr8_98863625_ENST00000521545_length(amino acids)=104AA_BP=
MGTVIGSQVKRLCPLRRGRKIHVNKNVNISIFFKFLILPHGLDESLFASSEDPHPKIKCSNSSFHYFTHFQAFLKMSPGSITRGAVEGRC

--------------------------------------------------------------

>31964_31964_3_FZD6-LAPTM4B_FZD6_chr8_104312512_ENST00000522566_LAPTM4B_chr8_98863625_ENST00000445593_length(amino acids)=95AA_BP=
MGSGAPLLLDSHPHPGPAFTKCSALDWFKEVIQLTLSSGIGIYLIYFCLTTWKRVFFSLQATSYCFELPSMSSHLLKCKHFQKNEDCLPC

--------------------------------------------------------------

>31964_31964_4_FZD6-LAPTM4B_FZD6_chr8_104312512_ENST00000522566_LAPTM4B_chr8_98863625_ENST00000521545_length(amino acids)=88AA_BP=62

--------------------------------------------------------------

>31964_31964_5_FZD6-LAPTM4B_FZD6_chr8_104312512_ENST00000523739_LAPTM4B_chr8_98863625_ENST00000445593_length(amino acids)=95AA_BP=
MGSGAPLLLDSHPHPGPAFTKCSALDWFKEVIQLTLSSGIGIYLIYFCLTTWKRVFFSLQATSYCFELPSMSSHLLKCKHFQKNEDCLPC

--------------------------------------------------------------

>31964_31964_6_FZD6-LAPTM4B_FZD6_chr8_104312512_ENST00000523739_LAPTM4B_chr8_98863625_ENST00000521545_length(amino acids)=86AA_BP=

--------------------------------------------------------------

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Fusion Protein Functional Features


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/chr8:104312512/chr8:98863625)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
FZD6

O60353

LAPTM4B

Q86VI4

FUNCTION: Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Together with FZD3, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear (By similarity). {ECO:0000250|UniProtKB:Q61089}.FUNCTION: Required for optimal lysosomal function (PubMed:21224396). Blocks EGF-stimulated EGFR intraluminal sorting and degradation. Conversely by binding with the phosphatidylinositol 4,5-bisphosphate, regulates its PIP5K1C interaction, inhibits HGS ubiquitination and relieves LAPTM4B inhibition of EGFR degradation (PubMed:25588945). Recruits SLC3A2 and SLC7A5 (the Leu transporter) to the lysosome, promoting entry of leucine and other essential amino acid (EAA) into the lysosome, stimulating activation of proton-transporting vacuolar (V)-ATPase protein pump (V-ATPase) and hence mTORC1 activation (PubMed:25998567). Plays a role as negative regulator of TGFB1 production in regulatory T cells (PubMed:26126825). Binds ceramide and facilitates its exit from late endosome in order to control cell death pathways (PubMed:26280656). {ECO:0000269|PubMed:21224396, ECO:0000269|PubMed:25588945, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:26126825, ECO:0000269|PubMed:26280656}.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
TgeneLAPTM4Bchr8:104312512chr8:98863625ENST0000052154557244_264201.0227.0TransmembraneHelical

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+2719_13259.0707.0DomainFZ
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+2719_13259.0707.0DomainFZ
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+3819_13227.0675.0DomainFZ
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+2719_20159.0707.0Topological domainExtracellular
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27223_23359.0707.0Topological domainCytoplasmic
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27255_28459.0707.0Topological domainExtracellular
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27306_32459.0707.0Topological domainCytoplasmic
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27346_37059.0707.0Topological domainExtracellular
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27392_41659.0707.0Topological domainCytoplasmic
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27438_47359.0707.0Topological domainExtracellular
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27495_70659.0707.0Topological domainCytoplasmic
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+2719_20159.0707.0Topological domainExtracellular
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27223_23359.0707.0Topological domainCytoplasmic
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27255_28459.0707.0Topological domainExtracellular
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27306_32459.0707.0Topological domainCytoplasmic
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27346_37059.0707.0Topological domainExtracellular
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27392_41659.0707.0Topological domainCytoplasmic
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27438_47359.0707.0Topological domainExtracellular
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27495_70659.0707.0Topological domainCytoplasmic
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+3819_20127.0675.0Topological domainExtracellular
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38223_23327.0675.0Topological domainCytoplasmic
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38255_28427.0675.0Topological domainExtracellular
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38306_32427.0675.0Topological domainCytoplasmic
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38346_37027.0675.0Topological domainExtracellular
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38392_41627.0675.0Topological domainCytoplasmic
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38438_47327.0675.0Topological domainExtracellular
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38495_70627.0675.0Topological domainCytoplasmic
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27202_22259.0707.0TransmembraneHelical%3B Name%3D1
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27234_25459.0707.0TransmembraneHelical%3B Name%3D2
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27285_30559.0707.0TransmembraneHelical%3B Name%3D3
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27325_34559.0707.0TransmembraneHelical%3B Name%3D4
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27371_39159.0707.0TransmembraneHelical%3B Name%3D5
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27417_43759.0707.0TransmembraneHelical%3B Name%3D6
HgeneFZD6chr8:104312512chr8:98863625ENST00000358755+27474_49459.0707.0TransmembraneHelical%3B Name%3D7
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27202_22259.0707.0TransmembraneHelical%3B Name%3D1
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27234_25459.0707.0TransmembraneHelical%3B Name%3D2
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27285_30559.0707.0TransmembraneHelical%3B Name%3D3
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27325_34559.0707.0TransmembraneHelical%3B Name%3D4
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27371_39159.0707.0TransmembraneHelical%3B Name%3D5
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27417_43759.0707.0TransmembraneHelical%3B Name%3D6
HgeneFZD6chr8:104312512chr8:98863625ENST00000522566+27474_49459.0707.0TransmembraneHelical%3B Name%3D7
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38202_22227.0675.0TransmembraneHelical%3B Name%3D1
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38234_25427.0675.0TransmembraneHelical%3B Name%3D2
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38285_30527.0675.0TransmembraneHelical%3B Name%3D3
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38325_34527.0675.0TransmembraneHelical%3B Name%3D4
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38371_39127.0675.0TransmembraneHelical%3B Name%3D5
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38417_43727.0675.0TransmembraneHelical%3B Name%3D6
HgeneFZD6chr8:104312512chr8:98863625ENST00000523739+38474_49427.0675.0TransmembraneHelical%3B Name%3D7
TgeneLAPTM4Bchr8:104312512chr8:98863625ENST0000044559357117_137292.0318.0TransmembraneHelical
TgeneLAPTM4Bchr8:104312512chr8:98863625ENST0000044559357163_183292.0318.0TransmembraneHelical
TgeneLAPTM4Bchr8:104312512chr8:98863625ENST0000044559357191_211292.0318.0TransmembraneHelical
TgeneLAPTM4Bchr8:104312512chr8:98863625ENST0000044559357244_264292.0318.0TransmembraneHelical
TgeneLAPTM4Bchr8:104312512chr8:98863625ENST0000052154557117_137201.0227.0TransmembraneHelical
TgeneLAPTM4Bchr8:104312512chr8:98863625ENST0000052154557163_183201.0227.0TransmembraneHelical
TgeneLAPTM4Bchr8:104312512chr8:98863625ENST0000052154557191_211201.0227.0TransmembraneHelical


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Fusion Protein-Protein Interaction


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)
GenePPI interactors


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
FZD6
LAPTM4B


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to FZD6-LAPTM4B


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 FZD6-LAPTM4B


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