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Center for Computational Systems Medicine level2
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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 Structure

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pLDDT scores

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Ramachandran Plot of Fusion Protein Structure

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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:TCF7L1-WIF1

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TCF7L1-WIF1
FusionPDB ID: 89808
FusionGDB2.0 ID: 89808
HgeneTgene
Gene symbol

TCF7L1

WIF1

Gene ID

83439

11197

Gene nametranscription factor 7 like 1WNT inhibitory factor 1
SynonymsTCF-3|TCF3WIF-1
Cytomap

2p11.2

12q14.3

Type of geneprotein-codingprotein-coding
Descriptiontranscription factor 7-like 1HMG box transcription factor 3transcription factor 7-like 1 (T-cell specific, HMG-box)wnt inhibitory factor 1
Modification date2020031320200313
UniProtAcc

Q9HCS4

Q9Y5W5

Ensembl transtripts involved in fusion geneENST idsENST00000494519, ENST00000282111, 
ENST00000286574, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 10 X 9=12607 X 11 X 6=462
# samples 1414
** MAII scorelog2(14/1260*10)=-3.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(14/462*10)=-1.72246602447109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: TCF7L1 [Title/Abstract] AND WIF1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TCF7L1(85361573)-WIF1(65471634), # samples:5
Anticipated loss of major functional domain due to fusion event.TCF7L1-WIF1 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.
TCF7L1-WIF1 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.
TCF7L1-WIF1 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.
TCF7L1-WIF1 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

check buttonFusion gene breakpoints across TCF7L1 (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 WIF1 (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
ChimerDB4BRCATCGA-E2-A1LI-01ATCF7L1chr2

85361572

+WIF1chr12

65471633

-
ChimerDB4BRCATCGA-E2-A1LI-01ATCF7L1chr2

85361573

-WIF1chr12

65471634

-
ChimerDB4BRCATCGA-E2-A1LI-01ATCF7L1chr2

85361573

+WIF1chr12

65471634

-
ChimerDB4BRCATCGA-E2-A1LITCF7L1chr2

85361573

+WIF1chr12

65471634

-


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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)
ENST00000282111TCF7L1chr285361573+ENST00000286574WIF1chr1265471634-22917161461567473
ENST00000282111TCF7L1chr285361572+ENST00000286574WIF1chr1265471633-22917161461567473

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
ENST00000282111ENST00000286574TCF7L1chr285361573+WIF1chr1265471634-0.0010458630.99895406
ENST00000282111ENST00000286574TCF7L1chr285361572+WIF1chr1265471633-0.0010458630.99895406

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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

>89808_89808_1_TCF7L1-WIF1_TCF7L1_chr2_85361572_ENST00000282111_WIF1_chr12_65471633_ENST00000286574_length(amino acids)=473AA_BP=190
MSNFVAAASAAGPQAGGRGAGPGRAGRGRLGAPRAAAPARGPTMPQLGGGGGGGGGGSGGGGGSSAGAAGGGDDLGANDELIPFQDEGGE
EQEPSSDSASAQRDLDEVKSSLVNESENQSSSSDSEAERRPQPVRDTFQKPRDYFAEVRRPQDSAFFKGPPYPGYPFLMIPDLSSPYLSN
GPLSPGGARTAEYFYEFLSLRSLDKGIMADPTVNVPLLGTVPHKASVVQVGFPCLGKQDGVAAFEVDVIVMNSEGNTILQTPQNAIFFKT
CQQAECPGGCRNGGFCNERRICECPDGFHGPHCEKALCTPRCMNGGLCVTPGFCICPPGFYGVNCDKANCSTTCFNGGTCFYPGKCICPP
GLEGEQCEISKCPQPCRNGGKCIGKSKCKCSKGYQGDLCSKPVCEPGCGAHGTCHEPNKCQCQEGWHGRHCNKRYEASLIHALRPAGAQL

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

>89808_89808_2_TCF7L1-WIF1_TCF7L1_chr2_85361573_ENST00000282111_WIF1_chr12_65471634_ENST00000286574_length(amino acids)=473AA_BP=190
MSNFVAAASAAGPQAGGRGAGPGRAGRGRLGAPRAAAPARGPTMPQLGGGGGGGGGGSGGGGGSSAGAAGGGDDLGANDELIPFQDEGGE
EQEPSSDSASAQRDLDEVKSSLVNESENQSSSSDSEAERRPQPVRDTFQKPRDYFAEVRRPQDSAFFKGPPYPGYPFLMIPDLSSPYLSN
GPLSPGGARTAEYFYEFLSLRSLDKGIMADPTVNVPLLGTVPHKASVVQVGFPCLGKQDGVAAFEVDVIVMNSEGNTILQTPQNAIFFKT
CQQAECPGGCRNGGFCNERRICECPDGFHGPHCEKALCTPRCMNGGLCVTPGFCICPPGFYGVNCDKANCSTTCFNGGTCFYPGKCICPP
GLEGEQCEISKCPQPCRNGGKCIGKSKCKCSKGYQGDLCSKPVCEPGCGAHGTCHEPNKCQCQEGWHGRHCNKRYEASLIHALRPAGAQL

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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/chr2:85361573/chr12:65471634)
- 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
TCF7L1

Q9HCS4

WIF1

Q9Y5W5

FUNCTION: Participates in the Wnt signaling pathway. Binds to DNA and acts as a repressor in the absence of CTNNB1, and as an activator in its presence. Necessary for the terminal differentiation of epidermal cells, the formation of keratohyalin granules and the development of the barrier function of the epidermis (By similarity). Down-regulates NQO1, leading to increased mitomycin c resistance. {ECO:0000250}.FUNCTION: Binds to WNT proteins and inhibits their activities. May be involved in mesoderm segmentation.

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
HgeneTCF7L1chr2:85361572chr12:65471633ENST00000282111+3125_29147.0589.0Compositional biasNote=Gly-rich
HgeneTCF7L1chr2:85361573chr12:65471634ENST00000282111+3125_29147.0589.0Compositional biasNote=Gly-rich
HgeneTCF7L1chr2:85361572chr12:65471633ENST00000282111+3121_74147.0589.0RegionCTNNB1-binding
HgeneTCF7L1chr2:85361573chr12:65471634ENST00000282111+3121_74147.0589.0RegionCTNNB1-binding
TgeneWIF1chr2:85361572chr12:65471633ENST00000286574110178_21096.0380.0DomainEGF-like 1
TgeneWIF1chr2:85361572chr12:65471633ENST00000286574110211_24296.0380.0DomainEGF-like 2
TgeneWIF1chr2:85361572chr12:65471633ENST00000286574110243_27196.0380.0DomainEGF-like 3
TgeneWIF1chr2:85361572chr12:65471633ENST00000286574110274_30696.0380.0DomainEGF-like 4
TgeneWIF1chr2:85361572chr12:65471633ENST00000286574110307_33896.0380.0DomainEGF-like 5
TgeneWIF1chr2:85361573chr12:65471634ENST00000286574110178_21096.0380.0DomainEGF-like 1
TgeneWIF1chr2:85361573chr12:65471634ENST00000286574110211_24296.0380.0DomainEGF-like 2
TgeneWIF1chr2:85361573chr12:65471634ENST00000286574110243_27196.0380.0DomainEGF-like 3
TgeneWIF1chr2:85361573chr12:65471634ENST00000286574110274_30696.0380.0DomainEGF-like 4
TgeneWIF1chr2:85361573chr12:65471634ENST00000286574110307_33896.0380.0DomainEGF-like 5

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneTCF7L1chr2:85361572chr12:65471633ENST00000282111+312117_326147.0589.0Compositional biasNote=Pro-rich
HgeneTCF7L1chr2:85361573chr12:65471634ENST00000282111+312117_326147.0589.0Compositional biasNote=Pro-rich
HgeneTCF7L1chr2:85361572chr12:65471633ENST00000282111+312346_414147.0589.0DNA bindingHMG box
HgeneTCF7L1chr2:85361573chr12:65471634ENST00000282111+312346_414147.0589.0DNA bindingHMG box
HgeneTCF7L1chr2:85361572chr12:65471633ENST00000282111+312421_427147.0589.0MotifNuclear localization signal
HgeneTCF7L1chr2:85361573chr12:65471634ENST00000282111+312421_427147.0589.0MotifNuclear localization signal
TgeneWIF1chr2:85361572chr12:65471633ENST0000028657411038_17796.0380.0DomainWIF
TgeneWIF1chr2:85361573chr12:65471634ENST0000028657411038_17796.0380.0DomainWIF


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Fusion Protein Structures

check button PDB and CIF files of the predicted fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
Fusion protein PDB link (fusion AA seq ID in FusionPDB)HgeneHchrHbpHstrandTgeneTchrTbpTstrandAA seqLen(AA seq)
PDB file >>>996_TCF7L1_85361573_WIF1_65471634_996_TCF7L1_85361573_WIF1_65471634_ranked_0.pdbTCF7L18536157285361573ENST00000286574WIF1chr1265471634-
MSNFVAAASAAGPQAGGRGAGPGRAGRGRLGAPRAAAPARGPTMPQLGGGGGGGGGGSGGGGGSSAGAAGGGDDLGANDELIPFQDEGGE
EQEPSSDSASAQRDLDEVKSSLVNESENQSSSSDSEAERRPQPVRDTFQKPRDYFAEVRRPQDSAFFKGPPYPGYPFLMIPDLSSPYLSN
GPLSPGGARTAEYFYEFLSLRSLDKGIMADPTVNVPLLGTVPHKASVVQVGFPCLGKQDGVAAFEVDVIVMNSEGNTILQTPQNAIFFKT
CQQAECPGGCRNGGFCNERRICECPDGFHGPHCEKALCTPRCMNGGLCVTPGFCICPPGFYGVNCDKANCSTTCFNGGTCFYPGKCICPP
GLEGEQCEISKCPQPCRNGGKCIGKSKCKCSKGYQGDLCSKPVCEPGCGAHGTCHEPNKCQCQEGWHGRHCNKRYEASLIHALRPAGAQL
473


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pLDDT score distribution

check button pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
TCF7L1_pLDDT.png
all structure
all structure
WIF1_pLDDT.png
all structure
all structure

check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
all structure


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Ramachandran Plot of Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.
Fusion AA seq ID in FusionPDB and their Ramachandran plots

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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
TCF7L1
WIF1all structure


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 TCF7L1-WIF1


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 TCF7L1-WIF1


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
HgeneTCF7L1C0040136Thyroid Neoplasm1CTD_human
HgeneTCF7L1C0151468Thyroid Gland Follicular Adenoma1CTD_human
HgeneTCF7L1C0549473Thyroid carcinoma1CTD_human
HgeneTCF7L1C0857439Pituitary hormone deficiency1GENOMICS_ENGLAND
TgeneWIF1C0009402Colorectal Carcinoma1CTD_human
TgeneWIF1C0009404Colorectal Neoplasms1CTD_human
TgeneWIF1C0014859Esophageal Neoplasms1CTD_human
TgeneWIF1C0024623Malignant neoplasm of stomach1CTD_human
TgeneWIF1C0027439Nasopharyngeal Neoplasms1CTD_human
TgeneWIF1C0038356Stomach Neoplasms1CTD_human
TgeneWIF1C0238301Cancer of Nasopharynx1CTD_human
TgeneWIF1C0546837Malignant neoplasm of esophagus1CTD_human
TgeneWIF1C1708349Hereditary Diffuse Gastric Cancer1CTD_human