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Center for Computational Systems Medicine level3
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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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Potential Active Site Information

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Potentially Interacting Small Molecules through Virtual Screening

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Biochemical Features of Small Molecules with ADME

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Drug Toxicity Information

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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:CDKN2D-WDFY2

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CDKN2D-WDFY2
FusionPDB ID: 15421
FusionGDB2.0 ID: 15421
HgeneTgene
Gene symbol

CDKN2D

WDFY2

Gene ID

1032

115825

Gene namecyclin dependent kinase inhibitor 2DWD repeat and FYVE domain containing 2
SynonymsINK4D|p19|p19-INK4DPROF|WDF2|ZFYVE22
Cytomap

19p13.2

13q14.3

Type of geneprotein-codingprotein-coding
Descriptioncyclin-dependent kinase 4 inhibitor DCDK inhibitor p19INK4dcell cycle inhibitor, Nur77 associating proteincyclin-dependent kinase 4 inhibitor D p19cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)inhibitor of cyclin-dependent kinase 4dWD repeat and FYVE domain-containing protein 2WD40 and FYVE domain containing 2WD40- and FYVE domain-containing protein 2propeller-FYVE proteinzinc finger FYVE domain-containing protein 22
Modification date2020031320200313
UniProtAcc

P55273

Q96P53

Ensembl transtripts involved in fusion geneENST idsENST00000335766, ENST00000393599, 
ENST00000460145, ENST00000298125, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 4 X 2=168 X 6 X 8=384
# samples 38
** MAII scorelog2(3/16*10)=0.906890595608518
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(8/384*10)=-2.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: CDKN2D [Title/Abstract] AND WDFY2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)
Anticipated loss of major functional domain due to fusion event.CDKN2D-WDFY2 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneCDKN2D

GO:0000079

regulation of cyclin-dependent protein serine/threonine kinase activity

8741839

HgeneCDKN2D

GO:0000082

G1/S transition of mitotic cell cycle

10208428

HgeneCDKN2D

GO:0007050

cell cycle arrest

10208428

HgeneCDKN2D

GO:0008285

negative regulation of cell proliferation

10208428

HgeneCDKN2D

GO:0030308

negative regulation of cell growth

10208428

HgeneCDKN2D

GO:0042326

negative regulation of phosphorylation

10208428

TgeneWDFY2

GO:0001934

positive regulation of protein phosphorylation

17313651


check buttonFusion gene breakpoints across CDKN2D (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonFusion gene breakpoints across WDFY2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.


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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
ChimerKB3..CDKN2Dchr19

10677733

-WDFY2chr13

52249305

+
ChimerKB3..CDKN2Dchr19

10679188

-WDFY2chr13

52249305

+


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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)
ENST00000335766CDKN2Dchr1910679188-ENST00000298125WDFY2chr1352249305+3533269431266407

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

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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

>15421_15421_1_CDKN2D-WDFY2_CDKN2D_chr19_10679188_ENST00000335766_WDFY2_chr13_52249305_ENST00000298125_length(amino acids)=407AA_BP=75
MAAASAAAAAQAQSRPRPARRREGRQCRHAAGGGSRRRPAEWGGGPGRRAGGAPPSAPGAGASRRPQPLRQDGAAAPCSCMSFNPETRRL
SIGLDNGTISEFILSEDYNKMTPVKNYQAHQSRVTMILFVLELEWVLSTGQDKQFAWHCSESGQRLGGYRTSAVASGLQFDVETRHVFIG
DHSGQVTILKLEQENCTLVTTFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWDIGGRKGTAIELQGHNDRVQALSYAQHTRQLISCGGD
GGIVVWNMDVERQETPEWLDSDSCQKCDQPFFWNFKQMWDSKKIGLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRVCDSCHEAITD

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

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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/chr19:/chr13:)
- 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
CDKN2D

P55273

WDFY2

Q96P53

FUNCTION: Interacts strongly with CDK4 and CDK6 and inhibits them. {ECO:0000269|PubMed:7739548, ECO:0000269|PubMed:8741839}.FUNCTION: Acts in an adapter protein-like fashion to mediate the interaction between the kinase PRKCZ and its substrate VAMP2 and increases the PRKCZ-dependent phosphorylation of VAMP2 (PubMed:17313651). Positively regulates adipocyte differentiation, by facilitating the phosphorylation and thus inactivation of the anti-adipogenetic transcription factor FOXO1 by the kinase AKT1 (PubMed:18388859). Plays a role in endosomal control of AKT2 signaling; required for insulin-stimulated AKT2 phosphorylation and glucose uptake and insulin-stimulated phosphorylation of AKT2 substrates (By similarity). Participates in transferrin receptor endocytosis (PubMed:16873553). {ECO:0000250|UniProtKB:Q8BUB4, ECO:0000269|PubMed:16873553, ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:18388859}.

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

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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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 (170) >>>170.pdbFusion protein BP residue: 75
CIF file (170) >>>170.cif
CDKN2Dchr1910679188-WDFY2chr1352249305+
MAAASAAAAAQAQSRPRPARRREGRQCRHAAGGGSRRRPAEWGGGPGRRA
GGAPPSAPGAGASRRPQPLRQDGAAAPCSCMSFNPETRRLSIGLDNGTIS
EFILSEDYNKMTPVKNYQAHQSRVTMILFVLELEWVLSTGQDKQFAWHCS
ESGQRLGGYRTSAVASGLQFDVETRHVFIGDHSGQVTILKLEQENCTLVT
TFRGHTGGVTALCWDPVQRVLFSGSSDHSVIMWDIGGRKGTAIELQGHND
RVQALSYAQHTRQLISCGGDGGIVVWNMDVERQETPEWLDSDSCQKCDQP
FFWNFKQMWDSKKIGLRQHHCRKCGKAVCGKCSSKRSSIPLMGFEFEVRV
CDSCHEAITDEERAPTATFHDSKHNIVHVHFDATRGWLLTSGTDKVIKLW
407
3D view using mol* of 170 (AA BP:75)


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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.
WDFY2_pLDDT.png
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.
CDKN2D_WDFY2_170_PAE.png (AA BP:75)
all structure
CDKN2D_WDFY2_170_pLDDT.png (AA BP:75)
all structure
CDKN2D_WDFY2_170_pLDDT_and_active_sites.png (AA BP:75)
all structure
CDKN2D_WDFY2_170_violinplot.png (AA BP:75)
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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Potential Active Site Information


check button The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.
Fusion AA seq ID in FusionPDBSite scoreSizeD scoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues
1701.0341741.065330.9950.4480.7220.9720.6490.9470.6851.216Chain A: 6,7,8,9,10,11,12,13,14,16,171,174,176,178
,188,199,200,202,214,217,219,233,234,235,236,237,2
40,241,242

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Potentially Interacting Small Molecules through Virtual Screening


check button The FDA-approved small molecule library molecules were subjected to virtual screening using the Glide.
Fusion AA seq ID in FusionPDBZINC IDDrugBank IDDrug nameDocking scoreGlide gscore

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check button Drug information from DrugBank of the top 20 interacting small molecules.
ZINC IDDrugBank IDDrug nameDrug typeSMILESDrug group

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Biochemical Features of Small Molecules


check button ADME (Absorption, Distribution, Metabolism, and Excretion) of drugs using QikProp(v3.9)
ZINC IDmol_MWdipoleSASAFOSAFISAPISAWPSAvolumedonorHBaccptHBIPHuman Oral AbsorptionPercent Human Oral AbsorptionRule Of FiveRule Of Three


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Drug Toxicity Information


check button Toxicity information of individual drugs using eToxPred
ZINC IDSmileSurface AccessibilityToxicity


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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
CDKN2DCDK4, TBC1D17, CDK6, BRCA1, APP, NR4A1, NR4A2, IKZF3, HSD17B14, C1orf94, INCA1, QKI, DMRTB1, TSG101, SH3GLB2, FHL3, LSM3, TEX11, NMI, SH3GLB1, CTBP1, BTG1, ZBTB32, GSC2, LNX1, YPEL3, NDUFB7, PICK1, VGLL1, NME4, MEOX2, CCND3, EIF4G1, GORASP2, NR4A3, PRDX5, PSMA1, THAP1, UQCC2, SDCBP, GLYR1, MTF2, GATAD2B, DDIT4L, LONRF1, FAM154A, FAM86C1, REL, CGGBP1, PRIMPOL, MSS51, KRT75, TSGA10IP, ZNF620, FAM228A, ZNF396, RUFY4, NIF3L1, ZNF774, TCTEX1D2, C5orf49, ZNF688, MEI4, CDKN2C, CDKN2A, AK2, CDKN2B, CDC37, MAPK1, DDX58, MTFP1, RARRES2, CEP19, MRPL30, PMCH, CDC42BPA, PTER, RBM12, HIST1H1A,


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
CDKN2Dall structure
WDFY2all 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 CDKN2D-WDFY2


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 CDKN2D-WDFY2


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
HgeneCDKN2DC0024623Malignant neoplasm of stomach1CTD_human
HgeneCDKN2DC0038356Stomach Neoplasms1CTD_human
HgeneCDKN2DC1708349Hereditary Diffuse Gastric Cancer1CTD_human