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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:TBC1D22A-AP3D1

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TBC1D22A-AP3D1
FusionPDB ID: 89282
FusionGDB2.0 ID: 89282
HgeneTgene
Gene symbol

TBC1D22A

AP3D1

Gene ID

25771

8943

Gene nameTBC1 domain family member 22Aadaptor related protein complex 3 subunit delta 1
SynonymsC22orf4|HSC79E021ADTD|HPS10|hBLVR
Cytomap

22q13.31

19p13.3

Type of geneprotein-codingprotein-coding
DescriptionTBC1 domain family member 22Aputative GTPase activatorAP-3 complex subunit delta-1AP-3 complex delta subunit, partial CDSadapter-related protein complex 3 subunit delta-1adaptor related protein complex 3 delta 1 subunitdelta adaptinsubunit of putative vesicle coat adaptor complex AP-3
Modification date2020031320200313
UniProtAcc.

O14617

Ensembl transtripts involved in fusion geneENST idsENST00000337137, ENST00000355704, 
ENST00000406733, ENST00000407381, 
ENST00000380995, ENST00000472791, 
ENST00000590683, ENST00000345016, 
ENST00000355272, ENST00000356926, 
ENST00000350812, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score34 X 18 X 14=856812 X 12 X 8=1152
# samples 3713
** MAII scorelog2(37/8568*10)=-4.53336130423394
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/1152*10)=-3.14755718841386
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: TBC1D22A [Title/Abstract] AND AP3D1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TBC1D22A(47433094)-AP3D1(2102267), # samples:3
Anticipated loss of major functional domain due to fusion event.TBC1D22A-AP3D1 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.
TBC1D22A-AP3D1 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.
TBC1D22A-AP3D1 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.
TBC1D22A-AP3D1 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.
TBC1D22A-AP3D1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
TBC1D22A-AP3D1 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

check buttonFusion gene breakpoints across TBC1D22A (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 AP3D1 (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
ChimerDB4UCSTCGA-NA-A4R1-01ATBC1D22Achr22

47433094

-AP3D1chr19

2102267

-
ChimerDB4UCSTCGA-NA-A4R1-01ATBC1D22Achr22

47433094

+AP3D1chr19

2102267

-
ChimerDB4UCSTCGA-NA-A4R1TBC1D22Achr22

47433094

+AP3D1chr19

2102267

-


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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)
ENST00000337137TBC1D22Achr2247433094+ENST00000350812AP3D1chr192102267-276814951661590474
ENST00000407381TBC1D22Achr2247433094+ENST00000350812AP3D1chr192102267-254012671151362415
ENST00000355704TBC1D22Achr2247433094+ENST00000350812AP3D1chr192102267-247412011061296396
ENST00000406733TBC1D22Achr2247433094+ENST00000350812AP3D1chr192102267-284915762411671476

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
ENST00000337137ENST00000350812TBC1D22Achr2247433094+AP3D1chr192102267-0.0056169670.994383
ENST00000407381ENST00000350812TBC1D22Achr2247433094+AP3D1chr192102267-0.0025124130.99748755
ENST00000355704ENST00000350812TBC1D22Achr2247433094+AP3D1chr192102267-0.0039061090.9960939
ENST00000406733ENST00000350812TBC1D22Achr2247433094+AP3D1chr192102267-0.0066905380.9933095

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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

>89282_89282_1_TBC1D22A-AP3D1_TBC1D22A_chr22_47433094_ENST00000337137_AP3D1_chr19_2102267_ENST00000350812_length(amino acids)=474AA_BP=442
MASDGARKQFWKRSNSKLPGSIQHVYGAQHPPFDPLLHGTLLRSTAKMPTTPVKAKRVSTFQEFESNTSDAWDAGEDDDELLAMAAESLN
SEVVMETANRVLRNHSQRQGRPTLQEGPGLQQKPRPEAEPPSPPSGDLRLVKSVSESHTSCPAESASDAAPLQRSQSLPHSATVTLGGTS
DPSTLSSSALSEREASRLDKFKQLLAGPNTDLEELRRLSWSGIPKPVRPMTWKLLSGYLPANVDRRPATLQRKQKEYFAFIEHYYDSRND
EVHQDTYRQIHIDIPRMSPEALILQPKVTEIFERILFIWAIRHPASGYVQGINDLVTPFFVVFICEYIEAEEVDTVDVSGVPAEVLCNIE
ADTYWCMSKLLDGIQDNYTFAQPGIQMKVKMLEELVSRIDEQVHRHLDQHEVRYLQFAFRWMNNLLMREVPLRCTIRLWDTYQGENSVSV

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>89282_89282_2_TBC1D22A-AP3D1_TBC1D22A_chr22_47433094_ENST00000355704_AP3D1_chr19_2102267_ENST00000350812_length(amino acids)=396AA_BP=364
MASDGARKQFWKRSNSKLPGSLLRSTAKMPTTPVKAKRVSTFQEFESNTSDAWDAGEDDDELLAMAAESLNSEVVMETANRVLRNHSQRQ
GRPTLQEGPGLQQKPRPEAEPPSPPSGDLRLVKSVSESHTSCPAEELRRLSWSGIPKPVRPMTWKLLSGYLPANVDRRPATLQRKQKEYF
AFIEHYYDSRNDEVHQDTYRQIHIDIPRMSPEALILQPKVTEIFERILFIWAIRHPASGYVQGINDLVTPFFVVFICEYIEAEEVDTVDV
SGVPAEVLCNIEADTYWCMSKLLDGIQDNYTFAQPGIQMKVKMLEELVSRIDEQVHRHLDQHEVRYLQFAFRWMNNLLMREVPLRCTIRL

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

>89282_89282_3_TBC1D22A-AP3D1_TBC1D22A_chr22_47433094_ENST00000406733_AP3D1_chr19_2102267_ENST00000350812_length(amino acids)=476AA_BP=444
MAPPGWGKTRLAVLGSRDSSGVSIQHVYGAQHPPFDPLLHGTLLRSTAKMPTTPVKAKRVSTFQEFESNTSDAWDAGEDDDELLAMAAES
LNSEVVMETANRVLRNHSQRQGRPTLQEGPGLQQKPRPEAEPPSPPSGDLRLVKSVSESHTSCPAESASDAAPLQRSQSLPHSATVTLGG
TSDPSTLSSSALSEREASRLDKFKQLLAGPNTDLEELRRLSWSGIPKPVRPMTWKLLSGYLPANVDRRPATLQRKQKEYFAFIEHYYDSR
NDEVHQDTYRQIHIDIPRMSPEALILQPKVTEIFERILFIWAIRHPASGYVQGINDLVTPFFVVFICEYIEAEEVDTVDVSGVPAEVLCN
IEADTYWCMSKLLDGIQDNYTFAQPGIQMKVKMLEELVSRIDEQVHRHLDQHEVRYLQFAFRWMNNLLMREVPLRCTIRLWDTYQGENSV

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

>89282_89282_4_TBC1D22A-AP3D1_TBC1D22A_chr22_47433094_ENST00000407381_AP3D1_chr19_2102267_ENST00000350812_length(amino acids)=415AA_BP=383
MASDGARKQFWKRSNSKLPGSIQHVYGAQHPPFDPLLHGTLLRSTAKMPTTPVKAKRVSTFQEFESNTSDAWDAGEDDDELLAMAAESLN
SEVVMETANRVLRNHSQRQGRPTLQEGPGLQQKPRPEAEPPSPPSGDLRLVKSVSESHTSCPAEELRRLSWSGIPKPVRPMTWKLLSGYL
PANVDRRPATLQRKQKEYFAFIEHYYDSRNDEVHQDTYRQIHIDIPRMSPEALILQPKVTEIFERILFIWAIRHPASGYVQGINDLVTPF
FVVFICEYIEAEEVDTVDVSGVPAEVLCNIEADTYWCMSKLLDGIQDNYTFAQPGIQMKVKMLEELVSRIDEQVHRHLDQHEVRYLQFAF

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

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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/chr22:47433094/chr19:2102267)
- 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
.AP3D1

O14617

FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.FUNCTION: Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. Involved in process of CD8+ T-cell and NK cell degranulation (PubMed:26744459). In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals (By similarity). {ECO:0000250|UniProtKB:O54774, ECO:0000269|PubMed:26744459}.

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
HgeneTBC1D22Achr22:47433094chr19:2102267ENST00000337137+1113222_446443.0518.0DomainRab-GAP TBC

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneTBC1D22Achr22:47433094chr19:2102267ENST00000355704+911222_446365.0440.0DomainRab-GAP TBC
HgeneTBC1D22Achr22:47433094chr19:2102267ENST00000380995+19222_4460325.0DomainRab-GAP TBC
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830659_6791122.01154.0Coiled coilOntology_term=ECO:0000255
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830725_7561122.01154.0Coiled coilOntology_term=ECO:0000255
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830845_8691122.01154.0Coiled coilOntology_term=ECO:0000255
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032659_6791184.01216.0Coiled coilOntology_term=ECO:0000255
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032725_7561184.01216.0Coiled coilOntology_term=ECO:0000255
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032845_8691184.01216.0Coiled coilOntology_term=ECO:0000255
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830828_8931122.01154.0Compositional biasNote=Lys-rich
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032828_8931184.01216.0Compositional biasNote=Lys-rich
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830142_1791122.01154.0RepeatNote=HEAT 3
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830180_2161122.01154.0RepeatNote=HEAT 4
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830254_2921122.01154.0RepeatNote=HEAT 5
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830299_3361122.01154.0RepeatNote=HEAT 6
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830338_3731122.01154.0RepeatNote=HEAT 7
TgeneAP3D1chr22:47433094chr19:2102267ENST00000345016283034_711122.01154.0RepeatNote=HEAT 1
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830375_4091122.01154.0RepeatNote=HEAT 8
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830431_4681122.01154.0RepeatNote=HEAT 9
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830497_5351122.01154.0RepeatNote=HEAT 10
TgeneAP3D1chr22:47433094chr19:2102267ENST000003450162830548_5851122.01154.0RepeatNote=HEAT 11
TgeneAP3D1chr22:47433094chr19:2102267ENST00000345016283077_1141122.01154.0RepeatNote=HEAT 2
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032142_1791184.01216.0RepeatNote=HEAT 3
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032180_2161184.01216.0RepeatNote=HEAT 4
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032254_2921184.01216.0RepeatNote=HEAT 5
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032299_3361184.01216.0RepeatNote=HEAT 6
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032338_3731184.01216.0RepeatNote=HEAT 7
TgeneAP3D1chr22:47433094chr19:2102267ENST00000355272303234_711184.01216.0RepeatNote=HEAT 1
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032375_4091184.01216.0RepeatNote=HEAT 8
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032431_4681184.01216.0RepeatNote=HEAT 9
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032497_5351184.01216.0RepeatNote=HEAT 10
TgeneAP3D1chr22:47433094chr19:2102267ENST000003552723032548_5851184.01216.0RepeatNote=HEAT 11
TgeneAP3D1chr22:47433094chr19:2102267ENST00000355272303277_1141184.01216.0RepeatNote=HEAT 2


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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 >>>998_TBC1D22A_47433094_AP3D1_2102267_998_TBC1D22A_47433094_AP3D1_2102267_ranked_0.pdbTBC1D22A4743309447433094ENST00000350812AP3D1chr192102267-
MAPPGWGKTRLAVLGSRDSSGVSIQHVYGAQHPPFDPLLHGTLLRSTAKMPTTPVKAKRVSTFQEFESNTSDAWDAGEDDDELLAMAAES
LNSEVVMETANRVLRNHSQRQGRPTLQEGPGLQQKPRPEAEPPSPPSGDLRLVKSVSESHTSCPAESASDAAPLQRSQSLPHSATVTLGG
TSDPSTLSSSALSEREASRLDKFKQLLAGPNTDLEELRRLSWSGIPKPVRPMTWKLLSGYLPANVDRRPATLQRKQKEYFAFIEHYYDSR
NDEVHQDTYRQIHIDIPRMSPEALILQPKVTEIFERILFIWAIRHPASGYVQGINDLVTPFFVVFICEYIEAEEVDTVDVSGVPAEVLCN
IEADTYWCMSKLLDGIQDNYTFAQPGIQMKVKMLEELVSRIDEQVHRHLDQHEVRYLQFAFRWMNNLLMREVPLRCTIRLWDTYQGENSV
476


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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.
TBC1D22A_pLDDT.png
all structure
all structure
AP3D1_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
TBC1D22A
AP3D1


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 TBC1D22A-AP3D1


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 TBC1D22A-AP3D1


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