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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:ZCCHC8-PTPN12

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZCCHC8-PTPN12
FusionPDB ID: 100721
FusionGDB2.0 ID: 100721
HgeneTgene
Gene symbol

ZCCHC8

PTPN12

Gene ID

55596

5782

Gene namezinc finger CCHC-type containing 8protein tyrosine phosphatase non-receptor type 12
SynonymsPFBMFT5PTP-PEST|PTPG1
Cytomap

12q24.31

7q11.23

Type of geneprotein-codingprotein-coding
Descriptionzinc finger CCHC domain-containing protein 8TRAMP-like complex RNA-binding factor ZCCHC8zinc finger, CCHC domain containing 8tyrosine-protein phosphatase non-receptor type 12protein-tyrosine phosphatase G1
Modification date2020031320200329
UniProtAcc

Q6NZY4

.
Ensembl transtripts involved in fusion geneENST idsENST00000336229, ENST00000536306, 
ENST00000543897, ENST00000538116, 
ENST00000248594, ENST00000415482, 
ENST00000435495, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 8=28814 X 11 X 7=1078
# samples 914
** MAII scorelog2(9/288*10)=-1.67807190511264
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(14/1078*10)=-2.94485844580754
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: ZCCHC8 [Title/Abstract] AND PTPN12 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZCCHC8(122964737)-PTPN12(77261665), # samples:3
Anticipated loss of major functional domain due to fusion event.ZCCHC8-PTPN12 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.
ZCCHC8-PTPN12 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.
ZCCHC8-PTPN12 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.
ZCCHC8-PTPN12 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.
ZCCHC8-PTPN12 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
ZCCHC8-PTPN12 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
ZCCHC8-PTPN12 seems lost the major protein functional domain in Tgene 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
TgenePTPN12

GO:0006470

protein dephosphorylation

27134172

TgenePTPN12

GO:0035335

peptidyl-tyrosine dephosphorylation

27134172


check buttonFusion gene breakpoints across ZCCHC8 (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 PTPN12 (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
ChimerDB4MESOTCGA-3H-AB3M-01AZCCHC8chr12

122964737

-PTPN12chr7

77261665

+
ChimerDB4MESOTCGA-3H-AB3MZCCHC8chr12

122964737

-PTPN12chr7

77261665

+


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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)
ENST00000536306ZCCHC8chr12122964737-ENST00000248594PTPN12chr777261665+243112938671358163
ENST00000536306ZCCHC8chr12122964737-ENST00000415482PTPN12chr777261665+164012938671358163
ENST00000536306ZCCHC8chr12122964737-ENST00000435495PTPN12chr777261665+198012938671358163
ENST00000543897ZCCHC8chr12122964737-ENST00000248594PTPN12chr777261665+3920278223562847163
ENST00000543897ZCCHC8chr12122964737-ENST00000415482PTPN12chr777261665+3129278223562847163
ENST00000543897ZCCHC8chr12122964737-ENST00000435495PTPN12chr777261665+3469278223562847163

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
ENST00000536306ENST00000248594ZCCHC8chr12122964737-PTPN12chr777261665+0.0037368190.9962632
ENST00000536306ENST00000415482ZCCHC8chr12122964737-PTPN12chr777261665+0.005517080.99448293
ENST00000536306ENST00000435495ZCCHC8chr12122964737-PTPN12chr777261665+0.0041753380.9958247
ENST00000543897ENST00000248594ZCCHC8chr12122964737-PTPN12chr777261665+0.0010519570.99894804
ENST00000543897ENST00000415482ZCCHC8chr12122964737-PTPN12chr777261665+0.0016202760.9983797
ENST00000543897ENST00000435495ZCCHC8chr12122964737-PTPN12chr777261665+0.001396450.9986035

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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

>100721_100721_1_ZCCHC8-PTPN12_ZCCHC8_chr12_122964737_ENST00000536306_PTPN12_chr7_77261665_ENST00000248594_length(amino acids)=163AA_BP=142
MKDCPMPRNAARISEKRKEYMDACGEANNQNFQQRYHAEEVEERFGRFKPGVISEELQDALGVTDKSLPPFIYRMRQLGYPPGWLKEAEL

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

>100721_100721_2_ZCCHC8-PTPN12_ZCCHC8_chr12_122964737_ENST00000536306_PTPN12_chr7_77261665_ENST00000415482_length(amino acids)=163AA_BP=142
MKDCPMPRNAARISEKRKEYMDACGEANNQNFQQRYHAEEVEERFGRFKPGVISEELQDALGVTDKSLPPFIYRMRQLGYPPGWLKEAEL

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

>100721_100721_3_ZCCHC8-PTPN12_ZCCHC8_chr12_122964737_ENST00000536306_PTPN12_chr7_77261665_ENST00000435495_length(amino acids)=163AA_BP=142
MKDCPMPRNAARISEKRKEYMDACGEANNQNFQQRYHAEEVEERFGRFKPGVISEELQDALGVTDKSLPPFIYRMRQLGYPPGWLKEAEL

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

>100721_100721_4_ZCCHC8-PTPN12_ZCCHC8_chr12_122964737_ENST00000543897_PTPN12_chr7_77261665_ENST00000248594_length(amino acids)=163AA_BP=142
MKDCPMPRNAARISEKRKEYMDACGEANNQNFQQRYHAEEVEERFGRFKPGVISEELQDALGVTDKSLPPFIYRMRQLGYPPGWLKEAEL

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

>100721_100721_5_ZCCHC8-PTPN12_ZCCHC8_chr12_122964737_ENST00000543897_PTPN12_chr7_77261665_ENST00000415482_length(amino acids)=163AA_BP=142
MKDCPMPRNAARISEKRKEYMDACGEANNQNFQQRYHAEEVEERFGRFKPGVISEELQDALGVTDKSLPPFIYRMRQLGYPPGWLKEAEL

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

>100721_100721_6_ZCCHC8-PTPN12_ZCCHC8_chr12_122964737_ENST00000543897_PTPN12_chr7_77261665_ENST00000435495_length(amino acids)=163AA_BP=142
MKDCPMPRNAARISEKRKEYMDACGEANNQNFQQRYHAEEVEERFGRFKPGVISEELQDALGVTDKSLPPFIYRMRQLGYPPGWLKEAEL

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

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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/chr12:122964737/chr7:77261665)
- 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
ZCCHC8

Q6NZY4

.
FUNCTION: Scaffolding subunit of the trimeric nuclear exosome targeting (NEXT) complex that is involved in the surveillance and turnover of aberrant transcripts and non-coding RNAs (PubMed:27871484). NEXT functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. May be involved in pre-mRNA splicing (Probable). It is required for 3'-end maturation of telomerase RNA component (TERC), TERC 3'-end targeting to the nuclear RNA exosome, and for telomerase function (PubMed:31488579). {ECO:0000269|PubMed:27871484, ECO:0000269|PubMed:31488579, ECO:0000305|PubMed:16263084}.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.

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
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000336229-111445_80380.0708.0Coiled coilOntology_term=ECO:0000255
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000536306-91245_80142.0470.0Coiled coilOntology_term=ECO:0000255
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000543897-91245_80142.0470.0Coiled coilOntology_term=ECO:0000255
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000336229-1114286_299380.0708.0RegionRBM7 binding
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000336229-1114309_324380.0708.0RegionRBM7 binding
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000336229-1114227_244380.0708.0Zinc fingerCCHC-type

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000336229-1114516_539380.0708.0Coiled coilOntology_term=ECO:0000255
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000536306-912516_539142.0470.0Coiled coilOntology_term=ECO:0000255
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000543897-912516_539142.0470.0Coiled coilOntology_term=ECO:0000255
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000336229-1114466_501380.0708.0Compositional biasPro-rich
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000536306-912466_501142.0470.0Compositional biasPro-rich
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000543897-912466_501142.0470.0Compositional biasPro-rich
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000336229-1114659_707380.0708.0RegionMTREX binding
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000536306-912286_299142.0470.0RegionRBM7 binding
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000536306-912309_324142.0470.0RegionRBM7 binding
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000536306-912659_707142.0470.0RegionMTREX binding
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000543897-912286_299142.0470.0RegionRBM7 binding
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000543897-912309_324142.0470.0RegionRBM7 binding
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000543897-912659_707142.0470.0RegionMTREX binding
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000536306-912227_244142.0470.0Zinc fingerCCHC-type
HgeneZCCHC8chr12:122964737chr7:77261665ENST00000543897-912227_244142.0470.0Zinc fingerCCHC-type
TgenePTPN12chr12:122964737chr7:77261665ENST00000248594121828_293665.3333333333334781.0DomainTyrosine-protein phosphatase
TgenePTPN12chr12:122964737chr7:77261665ENST00000435495111728_293535.3333333333334651.0DomainTyrosine-protein phosphatase
TgenePTPN12chr12:122964737chr7:77261665ENST000002485941218231_237665.3333333333334781.0RegionSubstrate binding
TgenePTPN12chr12:122964737chr7:77261665ENST00000248594121863_67665.3333333333334781.0RegionSubstrate binding
TgenePTPN12chr12:122964737chr7:77261665ENST000004354951117231_237535.3333333333334651.0RegionSubstrate binding
TgenePTPN12chr12:122964737chr7:77261665ENST00000435495111763_67535.3333333333334651.0RegionSubstrate binding


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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 >>>158_ZCCHC8_122964737_PTPN12_77261665_ranked_0.pdbZCCHC8122964737122964737ENST00000435495PTPN12chr777261665+
MKDCPMPRNAARISEKRKEYMDACGEANNQNFQQRYHAEEVEERFGRFKPGVISEELQDALGVTDKSLPPFIYRMRQLGYPPGWLKEAEL
163


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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.
ZCCHC8_pLDDT.png
all structure
all structure
PTPN12_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
ZCCHC8BRCA1, PPP2R1A, PPP2R2D, PPP2R2B, SIRT7, SKIV2L2, RBM7, CUL3, APP, U2AF1, THOC6, THOC1, U2AF2, USP7, PSMC2, MICB, TXNDC9, PSMA1, PSMC5, USP28, ZC3H15, PSMD13, PSMC4, PSMB6, PRPF40A, SOX2, CLK2, YWHAB, RPA3, RPA2, RPA1, DROSHA, RNF2, BMI1, RBM11, EXOSC3, EXOSC7, EXOSC8, RBM4B, LUC7L, PPP2R2C, INPPL1, NTRK1, XPO1, GBA, RET, SNCA, NCBP2, Osgep, Ncbp2, Tbck, ZC3H18, C1D, HNRNPF, EXOSC1, PPP2R2A, PYHIN1, CHD3, CHD4, RIOK1, ESR2, EZH2, CAT, RC3H2, ATG16L1, ACTC1, MYC, MECOM, AGRN, HIST1H4A, OASL, SUN2, SNRNP70, FUS, EWSR1, TAF15, MATR3, ITFG1, PLEKHA4, HNRNPD, MIB1, ESR1, EXOSC10, TRIM24, SLIRP, MKI67, EXOSC5, MPHOSPH6, EXOSC6, EXOSC2, EXOSC9, DIS3L, EXOSC4, EIF4E2, GIGYF2, HBS1L, ASH2L, CD3EAP, COX4I1, CYP2C9, DHX40, POLR1E, POLR2C, TERF2IP, NAA40, KCTD6, PABPC5, MAD2L1, KPNA1, HNRNPUL2, SNRPC, SRSF7, ORF10,


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
ZCCHC8all structure
PTPN12


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
TgenePTPN12chr12:122964737chr7:77261665ENST000002485941218345_438665.3333333333334781.0TGFB1I1
TgenePTPN12chr12:122964737chr7:77261665ENST000004354951117345_438535.3333333333334651.0TGFB1I1


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Related Drugs to ZCCHC8-PTPN12


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 ZCCHC8-PTPN12


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
HgeneZCCHC8C0020796Profound Mental Retardation1CTD_human
HgeneZCCHC8C0025363Mental Retardation, Psychosocial1CTD_human
HgeneZCCHC8C0917816Mental deficiency1CTD_human
HgeneZCCHC8C3714756Intellectual Disability1CTD_human