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Center for Computational Systems Medicine
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FusionGeneSummary

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FusionProtFeature

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FusionGeneSequence

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FusionGenePPI

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RelatedDrugs

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RelatedDiseases

Fusion gene ID: 40987

FusionGeneSummary for USP15_TPH2

check button Fusion gene summary
Fusion gene informationFusion gene name: USP15_TPH2
Fusion gene ID: 40987
HgeneTgene
Gene symbol

USP15

TPH2

Gene ID

9958

121278

Gene nameubiquitin specific peptidase 15tryptophan hydroxylase 2
SynonymsUNPH-2|UNPH4ADHD7|NTPH
Cytomap

12q14.1

12q21.1

Type of geneprotein-codingprotein-coding
Descriptionubiquitin carboxyl-terminal hydrolase 15deubiquitinating enzyme 15ubiquitin thioesterase 15ubiquitin thiolesterase 15ubiquitin-specific-processing protease 15tryptophan 5-hydroxylase 2neuronal tryptophan hydroxylasetryptophan 5-monooxygenase 2
Modification date2018052320180522
UniProtAcc

Q9Y4E8

Q8IWU9

Ensembl transtripts involved in fusion geneENST00000353364, ENST00000280377, 
ENST00000393654, ENST00000550632, 
ENST00000312635, 
ENST00000333850, 
ENST00000546576, 
Fusion gene scores* DoF score13 X 7 X 6=5465 X 4 X 3=60
# samples 134
** MAII scorelog2(13/546*10)=-2.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/60*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: USP15 [Title/Abstract] AND TPH2 [Title/Abstract] AND fusion [Title/Abstract]

Functional or gene categories assigned by FusionGDB annotation
* 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
HgeneUSP15

GO:0007179

transforming growth factor beta receptor signaling pathway

21947082

HgeneUSP15

GO:0016579

protein deubiquitination

16005295|22344298|27368102

HgeneUSP15

GO:0030509

BMP signaling pathway

21947082

HgeneUSP15

GO:0035520

monoubiquitinated protein deubiquitination

21947082

HgeneUSP15

GO:0035616

histone H2B conserved C-terminal lysine deubiquitination

24526689


check button Fusion gene information from three resources
(ChiTars (NAR, 2018), tumorfusions (NAR, 2018), Gao et al. (Cell, 2018))
* 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.
Data typeSourceCancer typeSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
TCGALDSARCTCGA-DX-A1KU-01AUSP15chr12

62699839

+TPH2chr12

72499428

+
* LD: Li Ding group's fusion gene list
  RV: Roel Verhaak group's fusion gene list
  ChiTaRs fusion database

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
intron-intronENST00000353364ENST00000333850USP15chr12

62699839

+TPH2chr12

72499428

+
intron-intronENST00000353364ENST00000546576USP15chr12

62699839

+TPH2chr12

72499428

+
intron-intronENST00000280377ENST00000333850USP15chr12

62699839

+TPH2chr12

72499428

+
intron-intronENST00000280377ENST00000546576USP15chr12

62699839

+TPH2chr12

72499428

+
intron-intronENST00000393654ENST00000333850USP15chr12

62699839

+TPH2chr12

72499428

+
intron-intronENST00000393654ENST00000546576USP15chr12

62699839

+TPH2chr12

72499428

+
intron-intronENST00000550632ENST00000333850USP15chr12

62699839

+TPH2chr12

72499428

+
intron-intronENST00000550632ENST00000546576USP15chr12

62699839

+TPH2chr12

72499428

+
intron-intronENST00000312635ENST00000333850USP15chr12

62699839

+TPH2chr12

72499428

+
intron-intronENST00000312635ENST00000546576USP15chr12

62699839

+TPH2chr12

72499428

+

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FusionProtFeatures for USP15_TPH2


check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
USP15

Q9Y4E8

TPH2

Q8IWU9

Hydrolase that removes conjugated ubiquitin from targetproteins and regulates various pathways such as the TGF-betareceptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways(PubMed:21947082, PubMed:22344298, PubMed:24852371,PubMed:16005295, PubMed:17318178, PubMed:19826004,PubMed:19576224). Acts as a key regulator of TGF-beta receptorsignaling pathway, but the precise mechanism is still unclear:according to a report, acts by promoting deubiquitination ofmonoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), therebyalleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports,regulates the TGF-beta receptor signaling pathway by mediatingdeubiquitination and stabilization of TGFBR1, leading to anenhanced TGF-beta signal (PubMed:22344298). Able to mediatedeubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them againstproteasomal degradation. May also regulate gene expression and/orDNA repair through the deubiquitination of histone H2B(PubMed:24526689). Acts as an inhibitor of mitophagy bycounteracting the action of parkin (PRKN): hydrolyzes cleavage of'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached byparkin on target proteins such as MFN2, thereby reducing parkin'sability to drive mitophagy (PubMed:24852371). Acts as anassociated component of COP9 signalosome complex (CSN) andregulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA anddeubiquitinates substrates bound to VCP (PubMed:16005295,PubMed:17318178, PubMed:19826004, PubMed:19576224). Involved inendosome organization by mediating deubiquitination of SQSTM1:ubiquitinated SQSTM1 forms a molecular bridge that restrainscognate vesicles in the perinuclear region and itsdeubiquitination releases target vesicles for fast transport intothe cell periphery (PubMed:27368102).{ECO:0000269|PubMed:16005295, ECO:0000269|PubMed:17318178,ECO:0000269|PubMed:19576224, ECO:0000269|PubMed:19826004,ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:22344298,ECO:0000269|PubMed:24526689, ECO:0000269|PubMed:24852371,ECO:0000269|PubMed:27368102}. (Microbial infection) Protects APC and humanpapillomavirus type 16 protein E6 against degradation via theubiquitin proteasome pathway. {ECO:0000269|PubMed:19553310}.

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.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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FusionGeneSequence for USP15_TPH2


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences.
(nt: nucleotides, aa: amino acids)

* Fusion amino acid sequences.

* Fusion transcript sequences (only coding sequence (CDS) region).

* Fusion transcript sequences (Full-length transcript).

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FusionGenePPI for USP15_TPH2


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 (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors
USP15CD40, PHB2, UBE2G2, DFFA, ADSL, ALDOA, CALML3, CKB, CSTF1, FABP4, KRT31, KRT33B, KRT34, KRT35, KRT81, KRT85, LGALS7, MYH2, MYH4, PGAM2, PSMD11, SELENBP1, PRPF4, PRPF3, RNF40, PPIH, LSM6, LSM4, PRPF31, LSM8, MEPCE, LSM2, TUT1, LRRC15, VSIG8, SART3, PSMD7, USP11, UBC, TERF2, USP15, SMAD1, SMAD2, SMAD3, SMAD4, UBE2S, TRAF6, FHL1, USP4, SMAD7, SMURF2, TGFBR1, CUL3, CUL4B, COPS5, CAND1, STK33, GRK5, SHC1, TRIM63, TRIM54, USP21, USP20, USP51, USP7, OTUB1, JOSD1, UCHL3, USP8, USP33, SENP8, USP14, STAM, BAP1, YOD1, UCHL1, SENP3, USP28, WAPAL, USP10, ZC3H13, HMG20B, ZMYM2, NOTCH1, BRAP, TRIM21, RBCK1, TRIM17, PHF7, RNF126, TRIM46, TRIM5, RNF144B, TRIM74, SMURF1, FN1, BIRC2, BIRC3, NPM1, SOX2, LMNA, NUSAP1, PLOD2, UGP2, HIST2H2BE, HIST2H2AC, RNF20, TRIM25, TRAF4, SMAD6, BMPR1A, ACVR1, BMPR1B, SHFM1, HUWE1, PLA2G2A, MAD1L1, SPDL1, CARD9, CCDC57, NXF1, ECHS1, BCAT1, EEF2KMT, SNUPN, OBFC1, TRPV5, PSMB9, DDX58, NTRK1, MED4, MKNK2, ID1, SORT1, ATL3, SGTB, TMEM132A, TCEAL4, FERMT3, BAG6, POU5F1, CTNNB1, ANAPC1, AXIN1, BTRC, GLTSCR2, TP53, MDM2, NFE2L1, WWP2, RORC, COPS7A, COPS7B, KEAP1, IRS2, CDH1, UBE2E3, UBE2E2, RNF19B, RHPN1, SPAG9, MCM2, MCM4, MCM6, IVNS1ABP, EPS15L1, GTF3C4, SMC1A, GAPVD1, ANK3, SBNO1, SMC3, CDK11A, SOX4, BCR, PPP4R2, HSF1, KIAA1468, MCM7, PLK1, ATG2B, SMEK1, WEE1, GTF3C2, CYLD, RNF26, YAP1TPH2DNAJC12, SYBU


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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RelatedDrugs for USP15_TPH2


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.0 2018-04-02)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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RelatedDiseases for USP15_TPH2


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
TgeneTPH2C0011581Depressive disorder6CTD_human;PSYGENET
TgeneTPH2C0005586Bipolar Disorder5PSYGENET
TgeneTPH2C0011570Mental Depression5PSYGENET
TgeneTPH2C0041696Unipolar Depression5PSYGENET
TgeneTPH2C0525045Mood Disorders5PSYGENET
TgeneTPH2C1269683Major Depressive Disorder5CTD_human;PSYGENET
TgeneTPH2C0033975Psychotic Disorders2PSYGENET
TgeneTPH2C0036341Schizophrenia2PSYGENET
TgeneTPH2C0600427Cocaine Dependence2PSYGENET
TgeneTPH2C0001956alcohol use disorder1PSYGENET
TgeneTPH2C0004352Autistic Disorder1CTD_human
TgeneTPH2C0005587Depression, Bipolar1PSYGENET
TgeneTPH2C0015967Fever1CTD_human
TgeneTPH2C0036349Paranoid Schizophrenia1PSYGENET
TgeneTPH2C0038586Substance Use Disorders1PSYGENET
TgeneTPH2C0085762Alcohol abuse1PSYGENET
TgeneTPH2C0338715Drug-induced depressive state1PSYGENET
TgeneTPH2C2751802ATTENTION DEFICIT-HYPERACTIVITY DISORDER, SUSCEPTIBILITY TO, 71UNIPROT