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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene Breakpoints

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Tumorigenic MoA (Mechanism of Action) Scenarios of Fusion Geness

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Fusion Genomic Features

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Fusion Gene ORF Annotations

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Fusion Protein Retained/Non-Retained Functional Features

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Fusion Transcript Sequences

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Fusion Protein Sequences

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Personalized Fusion Protein Sequences

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Fusion Gene Expressed Samples

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Related Drugs

Fusion gene:CCT8_ARHGEF25 (FusionGDB2 ID:HG10694TG115557)

Fusion Gene Summary for CCT8_ARHGEF25

check button Fusion gene summary
Fusion gene informationFusion gene name: CCT8_ARHGEF25
Fusion gene ID: hg10694tg115557
HgeneTgene
Gene symbol

CCT8

ARHGEF25

Gene ID

10694

115557

Gene namechaperonin containing TCP1 subunit 8Rho guanine nucleotide exchange factor 25
SynonymsC21orf112|Cctq|D21S246|PRED71GEFT|p63RhoGEF
Cytomap

21q21.3

12q13.3

Type of geneprotein-codingprotein-coding
DescriptionT-complex protein 1 subunit thetaCCT-thetaTCP-1-thetachaperonin containing T-complex polypeptide 1 subunit 8chaperonin containing TCP1, subunit 8 (theta)renal carcinoma antigen NY-REN-15rho guanine nucleotide exchange factor 25RAC/CDC42 exchange factorRho guanine nucleotide exchange factor (GEF) 25RhoA/RAC/CDC42 exchange factorguanine nucleotide exchange factor GEFTrac/Cdc42/Rho exchange factor GEFTrhoA/Rac/Cdc42 guanine nucleotide
Modification date2024040720240305
UniProtAcc..
Ensembl transtripts involved in fusion geneENST00000286788, ENST00000540844, 
ENST00000542732, ENST00000470450, 
Fusion gene scores* DoF score* DoF score (Degree of Frequency) = # partners X # break points X # disease types
5 X 9 X 3=135
* DoF score (Degree of Frequency) = # partners X # break points X # disease types
5 X 17 X 6=510
# samples 611
** MAII score** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)
log2(6/135*10)=-1.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)
log2(11/510*10)=-2.2129937233342
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: CCT8 [Title/Abstract] AND ARHGEF25 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointCCT8(30439876)-ARHGEF25(58013093), # samples:1


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Fusion Gene Breakpoints for CCT8_ARHGEF25


check button RNA-seq based exon junction arranged fusion gene breakpoints from 8 resources (TCGA, CCLE, cBioPortal, GenBank, ChimerDB, ChimerKB, ChildHoodFusions, and GTEx). For the expressed sample information, go to Fusion Gene Sample section.
HgeneHchrHbpTgeneTchrTbp
CCT8chr2130439876ARHGEF25chr1230439876
CCT8chr2130439879ARHGEF25chr1258013092
CCT8chr2129067558ARHGEF25chr1257619309


check button DNA-seq based exon junction arranged fusion gene breakpoints from dbVar. For the expressed sample information, go to Fusion Gene Sample section.
HgeneHchrHbpTgeneTchrTbpSV type


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Tumorigenic MoA (Mechanism of Action) Scenarios of Fusion Genes for CCT8_ARHGEF25


check button To generate these tumorigenic scenario annotations, we implemented a deduction-first, retrieval-later computational framework. The pipeline first applies rule-guided reasoning across ten core mechanistic categories (M1–M10) derived from fusion gene biology to infer candidate mechanisms, tumorigenic scenarios, targeting points, and targeting backgrounds. To ensure empirical accountability, a governed Python workflow retrieves literature candidates via NCBI E-utilities and Europe PMC using tiered searches. Using JSON Schema-constrained LLM evidence judges (GPT-5.6 Luna and Terra), retrieved articles are evaluated for specificity and confidence without de novo PMID generation. This produces two distinct versions: a strict version restricted to high- or medium-confidence fusion-specific evidence, and an extended version incorporating broader gene-, pathway-, and contextual evidence.
* We have 10 tumorigenic mechanism categories of fusion genes as shown below.
Constitutively Active Kinases, Catalytic Domain Dysregulation, & Transmembrane Ligand FusionsAberrant Chimeric Transcription Factor / Fusion Transcription Factor ActivityEpigenetic Reprogramming / Histone Modifier DysregulationChromatin Remodeling DysregulationCondensate-Driven Transcriptional Rewiring / LLPPromoter / Enhancer HijackingDominant-Negative AntagonismCell Cycle / Checkpoint Bypass / RNA Processing DysregulationSubcellular Mislocalization / Spatial DysregulationNuclear Body / Sub-organellar Architecture Disruption & Differentiation Blockade

* Strict version: Restricted to high- or medium-confidence fusion-specific evidence.
Fusion Gene NameMechanism CategoryMechanism PubMedTumorigenic ScenariosTumorigenic Scenario PubMedTargeting PointsTargeting PubMedMechanism BackgroundMechanism Background PubMed
CCT8-ARHGEF25
Constitutively Active Kinases, Catalytic Domain Dysregulation, & Transmembrane Ligand Fusions
M1
Juxtaposition of CCT8 to ARHGEF25 (GEFT) drives continuous RhoA/Rac1 activation, accelerating lamellipodia assembly and invasion.Rac1/RhoA inhibitors; downstream PAK inhibitorsInvasive carcinomas and sarcomas

* Extended version: Includes all strict-level fusion evidence plus broader gene-, pathway-, and low-confidence contextual evidence.
Fusion Gene NameMechanism CategoryMechanism PubMedTumorigenic ScenariosTumorigenic Scenario PubMedTargeting PointsTargeting PubMedMechanism BackgroundMechanism Background PubMed
CCT8-ARHGEF25
Constitutively Active Kinases, Catalytic Domain Dysregulation, & Transmembrane Ligand Fusions
M1
Juxtaposition of CCT8 to ARHGEF25 (GEFT) drives continuous RhoA/Rac1 activation, accelerating lamellipodia assembly and invasion.Evidence level: Limited indirect gene evidence; Confidence: Low; PMID: 41362935; Title: GNAQ inhibits tumorigenesis via the ARHGEF25-mediated RHOA pathway in NK/T-cell lymphoma.Rac1/RhoA inhibitors; downstream PAK inhibitorsEvidence level: Limited indirect gene evidence; Confidence: Low; PMID: 41362935; Title: GNAQ inhibits tumorigenesis via the ARHGEF25-mediated RHOA pathway in NK/T-cell lymphoma.Invasive carcinomas and sarcomasEvidence level: Limited indirect gene evidence; Confidence: Low; PMID: 42600521; Title: Mitochondrial RNA modification in colorectal cancer: From single-cell analysis to machine learning-based risk modeling.

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

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneCCT8

GO:0006457

protein folding

30955883

HgeneCCT8

GO:0061077

chaperone-mediated protein folding

22133715


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Fusion Genomic Features for CCT8_ARHGEF25


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence) of In-frame fusion genes. FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)
CCT8chr2130439876-ARHGEF25chr1258013093+6.17e-061.00e+00


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence) of 5UTR-3CSD fusion genes (N-truncated cases).
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)

check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence) of 5CDS-3UTR fusion genes (C-truncated cases).
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)

check buttonDistribution of six genomic regulatory feature tracks across a ±5 kb window centered on the fusion breakpoints. We input the breakpoint sequences into AlphaGenome and obtained predicted genome tracks at single-base-pair resolution for each modality by running a single forward pass over the reference sequence. Specifically, for each breakpoint, AlphaGenome processed and returned predicted track data across diverse modalities, which were then averaged across all tracks within each output type and visualized across the ±5 kb window. The left panel shows the 5'-gene breakpoint ±5 kb area, and the right panel shows the 3'-gene breakpoint area, with tracks grouped by category: chromatin accessibility (DNase-seq, ATAC-seq), active transcription (RNA-seq, CAGE), and chromatin binding (ChIP-Histone, ChIP-TF).
genomic feature

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Fusion Gene ORF Annotations for CCT8_ARHGEF25

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
5CDS-3UTRENST00000286788ENST00000477314CCT8chr21

30439876

-ARHGEF25chr12

58013093

+
5CDS-3UTRENST00000540844ENST00000477314CCT8chr21

30439876

-ARHGEF25chr12

58013093

+
5CDS-3UTRENST00000542732ENST00000477314CCT8chr21

30439876

-ARHGEF25chr12

58013093

+
5UTR-3UTRENST00000470450ENST00000477314CCT8chr21

30439876

-ARHGEF25chr12

58013093

+

check buttonORFfinder Result Based On The Fusion Transcript Sequences of the In-frame Fusion Genes.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(peptide)

check buttonORFfinder Result Based On The Fusion Transcript Sequences of the 5UTR-3CDS Fusion Genes for N-Truncated Protein Search.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(peptide)

check buttonORFfinder Result Based On The Fusion Transcript Sequences of the 5CDS-3UTR Fusion Genes for C-Truncated Protein Search.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(peptide)

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.
HenstTenstHgeneHchrHbpTgeneTchrTbpNo-coding scoreCoding score

check buttonDeepORF Prediction of The Coding Potential Based on The Fusion Transcript Sequence of 5UTR-3CDS Fusion Genes (Potential N-Truncated Proteins).
HenstTenstHgeneHchrHbpTgeneTchrTbpNo-coding scoreCoding score

check buttonDeepORF Prediction of The Coding Potential Based on The Fusion Transcript Sequence of 5CDS-3UTR Fusion Genes (Potential C-Truncated Proteins).
HenstTenstHgeneHchrHbpTgeneTchrTbpNo-coding scoreCoding score
ENST00000286788ENST00000477314CCT8chr2130439876ARHGEF25chr12580130930.00e+002.87e-02
ENST00000540844ENST00000477314CCT8chr2130439876ARHGEF25chr12580130930.00e+001.62e-01
ENST00000542732ENST00000477314CCT8chr2130439876ARHGEF25chr12580130930.00e+001.41e-02

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Fusion Protein Retained/Non-Retained Functional Features for CCT8_ARHGEF25

check buttonProtein Level Annotation from FGviewer
* Retention 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.
fgviewer annotation
- In-frame and retained protein feature among the 13 regional features (visualization across fusion protein length).
No matching images found for ${hg}_${tg}.

- In-frame and retained protein feature among the 13 regional features (texts).
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


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


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


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Fusion Transcript Sequence for CCT8_ARHGEF25

check button In-frame Fusion Transcript Sequences.

check button N-Truncated Transcript (5UTR-3CDS) Sequences

check button C-Truncated Transcript (5CDS-3UTR) Sequences
>CCT8_ARHGEF25_ENST00000286788_ENST00000477314_30439876_58013093 length=588nt
Breakpoint=588nt
GATCGGGGATCGTCAGCTTGGTTCTGGCCACAGAGGTTGCTCTTCTCGCGATGCTTCAGACCTGGCGGCAGGGAAAGGGTGGGCTAATTGGAGAGCCAGGAAGAGCGTGAGGCGGCCCCACGCTGCTTTCCCAGAAGGCTGTGCGTGCTC
CTCGCTTCCTCCGCGGTCTTCCGAGCGGTCGCGTGAACTGCTTCCTGCAGGCTGGCCATGGCGCTTCACGTTCCCAAGGCTCCGGGCTTTGCCCAGATGCTCAAGGAGGGAGCGAAACACTTTTCAGGATTAGAAGAGGCTGTGTATAGA
AACATACAAGCTTGCAAGGAGCTTGCCCAAACCACTCGTACAGCATATGGACCAAATGGAATGAACAAAATGGTTATCAACCACTTGGAGAAGTTGTTTGTGACAAACGATGCAGCAACTATTTTAAGAGAACTAGAAGTACAGCATCCT
GCTGCAAAAATGATTGTAATGGCTTCTCATATGCAAGAGCAAGAAGTTGGAGATGGCACAAACTTTGTTCTGGTATTTGCTGGAGCTCTCCTGGAATTAGCTGAAGAACTTCTGAGGATTGGCCTGTCAGTTTCAGAG

>CCT8_ARHGEF25_ENST00000540844_ENST00000477314_30439876_58013093 length=362nt
Breakpoint=362nt
GCTCCTCGCTTCCTCCGCGGTCTTCCGAGCGGTCGCGTGAACTGCTTCCTGCAGGCTGGCCATGGCGCTTCACGTTCCCAAGGCTCCGGGCTTTGCCCAGATGCTCAAGGAGGGAGCGAAACACTTTTCAGGATTAGAAGAGGCTGTGTA
TAGAAACATACAAGCTTGCAAGGAGCTTGCCCAAACCACTCGTACAGCATATGGACCAAATGGTACAGCATCCTGCTGCAAAAATGATTGTAATGGCTTCTCATATGCAAGAGCAAGAAGTTGGAGATGGCACAAACTTTGTTCTGGTAT
TTGCTGGAGCTCTCCTGGAATTAGCTGAAGAACTTCTGAGGATTGGCCTGTCAGTTTCAGAG

>CCT8_ARHGEF25_ENST00000542732_ENST00000477314_30439876_58013093 length=450nt
Breakpoint=450nt
ACTTCTCTTCTTCCGCGACCGGGAGAAGGCCGAGGGATCGGCGGCACGATCGACATTGTACACCTTGAAGGTGGACGGATGTGAAGCCGCGCGTTGTAGGGCTGAAGCTTACCAAAGAAAGGAAGAATGCACTTTTCAGGATTAGAAGAG
GCTGTGTATAGAAACATACAAGCTTGCAAGGAGCTTGCCCAAACCACTCGTACAGCATATGGACCAAATGGAATGAACAAAATGGTTATCAACCACTTGGAGAAGTTGTTTGTGACAAACGATGCAGCAACTATTTTAAGAGAACTAGAA
GTACAGCATCCTGCTGCAAAAATGATTGTAATGGCTTCTCATATGCAAGAGCAAGAAGTTGGAGATGGCACAAACTTTGTTCTGGTATTTGCTGGAGCTCTCCTGGAATTAGCTGAAGAACTTCTGAGGATTGGCCTGTCAGTTTCAGAG



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Fusion Protein Sequence for CCT8_ARHGEF25

check button In-frame Fusion Protein Sequences.

check button N-Truncated Protein (5UTR-3CDS) Sequences

check button C-Truncated Protein (5CDS-3UTR) Sequences

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Personalized Fusion Protein Sequence for CCT8_ARHGEF25


check button TCGA Kinase/DNA-binding Domain Mutated Fusion Protein Sequences
NumGene GroupDomain LociFusion Protein IDFusion Gene NamePartnerMutated Residue in WT ProteinSeq. LengthMutated Residue in Fusion Protein

check button CCLE Kinase/DNA-binding Domain Mutated Fusion Protein Sequences

NumGene GroupDomain LociFusion Protein IDFusion Gene NamePartnerMutated Residue in WT ProteinSeq. LengthMutated Residue in Fusion Protein

check button TCGA All Mutated Fusion Protein Sequences


Fusion Protein IDSample IDMutated PartnerAAchange in WTSeq. LengthAAchange in Fusion

check button CCLE All Mutated Fusion Protein Sequences


Fusion Protein IDSample IDMutated PartnerAAchange in WTSeq. LengthAAchange in Fusion

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Fusion Gene Exprssed Samples for CCT8_ARHGEF25


check buttonRNA-seq based fusion gene expressed samples.
SourceStudyDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDBBRCATCGA-EW-A6SA-01ACCT8

chr21

30439876-ARHGEF25

chr12

30439876

+
WashUBRCATCGA-EW-A6SA-01ACCT8

chr21

30439879-ARHGEF25

chr12

58013092

+
cBioPortalBRCA_TCGA_PAN_CAN_ATLAS_2018BRCATCGA-EW-A6SA-01CCT8

chr21

29067558ARHGEF25

chr12

57619309


check buttonDNA-seq based fusion gene expressed samples.
SourceStudyDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrandSV type


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Related Drugs for CCT8_ARHGEF25


check button PubMed Abstract Search With ['A-B' AND 'drug'], ['A::B' AND 'drug']
* For more details on the Studied, Reported, Approved Drugs targeting this fusion gene, Go to FusionPub.
PMIDFusion Gene NameDrugStudy Title

check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status