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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:CYP17A1-INTS8

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CYP17A1-INTS8
FusionPDB ID: 21000
FusionGDB2.0 ID: 21000
HgeneTgene
Gene symbol

CYP17A1

INTS8

Gene ID

1586

55656

Gene namecytochrome P450 family 17 subfamily A member 1integrator complex subunit 8
SynonymsCPT7|CYP17|P450C17|S17AHC8orf52|INT8|NEDCHS
Cytomap

10q24.32

8q22.1

Type of geneprotein-codingprotein-coding
Descriptionsteroid 17-alpha-hydroxylase/17,20 lyase17-alpha-hydroxyprogesterone aldolaseCYPXVIIcytochrome P450 17A1cytochrome P450, family 17, subfamily A, polypeptide 1cytochrome P450, subfamily XVII (steroid 17-alpha-hydroxylase), adrenal hyperplasiacytochrointegrator complex subunit 8protein kaonashi-1
Modification date2020031320200313
UniProtAcc

P05093

Main function of 5'-partner protein: FUNCTION: A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis (PubMed:9452426, PubMed:27339894, PubMed:22266943, PubMed:25301938). Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol (PubMed:9452426, PubMed:25301938) (Probable). Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione (PubMed:9452426, PubMed:27339894, PubMed:22266943, PubMed:25301938). Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA. Also 16-alpha hydroxylates androgens, relevant for estriol synthesis (PubMed:27339894, PubMed:25301938). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:9452426, PubMed:27339894, PubMed:22266943, PubMed:25301938). {ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:27339894, ECO:0000269|PubMed:9452426, ECO:0000305|PubMed:8027220}.

Q75QN2

Main function of 5'-partner protein: FUNCTION: Component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. {ECO:0000269|PubMed:28542170}.
Ensembl transtripts involved in fusion geneENST idsENST00000369887, ENST00000489268, 
ENST00000520845, ENST00000447247, 
ENST00000523731, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 6 X 3=1265 X 5 X 5=125
# samples 75
** MAII scorelog2(7/126*10)=-0.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/125*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CYP17A1 [Title/Abstract] AND INTS8 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CYP17A1 [Title/Abstract] AND INTS8 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CYP17A1(104596822)-INTS8(95861690), # samples:1
Anticipated loss of major functional domain due to fusion event.
* 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
HgeneCYP17A1

GO:0008202

steroid metabolic process

22266943

HgeneCYP17A1

GO:0042446

hormone biosynthetic process

22266943

HgeneCYP17A1

GO:0042448

progesterone metabolic process

22266943

TgeneINTS8

GO:0016180

snRNA processing

16239144



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/chr10:104596822/chr8:95861690)
- 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 buttonRetention analysis results 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, are available here.

check buttonFusion gene breakpoints across CYP17A1 (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 INTS8 (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 Amino Acid Sequences


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)
ENST00000369887CYP17A1chr10104596822-ENST00000523731INTS8chr895861690+37094691152196693
ENST00000369887CYP17A1chr10104596822-ENST00000447247INTS8chr895861690+24044691152145676

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
ENST00000369887ENST00000523731CYP17A1chr10104596822-INTS8chr895861690+0.0002272310.9997727
ENST00000369887ENST00000447247CYP17A1chr10104596822-INTS8chr895861690+0.0004598610.9995402

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for CYP17A1-INTS8

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CYP17A1chr10104596822INTS8chr895861690469118IKKGKDFSGRPQMVCSRSVNLEKASE

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Potential FusionNeoAntigen Information of CYP17A1-INTS8 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
CYP17A1-INTS8_104596822_95861690.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
CYP17A1-INTS8chr10104596822chr895861690469HLA-B42:01RPQMVCSRSV0.82390.7151919
CYP17A1-INTS8chr10104596822chr895861690469HLA-A30:01MVCSRSVNLEK0.99060.90591223

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Potential FusionNeoAntigen Information of CYP17A1-INTS8 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of CYP17A1-INTS8

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
2566FSGRPQMVCSRSVNCYP17A1INTS8chr10104596822chr895861690469

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CYP17A1-INTS8

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN2566FSGRPQMVCSRSVN-7.9962-8.1096
HLA-B14:023BVN2566FSGRPQMVCSRSVN-5.70842-6.74372
HLA-B52:013W392566FSGRPQMVCSRSVN-6.83737-6.95077
HLA-B52:013W392566FSGRPQMVCSRSVN-4.4836-5.5189
HLA-A11:014UQ22566FSGRPQMVCSRSVN-10.0067-10.1201
HLA-A11:014UQ22566FSGRPQMVCSRSVN-9.03915-10.0745
HLA-A24:025HGA2566FSGRPQMVCSRSVN-6.56204-6.67544
HLA-A24:025HGA2566FSGRPQMVCSRSVN-5.42271-6.45801
HLA-B44:053DX82566FSGRPQMVCSRSVN-7.85648-8.89178
HLA-B44:053DX82566FSGRPQMVCSRSVN-5.3978-5.5112
HLA-A02:016TDR2566FSGRPQMVCSRSVN-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of CYP17A1-INTS8

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
CYP17A1-INTS8chr10104596822chr8958616901223MVCSRSVNLEKATGGTATGTTCAAGATCAGTAAATTTAGAAAAA
CYP17A1-INTS8chr10104596822chr895861690919RPQMVCSRSVCGGCCTCAAATGGTATGTTCAAGATCAGTA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of CYP17A1-INTS8

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
Non-CancerCYP17A1-INTS8chr10104596822ENST00000369887chr895861690ENST00000447247TCGA-P8-A5KD-11A

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Potential target of CAR-T therapy development for CYP17A1-INTS8

check button Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to CYP17A1-INTS8

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 CYP17A1-INTS8

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