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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:SLIRP-CYP3A5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SLIRP-CYP3A5
FusionPDB ID: 83652
FusionGDB2.0 ID: 83652
HgeneTgene
Gene symbol

SLIRP

CYP3A5

Gene ID

81892

1577

Gene nameSRA stem-loop interacting RNA binding proteincytochrome P450 family 3 subfamily A member 5
SynonymsC14orf156|DC50|PD04872CP35|CYPIIIA5|P450PCN3|PCN3
Cytomap

14q24.3

7q22.1

Type of geneprotein-codingprotein-coding
DescriptionSRA stem-loop-interacting RNA-binding protein, mitochondrialcytochrome P450 3A5aryl hydrocarbon hydroxylasecytochrome P450 HLp2cytochrome P450, family 3, subfamily A, polypeptide 5cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 5cytochrome P450-PCN3flavoprotein-linked monooxygenasemicroso
Modification date2020031320200320
UniProtAcc.

P20815

Main function of 5'-partner protein: FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:2732228, PubMed:10681376, PubMed:11093772, PubMed:12865317). 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 (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:2732228, PubMed:10681376, PubMed:11093772). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228). {ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:2732228}.
Ensembl transtripts involved in fusion geneENST idsENST00000238688, ENST00000557342, 
ENST00000557431, ENST00000557623, 
ENST00000339843, ENST00000439761, 
ENST00000480723, ENST00000222982, 
ENST00000343703, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 5 X 3=1508 X 5 X 4=160
# samples 109
** MAII scorelog2(10/150*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/160*10)=-0.830074998557688
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SLIRP [Title/Abstract] AND CYP3A5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SLIRP [Title/Abstract] AND CYP3A5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SLIRP(78182222)-CYP3A5(99250402), # samples:1
Anticipated loss of major functional domain due to fusion event.SLIRP-CYP3A5 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.
SLIRP-CYP3A5 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.
* 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
TgeneCYP3A5

GO:0002933

lipid hydroxylation

14559847

TgeneCYP3A5

GO:0008202

steroid metabolic process

14559847

TgeneCYP3A5

GO:0008210

estrogen metabolic process

12865317

TgeneCYP3A5

GO:0009822

alkaloid catabolic process

15039299

TgeneCYP3A5

GO:0042573

retinoic acid metabolic process

11093772

TgeneCYP3A5

GO:0042737

drug catabolic process

15039299

TgeneCYP3A5

GO:0070989

oxidative demethylation

15039299



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/chr14:78182222/chr7:99250402)
- 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 SLIRP (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 CYP3A5 (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)
ENST00000557342SLIRPchr1478182222+ENST00000222982CYP3A5chr799250402-89930535787250
ENST00000557342SLIRPchr1478182222+ENST00000343703CYP3A5chr799250402-89330535787250
ENST00000238688SLIRPchr1478182222+ENST00000222982CYP3A5chr799250402-89129727779250
ENST00000238688SLIRPchr1478182222+ENST00000343703CYP3A5chr799250402-88529727779250
ENST00000557623SLIRPchr1478182222+ENST00000222982CYP3A5chr799250402-8672733755250
ENST00000557623SLIRPchr1478182222+ENST00000343703CYP3A5chr799250402-8612733755250
ENST00000557431SLIRPchr1478182222+ENST00000222982CYP3A5chr799250402-8672733755250
ENST00000557431SLIRPchr1478182222+ENST00000343703CYP3A5chr799250402-8612733755250

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
ENST00000557342ENST00000222982SLIRPchr1478182222+CYP3A5chr799250402-0.0008186590.99918133
ENST00000557342ENST00000343703SLIRPchr1478182222+CYP3A5chr799250402-0.0008605960.9991394
ENST00000238688ENST00000222982SLIRPchr1478182222+CYP3A5chr799250402-0.0008256780.9991743
ENST00000238688ENST00000343703SLIRPchr1478182222+CYP3A5chr799250402-0.0008727120.9991273
ENST00000557623ENST00000222982SLIRPchr1478182222+CYP3A5chr799250402-0.0008385980.99916136
ENST00000557623ENST00000343703SLIRPchr1478182222+CYP3A5chr799250402-0.0008968740.9991032
ENST00000557431ENST00000222982SLIRPchr1478182222+CYP3A5chr799250402-0.0008385980.99916136
ENST00000557431ENST00000343703SLIRPchr1478182222+CYP3A5chr799250402-0.0008968740.9991032

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 SLIRP-CYP3A5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SLIRPchr1478182222CYP3A5chr79925040227390ALQQENHIIDGVKAPPTYDAVVQMEY
SLIRPchr1478182222CYP3A5chr79925040229790ALQQENHIIDGVKAPPTYDAVVQMEY
SLIRPchr1478182222CYP3A5chr79925040230590ALQQENHIIDGVKAPPTYDAVVQMEY

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Potential FusionNeoAntigen Information of SLIRP-CYP3A5 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.
SLIRP-CYP3A5_78182222_99250402.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)
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B39:06NHIIDGVKA0.9970.5527514
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B39:01NHIIDGVKA0.99690.6376514
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B35:08DGVKAPPTY0.87010.852918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B35:01DGVKAPPTY0.83830.8406918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B15:02DGVKAPPTY0.70460.8972918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B35:05DGVKAPPTY0.60110.5714918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B39:06NHIIDGVKAP0.99060.6132515
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B45:01QENHIIDGVKA0.99970.8741314
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B50:02QENHIIDGVKA0.99930.53314
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B41:01QENHIIDGVKA0.99710.947314
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B15:07GVKAPPTY0.99910.67361018
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B39:05NHIIDGVKA0.99540.6168514
SLIRP-CYP3A5chr1478182222chr799250402297HLA-C04:06KAPPTYDAV0.9850.8831221
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B15:31DGVKAPPTY0.84340.7969918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B15:21DGVKAPPTY0.7220.862918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-C01:17KAPPTYDAV0.5020.94981221
SLIRP-CYP3A5chr1478182222chr799250402297HLA-C01:30KAPPTYDAV0.29960.96071221
SLIRP-CYP3A5chr1478182222chr799250402297HLA-C01:17KAPPTYDAVV0.86550.95071222
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B15:135GVKAPPTY0.99940.84031018
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B15:35GVKAPPTY0.99920.841018
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B15:50GVKAPPTY0.99860.83741018
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B15:39GVKAPPTY0.99790.77551018
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B39:31NHIIDGVKA0.99720.6367514
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B35:24DGVKAPPTY0.95940.8784918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B35:23DGVKAPPTY0.84230.8351918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B35:77DGVKAPPTY0.83830.8406918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B35:20DGVKAPPTY0.82150.9176918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B18:04DGVKAPPTY0.81540.8706918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B35:11DGVKAPPTY0.71380.8587918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B35:17DGVKAPPTY0.64850.7263918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B35:30DGVKAPPTY0.64850.7263918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-C01:03KAPPTYDAV0.60440.95071221
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B18:07DGVKAPPTY0.48940.8243918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-C01:02KAPPTYDAV0.48050.94941221
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B18:08DGVKAPPTY0.4570.8052918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B07:13KAPPTYDAV0.27690.85951221
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B15:08DGVKAPPTY0.1570.8143918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B15:11DGVKAPPTY0.14980.8096918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-B35:43DGVKAPPTY0.12240.8187918
SLIRP-CYP3A5chr1478182222chr799250402297HLA-C01:03KAPPTYDAVV0.9430.95041222
SLIRP-CYP3A5chr1478182222chr799250402297HLA-C01:02KAPPTYDAVV0.8690.95021222

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Potential FusionNeoAntigen Information of SLIRP-CYP3A5 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 SLIRP-CYP3A5

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
3364HIIDGVKAPPTYDASLIRPCYP3A5chr1478182222chr799250402297

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SLIRP-CYP3A5

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-B14:023BVN3364HIIDGVKAPPTYDA-6.65987-6.77167
HLA-B14:023BVN3364HIIDGVKAPPTYDA-5.13098-6.17408
HLA-B52:013W393364HIIDGVKAPPTYDA-6.46716-6.57896
HLA-B52:013W393364HIIDGVKAPPTYDA-5.19193-6.23503
HLA-A11:014UQ23364HIIDGVKAPPTYDA-8.59991-8.71171
HLA-A11:014UQ23364HIIDGVKAPPTYDA-7.01744-8.06054
HLA-A24:025HGA3364HIIDGVKAPPTYDA-7.66521-7.77701
HLA-A24:025HGA3364HIIDGVKAPPTYDA-5.07569-6.11879
HLA-B27:056PYJ3364HIIDGVKAPPTYDA-3.9447-4.9878
HLA-B44:053DX83364HIIDGVKAPPTYDA-5.29683-5.40863
HLA-B44:053DX83364HIIDGVKAPPTYDA-3.71262-4.75572
HLA-A02:016TDR3364HIIDGVKAPPTYDA-4.72338-5.76648
HLA-A02:016TDR3364HIIDGVKAPPTYDA-4.62978-4.74158

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Vaccine Design for the FusionNeoAntigens of SLIRP-CYP3A5

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
SLIRP-CYP3A5chr1478182222chr7992504021018GVKAPPTYGGAGTAAAGGCACCACCTACCTAT
SLIRP-CYP3A5chr1478182222chr7992504021221KAPPTYDAVAAGGCACCACCTACCTATGATGCCGTG
SLIRP-CYP3A5chr1478182222chr7992504021222KAPPTYDAVVAAGGCACCACCTACCTATGATGCCGTGGTA
SLIRP-CYP3A5chr1478182222chr799250402314QENHIIDGVKACAGGAAAATCATATTATAGATGGAGTAAAGGCA
SLIRP-CYP3A5chr1478182222chr799250402514NHIIDGVKAAATCATATTATAGATGGAGTAAAGGCA
SLIRP-CYP3A5chr1478182222chr799250402515NHIIDGVKAPAATCATATTATAGATGGAGTAAAGGCACCA
SLIRP-CYP3A5chr1478182222chr799250402918DGVKAPPTYGATGGAGTAAAGGCACCACCTACCTAT

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 SLIRP-CYP3A5

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-CancerSLIRP-CYP3A5chr1478182222ENST00000238688chr799250402ENST00000222982179N

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Potential target of CAR-T therapy development for SLIRP-CYP3A5

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 SLIRP-CYP3A5

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 SLIRP-CYP3A5

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