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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:ARHGAP12-KDM1A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ARHGAP12-KDM1A
FusionPDB ID: 5932
FusionGDB2.0 ID: 5932
HgeneTgene
Gene symbol

ARHGAP12

KDM1A

Gene ID

94134

23028

Gene nameRho GTPase activating protein 12lysine demethylase 1A
Synonyms-AOF2|BHC110|CPRF|KDM1|LSD1
Cytomap

10p11.22

1p36.12

Type of geneprotein-codingprotein-coding
Descriptionrho GTPase-activating protein 12rho-type GTPase-activating protein 12lysine-specific histone demethylase 1ABRAF35-HDAC complex protein BHC110FAD-binding protein BRAF35-HDAC complex, 110 kDa subunitamine oxidase (flavin containing) domain 2flavin-containing amine oxidase domain-containing protein 2lysine (K)-specific d
Modification date2020031320200329
UniProtAcc

Q8IWW6

Main function of 5'-partner protein: FUNCTION: GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000250}.

O60341

Main function of 5'-partner protein: FUNCTION: Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context (PubMed:15620353, PubMed:15811342, PubMed:16140033, PubMed:16079794, PubMed:16079795, PubMed:16223729). Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:21300290). Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me (PubMed:15620353, PubMed:20389281, PubMed:21300290, PubMed:23721412). May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity (PubMed:16140033, PubMed:16079794, PubMed:16885027, PubMed:21300290, PubMed:23721412). Also acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in AR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A (PubMed:16079795). Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7 (PubMed:20389281). {ECO:0000269|PubMed:12032298, ECO:0000269|PubMed:15620353, ECO:0000269|PubMed:15811342, ECO:0000269|PubMed:16079794, ECO:0000269|PubMed:16079795, ECO:0000269|PubMed:16140033, ECO:0000269|PubMed:16223729, ECO:0000269|PubMed:16885027, ECO:0000269|PubMed:16956976, ECO:0000269|PubMed:17805299, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:20389281, ECO:0000269|PubMed:20562920, ECO:0000269|PubMed:21300290, ECO:0000269|PubMed:23721412}.
Ensembl transtripts involved in fusion geneENST idsENST00000492028, ENST00000344936, 
ENST00000375245, ENST00000375250, 
ENST00000396144, ENST00000311380, 
ENST00000356634, ENST00000400181, 
ENST00000542151, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 8 X 7=5043 X 5 X 3=45
# samples 115
** MAII scorelog2(11/504*10)=-2.19592020997526
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/45*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: ARHGAP12 [Title/Abstract] AND KDM1A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ARHGAP12 [Title/Abstract] AND KDM1A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ARHGAP12(32106716)-KDM1A(23403721), # samples:1
Anticipated loss of major functional domain due to fusion event.ARHGAP12-KDM1A 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.
ARHGAP12-KDM1A 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.
ARHGAP12-KDM1A 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.
ARHGAP12-KDM1A 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.
ARHGAP12-KDM1A seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
ARHGAP12-KDM1A seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
ARHGAP12-KDM1A seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
TgeneKDM1A

GO:0033169

histone H3-K9 demethylation

16079795|20228790

TgeneKDM1A

GO:0034644

cellular response to UV

24217620

TgeneKDM1A

GO:0034720

histone H3-K4 demethylation

15620353|20228790|24217620

TgeneKDM1A

GO:0043433

negative regulation of DNA-binding transcription factor activity

19497860

TgeneKDM1A

GO:0045892

negative regulation of transcription, DNA-templated

19497860

TgeneKDM1A

GO:0045944

positive regulation of transcription by RNA polymerase II

20833138

TgeneKDM1A

GO:0051091

positive regulation of DNA-binding transcription factor activity

20833138



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/chr10:32106716/chr1:23403721)
- 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 ARHGAP12 (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 KDM1A (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)
ENST00000311380ARHGAP12chr1032106716-ENST00000356634KDM1Achr123403721+28161594192490823
ENST00000311380ARHGAP12chr1032106716-ENST00000400181KDM1Achr123403721+28151594192490823
ENST00000311380ARHGAP12chr1032106716-ENST00000542151KDM1Achr123403721+28161594192490823

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
ENST00000311380ENST00000356634ARHGAP12chr1032106716-KDM1Achr123403721+0.0006969770.999303
ENST00000311380ENST00000400181ARHGAP12chr1032106716-KDM1Achr123403721+0.0007000470.9992999
ENST00000311380ENST00000542151ARHGAP12chr1032106716-KDM1Achr123403721+0.0006969770.999303

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 ARHGAP12-KDM1A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ARHGAP12chr1032106716KDM1Achr1234037211594525DWFKVLSSTINNQDDDFEFTGSHLTV

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Potential FusionNeoAntigen Information of ARHGAP12-KDM1A 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.

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)

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Potential FusionNeoAntigen Information of ARHGAP12-KDM1A 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.
ARHGAP12-KDM1A_32106716_23403721.msa

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)
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0405WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0405FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0409WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0409FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0411WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0411FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0411DWFKVLSSTINNQDD015
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0411KVLSSTINNQDDDFE318
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0417WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0417FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0417DWFKVLSSTINNQDD015
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0417KVLSSTINNQDDDFE318
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0429WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0429FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0430WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0430FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0445WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0445FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0448WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0448FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0457WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0457FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0467WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0467FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0467KVLSSTINNQDDDFE318
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0477WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0477FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0483WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0483FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0484WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0484FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0487WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0489WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0489FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0491WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0491FKVLSSTINNQDDDF217
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0491DWFKVLSSTINNQDD015
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0491KVLSSTINNQDDDFE318
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0701NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0703NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0705NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0706NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0707NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0708NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0709NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0711NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0712NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0713NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0714NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0715NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0716NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0717NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-0719NQDDDFEFTGSHLTV1126
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-1001DWFKVLSSTINNQDD015
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-1003DWFKVLSSTINNQDD015
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-1410WFKVLSSTINNQDDD116
ARHGAP12-KDM1Achr1032106716chr1234037211594DRB1-1410FKVLSSTINNQDDDF217

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Fusion breakpoint peptide structures of ARHGAP12-KDM1A

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ARHGAP12-KDM1A

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

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Vaccine Design for the FusionNeoAntigens of ARHGAP12-KDM1A

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

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ARHGAP12-KDM1Achr1032106716chr123403721015DWFKVLSSTINNQDDGATTGGTTTAAAGTTCTTAGTAGTACAATCAATAATCAGGATGAT
ARHGAP12-KDM1Achr1032106716chr123403721116WFKVLSSTINNQDDDTGGTTTAAAGTTCTTAGTAGTACAATCAATAATCAGGATGATGAC
ARHGAP12-KDM1Achr1032106716chr1234037211126NQDDDFEFTGSHLTVAATCAGGATGATGACTTTGAGTTCACTGGCAGCCACCTGACAGTA
ARHGAP12-KDM1Achr1032106716chr123403721217FKVLSSTINNQDDDFTTTAAAGTTCTTAGTAGTACAATCAATAATCAGGATGATGACTTT
ARHGAP12-KDM1Achr1032106716chr123403721318KVLSSTINNQDDDFEAAAGTTCTTAGTAGTACAATCAATAATCAGGATGATGACTTTGAG

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Information of the samples that have these potential fusion neoantigens of ARHGAP12-KDM1A

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

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Potential target of CAR-T therapy development for ARHGAP12-KDM1A

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 ARHGAP12-KDM1A

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 ARHGAP12-KDM1A

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