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Center for Computational Systems Medicine level3
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein Structure

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pLDDT scores

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Ramachandran Plot of Fusion Protein Structure

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Potential Active Site Information

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Potentially Interacting Small Molecules through Virtual Screening

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Biochemical Features of Small Molecules with ADME

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Drug Toxicity Information

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:TOP3A-KMT2A

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TOP3A-KMT2A
FusionPDB ID: 93103
FusionGDB2.0 ID: 93103
HgeneTgene
Gene symbol

TOP3A

KMT2A

Gene ID

7156

4297

Gene nameDNA topoisomerase III alphalysine methyltransferase 2A
SynonymsMGRISCE2|PEOB5|TOP3|ZGRF7ALL-1|CXXC7|HRX|HTRX1|MLL|MLL1|MLL1A|TRX1|WDSTS
Cytomap

17p11.2

11q23.3

Type of geneprotein-codingprotein-coding
DescriptionDNA topoisomerase 3-alphatopo III-alphatopoisomerase (DNA) III alphazinc finger, GRF-type containing 7histone-lysine N-methyltransferase 2ACXXC-type zinc finger protein 7lysine (K)-specific methyltransferase 2Alysine N-methyltransferase 2Amixed lineage leukemia 1myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila)trithorax-like
Modification date2020031320200319
UniProtAcc

Q13472

Q03164

Ensembl transtripts involved in fusion geneENST idsENST00000321105, ENST00000542570, 
ENST00000582230, ENST00000540524, 
ENST00000354520, ENST00000420751, 
ENST00000389506, ENST00000534358, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 10 X 6=54031 X 72 X 3=6696
# samples 1279
** MAII scorelog2(12/540*10)=-2.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(79/6696*10)=-3.08337496948588
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: TOP3A [Title/Abstract] AND KMT2A [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)
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
HgeneTOP3A

GO:0006265

DNA topological change

20445207

TgeneKMT2A

GO:0044648

histone H3-K4 dimethylation

25561738

TgeneKMT2A

GO:0045944

positive regulation of transcription by RNA polymerase II

20861184

TgeneKMT2A

GO:0051568

histone H3-K4 methylation

19556245

TgeneKMT2A

GO:0065003

protein-containing complex assembly

15199122

TgeneKMT2A

GO:0080182

histone H3-K4 trimethylation

20861184

TgeneKMT2A

GO:0097692

histone H3-K4 monomethylation

25561738|26324722


check buttonFusion gene breakpoints across TOP3A (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonFusion gene breakpoints across KMT2A (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.


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Fusion Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerKB3..TOP3Achr17

18217912

-KMT2Achr11

118355576

ChimerKB3..TOP3Achr17

18217912

-KMT2Achr11

118355576

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Fusion ORF Analysis


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)
ENST00000321105TOP3Achr1718217912-ENST00000534358KMT2Achr11118355576+127483956880952675
ENST00000321105TOP3Achr1718217912-ENST00000389506KMT2Achr11118355576+98323956880862672

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

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Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>93103_93103_1_TOP3A-KMT2A_TOP3A_chr17_18217912_ENST00000321105_KMT2A_chr11_118355576_ENST00000389506_length(amino acids)=2672AA_BP=109
MKLQRPAGWWGRDRSEALVPFRWAPFEPHLWLPQDAPAAGERLRARGLRMIFPVARYALRWLRRPEDRAFSRAAMEMALRGVRKVLCVAE
KNDAAKGIADLLSNGRMRREDCEAENVWEMGGLGILTSVPITPRVVCFLCASSGHVEFVYCQVCCEPFHKFCLEENERPLEDQLENWCCR
RCKFCHVCGRQHQATKQLLECNKCRNSYHPECLGPNYPTKPTKKKKVWICTKCVRCKSCGSTTPGKGWDAQWSHDFSLCHDCAKLFAKGN
FCPLCDKCYDDDDYESKMMQCGKCDRWVHSKCENLSDEMYEILSNLPESVAYTCVNCTERHPAEWRLALEKELQISLKQVLTALLNSRTT
SHLLRYRQAAKPPDLNPETEESIPSRSSPEGPDPPVLTEVSKQDDQQPLDLEGVKRKMDQGNYTSVLEFSDDIVKIIQAAINSDGGQPEI
KKANSMVKSFFIRQMERVFPWFSVKKSRFWEPNKVSSNSGMLPNAVLPPSLDHNYAQWQEREENSHTEQPPLMKKIIPAPKPKGPGEPDS
PTPLHPPTPPILSTDRSREDSPELNPPPGIEDNRQCALCLTYGDDSANDAGRLLYIGQNEWTHVNCALWSAEVFEDDDGSLKNVHMAVIR
GKQLRCEFCQKPGATVGCCLTSCTSNYHFMCSRAKNCVFLDDKKVYCQRHRDLIKGEVVPENGFEVFRRVFVDFEGISLRRKFLNGLEPE
NIHMMIGSMTIDCLGILNDLSDCEDKLFPIGYQCSRVYWSTTDARKRCVYTCKIVECRPPVVEPDINSTVEHDENRTIAHSPTSFTESSS
KESQNTAEIISPPSPDRPPHSQTSGSCYYHVISKVPRIRTPSYSPTQRSPGCRPLPSAGSPTPTTHEIVTVGDPLLSSGLRSIGSRRHST
SSLSPQRSKLRIMSPMRTGNTYSRNNVSSVSTTGTATDLESSAKVVDHVLGPLNSSTSLGQNTSTSSNLQRTVVTVGNKNSHLDGSSSSE
MKQSSASDLVSKSSSLKGEKTKVLSSKSSEGSAHNVAYPGIPKLAPQVHNTTSRELNVSKIGSFAEPSSVSFSSKEALSFPHLHLRGQRN
DRDQHTDSTQSANSSPDEDTEVKTLKLSGMSNRSSIINEHMGSSSRDRRQKGKKSCKETFKEKHSSKSFLEPGQVTTGEEGNLKPEFMDE
VLTPEYMGQRPCNNVSSDKIGDKGLSMPGVPKAPPMQVEGSAKELQAPRKRTVKVTLTPLKMENESQSKNALKESSPASPLQIESTSPTE
PISASENPGDGPVAQPSPNNTSCQDSQSNNYQNLPVQDRNLMLPDGPKPQEDGSFKRRYPRRSARARSNMFFGLTPLYGVRSYGEEDIPF
YSSSTGKKRGKRSAEGQVDGADDLSTSDEDDLYYYNFTRTVISSGGEERLASHNLFREEEQCDLPKISQLDGVDDGTESDTSVTATTRKS
SQIPKRNGKENGTENLKIDRPEDAGEKEHVTKSSVGHKNEPKMDNCHSVSRVKTQGQDSLEAQLSSLESSRRVHTSTPSDKNLLDTYNTE
LLKSDSDNNNSDDCGNILPSDIMDFVLKNTPSMQALGESPESSSSELLNLGEGLGLDSNREKDMGLFEVFSQQLPTTEPVDSSVSSSISA
EEQFELPLELPSDLSVLTTRSPTVPSQNPSRLAVISDSGEKRVTITEKSVASSESDPALLSPGVDPTPEGHMTPDHFIQGHMDADHISSP
PCGSVEQGHGNNQDLTRNSSTPGLQVPVSPTVPIQNQKYVPNSTDSPGPSQISNAAVQTTPPHLKPATEKLIVVNQNMQPLYVLQTLPNG
VTQKIQLTSSVSSTPSVMETNTSVLGPMGGGLTLTTGLNPSLPTSQSLFPSASKGLLPMSHHQHLHSFPAATQSSFPPNISNPPSGLLIG
VQPPPDPQLLVSESSQRTDLSTTVATPSSGLKKRPISRLQTRKNKKLAPSSTPSNIAPSDVVSNMTLINFTPSQLPNHPSLLDLGSLNTS
SHRTVPNIIKRSKSSIMYFEPAPLLPQSVGGTAATAAGTSTISQDTSHLTSGSVSGLASSSSVLNVVSMQTTTTPTSSASVPGHVTLTNP
RLLGTPDIGSISNLLIKASQQSLGIQDQPVALPPSSGMFPQLGTSQTPSTAAITAASSICVLPSTQTTGITAASPSGEADEHYQLQHVNQ
LLASKTGIHSSQRDLDSASGPQVSNFTQTVDAPNSMGLEQNKALSSAVQASPTSPGGSPSSPSSGQRSASPSVPGPTKPKPKTKRFQLPL
DKGNGKKHKVSHLRTSSSEAHIPDQETTSLTSGTGTPGAEAEQQDTASVEQSSQKECGQPAGQVAVLPEVQVTQNPANEQESAEPKTVEE
EESNFSSPLMLWLQQEQKRKESITEKKPKKGLVFEISSDDGFQICAESIEDAWKSLTDKVQEARSNARLKQLSFAGVNGLRMLGILHDAV
VFLIEQLSGAKHCRNYKFRFHKPEEANEPPLNPHGSARAEVHLRKSAFDMFNFLASKHRQPPEYNPNDEEEEEVQLKSARRATSMDLPMP
MRFRHLKKTSKEAVGVYRSPIHGRGLFCKRNIDAGEMVIEYAGNVIRSIQTDKREKYYDSKGIGCYMFRIDDSEVVDATMHGNAARFINH

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>93103_93103_2_TOP3A-KMT2A_TOP3A_chr17_18217912_ENST00000321105_KMT2A_chr11_118355576_ENST00000534358_length(amino acids)=2675AA_BP=109
MKLQRPAGWWGRDRSEALVPFRWAPFEPHLWLPQDAPAAGERLRARGLRMIFPVARYALRWLRRPEDRAFSRAAMEMALRGVRKVLCVAE
KNDAAKGIADLLSNGRMRREDCEAENVWEMGGLGILTSVPITPRVVCFLCASSGHVEFVYCQVCCEPFHKFCLEENERPLEDQLENWCCR
RCKFCHVCGRQHQATKQLLECNKCRNSYHPECLGPNYPTKPTKKKKVWICTKCVRCKSCGSTTPGKGWDAQWSHDFSLCHDCAKLFAKGN
FCPLCDKCYDDDDYESKMMQCGKCDRWVHSKCENLSGTEDEMYEILSNLPESVAYTCVNCTERHPAEWRLALEKELQISLKQVLTALLNS
RTTSHLLRYRQAAKPPDLNPETEESIPSRSSPEGPDPPVLTEVSKQDDQQPLDLEGVKRKMDQGNYTSVLEFSDDIVKIIQAAINSDGGQ
PEIKKANSMVKSFFIRQMERVFPWFSVKKSRFWEPNKVSSNSGMLPNAVLPPSLDHNYAQWQEREENSHTEQPPLMKKIIPAPKPKGPGE
PDSPTPLHPPTPPILSTDRSREDSPELNPPPGIEDNRQCALCLTYGDDSANDAGRLLYIGQNEWTHVNCALWSAEVFEDDDGSLKNVHMA
VIRGKQLRCEFCQKPGATVGCCLTSCTSNYHFMCSRAKNCVFLDDKKVYCQRHRDLIKGEVVPENGFEVFRRVFVDFEGISLRRKFLNGL
EPENIHMMIGSMTIDCLGILNDLSDCEDKLFPIGYQCSRVYWSTTDARKRCVYTCKIVECRPPVVEPDINSTVEHDENRTIAHSPTSFTE
SSSKESQNTAEIISPPSPDRPPHSQTSGSCYYHVISKVPRIRTPSYSPTQRSPGCRPLPSAGSPTPTTHEIVTVGDPLLSSGLRSIGSRR
HSTSSLSPQRSKLRIMSPMRTGNTYSRNNVSSVSTTGTATDLESSAKVVDHVLGPLNSSTSLGQNTSTSSNLQRTVVTVGNKNSHLDGSS
SSEMKQSSASDLVSKSSSLKGEKTKVLSSKSSEGSAHNVAYPGIPKLAPQVHNTTSRELNVSKIGSFAEPSSVSFSSKEALSFPHLHLRG
QRNDRDQHTDSTQSANSSPDEDTEVKTLKLSGMSNRSSIINEHMGSSSRDRRQKGKKSCKETFKEKHSSKSFLEPGQVTTGEEGNLKPEF
MDEVLTPEYMGQRPCNNVSSDKIGDKGLSMPGVPKAPPMQVEGSAKELQAPRKRTVKVTLTPLKMENESQSKNALKESSPASPLQIESTS
PTEPISASENPGDGPVAQPSPNNTSCQDSQSNNYQNLPVQDRNLMLPDGPKPQEDGSFKRRYPRRSARARSNMFFGLTPLYGVRSYGEED
IPFYSSSTGKKRGKRSAEGQVDGADDLSTSDEDDLYYYNFTRTVISSGGEERLASHNLFREEEQCDLPKISQLDGVDDGTESDTSVTATT
RKSSQIPKRNGKENGTENLKIDRPEDAGEKEHVTKSSVGHKNEPKMDNCHSVSRVKTQGQDSLEAQLSSLESSRRVHTSTPSDKNLLDTY
NTELLKSDSDNNNSDDCGNILPSDIMDFVLKNTPSMQALGESPESSSSELLNLGEGLGLDSNREKDMGLFEVFSQQLPTTEPVDSSVSSS
ISAEEQFELPLELPSDLSVLTTRSPTVPSQNPSRLAVISDSGEKRVTITEKSVASSESDPALLSPGVDPTPEGHMTPDHFIQGHMDADHI
SSPPCGSVEQGHGNNQDLTRNSSTPGLQVPVSPTVPIQNQKYVPNSTDSPGPSQISNAAVQTTPPHLKPATEKLIVVNQNMQPLYVLQTL
PNGVTQKIQLTSSVSSTPSVMETNTSVLGPMGGGLTLTTGLNPSLPTSQSLFPSASKGLLPMSHHQHLHSFPAATQSSFPPNISNPPSGL
LIGVQPPPDPQLLVSESSQRTDLSTTVATPSSGLKKRPISRLQTRKNKKLAPSSTPSNIAPSDVVSNMTLINFTPSQLPNHPSLLDLGSL
NTSSHRTVPNIIKRSKSSIMYFEPAPLLPQSVGGTAATAAGTSTISQDTSHLTSGSVSGLASSSSVLNVVSMQTTTTPTSSASVPGHVTL
TNPRLLGTPDIGSISNLLIKASQQSLGIQDQPVALPPSSGMFPQLGTSQTPSTAAITAASSICVLPSTQTTGITAASPSGEADEHYQLQH
VNQLLASKTGIHSSQRDLDSASGPQVSNFTQTVDAPNSMGLEQNKALSSAVQASPTSPGGSPSSPSSGQRSASPSVPGPTKPKPKTKRFQ
LPLDKGNGKKHKVSHLRTSSSEAHIPDQETTSLTSGTGTPGAEAEQQDTASVEQSSQKECGQPAGQVAVLPEVQVTQNPANEQESAEPKT
VEEEESNFSSPLMLWLQQEQKRKESITEKKPKKGLVFEISSDDGFQICAESIEDAWKSLTDKVQEARSNARLKQLSFAGVNGLRMLGILH
DAVVFLIEQLSGAKHCRNYKFRFHKPEEANEPPLNPHGSARAEVHLRKSAFDMFNFLASKHRQPPEYNPNDEEEEEVQLKSARRATSMDL
PMPMRFRHLKKTSKEAVGVYRSPIHGRGLFCKRNIDAGEMVIEYAGNVIRSIQTDKREKYYDSKGIGCYMFRIDDSEVVDATMHGNAARF

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Fusion Protein Functional Features


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/chr17:/chr11:)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
TOP3A

Q13472

KMT2A

Q03164

FUNCTION: Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. As an essential component of the RMI complex it is involved in chromosome separation and the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Has DNA decatenation activity (PubMed:30057030). It is required for mtDNA decatenation and segregation after completion of replication, in a process that does not require BLM, RMI1 and RMI2 (PubMed:29290614). {ECO:0000269|PubMed:20445207, ECO:0000269|PubMed:29290614, ECO:0000269|PubMed:30057030, ECO:0000269|PubMed:8622991}.FUNCTION: Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:24235145, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:25561738, PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20677832, PubMed:20010842). Promotes PPP1R15A-induced apoptosis (PubMed:10490642). Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-ARNTL/BMAL1 heterodimer (By similarity). Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-ARNTL/BMAL1 to chromatin (By similarity). Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}.

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.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Protein Structures

check button PDB and CIF files of the predicted fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
Fusion protein PDB link (fusion AA seq ID in FusionPDB)HgeneHchrHbpHstrandTgeneTchrTbpTstrandAA seqLen(AA seq)
PDB file (1182)TOP3Achr1718217912-KMT2Achr11118355576+
MKLQRPAGWWGRDRSEALVPFRWAPFEPHLWLPQDAPAAGERLRARGLRM
IFPVARYALRWLRRPEDRAFSRAAMEMALRGVRKVLCVAEKNDAAKGIAD
LLSNGRMRREDCEAENVWEMGGLGILTSVPITPRVVCFLCASSGHVEFVY
CQVCCEPFHKFCLEENERPLEDQLENWCCRRCKFCHVCGRQHQATKQLLE
CNKCRNSYHPECLGPNYPTKPTKKKKVWICTKCVRCKSCGSTTPGKGWDA
QWSHDFSLCHDCAKLFAKGNFCPLCDKCYDDDDYESKMMQCGKCDRWVHS
KCENLSDEMYEILSNLPESVAYTCVNCTERHPAEWRLALEKELQISLKQV
LTALLNSRTTSHLLRYRQAAKPPDLNPETEESIPSRSSPEGPDPPVLTEV
SKQDDQQPLDLEGVKRKMDQGNYTSVLEFSDDIVKIIQAAINSDGGQPEI
KKANSMVKSFFIRQMERVFPWFSVKKSRFWEPNKVSSNSGMLPNAVLPPS
LDHNYAQWQEREENSHTEQPPLMKKIIPAPKPKGPGEPDSPTPLHPPTPP
ILSTDRSREDSPELNPPPGIEDNRQCALCLTYGDDSANDAGRLLYIGQNE
WTHVNCALWSAEVFEDDDGSLKNVHMAVIRGKQLRCEFCQKPGATVGCCL
TSCTSNYHFMCSRAKNCVFLDDKKVYCQRHRDLIKGEVVPENGFEVFRRV
FVDFEGISLRRKFLNGLEPENIHMMIGSMTIDCLGILNDLSDCEDKLFPI
GYQCSRVYWSTTDARKRCVYTCKIVECRPPVVEPDINSTVEHDENRTIAH
SPTSFTESSSKESQNTAEIISPPSPDRPPHSQTSGSCYYHVISKVPRIRT
PSYSPTQRSPGCRPLPSAGSPTPTTHEIVTVGDPLLSSGLRSIGSRRHST
SSLSPQRSKLRIMSPMRTGNTYSRNNVSSVSTTGTATDLESSAKVVDHVL
GPLNSSTSLGQNTSTSSNLQRTVVTVGNKNSHLDGSSSSEMKQSSASDLV
SKSSSLKGEKTKVLSSKSSEGSAHNVAYPGIPKLAPQVHNTTSRELNVSK
IGSFAEPSSVSFSSKEALSFPHLHLRGQRNDRDQHTDSTQSANSSPDEDT
EVKTLKLSGMSNRSSIINEHMGSSSRDRRQKGKKSCKETFKEKHSSKSFL
EPGQVTTGEEGNLKPEFMDEVLTPEYMGQRPCNNVSSDKIGDKGLSMPGV
PKAPPMQVEGSAKELQAPRKRTVKVTLTPLKMENESQSKNALKESSPASP
LQIESTSPTEPISASENPGDGPVAQPSPNNTSCQDSQSNNYQNLPVQDRN
LMLPDGPKPQEDGSFKRRYPRRSARARSNMFFGLTPLYGVRSYGEEDIPF
YSSSTGKKRGKRSAEGQVDGADDLSTSDEDDLYYYNFTRTVISSGGEERL
ASHNLFREEEQCDLPKISQLDGVDDGTESDTSVTATTRKSSQIPKRNGKE
NGTENLKIDRPEDAGEKEHVTKSSVGHKNEPKMDNCHSVSRVKTQGQDSL
EAQLSSLESSRRVHTSTPSDKNLLDTYNTELLKSDSDNNNSDDCGNILPS
DIMDFVLKNTPSMQALGESPESSSSELLNLGEGLGLDSNREKDMGLFEVF
SQQLPTTEPVDSSVSSSISAEEQFELPLELPSDLSVLTTRSPTVPSQNPS
RLAVISDSGEKRVTITEKSVASSESDPALLSPGVDPTPEGHMTPDHFIQG
HMDADHISSPPCGSVEQGHGNNQDLTRNSSTPGLQVPVSPTVPIQNQKYV
PNSTDSPGPSQISNAAVQTTPPHLKPATEKLIVVNQNMQPLYVLQTLPNG
VTQKIQLTSSVSSTPSVMETNTSVLGPMGGGLTLTTGLNPSLPTSQSLFP
SASKGLLPMSHHQHLHSFPAATQSSFPPNISNPPSGLLIGVQPPPDPQLL
VSESSQRTDLSTTVATPSSGLKKRPISRLQTRKNKKLAPSSTPSNIAPSD
VVSNMTLINFTPSQLPNHPSLLDLGSLNTSSHRTVPNIIKRSKSSIMYFE
PAPLLPQSVGGTAATAAGTSTISQDTSHLTSGSVSGLASSSSVLNVVSMQ
TTTTPTSSASVPGHVTLTNPRLLGTPDIGSISNLLIKASQQSLGIQDQPV
ALPPSSGMFPQLGTSQTPSTAAITAASSICVLPSTQTTGITAASPSGEAD
EHYQLQHVNQLLASKTGIHSSQRDLDSASGPQVSNFTQTVDAPNSMGLEQ
NKALSSAVQASPTSPGGSPSSPSSGQRSASPSVPGPTKPKPKTKRFQLPL
DKGNGKKHKVSHLRTSSSEAHIPDQETTSLTSGTGTPGAEAEQQDTASVE
QSSQKECGQPAGQVAVLPEVQVTQNPANEQESAEPKTVEEEESNFSSPLM
LWLQQEQKRKESITEKKPKKGLVFEISSDDGFQICAESIEDAWKSLTDKV
QEARSNARLKQLSFAGVNGLRMLGILHDAVVFLIEQLSGAKHCRNYKFRF
HKPEEANEPPLNPHGSARAEVHLRKSAFDMFNFLASKHRQPPEYNPNDEE
EEEVQLKSARRATSMDLPMPMRFRHLKKTSKEAVGVYRSPIHGRGLFCKR
NIDAGEMVIEYAGNVIRSIQTDKREKYYDSKGIGCYMFRIDDSEVVDATM
HGNAARFINHSCEPNCYSRVINIDGQKHIVIFAMRKIYRGEELTYDYKFP
2672
PDB file (1183)TOP3Achr1718217912-KMT2Achr11118355576+
MKLQRPAGWWGRDRSEALVPFRWAPFEPHLWLPQDAPAAGERLRARGLRM
IFPVARYALRWLRRPEDRAFSRAAMEMALRGVRKVLCVAEKNDAAKGIAD
LLSNGRMRREDCEAENVWEMGGLGILTSVPITPRVVCFLCASSGHVEFVY
CQVCCEPFHKFCLEENERPLEDQLENWCCRRCKFCHVCGRQHQATKQLLE
CNKCRNSYHPECLGPNYPTKPTKKKKVWICTKCVRCKSCGSTTPGKGWDA
QWSHDFSLCHDCAKLFAKGNFCPLCDKCYDDDDYESKMMQCGKCDRWVHS
KCENLSGTEDEMYEILSNLPESVAYTCVNCTERHPAEWRLALEKELQISL
KQVLTALLNSRTTSHLLRYRQAAKPPDLNPETEESIPSRSSPEGPDPPVL
TEVSKQDDQQPLDLEGVKRKMDQGNYTSVLEFSDDIVKIIQAAINSDGGQ
PEIKKANSMVKSFFIRQMERVFPWFSVKKSRFWEPNKVSSNSGMLPNAVL
PPSLDHNYAQWQEREENSHTEQPPLMKKIIPAPKPKGPGEPDSPTPLHPP
TPPILSTDRSREDSPELNPPPGIEDNRQCALCLTYGDDSANDAGRLLYIG
QNEWTHVNCALWSAEVFEDDDGSLKNVHMAVIRGKQLRCEFCQKPGATVG
CCLTSCTSNYHFMCSRAKNCVFLDDKKVYCQRHRDLIKGEVVPENGFEVF
RRVFVDFEGISLRRKFLNGLEPENIHMMIGSMTIDCLGILNDLSDCEDKL
FPIGYQCSRVYWSTTDARKRCVYTCKIVECRPPVVEPDINSTVEHDENRT
IAHSPTSFTESSSKESQNTAEIISPPSPDRPPHSQTSGSCYYHVISKVPR
IRTPSYSPTQRSPGCRPLPSAGSPTPTTHEIVTVGDPLLSSGLRSIGSRR
HSTSSLSPQRSKLRIMSPMRTGNTYSRNNVSSVSTTGTATDLESSAKVVD
HVLGPLNSSTSLGQNTSTSSNLQRTVVTVGNKNSHLDGSSSSEMKQSSAS
DLVSKSSSLKGEKTKVLSSKSSEGSAHNVAYPGIPKLAPQVHNTTSRELN
VSKIGSFAEPSSVSFSSKEALSFPHLHLRGQRNDRDQHTDSTQSANSSPD
EDTEVKTLKLSGMSNRSSIINEHMGSSSRDRRQKGKKSCKETFKEKHSSK
SFLEPGQVTTGEEGNLKPEFMDEVLTPEYMGQRPCNNVSSDKIGDKGLSM
PGVPKAPPMQVEGSAKELQAPRKRTVKVTLTPLKMENESQSKNALKESSP
ASPLQIESTSPTEPISASENPGDGPVAQPSPNNTSCQDSQSNNYQNLPVQ
DRNLMLPDGPKPQEDGSFKRRYPRRSARARSNMFFGLTPLYGVRSYGEED
IPFYSSSTGKKRGKRSAEGQVDGADDLSTSDEDDLYYYNFTRTVISSGGE
ERLASHNLFREEEQCDLPKISQLDGVDDGTESDTSVTATTRKSSQIPKRN
GKENGTENLKIDRPEDAGEKEHVTKSSVGHKNEPKMDNCHSVSRVKTQGQ
DSLEAQLSSLESSRRVHTSTPSDKNLLDTYNTELLKSDSDNNNSDDCGNI
LPSDIMDFVLKNTPSMQALGESPESSSSELLNLGEGLGLDSNREKDMGLF
EVFSQQLPTTEPVDSSVSSSISAEEQFELPLELPSDLSVLTTRSPTVPSQ
NPSRLAVISDSGEKRVTITEKSVASSESDPALLSPGVDPTPEGHMTPDHF
IQGHMDADHISSPPCGSVEQGHGNNQDLTRNSSTPGLQVPVSPTVPIQNQ
KYVPNSTDSPGPSQISNAAVQTTPPHLKPATEKLIVVNQNMQPLYVLQTL
PNGVTQKIQLTSSVSSTPSVMETNTSVLGPMGGGLTLTTGLNPSLPTSQS
LFPSASKGLLPMSHHQHLHSFPAATQSSFPPNISNPPSGLLIGVQPPPDP
QLLVSESSQRTDLSTTVATPSSGLKKRPISRLQTRKNKKLAPSSTPSNIA
PSDVVSNMTLINFTPSQLPNHPSLLDLGSLNTSSHRTVPNIIKRSKSSIM
YFEPAPLLPQSVGGTAATAAGTSTISQDTSHLTSGSVSGLASSSSVLNVV
SMQTTTTPTSSASVPGHVTLTNPRLLGTPDIGSISNLLIKASQQSLGIQD
QPVALPPSSGMFPQLGTSQTPSTAAITAASSICVLPSTQTTGITAASPSG
EADEHYQLQHVNQLLASKTGIHSSQRDLDSASGPQVSNFTQTVDAPNSMG
LEQNKALSSAVQASPTSPGGSPSSPSSGQRSASPSVPGPTKPKPKTKRFQ
LPLDKGNGKKHKVSHLRTSSSEAHIPDQETTSLTSGTGTPGAEAEQQDTA
SVEQSSQKECGQPAGQVAVLPEVQVTQNPANEQESAEPKTVEEEESNFSS
PLMLWLQQEQKRKESITEKKPKKGLVFEISSDDGFQICAESIEDAWKSLT
DKVQEARSNARLKQLSFAGVNGLRMLGILHDAVVFLIEQLSGAKHCRNYK
FRFHKPEEANEPPLNPHGSARAEVHLRKSAFDMFNFLASKHRQPPEYNPN
DEEEEEVQLKSARRATSMDLPMPMRFRHLKKTSKEAVGVYRSPIHGRGLF
CKRNIDAGEMVIEYAGNVIRSIQTDKREKYYDSKGIGCYMFRIDDSEVVD
ATMHGNAARFINHSCEPNCYSRVINIDGQKHIVIFAMRKIYRGEELTYDY
2675


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pLDDT score distribution

check button pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
TOP3A_pLDDT.png
all structure
KMT2A_pLDDT.png
all structure
all structure

check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.


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Ramachandran Plot of Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.
Fusion AA seq ID in FusionPDB and their Ramachandran plots
TOP3A_KMT2A_1183.png
all structure

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Potential Active Site Information


check button The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.
Fusion AA seq ID in FusionPDBSite scoreSizeD scoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues
11831.0236251.0461752.730.5510.7210.9340.56910.5690.663Chain A: 19,20,21,22,23,24,25,26,28,29,30,134,135,
144,145,146,147,148,149,150,152,160,161,164,165,16
6,167,168,169,170,171,172,173,174,175,176,177,178,
179,180,181,182,183,184,186,191,192,197,198,199,20
0,202,205,206,207,221,225,226,227,228,526,527,528,
529,530,531,532,533,700,760,762,763,767,768,769,77
0,771,772,1064,1065,1066,1068,2382,2383,2407,2408,
2411,2412,2413,2414,2415,2416

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Potentially Interacting Small Molecules through Virtual Screening


check button The FDA-approved small molecule library molecules were subjected to virtual screening using the Glide.
Fusion AA seq ID in FusionPDBZINC IDDrugBank IDDrug nameDocking scoreGlide gscore

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check button Drug information from DrugBank of the top 20 interacting small molecules.
ZINC IDDrugBank IDDrug nameDrug typeSMILESDrug group

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Biochemical Features of Small Molecules


check button ADME (Absorption, Distribution, Metabolism, and Excretion) of drugs using QikProp(v3.9)
ZINC IDmol_MWdipoleSASAFOSAFISAPISAWPSAvolumedonorHBaccptHBIPHuman Oral AbsorptionPercent Human Oral AbsorptionRule Of FiveRule Of Three


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Drug Toxicity Information


check button Toxicity information of individual drugs using eToxPred
ZINC IDSmileSurface AccessibilityToxicity


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Fusion Protein-Protein Interaction


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 from validated records (BIOGRID-3.4.160)
GenePPI interactors
KMT2APPIE, PPP1R15A, KMT2A, ASH2L, HCFC1, HCFC2, MEN1, RBBP5, WDR5, AVP, INS, OXT, MAP3K5, HDAC1, CTBP1, CBX4, BMI1, CREBBP, SMARCB1, CXXC1, MYB, CTNNB1, SNW1, E2F2, E2F4, E2F6, PSIP1, MLLT4, POLR2A, KAT8, RNF2, TP53, tat, SBF1, MTM1, SET, HIST1H3A, HIST1H4A, KAT6A, ELL, AFF1, AFF4, CDK9, CCNT1, CTR9, LEO1, PAF1, CDC73, WDR61, MLLT3, DOT1L, SKP2, HIST3H3, SVIL, HIST2H3C, SIN3A, MLLT1, RUNX1, CBFB, H3F3A, SIRT7, ASB2, TCEB1, TCEB2, CBX8, TOP1, TAF6, NCL, HECW2, LGR4, CSNK2A2, SENP3, SYMPK, PKN1, PIH1D1, KRAS, TAF1, CHD3, SMARCA2, SMARCC2, SMARCC1, HDAC2, RBBP4, RBBP7, TBP, MBD3, SAP30, RAN, TAF9, TASP1, HIST1H2BG, EWSR1, DYNLT1, KIF11, ING4, Cbx1, Set, ZNF131, ASB7, AR, CSNK2A1, OGT, BRD4, KDM5B, KDM5D, KDM6B, CKS1B, CKS2, CHD4, ESR2, AGR2, EZH2, FBXW7, SOX2, MED17, WDR82, ACTR8, GEMIN5, RUVBL1, MCM2, RTF1, MED15, MED8, MRGBP, MED14, HIST1H2BB, HIST1H2AB, KIAA1429, SP1, MYC, NR2C2, IRF2, PLEKHA4, DPY30, PTEN, NPM1, RPL13, CCT6A, TMCO1, ITGB1, ESR1, MYCN, SUPT5H, CIT, Pik3r2, FASN, LDLR, CDC27, KMT2B, SETD1A, KDM6A, KANSL2, BUB3, SETD1B, KANSL1, RERE, MCRS1, KMT2C, ZZZ3, MBIP, YEATS2, PAXIP1, KANSL3, KMT2D, BOD1L1, CSRP2BP, ZNF608, ATN1, PHF20L1, PHF20, NCOA6, TADA3, APEX1, ASF1A, CBX3, CD3EAP, CENPA, NUP50, POLR1E, TERF2IP, ZNF330, NAA40, PRKRA, SRSF4, KRR1, RPL13A, ABT1, CSNK2B, OASL, SRSF5, SRSF6, RPS9, FGFBP1, RPLP0, RPL36, KAL1, RPL3, PML, ELF1, ELF2, FEV, NHLH1, EN1, KLF12, KLF3, NFIX, NFYC, YY1, BRD3,
TOP3ABLM, FANCA, RECQL5, APITD1, FANCM, RMI1, RPA1, FANCG, Ercc6l, Top3a, Rmi1, RAD21, TERF2, LSM11, MIB1, RPA3, RPA2, C17orf70, ECHDC2, LIG3, MRM1, RMI2, OXLD1, DCUN1D4, TTF2, NTRK1, CEP162, TSNAX, CCDC69, SDHB, C4orf26, MARCKSL1, ATP5D, COX7A2, BPNT1, YBEY, MRPL21, NIT1, METTL2A, SLX1A, THEM4, MECP2, TMEM70, CHEK1, BRCA2, WEE1, PALB2, RAD17, LLGL1, MSH2, NF1, RPS11, CDC73, CDC6, MAP3K4, TTN, FH, FANCD2, EGLN3, HERC2, SNAI1, BRCA1, TDRD3, SPIDR, ETAA1, FBXO38, HIST1H4A, PLEKHA4, METTL17, MTIF2, MTRF1, SSBP1, TSFM, TMEM79, AARS2, PDHA1, MALSU1, HINT2, LINC01565, ICAM4, MAP7, COX5B, SSC4D, NDUFV3, NAA38, HMGA2, FEM1A, PIP, MRPS18B, ATPAF1, UQCRFS1, PDP1, XPA, MRPL23, BTF3,


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
TOP3Aall structure
KMT2Aall structure


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to TOP3A-KMT2A


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 TOP3A-KMT2A


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
HgeneTOP3AC4748176MICROCEPHALY, GROWTH RESTRICTION, AND INCREASED SISTER CHROMATID EXCHANGE 21GENOMICS_ENGLAND;UNIPROT
HgeneTOP3AC4748184PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 51GENOMICS_ENGLAND;UNIPROT
TgeneKMT2AC2826025Mixed phenotype acute leukemia3ORPHANET
TgeneKMT2AC0023418leukemia2CTD_human
TgeneKMT2AC0023452Childhood Acute Lymphoblastic Leukemia2CTD_human
TgeneKMT2AC0023453L2 Acute Lymphoblastic Leukemia2CTD_human
TgeneKMT2AC0023466Leukemia, Monocytic, Chronic2CTD_human
TgeneKMT2AC0023467Leukemia, Myelocytic, Acute2CTD_human
TgeneKMT2AC0023470Myeloid Leukemia2CTD_human
TgeneKMT2AC0026998Acute Myeloid Leukemia, M12CTD_human
TgeneKMT2AC1854630Growth Deficiency and Mental Retardation with Facial Dysmorphism2CTD_human;GENOMICS_ENGLAND;ORPHANET
TgeneKMT2AC1879321Acute Myeloid Leukemia (AML-M2)2CTD_human
TgeneKMT2AC1961102Precursor Cell Lymphoblastic Leukemia Lymphoma2CTD_human
TgeneKMT2AC0001418Adenocarcinoma1CTD_human
TgeneKMT2AC0004403Autosome Abnormalities1CTD_human
TgeneKMT2AC0005684Malignant neoplasm of urinary bladder1CTD_human
TgeneKMT2AC0005695Bladder Neoplasm1CTD_human
TgeneKMT2AC0007138Carcinoma, Transitional Cell1CTD_human
TgeneKMT2AC0008625Chromosome Aberrations1CTD_human
TgeneKMT2AC0023448Lymphoid leukemia1CTD_human
TgeneKMT2AC0023465Acute monocytic leukemia1CTD_human
TgeneKMT2AC0023479Acute myelomonocytic leukemia1CTD_human
TgeneKMT2AC0024623Malignant neoplasm of stomach1CTD_human
TgeneKMT2AC0033578Prostatic Neoplasms1CTD_human
TgeneKMT2AC0036341Schizophrenia1PSYGENET
TgeneKMT2AC0038356Stomach Neoplasms1CTD_human
TgeneKMT2AC0149925Small cell carcinoma of lung1CTD_human
TgeneKMT2AC0205641Adenocarcinoma, Basal Cell1CTD_human
TgeneKMT2AC0205642Adenocarcinoma, Oxyphilic1CTD_human
TgeneKMT2AC0205643Carcinoma, Cribriform1CTD_human
TgeneKMT2AC0205644Carcinoma, Granular Cell1CTD_human
TgeneKMT2AC0205645Adenocarcinoma, Tubular1CTD_human
TgeneKMT2AC0270972Cornelia De Lange Syndrome1ORPHANET
TgeneKMT2AC0280141Acute Undifferentiated Leukemia1ORPHANET
TgeneKMT2AC0376358Malignant neoplasm of prostate1CTD_human
TgeneKMT2AC0856823Undifferentiated type acute leukemia1ORPHANET
TgeneKMT2AC1535926Neurodevelopmental Disorders1CTD_human
TgeneKMT2AC1708349Hereditary Diffuse Gastric Cancer1CTD_human
TgeneKMT2AC2239176Liver carcinoma1CTD_human
TgeneKMT2AC2930974Acute erythroleukemia1CTD_human
TgeneKMT2AC2930975Acute erythroleukemia - M6a subtype1CTD_human
TgeneKMT2AC2930976Acute myeloid leukemia FAB-M61CTD_human
TgeneKMT2AC2930977Acute erythroleukemia - M6b subtype1CTD_human