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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:TFAP2A-MAK

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TFAP2A-MAK
FusionPDB ID: 90258
FusionGDB2.0 ID: 90258
HgeneTgene
Gene symbol

TFAP2A

MAK

Gene ID

7020

57538

Gene nametranscription factor AP-2 alphaalpha kinase 3
SynonymsAP-2|AP-2alpha|AP2TF|BOFS|TFAP2CMH27|MAK|MIDORI
Cytomap

6p24.3

15q25.3

Type of geneprotein-codingprotein-coding
Descriptiontranscription factor AP-2-alphaAP-2 transcription factoractivating enhancer-binding protein 2-alphaactivator protein 2transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha)alpha-protein kinase 3muscle alpha-kinasemuscle alpha-protein kinasemyocyte induction differentiation originator
Modification date2020032820200313
UniProtAcc.

Q9BXY0

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000319516, ENST00000379604, 
ENST00000379608, ENST00000379613, 
ENST00000482890, ENST00000497266, 
ENST00000538030, ENST00000536370, 
ENST00000313243, ENST00000354489, 
ENST00000474039, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 3=484 X 4 X 4=64
# samples 44
** MAII scorelog2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/64*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TFAP2A [Title/Abstract] AND MAK [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TFAP2A [Title/Abstract] AND MAK [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TFAP2A(10404741)-MAK(10764839), # samples:3
Anticipated loss of major functional domain due to fusion event.TFAP2A-MAK 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.
TFAP2A-MAK 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.
TFAP2A-MAK 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.
TFAP2A-MAK 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.
TFAP2A-MAK seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
TFAP2A-MAK seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
TFAP2A-MAK seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
TFAP2A-MAK seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
TFAP2A-MAK seems lost the major protein functional domain in Tgene partner, which is a kinase 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
HgeneTFAP2A

GO:0000122

negative regulation of transcription by RNA polymerase II

8321221|9520389|20066163

HgeneTFAP2A

GO:0008285

negative regulation of cell proliferation

20607706

HgeneTFAP2A

GO:0030501

positive regulation of bone mineralization

19578371

HgeneTFAP2A

GO:0043066

negative regulation of apoptotic process

20066163

HgeneTFAP2A

GO:0043525

positive regulation of neuron apoptotic process

20607706

HgeneTFAP2A

GO:0045595

regulation of cell differentiation

20607706

HgeneTFAP2A

GO:0045892

negative regulation of transcription, DNA-templated

20607706

HgeneTFAP2A

GO:0045893

positive regulation of transcription, DNA-templated

12586840

HgeneTFAP2A

GO:0045944

positive regulation of transcription by RNA polymerase II

7555706|7559606|11278550|20808827

HgeneTFAP2A

GO:0070172

positive regulation of tooth mineralization

19578371

HgeneTFAP2A

GO:0071281

cellular response to iron ion

20808827

HgeneTFAP2A

GO:2000378

negative regulation of reactive oxygen species metabolic process

20066163



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/chr6:10404741/chr6:10764839)
- 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 TFAP2A (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 MAK (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)
ENST00000379613TFAP2Achr610404741-ENST00000313243MAKchr610764839-29111027981081327
ENST00000379613TFAP2Achr610404741-ENST00000474039MAKchr610764839-29111027981081327
ENST00000379604TFAP2Achr610404741-ENST00000313243MAKchr610764839-29001016871070327
ENST00000379604TFAP2Achr610404741-ENST00000474039MAKchr610764839-29001016871070327
ENST00000319516TFAP2Achr610404741-ENST00000313243MAKchr610764839-2824940101994297
ENST00000319516TFAP2Achr610404741-ENST00000474039MAKchr610764839-2824940101994297
ENST00000379608TFAP2Achr610404741-ENST00000313243MAKchr610764839-340815247781578266
ENST00000379608TFAP2Achr610404741-ENST00000474039MAKchr610764839-340815247781578266
ENST00000482890TFAP2Achr610404741-ENST00000313243MAKchr610764839-300111172421171309
ENST00000482890TFAP2Achr610404741-ENST00000474039MAKchr610764839-300111172421171309

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
ENST00000379613ENST00000313243TFAP2Achr610404741-MAKchr610764839-0.0091775320.99082243
ENST00000379613ENST00000474039TFAP2Achr610404741-MAKchr610764839-0.0091775320.99082243
ENST00000379604ENST00000313243TFAP2Achr610404741-MAKchr610764839-0.009118060.9908819
ENST00000379604ENST00000474039TFAP2Achr610404741-MAKchr610764839-0.009118060.9908819
ENST00000319516ENST00000313243TFAP2Achr610404741-MAKchr610764839-0.019213440.9807866
ENST00000319516ENST00000474039TFAP2Achr610404741-MAKchr610764839-0.019213440.9807866
ENST00000379608ENST00000313243TFAP2Achr610404741-MAKchr610764839-0.0235546340.9764454
ENST00000379608ENST00000474039TFAP2Achr610404741-MAKchr610764839-0.0235546340.9764454
ENST00000482890ENST00000313243TFAP2Achr610404741-MAKchr610764839-0.0053496060.9946504
ENST00000482890ENST00000474039TFAP2Achr610404741-MAKchr610764839-0.0053496060.9946504

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 TFAP2A-MAK

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TFAP2Achr610404741MAKchr6107648391016309ECLNASLLGGVLRRIYLEHKNWSGAV
TFAP2Achr610404741MAKchr6107648391027309ECLNASLLGGVLRRIYLEHKNWSGAV
TFAP2Achr610404741MAKchr6107648391117291ECLNASLLGGVLRRIYLEHKNWSGAV
TFAP2Achr610404741MAKchr6107648391524248ECLNASLLGGVLRRIYLEHKNWSGAV
TFAP2Achr610404741MAKchr610764839940279ECLNASLLGGVLRRIYLEHKNWSGAV

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Potential FusionNeoAntigen Information of TFAP2A-MAK 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.
TFAP2A-MAK_10404741_10764839.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)
TFAP2A-MAKchr610404741chr610764839940HLA-A31:06SLLGGVLRR0.97570.5568514
TFAP2A-MAKchr610404741chr610764839940HLA-A74:11SLLGGVLRR0.9620.6986514
TFAP2A-MAKchr610404741chr610764839940HLA-A74:09SLLGGVLRR0.9620.6986514
TFAP2A-MAKchr610404741chr610764839940HLA-A74:03SLLGGVLRR0.9620.6986514
TFAP2A-MAKchr610404741chr610764839940HLA-A31:02SLLGGVLRR0.83540.6708514
TFAP2A-MAKchr610404741chr610764839940HLA-B27:02RRIYLEHKNW0.99950.84451222
TFAP2A-MAKchr610404741chr610764839940HLA-A02:13SLLGGVLRRI0.98540.7145515
TFAP2A-MAKchr610404741chr610764839940HLA-A02:27SLLGGVLRRI0.98110.6662515
TFAP2A-MAKchr610404741chr610764839940HLA-A02:11SLLGGVLRRI0.97790.6956515
TFAP2A-MAKchr610404741chr610764839940HLA-A02:24SLLGGVLRRI0.97670.6723515
TFAP2A-MAKchr610404741chr610764839940HLA-A02:67SLLGGVLRRI0.97670.6723515
TFAP2A-MAKchr610404741chr610764839940HLA-A02:30SLLGGVLRRI0.97670.6723515
TFAP2A-MAKchr610404741chr610764839940HLA-A02:60SLLGGVLRRI0.9760.6087515
TFAP2A-MAKchr610404741chr610764839940HLA-A02:16SLLGGVLRRI0.97340.6008515
TFAP2A-MAKchr610404741chr610764839940HLA-A74:03ASLLGGVLRR0.97070.7793414
TFAP2A-MAKchr610404741chr610764839940HLA-A74:11ASLLGGVLRR0.97070.7793414
TFAP2A-MAKchr610404741chr610764839940HLA-A74:09ASLLGGVLRR0.97070.7793414
TFAP2A-MAKchr610404741chr610764839940HLA-A31:06ASLLGGVLRR0.96180.6007414
TFAP2A-MAKchr610404741chr610764839940HLA-A02:38SLLGGVLRRI0.94940.6871515
TFAP2A-MAKchr610404741chr610764839940HLA-A11:04ASLLGGVLRR0.92880.5116414
TFAP2A-MAKchr610404741chr610764839940HLA-A02:35SLLGGVLRRI0.87610.7091515
TFAP2A-MAKchr610404741chr610764839940HLA-A02:29SLLGGVLRRI0.83660.6792515
TFAP2A-MAKchr610404741chr610764839940HLA-A02:20SLLGGVLRRI0.82220.6776515
TFAP2A-MAKchr610404741chr610764839940HLA-B15:25SLLGGVLRRIY0.95770.959516
TFAP2A-MAKchr610404741chr610764839940HLA-A80:01SLLGGVLRRIY0.94680.5003516
TFAP2A-MAKchr610404741chr610764839940HLA-A31:01SLLGGVLRR0.95930.6602514
TFAP2A-MAKchr610404741chr610764839940HLA-B27:03RRIYLEHKNW0.99260.96131222
TFAP2A-MAKchr610404741chr610764839940HLA-A02:01SLLGGVLRRI0.97670.6723515
TFAP2A-MAKchr610404741chr610764839940HLA-A31:01ASLLGGVLRR0.97020.7219414
TFAP2A-MAKchr610404741chr610764839940HLA-A74:01SLLGGVLRR0.9620.6986514
TFAP2A-MAKchr610404741chr610764839940HLA-A74:01ASLLGGVLRR0.97070.7793414
TFAP2A-MAKchr610404741chr610764839940HLA-A32:01RRIYLEHKNW0.75790.96581222

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Potential FusionNeoAntigen Information of TFAP2A-MAK 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.
TFAP2A-MAK_10404741_10764839.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)
TFAP2A-MAKchr610404741chr610764839940DRB1-1437LRRIYLEHKNWSGAV1126
TFAP2A-MAKchr610404741chr610764839940DRB1-1480LRRIYLEHKNWSGAV1126

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Fusion breakpoint peptide structures of TFAP2A-MAK

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
5218LLGGVLRRIYLEHKTFAP2AMAKchr610404741chr610764839940

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TFAP2A-MAK

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-B14:023BVN5218LLGGVLRRIYLEHK-5.89991-6.01331
HLA-B14:023BVN5218LLGGVLRRIYLEHK-4.1331-5.1684
HLA-B27:093CZF5218LLGGVLRRIYLEHK10000.110000
HLA-B52:013W395218LLGGVLRRIYLEHK-5.79162-5.90502
HLA-B52:013W395218LLGGVLRRIYLEHK-4.50212-5.53742
HLA-B18:014JQV5218LLGGVLRRIYLEHK-7.21332-8.24862
HLA-B18:014JQV5218LLGGVLRRIYLEHK-5.12387-5.23727
HLA-A11:014UQ25218LLGGVLRRIYLEHK-8.65958-8.77298
HLA-A11:014UQ25218LLGGVLRRIYLEHK-5.71034-6.74564
HLA-A24:025HGA5218LLGGVLRRIYLEHK-6.76463-6.87803
HLA-A24:025HGA5218LLGGVLRRIYLEHK-5.91906-6.95436
HLA-B27:056PYJ5218LLGGVLRRIYLEHK-5.96168-6.99698
HLA-B27:056PYJ5218LLGGVLRRIYLEHK-4.11716-4.23056
HLA-B27:036PZ55218LLGGVLRRIYLEHK-4.97412-6.00942
HLA-B27:036PZ55218LLGGVLRRIYLEHK-1.04645-1.15985
HLA-B44:053DX85218LLGGVLRRIYLEHK-6.19701-6.31041
HLA-B44:053DX85218LLGGVLRRIYLEHK-3.77766-4.81296
HLA-A02:016TDR5218LLGGVLRRIYLEHK-4.17517-5.21047

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Vaccine Design for the FusionNeoAntigens of TFAP2A-MAK

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
TFAP2A-MAKchr610404741chr6107648391222RRIYLEHKNWGAGAATATACCTGGAACACAAAAACTGGTC
TFAP2A-MAKchr610404741chr610764839414ASLLGGVLRRGTCGCTGCTGGGCGGAGTGCTCCGGAGAAT
TFAP2A-MAKchr610404741chr610764839514SLLGGVLRRGCTGCTGGGCGGAGTGCTCCGGAGAAT
TFAP2A-MAKchr610404741chr610764839515SLLGGVLRRIGCTGCTGGGCGGAGTGCTCCGGAGAATATA
TFAP2A-MAKchr610404741chr610764839516SLLGGVLRRIYGCTGCTGGGCGGAGTGCTCCGGAGAATATACCT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TFAP2A-MAKchr610404741chr6107648391126LRRIYLEHKNWSGAVCCGGAGAATATACCTGGAACACAAAAACTGGTCGGGGGCAGTTTT

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Information of the samples that have these potential fusion neoantigens of TFAP2A-MAK

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
BRCATFAP2A-MAKchr610404741ENST00000319516chr610764839ENST00000313243TCGA-AN-A0AR-01A

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Potential target of CAR-T therapy development for TFAP2A-MAK

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 TFAP2A-MAK

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 TFAP2A-MAK

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