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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:LETM1-MAEA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LETM1-MAEA
FusionPDB ID: 44485
FusionGDB2.0 ID: 44485
HgeneTgene
Gene symbol

LETM1

MAEA

Gene ID

3954

10296

Gene nameleucine zipper and EF-hand containing transmembrane protein 1macrophage erythroblast attacher, E3 ubiquitin ligase
SynonymsSLC55A1EMLP|EMP|GID9|HLC-10|P44EMLP|PIG5
Cytomap

4p16.3

4p16.3

Type of geneprotein-codingprotein-coding
Descriptionmitochondrial proton/calcium exchanger proteinLETM1 and EF-hand domain-containing protein 1, mitochondrialMdm38 homologleucine zipper-EF-hand containing transmembrane protein 1E3 ubiquitin-protein transferase MAEAGID complex subunit 9, FYV10 homologcell proliferation-inducing gene 5 proteinerythroblast macrophage proteinhuman lung cancer oncogene 10 proteinlung cancer-related protein 10macrophage erythroblast attacher
Modification date2020032820200314
UniProtAcc

O95202

Main function of 5'-partner protein: FUNCTION: Mitochondrial proton/calcium antiporter that mediates proton-dependent calcium efflux from mitochondrion (PubMed:19797662). Crucial for the maintenance of mitochondrial tubular networks and for the assembly of the supercomplexes of the respiratory chain (PubMed:18628306). Required for the maintenance of the tubular shape and cristae organization (PubMed:18628306). In contrast to SLC8B1/NCLX, does not constitute the major factor for mitochondrial calcium extrusion (PubMed:24898248). {ECO:0000269|PubMed:18628306, ECO:0000269|PubMed:19797662, ECO:0000269|PubMed:24898248}.

Q7L5Y9

Main function of 5'-partner protein: FUNCTION: Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. MAEA and RMND5A are both required for catalytic activity of the CTLH E3 ubiquitin-protein ligase complex (PubMed:29911972). MAEA is required for normal cell proliferation (PubMed:29911972). The CTLH E3 ubiquitin-protein ligase complex is not required for the degradation of enzymes involved in gluconeogenesis, such as FBP1 (PubMed:29911972). Plays a role in erythroblast enucleation during erythrocyte maturation and in the development of mature macrophages (By similarity). Mediates the attachment of erythroid cell to mature macrophages; this MAEA-mediated contact inhibits erythroid cell apoptosis (PubMed:9763581). Participates in erythroblastic island formation, which is the functional unit of definitive erythropoiesis. Associates with F-actin to regulate actin distribution in erythroblasts and macrophages (By similarity). May contribute to nuclear architecture and cells division events (Probable). {ECO:0000250|UniProtKB:Q4VC33, ECO:0000269|PubMed:29911972, ECO:0000269|PubMed:9763581, ECO:0000305|PubMed:16510120}.
Ensembl transtripts involved in fusion geneENST idsENST00000302787, ENST00000512189, 
ENST00000512289, ENST00000264750, 
ENST00000303400, ENST00000452175, 
ENST00000505177, ENST00000505839, 
ENST00000510794, ENST00000514708, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 13 X 7=9108 X 9 X 5=360
# samples 1211
** MAII scorelog2(12/910*10)=-2.92283213947754
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/360*10)=-1.71049338280502
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LETM1 [Title/Abstract] AND MAEA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LETM1 [Title/Abstract] AND MAEA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LETM1(1857595)-MAEA(1326544), # samples:1
LETM1(1817390)-MAEA(1332861), # samples:1
Anticipated loss of major functional domain due to fusion event.LETM1-MAEA 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.
LETM1-MAEA 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.
LETM1-MAEA 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.
LETM1-MAEA 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.
LETM1-MAEA seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
LETM1-MAEA seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
LETM1-MAEA seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneLETM1

GO:0006851

mitochondrial calcium ion transmembrane transport

19797662

HgeneLETM1

GO:0051560

mitochondrial calcium ion homeostasis

19797662

HgeneLETM1

GO:0099093

calcium export from the mitochondrion

19797662

TgeneMAEA

GO:0007155

cell adhesion

9763581

TgeneMAEA

GO:0033033

negative regulation of myeloid cell apoptotic process

9763581



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/chr4:1857595/chr4:1326544)
- 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 LETM1 (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 MAEA (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)
ENST00000302787LETM1chr41857595-ENST00000514708MAEAchr41326544+18493795431181
ENST00000302787LETM1chr41817390-ENST00000452175MAEAchr41332861+265823672972462721
ENST00000302787LETM1chr41817390-ENST00000514708MAEAchr41332861+340223672972462721

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
ENST00000302787ENST00000514708LETM1chr41857595-MAEAchr41326544+0.280354440.7196456
ENST00000302787ENST00000452175LETM1chr41817390-MAEAchr41332861+0.0197273250.9802727
ENST00000302787ENST00000514708LETM1chr41817390-MAEAchr41332861+0.0124072640.98759276

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 LETM1-MAEA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LETM1chr41817390MAEAchr413328612367690NKDGKVNIDDLVKSLLSIRQDDKVVC

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Potential FusionNeoAntigen Information of LETM1-MAEA 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.
LETM1-MAEA_1817390_1332861.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)
LETM1-MAEAchr41817390chr413328612367HLA-A02:21NIDDLVKSL0.8190.567615
LETM1-MAEAchr41817390chr413328612367HLA-A02:38NIDDLVKSL0.77390.5013615
LETM1-MAEAchr41817390chr413328612367HLA-B35:02NIDDLVKSL0.53720.8866615
LETM1-MAEAchr41817390chr413328612367HLA-B35:04NIDDLVKSL0.53720.8866615
LETM1-MAEAchr41817390chr413328612367HLA-B39:08IDDLVKSL0.99560.6832715
LETM1-MAEAchr41817390chr413328612367HLA-C04:07NIDDLVKSL0.99990.6419615
LETM1-MAEAchr41817390chr413328612367HLA-C05:09NIDDLVKSL0.99990.9277615
LETM1-MAEAchr41817390chr413328612367HLA-C04:10NIDDLVKSL0.99990.6457615
LETM1-MAEAchr41817390chr413328612367HLA-C08:15NIDDLVKSL0.99990.9575615
LETM1-MAEAchr41817390chr413328612367HLA-C01:17NIDDLVKSL0.99980.8728615
LETM1-MAEAchr41817390chr413328612367HLA-C03:19NIDDLVKSL0.99750.9893615
LETM1-MAEAchr41817390chr413328612367HLA-C03:07NIDDLVKSL0.99710.9628615
LETM1-MAEAchr41817390chr413328612367HLA-C04:06NIDDLVKSL0.99250.7457615
LETM1-MAEAchr41817390chr413328612367HLA-C08:13NIDDLVKSL0.98230.9057615
LETM1-MAEAchr41817390chr413328612367HLA-C08:04NIDDLVKSL0.98230.9057615
LETM1-MAEAchr41817390chr413328612367HLA-C01:30NIDDLVKSL0.96560.9171615
LETM1-MAEAchr41817390chr413328612367HLA-C04:14NIDDLVKSL0.9580.6391615
LETM1-MAEAchr41817390chr413328612367HLA-C08:03NIDDLVKSL0.92370.9663615
LETM1-MAEAchr41817390chr413328612367HLA-C07:13NIDDLVKSL0.82010.8401615
LETM1-MAEAchr41817390chr413328612367HLA-B14:03NIDDLVKSL0.78070.8014615
LETM1-MAEAchr41817390chr413328612367HLA-B39:08IDDLVKSLL0.72410.764716
LETM1-MAEAchr41817390chr413328612367HLA-C07:29NIDDLVKSL0.71210.8656615
LETM1-MAEAchr41817390chr413328612367HLA-B39:10NIDDLVKSL0.66380.748615
LETM1-MAEAchr41817390chr413328612367HLA-B35:12NIDDLVKSL0.53720.8866615
LETM1-MAEAchr41817390chr413328612367HLA-C05:09NIDDLVKSLL10.9634616
LETM1-MAEAchr41817390chr413328612367HLA-C08:15NIDDLVKSLL0.99990.967616
LETM1-MAEAchr41817390chr413328612367HLA-C08:15VNIDDLVKSL0.9990.9699515
LETM1-MAEAchr41817390chr413328612367HLA-A02:07NIDDLVKSLL0.69020.5399616
LETM1-MAEAchr41817390chr413328612367HLA-A02:07VNIDDLVKSL0.63580.6424515
LETM1-MAEAchr41817390chr413328612367HLA-C01:03NIDDLVKSL0.99990.8693615
LETM1-MAEAchr41817390chr413328612367HLA-C04:01NIDDLVKSL0.99990.6419615
LETM1-MAEAchr41817390chr413328612367HLA-C04:03NIDDLVKSL0.99990.6853615
LETM1-MAEAchr41817390chr413328612367HLA-C18:01NIDDLVKSL0.99990.6577615
LETM1-MAEAchr41817390chr413328612367HLA-C08:02NIDDLVKSL0.99990.9575615
LETM1-MAEAchr41817390chr413328612367HLA-C05:01NIDDLVKSL0.99990.9277615
LETM1-MAEAchr41817390chr413328612367HLA-C01:02NIDDLVKSL0.99980.8661615
LETM1-MAEAchr41817390chr413328612367HLA-C03:03NIDDLVKSL0.99770.9863615
LETM1-MAEAchr41817390chr413328612367HLA-C03:04NIDDLVKSL0.99770.9863615
LETM1-MAEAchr41817390chr413328612367HLA-C03:67NIDDLVKSL0.99470.975615
LETM1-MAEAchr41817390chr413328612367HLA-C04:04NIDDLVKSL0.98290.7068615
LETM1-MAEAchr41817390chr413328612367HLA-C03:06NIDDLVKSL0.98240.985615
LETM1-MAEAchr41817390chr413328612367HLA-C08:01NIDDLVKSL0.92370.9663615
LETM1-MAEAchr41817390chr413328612367HLA-C07:04NIDDLVKSL0.86570.9023615
LETM1-MAEAchr41817390chr413328612367HLA-C17:01NIDDLVKSL0.82140.8524615
LETM1-MAEAchr41817390chr413328612367HLA-A02:06NIDDLVKSL0.8190.567615
LETM1-MAEAchr41817390chr413328612367HLA-B35:09NIDDLVKSL0.53720.8866615
LETM1-MAEAchr41817390chr413328612367HLA-A69:01NIDDLVKSL0.35130.6667615
LETM1-MAEAchr41817390chr413328612367HLA-B07:13NIDDLVKSL0.23590.7973615
LETM1-MAEAchr41817390chr413328612367HLA-C04:03NIDDLVKSLL10.7502616
LETM1-MAEAchr41817390chr413328612367HLA-C05:01NIDDLVKSLL10.9634616
LETM1-MAEAchr41817390chr413328612367HLA-C08:02NIDDLVKSLL0.99990.967616
LETM1-MAEAchr41817390chr413328612367HLA-C08:02VNIDDLVKSL0.9990.9699515

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Potential FusionNeoAntigen Information of LETM1-MAEA 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.
LETM1-MAEA_1817390_1332861.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)
LETM1-MAEAchr41817390chr413328612367DRB1-0415DDLVKSLLSIRQDDK823
LETM1-MAEAchr41817390chr413328612367DRB1-0436DDLVKSLLSIRQDDK823
LETM1-MAEAchr41817390chr413328612367DRB1-0440DDLVKSLLSIRQDDK823
LETM1-MAEAchr41817390chr413328612367DRB1-0442DDLVKSLLSIRQDDK823
LETM1-MAEAchr41817390chr413328612367DRB1-0453DDLVKSLLSIRQDDK823
LETM1-MAEAchr41817390chr413328612367DRB1-0455DDLVKSLLSIRQDDK823
LETM1-MAEAchr41817390chr413328612367DRB1-0456DDLVKSLLSIRQDDK823
LETM1-MAEAchr41817390chr413328612367DRB1-0458DDLVKSLLSIRQDDK823
LETM1-MAEAchr41817390chr413328612367DRB1-0468DDLVKSLLSIRQDDK823
LETM1-MAEAchr41817390chr413328612367DRB1-0470DDLVKSLLSIRQDDK823
LETM1-MAEAchr41817390chr413328612367DRB1-1002DDLVKSLLSIRQDDK823

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Fusion breakpoint peptide structures of LETM1-MAEA

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
6191NIDDLVKSLLSIRQLETM1MAEAchr41817390chr413328612367

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LETM1-MAEA

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-B14:023BVN6191NIDDLVKSLLSIRQ-7.15543-7.26883
HLA-B14:023BVN6191NIDDLVKSLLSIRQ-4.77435-5.80965
HLA-B52:013W396191NIDDLVKSLLSIRQ-6.80875-6.92215
HLA-B52:013W396191NIDDLVKSLLSIRQ-4.20386-5.23916
HLA-A11:014UQ26191NIDDLVKSLLSIRQ-7.5194-8.5547
HLA-A11:014UQ26191NIDDLVKSLLSIRQ-6.9601-7.0735
HLA-A24:025HGA6191NIDDLVKSLLSIRQ-7.52403-7.63743
HLA-A24:025HGA6191NIDDLVKSLLSIRQ-5.82433-6.85963
HLA-B27:056PYJ6191NIDDLVKSLLSIRQ-3.28285-4.31815
HLA-B44:053DX86191NIDDLVKSLLSIRQ-5.91172-6.94702
HLA-B44:053DX86191NIDDLVKSLLSIRQ-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of LETM1-MAEA

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
LETM1-MAEAchr41817390chr41332861515VNIDDLVKSLGTCAACATCGACGACCTCGTCAAGTCTCTG
LETM1-MAEAchr41817390chr41332861615NIDDLVKSLAACATCGACGACCTCGTCAAGTCTCTG
LETM1-MAEAchr41817390chr41332861616NIDDLVKSLLAACATCGACGACCTCGTCAAGTCTCTGCTT
LETM1-MAEAchr41817390chr41332861715IDDLVKSLATCGACGACCTCGTCAAGTCTCTG
LETM1-MAEAchr41817390chr41332861716IDDLVKSLLATCGACGACCTCGTCAAGTCTCTGCTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
LETM1-MAEAchr41817390chr41332861823DDLVKSLLSIRQDDKGACGACCTCGTCAAGTCTCTGCTTTCTATCCGTCAAGATGATAAA

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Information of the samples that have these potential fusion neoantigens of LETM1-MAEA

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
STADLETM1-MAEAchr41817390ENST00000302787chr41332861ENST00000452175TCGA-HU-A4GP

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Potential target of CAR-T therapy development for LETM1-MAEA

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
HgeneLETM1chr4:1817390chr4:1332861ENST00000302787-1314209_229690740.0TransmembraneHelical

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 LETM1-MAEA

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 LETM1-MAEA

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