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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-RGS12

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LETM1-RGS12
FusionPDB ID: 44490
FusionGDB2.0 ID: 44490
HgeneTgene
Gene symbol

LETM1

RGS12

Gene ID

3954

6002

Gene nameleucine zipper and EF-hand containing transmembrane protein 1regulator of G protein signaling 12
SynonymsSLC55A1-
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 1regulator of G-protein signaling 12regulator of G-protein signalling 12
Modification date2020032820200313
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}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000302787, ENST00000512189, 
ENST00000338806, ENST00000508158, 
ENST00000538395, ENST00000306648, 
ENST00000336727, ENST00000344733, 
ENST00000382788, ENST00000543385, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 13 X 7=9106 X 8 X 5=240
# samples 128
** MAII scorelog2(12/910*10)=-2.92283213947754
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/240*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LETM1 [Title/Abstract] AND RGS12 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LETM1 [Title/Abstract] AND RGS12 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LETM1(1824714)-RGS12(3344663), # samples:2
Anticipated loss of major functional domain due to fusion event.LETM1-RGS12 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-RGS12 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-RGS12 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-RGS12 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
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



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/chr4:1824714/chr4:3344663)
- 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 RGS12 (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)
ENST00000302787LETM1chr41824714-ENST00000543385RGS12chr43344663+254017732971895532
ENST00000302787LETM1chr41824714-ENST00000336727RGS12chr43344663+5228177329740221241
ENST00000302787LETM1chr41824714-ENST00000344733RGS12chr43344663+4457177329742351312
ENST00000302787LETM1chr41824714-ENST00000382788RGS12chr43344663+5301177329740221241
ENST00000302787LETM1chr41824714-ENST00000306648RGS12chr43344663+3485177329733651022

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
ENST00000302787ENST00000543385LETM1chr41824714-RGS12chr43344663+0.0385931730.9614068
ENST00000302787ENST00000336727LETM1chr41824714-RGS12chr43344663+0.0038772760.99612266
ENST00000302787ENST00000344733LETM1chr41824714-RGS12chr43344663+0.0056840740.9943159
ENST00000302787ENST00000382788LETM1chr41824714-RGS12chr43344663+0.0035164060.99648356
ENST00000302787ENST00000306648LETM1chr41824714-RGS12chr43344663+0.0066744580.9933255

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-RGS12

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LETM1chr41824714RGS12chr433446631773490QEHREKELQKRSEVAGSKFGRGTGLT

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Potential FusionNeoAntigen Information of LETM1-RGS12 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-RGS12_1824714_3344663.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-RGS12chr41824714chr433446631773HLA-B44:03SEVAGSKF0.99960.98281119
LETM1-RGS12chr41824714chr433446631773HLA-B08:01ELQKRSEV0.99960.7039614
LETM1-RGS12chr41824714chr433446631773HLA-B08:09ELQKRSEV0.99950.7784614
LETM1-RGS12chr41824714chr433446631773HLA-B18:01SEVAGSKF0.9980.98431119
LETM1-RGS12chr41824714chr433446631773HLA-B50:02KELQKRSEV0.99740.7904514
LETM1-RGS12chr41824714chr433446631773HLA-B45:01KELQKRSEV0.99680.9483514
LETM1-RGS12chr41824714chr433446631773HLA-B27:05KRSEVAGSK0.9930.8404918
LETM1-RGS12chr41824714chr433446631773HLA-B08:09ELQKRSEVA0.99160.8579615
LETM1-RGS12chr41824714chr433446631773HLA-A26:03EVAGSKFGR0.99060.5141221
LETM1-RGS12chr41824714chr433446631773HLA-B41:01KELQKRSEV0.92040.941514
LETM1-RGS12chr41824714chr433446631773HLA-B15:17RSEVAGSKF0.71250.98171019
LETM1-RGS12chr41824714chr433446631773HLA-B15:16RSEVAGSKF0.66970.85881019
LETM1-RGS12chr41824714chr433446631773HLA-B39:13KELQKRSEV0.47450.9738514
LETM1-RGS12chr41824714chr433446631773HLA-B50:01KELQKRSEV0.42270.8049514
LETM1-RGS12chr41824714chr433446631773HLA-B27:02KRSEVAGSKF0.99980.6139919
LETM1-RGS12chr41824714chr433446631773HLA-B27:04KRSEVAGSKF0.99970.849919
LETM1-RGS12chr41824714chr433446631773HLA-B27:05KRSEVAGSKF0.99970.8266919
LETM1-RGS12chr41824714chr433446631773HLA-B27:07KRSEVAGSKF0.99850.5059919
LETM1-RGS12chr41824714chr433446631773HLA-B45:01KELQKRSEVA0.98890.9606515
LETM1-RGS12chr41824714chr433446631773HLA-B41:01KELQKRSEVA0.91010.9606515
LETM1-RGS12chr41824714chr433446631773HLA-B50:01KELQKRSEVA0.74620.8139515
LETM1-RGS12chr41824714chr433446631773HLA-A74:11RSEVAGSKFGR0.97890.55011021
LETM1-RGS12chr41824714chr433446631773HLA-A74:09RSEVAGSKFGR0.97890.55011021
LETM1-RGS12chr41824714chr433446631773HLA-A74:03RSEVAGSKFGR0.97890.55011021
LETM1-RGS12chr41824714chr433446631773HLA-B44:10SEVAGSKF0.99820.51421119
LETM1-RGS12chr41824714chr433446631773HLA-B40:06KELQKRSEV0.99960.6581514
LETM1-RGS12chr41824714chr433446631773HLA-C05:09RSEVAGSKF0.99910.9831019
LETM1-RGS12chr41824714chr433446631773HLA-C08:15RSEVAGSKF0.99610.99221019
LETM1-RGS12chr41824714chr433446631773HLA-B27:14KRSEVAGSK0.99060.7953918
LETM1-RGS12chr41824714chr433446631773HLA-B40:03KELQKRSEV0.96280.6784514
LETM1-RGS12chr41824714chr433446631773HLA-B27:03KRSEVAGSK0.73710.8506918
LETM1-RGS12chr41824714chr433446631773HLA-C07:95KRSEVAGSKF0.99780.8416919
LETM1-RGS12chr41824714chr433446631773HLA-C07:19KRSEVAGSKF0.99690.8703919
LETM1-RGS12chr41824714chr433446631773HLA-B40:06KELQKRSEVA0.99680.7046515
LETM1-RGS12chr41824714chr433446631773HLA-B27:03KRSEVAGSKF0.99390.8416919
LETM1-RGS12chr41824714chr433446631773HLA-C07:46KRSEVAGSKF0.99130.9466919
LETM1-RGS12chr41824714chr433446631773HLA-B08:18ELQKRSEV0.99960.7039614
LETM1-RGS12chr41824714chr433446631773HLA-B44:07SEVAGSKF0.99960.98281119
LETM1-RGS12chr41824714chr433446631773HLA-B44:13SEVAGSKF0.99960.98281119
LETM1-RGS12chr41824714chr433446631773HLA-B44:26SEVAGSKF0.99960.98281119
LETM1-RGS12chr41824714chr433446631773HLA-B18:08SEVAGSKF0.99830.97881119
LETM1-RGS12chr41824714chr433446631773HLA-B18:06SEVAGSKF0.99810.98721119
LETM1-RGS12chr41824714chr433446631773HLA-B18:05SEVAGSKF0.9980.98431119
LETM1-RGS12chr41824714chr433446631773HLA-B18:11SEVAGSKF0.99780.97931119
LETM1-RGS12chr41824714chr433446631773HLA-B18:03SEVAGSKF0.99680.98211119
LETM1-RGS12chr41824714chr433446631773HLA-C05:01RSEVAGSKF0.99910.9831019
LETM1-RGS12chr41824714chr433446631773HLA-B40:04KELQKRSEV0.99750.7957514
LETM1-RGS12chr41824714chr433446631773HLA-C08:02RSEVAGSKF0.99610.99221019
LETM1-RGS12chr41824714chr433446631773HLA-B27:10KRSEVAGSK0.98470.9241918
LETM1-RGS12chr41824714chr433446631773HLA-B41:03KELQKRSEV0.92770.8381514
LETM1-RGS12chr41824714chr433446631773HLA-B57:04RSEVAGSKF0.60080.90221019
LETM1-RGS12chr41824714chr433446631773HLA-B39:02KELQKRSEV0.45010.9748514
LETM1-RGS12chr41824714chr433446631773HLA-B50:05KELQKRSEV0.42270.8049514
LETM1-RGS12chr41824714chr433446631773HLA-B50:04KELQKRSEV0.42270.8049514
LETM1-RGS12chr41824714chr433446631773HLA-B57:02RSEVAGSKF0.3720.98071019
LETM1-RGS12chr41824714chr433446631773HLA-B27:08KRSEVAGSKF0.99970.7797919
LETM1-RGS12chr41824714chr433446631773HLA-B27:10KRSEVAGSKF0.99970.9279919
LETM1-RGS12chr41824714chr433446631773HLA-B27:06KRSEVAGSKF0.99930.8379919
LETM1-RGS12chr41824714chr433446631773HLA-B27:09KRSEVAGSKF0.99850.7885919
LETM1-RGS12chr41824714chr433446631773HLA-C07:01KRSEVAGSKF0.9980.837919
LETM1-RGS12chr41824714chr433446631773HLA-C07:22KRSEVAGSKF0.9960.8418919
LETM1-RGS12chr41824714chr433446631773HLA-B50:05KELQKRSEVA0.74620.8139515
LETM1-RGS12chr41824714chr433446631773HLA-B50:04KELQKRSEVA0.74620.8139515
LETM1-RGS12chr41824714chr433446631773HLA-A74:01RSEVAGSKFGR0.97890.55011021

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Potential FusionNeoAntigen Information of LETM1-RGS12 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of LETM1-RGS12

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
1915ELQKRSEVAGSKFGLETM1RGS12chr41824714chr433446631773

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LETM1-RGS12

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-B14:023BVN1915ELQKRSEVAGSKFG-7.16221-7.27561
HLA-B14:023BVN1915ELQKRSEVAGSKFG-5.14509-6.18039
HLA-B52:013W391915ELQKRSEVAGSKFG-7.07493-8.11023
HLA-B52:013W391915ELQKRSEVAGSKFG-7.05248-7.16588
HLA-A24:025HGA1915ELQKRSEVAGSKFG-7.9264-8.0398
HLA-A24:025HGA1915ELQKRSEVAGSKFG-6.26919-7.30449
HLA-B44:053DX81915ELQKRSEVAGSKFG-5.66824-5.78164
HLA-B44:053DX81915ELQKRSEVAGSKFG-2.33599-3.37129

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Vaccine Design for the FusionNeoAntigens of LETM1-RGS12

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-RGS12chr41824714chr433446631019RSEVAGSKFGAGGTGGCGGGCTCAAAATTTGGGCGG
LETM1-RGS12chr41824714chr433446631021RSEVAGSKFGRGAGGTGGCGGGCTCAAAATTTGGGCGGGGAACT
LETM1-RGS12chr41824714chr433446631119SEVAGSKFGTGGCGGGCTCAAAATTTGGGCGG
LETM1-RGS12chr41824714chr433446631221EVAGSKFGRGCGGGCTCAAAATTTGGGCGGGGAACT
LETM1-RGS12chr41824714chr43344663514KELQKRSEVCTGCAGAAGCGCTCGGAGGTGGCGGGC
LETM1-RGS12chr41824714chr43344663515KELQKRSEVACTGCAGAAGCGCTCGGAGGTGGCGGGCTCA
LETM1-RGS12chr41824714chr43344663614ELQKRSEVCAGAAGCGCTCGGAGGTGGCGGGC
LETM1-RGS12chr41824714chr43344663615ELQKRSEVACAGAAGCGCTCGGAGGTGGCGGGCTCA
LETM1-RGS12chr41824714chr43344663918KRSEVAGSKTCGGAGGTGGCGGGCTCAAAATTTGGG
LETM1-RGS12chr41824714chr43344663919KRSEVAGSKFTCGGAGGTGGCGGGCTCAAAATTTGGGCGG

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

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Information of the samples that have these potential fusion neoantigens of LETM1-RGS12

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
ESCALETM1-RGS12chr41824714ENST00000302787chr43344663ENST00000306648TCGA-JY-A938

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Potential target of CAR-T therapy development for LETM1-RGS12

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
HgeneLETM1chr4:1824714chr4:3344663ENST00000302787-914209_229492740.0TransmembraneHelical

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-RGS12

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-RGS12

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