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Center for Computational Systems Medicine level2
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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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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:CTDSP2-LGR5

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CTDSP2-LGR5
FusionPDB ID: 20175
FusionGDB2.0 ID: 20175
HgeneTgene
Gene symbol

CTDSP2

LGR5

Gene ID

10106

8549

Gene nameCTD small phosphatase 2leucine rich repeat containing G protein-coupled receptor 5
SynonymsOS4|PSR2|SCP2FEX|GPR49|GPR67|GRP49|HG38
Cytomap

12q14.1

12q21.1

Type of geneprotein-codingprotein-coding
Descriptioncarboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase 2NLI-interacting factor 2conserved gene amplified in osteosarcomanuclear LIM interactor-interaleucine-rich repeat-containing G-protein coupled receptor 5G-protein coupled receptor 49G-protein coupled receptor 67G-protein coupled receptor HG38orphan G protein-coupled receptor HG38
Modification date2020031320200329
UniProtAcc

O14595

O75473

Ensembl transtripts involved in fusion geneENST idsENST00000398073, ENST00000547701, 
ENST00000548823, 
ENST00000536515, 
ENST00000540815, ENST00000266674, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score32 X 8 X 10=256013 X 15 X 9=1755
# samples 3720
** MAII scorelog2(37/2560*10)=-2.79054663437105
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(20/1755*10)=-3.1333991254172
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: CTDSP2 [Title/Abstract] AND LGR5 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CTDSP2(58217687)-LGR5(71946853), # samples:2
Anticipated loss of major functional domain due to fusion event.CTDSP2-LGR5 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.
CTDSP2-LGR5 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.
CTDSP2-LGR5 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
CTDSP2-LGR5 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneCTDSP2

GO:0006470

protein dephosphorylation

12721286

TgeneLGR5

GO:0090263

positive regulation of canonical Wnt signaling pathway

21693646|22815884


check buttonFusion gene breakpoints across CTDSP2 (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 LGR5 (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 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
ChimerDB4SARCTCGA-DX-A1KZ-01ACTDSP2chr12

58217687

-LGR5chr12

71946853

+
ChimerDB4SARCTCGA-DX-AB3A-01ACTDSP2chr12

58240155

-LGR5chr12

71898394

+
ChimerDB4SARCTCGA-RN-AAAQ-01ACTDSP2chr12

58217687

-LGR5chr12

71946853

+


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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)
ENST00000547701CTDSP2chr1258217687-ENST00000266674LGR5chr1271946853+45937216893016775

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
ENST00000547701ENST00000266674CTDSP2chr1258217687-LGR5chr1271946853+0.0013058220.99869424

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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

>20175_20175_1_CTDSP2-LGR5_CTDSP2_chr12_58217687_ENST00000547701_LGR5_chr12_71946853_ENST00000266674_length(amino acids)=775AA_BP=11
MLLTYSTPRMQRLDANHISYVPPSCFSGLHSLRHLWLDDNALTEIPVQAFRSLSALQAMTLALNKIHHIPDYAFGNLSSLVVLHLHNNRI
HSLGKKCFDGLHSLETLDLNYNNLDEFPTAIRTLSNLKELGFHSNNIRSIPEKAFVGNPSLITIHFYDNPIQFVGRSAFQHLPELRTLTL
NGASQITEFPDLTGTANLESLTLTGAQISSLPQTVCNQLPNLQVLDLSYNLLEDLPSFSVCQKLQKIDLRHNEIYEIKVDTFQQLLSLRS
LNLAWNKIAIIHPNAFSTLPSLIKLDLSSNLLSSFPITGLHGLTHLKLTGNHALQSLISSENFPELKVIEMPYAYQCCAFGVCENAYKIS
NQWNKGDNSSMDDLHKKDAGMFQAQDERDLEDFLLDFEEDLKALHSVQCSPSPGPFKPCEHLLDGWLIRIGVWTIAVLALTCNALVTSTV
FRSPLYISPIKLLIGVIAAVNMLTGVSSAVLAGVDAFTFGSFARHGAWWENGVGCHVIGFLSIFASESSVFLLTLAALERGFSVKYSAKF
ETKAPFSSLKVIILLCALLALTMAAVPLLGGSKYGASPLCLPLPFGEPSTMGYMVALILLNSLCFLMMTIAYTKLYCNLDKGDLENIWDC
SMVKHIALLLFTNCILNCPVAFLSFSSLINLTFISPEVIKFILLVVVPLPACLNPLLYILFNPHFKEDLVSLRKQTYVWTRSKHPSLMSI

--------------------------------------------------------------

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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/chr12:58217687/chr12:71946853)
- 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
CTDSP2

O14595

LGR5

O75473

FUNCTION: Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residue repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. May contribute to the development of sarcomas. {ECO:0000269|PubMed:12721286, ECO:0000269|PubMed:15681389}.FUNCTION: Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a stem cell marker of the intestinal epithelium and the hair follicle. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Involved in the development and/or maintenance of the adult intestinal stem cells during postembryonic development. {ECO:0000269|PubMed:21693646, ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22815884, ECO:0000269|PubMed:23809763}.

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
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318163_184142.66666666666666908.0RepeatNote=LRR 5
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318187_208142.66666666666666908.0RepeatNote=LRR 6
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318211_232142.66666666666666908.0RepeatNote=LRR 7
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318235_256142.66666666666666908.0RepeatNote=LRR 8
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318258_279142.66666666666666908.0RepeatNote=LRR 9
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318282_303142.66666666666666908.0RepeatNote=LRR 10
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318306_328142.66666666666666908.0RepeatNote=LRR 11
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318329_350142.66666666666666908.0RepeatNote=LRR 12
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318353_374142.66666666666666908.0RepeatNote=LRR 13
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318375_396142.66666666666666908.0RepeatNote=LRR 14
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318399_420142.66666666666666908.0RepeatNote=LRR 15
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318423_446142.66666666666666908.0RepeatNote=LRR 16
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317163_184142.66666666666666884.0RepeatNote=LRR 5
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317187_208142.66666666666666884.0RepeatNote=LRR 6
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317211_232142.66666666666666884.0RepeatNote=LRR 7
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317235_256142.66666666666666884.0RepeatNote=LRR 8
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317258_279142.66666666666666884.0RepeatNote=LRR 9
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317282_303142.66666666666666884.0RepeatNote=LRR 10
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317306_328142.66666666666666884.0RepeatNote=LRR 11
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317329_350142.66666666666666884.0RepeatNote=LRR 12
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317353_374142.66666666666666884.0RepeatNote=LRR 13
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317375_396142.66666666666666884.0RepeatNote=LRR 14
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317399_420142.66666666666666884.0RepeatNote=LRR 15
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317423_446142.66666666666666884.0RepeatNote=LRR 16
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318583_593142.66666666666666908.0Topological domainCytoplasmic
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318615_638142.66666666666666908.0Topological domainExtracellular
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318660_682142.66666666666666908.0Topological domainCytoplasmic
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318704_722142.66666666666666908.0Topological domainExtracellular
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318744_767142.66666666666666908.0Topological domainCytoplasmic
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318789_802142.66666666666666908.0Topological domainExtracellular
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318824_907142.66666666666666908.0Topological domainCytoplasmic
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317583_593142.66666666666666884.0Topological domainCytoplasmic
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317615_638142.66666666666666884.0Topological domainExtracellular
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317660_682142.66666666666666884.0Topological domainCytoplasmic
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317704_722142.66666666666666884.0Topological domainExtracellular
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317744_767142.66666666666666884.0Topological domainCytoplasmic
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317789_802142.66666666666666884.0Topological domainExtracellular
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317824_907142.66666666666666884.0Topological domainCytoplasmic
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318562_582142.66666666666666908.0TransmembraneHelical%3B Name%3D1
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318594_614142.66666666666666908.0TransmembraneHelical%3B Name%3D2
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318639_659142.66666666666666908.0TransmembraneHelical%3B Name%3D3
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318683_703142.66666666666666908.0TransmembraneHelical%3B Name%3D4
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318723_743142.66666666666666908.0TransmembraneHelical%3B Name%3D5
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318768_788142.66666666666666908.0TransmembraneHelical%3B Name%3D6
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318803_823142.66666666666666908.0TransmembraneHelical%3B Name%3D7
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317562_582142.66666666666666884.0TransmembraneHelical%3B Name%3D1
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317594_614142.66666666666666884.0TransmembraneHelical%3B Name%3D2
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317639_659142.66666666666666884.0TransmembraneHelical%3B Name%3D3
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317683_703142.66666666666666884.0TransmembraneHelical%3B Name%3D4
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317723_743142.66666666666666884.0TransmembraneHelical%3B Name%3D5
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317768_788142.66666666666666884.0TransmembraneHelical%3B Name%3D6
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317803_823142.66666666666666884.0TransmembraneHelical%3B Name%3D7

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneCTDSP2chr12:58217687chr12:71946853ENST00000398073-7897_255230.0272.0DomainFCP1 homology
TgeneLGR5chr12:58217687chr12:71946853ENST0000026667431825_66142.66666666666666908.0DomainNote=LRRNT
TgeneLGR5chr12:58217687chr12:71946853ENST0000054081531725_66142.66666666666666884.0DomainNote=LRRNT
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318115_136142.66666666666666908.0RepeatNote=LRR 3
TgeneLGR5chr12:58217687chr12:71946853ENST00000266674318139_160142.66666666666666908.0RepeatNote=LRR 4
TgeneLGR5chr12:58217687chr12:71946853ENST0000026667431867_90142.66666666666666908.0RepeatNote=LRR 1
TgeneLGR5chr12:58217687chr12:71946853ENST0000026667431891_112142.66666666666666908.0RepeatNote=LRR 2
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317115_136142.66666666666666884.0RepeatNote=LRR 3
TgeneLGR5chr12:58217687chr12:71946853ENST00000540815317139_160142.66666666666666884.0RepeatNote=LRR 4
TgeneLGR5chr12:58217687chr12:71946853ENST0000054081531767_90142.66666666666666884.0RepeatNote=LRR 1
TgeneLGR5chr12:58217687chr12:71946853ENST0000054081531791_112142.66666666666666884.0RepeatNote=LRR 2
TgeneLGR5chr12:58217687chr12:71946853ENST0000026667431822_561142.66666666666666908.0Topological domainExtracellular
TgeneLGR5chr12:58217687chr12:71946853ENST0000054081531722_561142.66666666666666884.0Topological domainExtracellular


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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 >>>1555_CTDSP2_58217687_LGR5_71946853_ranked_0.pdbCTDSP25821768758217687ENST00000266674LGR5chr1271946853+
MLLTYSTPRMQRLDANHISYVPPSCFSGLHSLRHLWLDDNALTEIPVQAFRSLSALQAMTLALNKIHHIPDYAFGNLSSLVVLHLHNNRI
HSLGKKCFDGLHSLETLDLNYNNLDEFPTAIRTLSNLKELGFHSNNIRSIPEKAFVGNPSLITIHFYDNPIQFVGRSAFQHLPELRTLTL
NGASQITEFPDLTGTANLESLTLTGAQISSLPQTVCNQLPNLQVLDLSYNLLEDLPSFSVCQKLQKIDLRHNEIYEIKVDTFQQLLSLRS
LNLAWNKIAIIHPNAFSTLPSLIKLDLSSNLLSSFPITGLHGLTHLKLTGNHALQSLISSENFPELKVIEMPYAYQCCAFGVCENAYKIS
NQWNKGDNSSMDDLHKKDAGMFQAQDERDLEDFLLDFEEDLKALHSVQCSPSPGPFKPCEHLLDGWLIRIGVWTIAVLALTCNALVTSTV
FRSPLYISPIKLLIGVIAAVNMLTGVSSAVLAGVDAFTFGSFARHGAWWENGVGCHVIGFLSIFASESSVFLLTLAALERGFSVKYSAKF
ETKAPFSSLKVIILLCALLALTMAAVPLLGGSKYGASPLCLPLPFGEPSTMGYMVALILLNSLCFLMMTIAYTKLYCNLDKGDLENIWDC
SMVKHIALLLFTNCILNCPVAFLSFSSLINLTFISPEVIKFILLVVVPLPACLNPLLYILFNPHFKEDLVSLRKQTYVWTRSKHPSLMSI
775


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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.
CTDSP2_pLDDT.png
all structure
all structure
LGR5_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.
all structure


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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

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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


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
CTDSP2
LGR5all 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 CTDSP2-LGR5


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 CTDSP2-LGR5


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
TgeneLGR5C0007102Malignant tumor of colon1CTD_human
TgeneLGR5C0009375Colonic Neoplasms1CTD_human
TgeneLGR5C0009402Colorectal Carcinoma1CTD_human
TgeneLGR5C0009404Colorectal Neoplasms1CTD_human