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Center for Computational Systems Medicine level1
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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-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:CD274-KDM4C

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CD274-KDM4C
FusionPDB ID: 14432
FusionGDB2.0 ID: 14432
HgeneTgene
Gene symbol

CD274

KDM4C

Gene ID

29126

23081

Gene nameCD274 moleculelysine demethylase 4C
SynonymsB7-H|B7H1|PD-L1|PDCD1L1|PDCD1LG1|PDL1|hPD-L1GASC1|JHDM3C|JMJD2C|TDRD14C
Cytomap

9p24.1

9p24.1

Type of geneprotein-codingprotein-coding
Descriptionprogrammed cell death 1 ligand 1B7 homolog 1CD274 antigenPDCD1 ligand 1lysine-specific demethylase 4CJmjC domain-containing histone demethylation protein 3Cgene amplified in squamous cell carcinoma 1 proteinjumonji domain-containing protein 2Clysine (K)-specific demethylase 4Ctudor domain containing 14C
Modification date2020032920200329
UniProtAcc

Q9NZQ7

Q9H3R0

Ensembl transtripts involved in fusion geneENST idsENST00000381573, ENST00000381577, 
ENST00000498261, 
ENST00000489243, 
ENST00000381306, ENST00000381309, 
ENST00000401787, ENST00000442236, 
ENST00000536108, ENST00000543771, 
ENST00000428870, ENST00000535193, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 2 X 2=1222 X 22 X 7=3388
# samples 326
** MAII scorelog2(3/12*10)=1.32192809488736
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(26/3388*10)=-3.70385034630374
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: CD274 [Title/Abstract] AND KDM4C [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CD274(5465606)-KDM4C(6792971), # samples:1
Anticipated loss of major functional domain due to fusion event.CD274-KDM4C 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.
CD274-KDM4C 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.
CD274-KDM4C 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.
CD274-KDM4C 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
HgeneCD274

GO:0006955

immune response

10581077

HgeneCD274

GO:0007165

signal transduction

10581077

HgeneCD274

GO:0007166

cell surface receptor signaling pathway

10581077

HgeneCD274

GO:0031295

T cell costimulation

10581077

HgeneCD274

GO:0034097

response to cytokine

17489864

HgeneCD274

GO:1905399

regulation of activated CD4-positive, alpha-beta T cell apoptotic process

24187568

HgeneCD274

GO:1905404

positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process

24187568

HgeneCD274

GO:2000562

negative regulation of CD4-positive, alpha-beta T cell proliferation

24691993

HgeneCD274

GO:2001181

positive regulation of interleukin-10 secretion

10581077

TgeneKDM4C

GO:0006357

regulation of transcription by RNA polymerase II

17277772

TgeneKDM4C

GO:0033169

histone H3-K9 demethylation

18066052|21914792

TgeneKDM4C

GO:0070544

histone H3-K36 demethylation

21914792


check buttonFusion gene breakpoints across CD274 (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 KDM4C (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
ChimerDB4STADTCGA-BR-6706CD274chr9

5465606

+KDM4Cchr9

6792971

+


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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)
ENST00000381573CD274chr95465606+ENST00000535193KDM4Cchr96792971+3826556930141001
ENST00000381577CD274chr95465606+ENST00000535193KDM4Cchr96792971+41468768633341082

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
ENST00000381573ENST00000535193CD274chr95465606+KDM4Cchr96792971+0.0017863120.99821377
ENST00000381577ENST00000535193CD274chr95465606+KDM4Cchr96792971+0.0018170580.99818295

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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

>14432_14432_1_CD274-KDM4C_CD274_chr9_5465606_ENST00000381573_KDM4C_chr9_6792971_ENST00000535193_length(amino acids)=1001AA_BP=1
MSSWRVPRGPSSAQLPEAPHQPRFCPPAGHSRKMRIFAVFIFMTYWHLLNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD
HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPELPLAHPPNERTHLVILGAILLCLGVALTFIFRL
RKDTALTIMEVAEVESPLNPSCKIMTFRPSMEEFREFNKYLAYMESKGAHRAGLAKVIPPKEWKPRQCYDDIDNLLIPAPIQQMVTGQSG
LFTQYNIQKKAMTVKEFRQLANSGKYCTPRYLDYEDLERKYWKNLTFVAPIYGADINGSIYDEGVDEWNIARLNTVLDVVEEECGISIEG
VNTPYLYFGMWKTTFAWHTEDMDLYSINYLHFGEPKSWYAIPPEHGKRLERLAQGFFPSSSQGCDAFLRHKMTLISPSVLKKYGIPFDKI
TQEAGEFMITFPYGYHAGFNHGFNCAESTNFATVRWIDYGKVAKLCTCRKDMVKISMDIFVRKFQPDRYQLWKQGKDIYTIDHTKPTPAS
TPEVKAWLQRRRKVRKASRSFQCARSTSKRPKADEEEEVSDEVDGAEVPNPDSVTDDLKVSEKSEAAVKLRNTEASSEEESSASRMQVEQ
NLSDHIKLSGNSCLSTSVTEDIKTEDDKAYAYRSVPSISSEADDSIPLSSGYEKPEKSDPSELSWPKSPESCSSVAESNGVLTEGEESDV
ESHGNGLEPGEIPAVPSGERNSFKVPSIAEGENKTSKSWRHPLSRPPARSPMTLVKQQAPSDEELPEVLSIEEEVEETESWAKPLIHLWQ
TKSPNFAAEQEYNATVARMKPHCAICTLLMPYHKPDSSNEENDARWETKLDEVVTSEGKTKPLIPEMCFIYSEENIEYSPPNAFLEEDGT
SLLISCAKCCVRVHASCYGIPSHEICDGWLCARCKRNAWTAECCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIP

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>14432_14432_2_CD274-KDM4C_CD274_chr9_5465606_ENST00000381577_KDM4C_chr9_6792971_ENST00000535193_length(amino acids)=1082AA_BP=0
MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKD
QLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTT
TTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPELPLAHPPNERTHLVILGAILLCLGVALTFIFRLRKDTALTIM
EVAEVESPLNPSCKIMTFRPSMEEFREFNKYLAYMESKGAHRAGLAKVIPPKEWKPRQCYDDIDNLLIPAPIQQMVTGQSGLFTQYNIQK
KAMTVKEFRQLANSGKYCTPRYLDYEDLERKYWKNLTFVAPIYGADINGSIYDEGVDEWNIARLNTVLDVVEEECGISIEGVNTPYLYFG
MWKTTFAWHTEDMDLYSINYLHFGEPKSWYAIPPEHGKRLERLAQGFFPSSSQGCDAFLRHKMTLISPSVLKKYGIPFDKITQEAGEFMI
TFPYGYHAGFNHGFNCAESTNFATVRWIDYGKVAKLCTCRKDMVKISMDIFVRKFQPDRYQLWKQGKDIYTIDHTKPTPASTPEVKAWLQ
RRRKVRKASRSFQCARSTSKRPKADEEEEVSDEVDGAEVPNPDSVTDDLKVSEKSEAAVKLRNTEASSEEESSASRMQVEQNLSDHIKLS
GNSCLSTSVTEDIKTEDDKAYAYRSVPSISSEADDSIPLSSGYEKPEKSDPSELSWPKSPESCSSVAESNGVLTEGEESDVESHGNGLEP
GEIPAVPSGERNSFKVPSIAEGENKTSKSWRHPLSRPPARSPMTLVKQQAPSDEELPEVLSIEEEVEETESWAKPLIHLWQTKSPNFAAE
QEYNATVARMKPHCAICTLLMPYHKPDSSNEENDARWETKLDEVVTSEGKTKPLIPEMCFIYSEENIEYSPPNAFLEEDGTSLLISCAKC
CVRVHASCYGIPSHEICDGWLCARCKRNAWTAECCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLGRL

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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/chr9:5465606/chr9:6792971)
- 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
CD274

Q9NZQ7

KDM4C

Q9H3R0

FUNCTION: Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813417, PubMed:28813410). As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response (PubMed:11015443, PubMed:28813417, PubMed:28813410). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) (PubMed:10581077). {ECO:0000269|PubMed:10581077, ECO:0000269|PubMed:11015443, ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:28813417}.; FUNCTION: The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival (PubMed:28813417, PubMed:28813410). The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function (By similarity). The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (By similarity). {ECO:0000250|UniProtKB:Q9EP73, ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:28813417}.FUNCTION: Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. {ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}.

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
HgeneCD274chr9:5465606chr9:6792971ENST00000381573+4619_127149.33333333333334177.0DomainNote=Ig-like V-type
HgeneCD274chr9:5465606chr9:6792971ENST00000381577+57133_225263.3333333333333291.0DomainNote=Ig-like C2-type
HgeneCD274chr9:5465606chr9:6792971ENST00000381577+5719_127263.3333333333333291.0DomainNote=Ig-like V-type
HgeneCD274chr9:5465606chr9:6792971ENST00000381577+5719_238263.3333333333333291.0Topological domainExtracellular
HgeneCD274chr9:5465606chr9:6792971ENST00000381577+57239_259263.3333333333333291.0TransmembraneHelical
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000381306021144_31001048.0DomainJmjC
TgeneKDM4Cchr9:5465606chr9:6792971ENST0000038130602116_5801048.0DomainJmjN
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000381306021877_93401048.0DomainNote=Tudor 1
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000381306021935_99101048.0DomainNote=Tudor 2
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000381309022144_31001057.0DomainJmjC
TgeneKDM4Cchr9:5465606chr9:6792971ENST0000038130902216_5801057.0DomainJmjN
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000381309022877_93401057.0DomainNote=Tudor 1
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000381309022935_99101057.0DomainNote=Tudor 2
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000535193018144_31016.333333333333332836.0DomainJmjC
TgeneKDM4Cchr9:5465606chr9:6792971ENST0000053519301816_5816.333333333333332836.0DomainJmjN
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000535193018877_93416.333333333333332836.0DomainNote=Tudor 1
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000535193018935_99116.333333333333332836.0DomainNote=Tudor 2
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000543771018144_3100814.0DomainJmjC
TgeneKDM4Cchr9:5465606chr9:6792971ENST0000054377101816_580814.0DomainJmjN
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000543771018877_9340814.0DomainNote=Tudor 1
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000543771018935_9910814.0DomainNote=Tudor 2
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000381306021689_74701048.0Zinc fingerNote=PHD-type 1
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000381306021752_78501048.0Zinc fingerC2HC pre-PHD-type
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000381306021808_86501048.0Zinc fingerPHD-type 2
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000381309022689_74701057.0Zinc fingerNote=PHD-type 1
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000381309022752_78501057.0Zinc fingerC2HC pre-PHD-type
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000381309022808_86501057.0Zinc fingerPHD-type 2
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000535193018689_74716.333333333333332836.0Zinc fingerNote=PHD-type 1
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000535193018752_78516.333333333333332836.0Zinc fingerC2HC pre-PHD-type
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000535193018808_86516.333333333333332836.0Zinc fingerPHD-type 2
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000543771018689_7470814.0Zinc fingerNote=PHD-type 1
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000543771018752_7850814.0Zinc fingerC2HC pre-PHD-type
TgeneKDM4Cchr9:5465606chr9:6792971ENST00000543771018808_8650814.0Zinc fingerPHD-type 2

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneCD274chr9:5465606chr9:6792971ENST00000381573+46133_225149.33333333333334177.0DomainNote=Ig-like C2-type
HgeneCD274chr9:5465606chr9:6792971ENST00000381573+4619_238149.33333333333334177.0Topological domainExtracellular
HgeneCD274chr9:5465606chr9:6792971ENST00000381573+46260_290149.33333333333334177.0Topological domainCytoplasmic
HgeneCD274chr9:5465606chr9:6792971ENST00000381577+57260_290263.3333333333333291.0Topological domainCytoplasmic
HgeneCD274chr9:5465606chr9:6792971ENST00000381573+46239_259149.33333333333334177.0TransmembraneHelical


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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
CD274
KDM4C


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 CD274-KDM4C


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 CD274-KDM4C


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