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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:ARFGEF2-HNF4A

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ARFGEF2-HNF4A
FusionPDB ID: 5869
FusionGDB2.0 ID: 5869
HgeneTgene
Gene symbol

ARFGEF2

HNF4A

Gene ID

10564

6927

Gene nameADP ribosylation factor guanine nucleotide exchange factor 2HNF1 homeobox A
SynonymsBIG2|PVNH2|dJ1164I10.1HNF-1A|HNF1|HNF4A|IDDM20|LFB1|MODY3|TCF-1|TCF1
Cytomap

20q13.13

12q24.31

Type of geneprotein-codingprotein-coding
Descriptionbrefeldin A-inhibited guanine nucleotide-exchange protein 2ADP-ribosylation factor guanine nucleotide-exchange factor 2 (brefeldin A-inhibited)brefeldin A-inhibited GEP 2hepatocyte nuclear factor 1-alphaHNF-1-alphaalbumin proximal factorhepatic nuclear factor 1interferon production regulator factorliver-specific transcription factor LF-B1transcription factor 1, hepatictruncated hepatocyte nuclear factor 1 alpha
Modification date2020031320200313
UniProtAcc

Q9Y6D5

P41235

Ensembl transtripts involved in fusion geneENST idsENST00000371917, ENST00000493140, 
ENST00000316099, ENST00000316673, 
ENST00000415691, ENST00000443598, 
ENST00000457232, ENST00000609795, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 13 X 9=17556 X 6 X 5=180
# samples 157
** MAII scorelog2(15/1755*10)=-3.54843662469604
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/180*10)=-1.36257007938471
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: ARFGEF2 [Title/Abstract] AND HNF4A [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ARFGEF2(47538547)-HNF4A(43034698), # samples:2
Anticipated loss of major functional domain due to fusion event.ARFGEF2-HNF4A 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.
ARFGEF2-HNF4A 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.
ARFGEF2-HNF4A 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.
ARFGEF2-HNF4A 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
HgeneARFGEF2

GO:0001881

receptor recycling

16477018

HgeneARFGEF2

GO:0035556

intracellular signal transduction

12571360

TgeneHNF4A

GO:0001779

natural killer cell differentiation

11301190

TgeneHNF4A

GO:0006357

regulation of transcription by RNA polymerase II

10330009

TgeneHNF4A

GO:0045893

positive regulation of transcription, DNA-templated

1989880|11980910|12453420


check buttonFusion gene breakpoints across ARFGEF2 (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 HNF4A (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-A1KX-01AARFGEF2chr20

47538547

-HNF4Achr20

43034698

+
ChimerDB4SARCTCGA-DX-A1KX-01AARFGEF2chr20

47538547

+HNF4Achr20

43034698

+


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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)
ENST00000371917ARFGEF2chr2047538547+ENST00000316673HNF4Achr2043034698+143712101430476
ENST00000371917ARFGEF2chr2047538547+ENST00000609795HNF4Achr2043034698+126012101259419
ENST00000371917ARFGEF2chr2047538547+ENST00000457232HNF4Achr2043034698+140712101400466
ENST00000371917ARFGEF2chr2047538547+ENST00000443598HNF4Achr2043034698+152012101259419
ENST00000371917ARFGEF2chr2047538547+ENST00000316099HNF4Achr2043034698+461112101430476
ENST00000371917ARFGEF2chr2047538547+ENST00000415691HNF4Achr2043034698+223612101400466

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
ENST00000371917ENST00000316673ARFGEF2chr2047538547+HNF4Achr2043034698+0.0083631980.9916368
ENST00000371917ENST00000609795ARFGEF2chr2047538547+HNF4Achr2043034698+0.0131954870.9868045
ENST00000371917ENST00000457232ARFGEF2chr2047538547+HNF4Achr2043034698+0.0049841470.9950159
ENST00000371917ENST00000443598ARFGEF2chr2047538547+HNF4Achr2043034698+0.0104758940.98952407
ENST00000371917ENST00000316099ARFGEF2chr2047538547+HNF4Achr2043034698+0.0093497710.9906502
ENST00000371917ENST00000415691ARFGEF2chr2047538547+HNF4Achr2043034698+0.010237850.9897621

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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

>5869_5869_1_ARFGEF2-HNF4A_ARFGEF2_chr20_47538547_ENST00000371917_HNF4A_chr20_43034698_ENST00000316099_length(amino acids)=476AA_BP=40
MQESQTKSMFVSRALEKILADKEVKRPQHSQLRRACQVALDTSPSEGTNLNAPNSLGVSALCAICGDRATGKHYGASSCDGCKGFFRRSV
RKNHMYSCRFSRQCVVDKDKRNQCRYCRLKKCFRAGMKKEAVQNERDRISTRRSSYEDSSLPSINALLQAEVLSRQITSPVSGINGDIRA
KKIASIADVCESMKEQLLVLVEWAKYIPAFCELPLDDQVALLRAHAGEHLLLGATKRSMVFKDVLLLGNDYIVPRHCPELAEMSRVSIRI
LDELVLPFQELQIDDNEYAYLKAIIFFDPDAKGLSDPGKIKRLRSQVQVSLEDYINDRQYDSRGRFGELLLLLPTLQSITWQMIEQIQFI
KLFGMAKIDNLLQEMLLGGSPSDAPHAHHPLHPHLMQEHMGTNVIVANTMPTHLSNGQMCEWPRPRGQAATPETPQPSPPGGSGSEPYKL

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

>5869_5869_2_ARFGEF2-HNF4A_ARFGEF2_chr20_47538547_ENST00000371917_HNF4A_chr20_43034698_ENST00000316673_length(amino acids)=476AA_BP=40
MQESQTKSMFVSRALEKILADKEVKRPQHSQLRRACQVALDTSPSEGTNLNAPNSLGVSALCAICGDRATGKHYGASSCDGCKGFFRRSV
RKNHMYSCRFSRQCVVDKDKRNQCRYCRLKKCFRAGMKKEAVQNERDRISTRRSSYEDSSLPSINALLQAEVLSRQITSPVSGINGDIRA
KKIASIADVCESMKEQLLVLVEWAKYIPAFCELPLDDQVALLRAHAGEHLLLGATKRSMVFKDVLLLGNDYIVPRHCPELAEMSRVSIRI
LDELVLPFQELQIDDNEYAYLKAIIFFDPDAKGLSDPGKIKRLRSQVQVSLEDYINDRQYDSRGRFGELLLLLPTLQSITWQMIEQIQFI
KLFGMAKIDNLLQEMLLGGSPSDAPHAHHPLHPHLMQEHMGTNVIVANTMPTHLSNGQMCEWPRPRGQAATPETPQPSPPGGSGSEPYKL

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

>5869_5869_3_ARFGEF2-HNF4A_ARFGEF2_chr20_47538547_ENST00000371917_HNF4A_chr20_43034698_ENST00000415691_length(amino acids)=466AA_BP=40
MQESQTKSMFVSRALEKILADKEVKRPQHSQLRRACQVALDTSPSEGTNLNAPNSLGVSALCAICGDRATGKHYGASSCDGCKGFFRRSV
RKNHMYSCRFSRQCVVDKDKRNQCRYCRLKKCFRAGMKKEAVQNERDRISTRRSSYEDSSLPSINALLQAEVLSRQITSPVSGINGDIRA
KKIASIADVCESMKEQLLVLVEWAKYIPAFCELPLDDQVALLRAHAGEHLLLGATKRSMVFKDVLLLGNDYIVPRHCPELAEMSRVSIRI
LDELVLPFQELQIDDNEYAYLKAIIFFDPDAKGLSDPGKIKRLRSQVQVSLEDYINDRQYDSRGRFGELLLLLPTLQSITWQMIEQIQFI
KLFGMAKIDNLLQEMLLGGSPSDAPHAHHPLHPHLMQEHMGTNVIVANTMPTHLSNGQMSTPETPQPSPPGGSGSEPYKLLPGAVATIVK

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

>5869_5869_4_ARFGEF2-HNF4A_ARFGEF2_chr20_47538547_ENST00000371917_HNF4A_chr20_43034698_ENST00000443598_length(amino acids)=419AA_BP=40
MQESQTKSMFVSRALEKILADKEVKRPQHSQLRRACQVALDTSPSEGTNLNAPNSLGVSALCAICGDRATGKHYGASSCDGCKGFFRRSV
RKNHMYSCRFSRQCVVDKDKRNQCRYCRLKKCFRAGMKKEAVQNERDRISTRRSSYEDSSLPSINALLQAEVLSRQITSPVSGINGDIRA
KKIASIADVCESMKEQLLVLVEWAKYIPAFCELPLDDQVALLRAHAGEHLLLGATKRSMVFKDVLLLGNDYIVPRHCPELAEMSRVSIRI
LDELVLPFQELQIDDNEYAYLKAIIFFDPDAKGLSDPGKIKRLRSQVQVSLEDYINDRQYDSRGRFGELLLLLPTLQSITWQMIEQIQFI

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

>5869_5869_5_ARFGEF2-HNF4A_ARFGEF2_chr20_47538547_ENST00000371917_HNF4A_chr20_43034698_ENST00000457232_length(amino acids)=466AA_BP=40
MQESQTKSMFVSRALEKILADKEVKRPQHSQLRRACQVALDTSPSEGTNLNAPNSLGVSALCAICGDRATGKHYGASSCDGCKGFFRRSV
RKNHMYSCRFSRQCVVDKDKRNQCRYCRLKKCFRAGMKKEAVQNERDRISTRRSSYEDSSLPSINALLQAEVLSRQITSPVSGINGDIRA
KKIASIADVCESMKEQLLVLVEWAKYIPAFCELPLDDQVALLRAHAGEHLLLGATKRSMVFKDVLLLGNDYIVPRHCPELAEMSRVSIRI
LDELVLPFQELQIDDNEYAYLKAIIFFDPDAKGLSDPGKIKRLRSQVQVSLEDYINDRQYDSRGRFGELLLLLPTLQSITWQMIEQIQFI
KLFGMAKIDNLLQEMLLGGSPSDAPHAHHPLHPHLMQEHMGTNVIVANTMPTHLSNGQMSTPETPQPSPPGGSGSEPYKLLPGAVATIVK

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

>5869_5869_6_ARFGEF2-HNF4A_ARFGEF2_chr20_47538547_ENST00000371917_HNF4A_chr20_43034698_ENST00000609795_length(amino acids)=419AA_BP=40
MQESQTKSMFVSRALEKILADKEVKRPQHSQLRRACQVALDTSPSEGTNLNAPNSLGVSALCAICGDRATGKHYGASSCDGCKGFFRRSV
RKNHMYSCRFSRQCVVDKDKRNQCRYCRLKKCFRAGMKKEAVQNERDRISTRRSSYEDSSLPSINALLQAEVLSRQITSPVSGINGDIRA
KKIASIADVCESMKEQLLVLVEWAKYIPAFCELPLDDQVALLRAHAGEHLLLGATKRSMVFKDVLLLGNDYIVPRHCPELAEMSRVSIRI
LDELVLPFQELQIDDNEYAYLKAIIFFDPDAKGLSDPGKIKRLRSQVQVSLEDYINDRQYDSRGRFGELLLLLPTLQSITWQMIEQIQFI

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

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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/chr20:47538547/chr20:43034698)
- 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
ARFGEF2

Q9Y6D5

HNF4A

P41235

FUNCTION: Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the regulation of Golgi vesicular transport. Required for the integrity of the endosomal compartment. Involved in trafficking from the trans-Golgi network (TGN) to endosomes and is required for membrane association of the AP-1 complex and GGA1. Seems to be involved in recycling of the transferrin receptor from recycling endosomes to the plasma membrane. Probably is involved in the exit of GABA(A) receptors from the endoplasmic reticulum. Involved in constitutive release of tumor necrosis factor receptor 1 via exosome-like vesicles; the function seems to involve PKA and specifically PRKAR2B. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. {ECO:0000269|PubMed:12051703, ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15385626, ECO:0000269|PubMed:16477018, ECO:0000269|PubMed:17276987, ECO:0000269|PubMed:18625701, ECO:0000269|PubMed:20360857}.FUNCTION: Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes (PubMed:30597922). Activates the transcription of CYP2C38 (By similarity). Represses the CLOCK-ARNTL/BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698). {ECO:0000250|UniProtKB:P49698, ECO:0000269|PubMed:30530698, ECO:0000269|PubMed:30597922}.

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
TgeneHNF4Achr20:47538547chr20:43034698ENST0000031609901057_13238.333333333333336475.0DNA bindingNuclear receptor
TgeneHNF4Achr20:47538547chr20:43034698ENST0000031667301057_13216.333333333333332453.0DNA bindingNuclear receptor
TgeneHNF4Achr20:47538547chr20:43034698ENST0000041569101057_13238.333333333333336465.0DNA bindingNuclear receptor
TgeneHNF4Achr20:47538547chr20:43034698ENST000004435980857_13238.333333333333336418.0DNA bindingNuclear receptor
TgeneHNF4Achr20:47538547chr20:43034698ENST0000045723201057_13216.333333333333332443.0DNA bindingNuclear receptor
TgeneHNF4Achr20:47538547chr20:43034698ENST00000316099010147_37738.333333333333336475.0DomainNR LBD
TgeneHNF4Achr20:47538547chr20:43034698ENST00000316673010147_37716.333333333333332453.0DomainNR LBD
TgeneHNF4Achr20:47538547chr20:43034698ENST00000415691010147_37738.333333333333336465.0DomainNR LBD
TgeneHNF4Achr20:47538547chr20:43034698ENST0000044359808147_37738.333333333333336418.0DomainNR LBD
TgeneHNF4Achr20:47538547chr20:43034698ENST00000457232010147_37716.333333333333332443.0DomainNR LBD
TgeneHNF4Achr20:47538547chr20:43034698ENST00000316099010368_37638.333333333333336475.0Motif9aaTAD
TgeneHNF4Achr20:47538547chr20:43034698ENST00000316673010368_37616.333333333333332453.0Motif9aaTAD
TgeneHNF4Achr20:47538547chr20:43034698ENST00000415691010368_37638.333333333333336465.0Motif9aaTAD
TgeneHNF4Achr20:47538547chr20:43034698ENST0000044359808368_37638.333333333333336418.0Motif9aaTAD
TgeneHNF4Achr20:47538547chr20:43034698ENST00000457232010368_37616.333333333333332443.0Motif9aaTAD
TgeneHNF4Achr20:47538547chr20:43034698ENST0000031609901060_8038.333333333333336475.0Zinc fingerNR C4-type
TgeneHNF4Achr20:47538547chr20:43034698ENST0000031609901096_12038.333333333333336475.0Zinc fingerNR C4-type
TgeneHNF4Achr20:47538547chr20:43034698ENST0000031667301060_8016.333333333333332453.0Zinc fingerNR C4-type
TgeneHNF4Achr20:47538547chr20:43034698ENST0000031667301096_12016.333333333333332453.0Zinc fingerNR C4-type
TgeneHNF4Achr20:47538547chr20:43034698ENST0000041569101060_8038.333333333333336465.0Zinc fingerNR C4-type
TgeneHNF4Achr20:47538547chr20:43034698ENST0000041569101096_12038.333333333333336465.0Zinc fingerNR C4-type
TgeneHNF4Achr20:47538547chr20:43034698ENST000004435980860_8038.333333333333336418.0Zinc fingerNR C4-type
TgeneHNF4Achr20:47538547chr20:43034698ENST000004435980896_12038.333333333333336418.0Zinc fingerNR C4-type
TgeneHNF4Achr20:47538547chr20:43034698ENST0000045723201060_8016.333333333333332443.0Zinc fingerNR C4-type
TgeneHNF4Achr20:47538547chr20:43034698ENST0000045723201096_12016.333333333333332443.0Zinc fingerNR C4-type

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneARFGEF2chr20:47538547chr20:43034698ENST00000371917+139654_78540.3333333333333361786.0DomainSEC7


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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
ARFGEF2
HNF4A


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 ARFGEF2-HNF4A


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 ARFGEF2-HNF4A


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